Fundamentals of VETERINARY CLINICAL PATHOLOGY. Second Edition

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2 Fundamentals of VETERINARY CLINICAL PATHOLOGY Second Edition

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4 Fundamentals of VETERINARY CLINICAL PATHOLOGY Second Edition Steven L. Stockham Michael A. Scott

5 Steven L. Stockham, DVM, MS, Diplomate, American College of Veterinary Pathologists (Clinical Pathology); Professor in the Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas. Michael A. Scott, DVM, PhD, Diplomate, American College of Veterinary Pathologists (Clinical Pathology), Assistant Professor in the Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan Blackwell Publishing All rights reserved Blackwell Publishing Professional 2121 State Avenue, Ames, Iowa 50014, USA Orders: Office: Fax: Web site: Blackwell Publishing Ltd 9600 Garsington Road, Oxford OX4 2DQ, UK Tel.: +44 (0) Blackwell Publishing Asia 550 Swanston Street, Carlton, Victoria 3053, Australia Tel.: +61 (0) Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee code for users of the Transactional Reporting Service is ISBN-13: /2008. First edition, 2002 Second edition, 2008 Library of Congress Cataloging-in-Publication Data Stockham, Steven L. Fundamentals of veterinary clinical pathology / Steven L. Stockham, Michael A. Scott. 2nd ed. p. ; cm. Includes bibliographical references and index. ISBN-13: (alk. paper) ISBN-10: (alk. paper) 1. Veterinary clinical pathology. I. Scott, Michael A. (Michael Alan), 1957 II. Title. [DNLM: 1. Animal Diseases pathology. 2. Clinical Laboratory Techniques veterinary. 3. Pathology, Veterinary methods. SF S864f 2008] SF772.6.S dc22 The last digit is the print number:

6 CONTENTS Preface vii Acknowledgments ix 1 Introductory Concepts 3 2 Leukocytes 53 3 Erythrocytes Platelets Hemostasis Bone Marrow and Lymph Node Proteins Urinary System Monovalent Electrolytes and Osmolality Blood Gases, Blood ph, and Strong Ion Difference Calcium, Phosphorus, Magnesium, and Their Regulatory Hormones Enzymes Liver Function Glucose, Ketoamines, and Related Regulatory Hormones Exocrine Pancreas and Intestine Lipids Thyroid Function Adrenocortical Function Cavitary Effusions 831 * Color plates between pages 494 and 495 Index 869 v

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8 PREFACE Writing this second edition was motivated by our desire to synthesize and incorporate newer information related to fundamentals of veterinary clinical pathology, and it was driven by the same goals as the first edition: to explain the physiologic, pathologic, and analytical conditions or disorders responsible for abnormal laboratory data, and to do so using consistent terms and a uniform format. Whenever possible, diseases and conditions are grouped by common mechanisms or processes to promote a conceptual understanding of laboratory data that can be generally applied across many species. The content of the first edition was largely preserved, but the second edition contains additional disorders, diagnostic tests, illustrations, references, and pathophysiologic explanations. There are four major changes: (1) the analytical aspects in Chapter 2 of the first edition are now distributed into their respective chapters on leukocytes, erythrocytes, and platelets (Chapters 2 4), (2) the Hemostasis chapter of the first edition is split into two chapters, one focused on nonhemostasis aspects of platelets (Chapter 4) and the other on hemostasis (Chapter 5), (3) a new chapter on cavitary effusions (Chapter 19) focuses on the pathophysiologic processes that create cavitary effusions and relates them to inflammatory, renal, hepatic, electrolyte, protein, and lipoprotein disorders, and (4) the color plate section is revised and expanded to include microscopic images of bone marrow, lymph nodes, and cavitary effusions. Even though the second edition contains more information than the first, it remains focused on disorders occurring in North America and does not address some of the more specialized aspects of veterinary clinical pathology such as therapeutic drug monitoring and molecular diagnostic assays. Coverage of diagnostic cytology is limited because a second volume would be required to do justice to it. Lastly, material is again restricted mostly to dogs, cats, horses, and cattle because these species provide the basis for a fundamental understanding of veterinary clinical pathology. Regrettably, we will likely uncover mistakes in the second edition as we did in the first. Corrections for these mistakes will be available at this textbook s Web site (search FVCP Stockham or FVCP Scott), which is linked to the publisher s Web site and the authors Web sites. Also available in the textbook s Web site are lists of suggested specific objectives that may be used as study guides, and electronic copies of the book s figures available exclusively for educational purposes. Once again, we found the writing of the second edition to be a great learning experience and hope that our efforts facilitate the learning of others. vii

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10 ACKNOWLEDGMENTS FIRST EDITION Many people directly and indirectly assisted in the writing of this book. We thank our fantastic families for providing the never-ending support for our professional pursuits. We thank our excellent veterinary and graduate students for their active participation in their learning their questions frequently provided stimuli for finding better explanations, and their answers provided insight into what they were or were not learning. We thank our mentors (Drs. Jan Krehbiel, Doug Weiss, Harold Tvedten, and Julia Stickle) and coresidents at Michigan State University, who provided excellent specialty training. We thank Dr. Jenni Donald, who actively participated in the planning, reviewing, and critiquing of chapters. We also thank the technologists in the Clinical Pathology Laboratory at the University of Missouri, and especially Kathy Curtis, MT (ASCP), for helping us pursue many unanswered questions and for documenting certain abnormalities. We also appreciate the assistance of Howard Wilson and Don Connors during the generation of the plates and figures. The senior author would not have accepted the challenge of writing this text without the persistent encouragement of a longtime friend, colleague, and excellent teacher Donald A. Schmidt, DVM, PhD, Diplomate, ACVP, Professor Emeritus. Very few people have the opportunity to work with such a great person who was also one of the pioneers in the specialty of veterinary clinical pathology. His statement that students must come first, they are the reason we are here provided the justification for many career decisions. For over 25 years at the University of Missouri, veterinary students (and this senior author) were extremely fortunate to have Dr. Schmidt as a teacher. The specialty in veterinary clinical pathology grew out of the increased use of laboratory tests in veterinary medicine, was promoted in the early 1960s by a society now known as the American Society for Veterinary Clinical Pathology (ASVCP), and then formalized in the early 1970s by the American College of Veterinary Pathologists (ACVP). The authors extend thanks to the ASVCP and ACVP members (and especially charter members and contemporary colleagues) for their leadership, investigations, and instruction. We have made great advances in our understanding of diseases of domestic mammals in the past 40 years, but there are many facts we do not know and processes we do not understand. The clinical laboratories, their dedicated personnel, and their expanding analytical procedures will play a key role in future advances. SECOND EDITION We are still greatly appreciative of the many people who directly or indirectly assisted in the writing of the first edition, and we extend sincere thanks to colleagues, students, and family who supported our efforts to produce the second edition. We appreciate the faculty in our departments and colleges who value the scholarly activities of teaching and the writing of a textbook, and we are especially thankful for the unwavering support of our spouses and for the encouraging feedback offered by veterinary students, residents, and fellow clinical pathologists. ix

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12 Fundamentals of VETERINARY CLINICAL PATHOLOGY Second Edition

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14 Chapter 1 INTRODUCTORY CONCEPTS Clinical Pathology Samples I. Blood Samples and Specimens II. Urine Samples III. Other Body Fluid Samples Major Types of Laboratory Assays Significant Figures Units Reference Intervals Quality of Laboratory Results I. Major Determinants II. Analytical Properties of Assays III. Quality assurance Differences in Laboratory Methods and Their Results Comparison of Assays Which Laboratory Do You Use? Evaluating and Validating Laboratory Methods Diagnostic Properties and Predictive Value of Laboratory Assays Receiver Operating Characteristic (ROC) Curves Herd-based Testing for Cattle

15 4 FUNDAMENTALS OF VETERINARY CLINICAL PATHOLOGY Table 1.1. Abbreviations and symbols in this chapter [ft 4 ] ed Free thyroxine concentration by equilibrium dialysis [x] x concentration (x = analyte) BHB β-hydroxybutyrate Ca 2+ Calcium CLSI Clinical Laboratory Standards Institute CV Coefficient of variation EDTA Ethylenediaminetetraacetic acid fca 2+ Free ionized calcium FN False negative FP False positive ft 4 Free thyroxine IFCC International Federation of Clinical Chemistry IUPAC International Union of Pure and Applied Chemistry K 2 EDTA Dipotassium salt of ethylenediaminetetraacetic acid K 3 EDTA Tripotassium salt of ethylenediaminetetraacetic acid Na 2 EDTA Disodium salt of ethylenediaminetetraacetic acid NCCLS National Committee for Clinical Laboratory Standards NEFA Nonesterified fatty acids (fatty acids) NIST National Institute of Standards and Technology PV( ) Predictive value of a negative test PV(+) Predictive value of a positive test ROC Receiver operating characteristic sd Standard deviation SI Système International d Unités T 3 Triiodothyronine tca 2+ Total calcium TE a Total error allowable TN True negative TP True positive TRH Thyrotropin-releasing hormone tt 4 Total thyroxine U International unit USD Usual standard deviation WRI Within reference interval Note: See Table 1.4 for abbreviations of units of measurement and the figure legends for abbreviations unique to figures. CLINICAL PATHOLOGY I. What is clinical pathology? A. Definitions 1 1. Pathology is the branch of medicine that deals with the basis of disease, especially those structural and functional changes in organs and tissues causing or caused by a disease. In general terms, it is the study of disease.