Contributors

Editors
Stephen J. McPhee, MD
Professor of Medicine
Division of General Internal Medicine
Department of Medicine
University of California, San Francisco
San Francisco, California

Gary D. Hammer, MD, PhD

Millie Schembechler Professor of Adrenal Cancer
Director, Endocrine Oncology Program
Comprehensive Cancer Center
University of Michigan
Ann Arbor, Michigan

Contributors
Eva M. Aagaard, MD
Associate Professor of Medicine, University of Colorado
Denver School of Medicine, Aurora, Colorado
Case Studies and Answers

Gregory Barsh, MD, PhD

Professor of Pediatrics and Genetics, Stanford University
School of Medicine
Genetic Disease

Douglas C. Bauer, MD
Professor of Medicine, Epidemiology and Biostatistics, Division of General Internal Medicine,
University of California, San Francisco
Thyroid Disease

Karen C. Bloch, MD, MPH

Assistant Professor, Infectious Diseases and Preventive Medicine, Vanderbilt University Medical
Center
Infectious Diseases

Nigel Bunnett, PhD

Professor, University of California, San Francisco
Gastrointestinal Disease

J. Ben Davoren, MD, PhD

Clinical Professor of Medicine, University of California San Francisco; Director, Clinical
Informatics, San Francisco VA Medical Center
Blood Disorders

Tobias Else, MD
Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of
Michigan, Ann Arbor
Disorders of the Adrenal Medulla; Disorders of the Hypothalamus & Pituitary Gland; Disorders
of the Adrenal Cortex

Mikkel Fode
PhD trainee, Department of Urology, Herlev Hospital, Herlev, Denmark
Disorders of the Male Reproductive Tract

Jonathan D. Fuchs, MD, MPH

Assistant Clinical Professor of Medicine, Department of Medicine, University of California, San
Francisco;
Director, Vaccine Studies, HIV Research Section, San Francisco Department of Health, San
Francisco, California
Case Studies and Answers

Janet L. Funk, MD
Associate Professor of Medicine, University of Arizona, Tucson, Arizona
Disorders of the Endocrine Pancreas

Allan C. Gelber, MD, MPH, PhD

Associate Professor of Medicine; Director, Rheumatology Fellowship Program, Johns Hopkins
University School of Medicine
Inflammatory Rheumatic Diseases

Gary D. Hammer, MD, PhD

Millie Schembechler Professor of Adrenal Cancer; Director, Endocrine Oncology Program;
Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan
Disorders of the Adrenal Medulla; Disorders of the Hypothalamus & Pituitary Gland; Disorders
of the Adrenal Cortex

Joachim H. Ix, MD
Assistant Professor, Division of Nephrology, Department of Medicine, University of California
San Diego, The Veteran Affairs San Diego Healthcare Systems, San Diego, California
Renal Disease
Mandana Khalili, MD
Associate Professor of Medicine, University of California San Francisco, San Francisco,
California; Department of Medicine, Director of Clinical Hepatology, San Francisco General
Hospital, San Francisco, California
Liver Disease

Jeffrey L. Kishiyama, MD
Associate Clinical Professor of Medicine, University of California, San Francisco
Disorders of the Immune System

Fred M. Kusumoto, MD
Associate Professor of Medicine, Director of Electrophysiology and Pacing, Division of
Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Jacksonville, Florida
Cardiovascular Disorders: Heart Disease

Yeong Kwok, MD
Assistant Professor of Medicine, Division of General Medicine, Department of Medicine,
University of Michigan
Case Studies and Answers

Stuart M. Levine, MD
Assistant Professor of Medicine, Division of Rheumatology; Co-Director, The Johns Hopkins
Vasculitis Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Inflammatory Rheumatic Diseases

Charles E. Liao, MD
University of California at San Francisco, School of Medicine; San Francisco General Hospital
Liver Disease

Catherine Lomen-Hoerth, MD, PhD

Associate Professor of Neurology, Director, ALS Center, Department of Neurology, University of
California, San Francisco
Nervous System Disorders

Timothy H. McCalmont, MD
Professor of Clinical Pathology & Dermatology, University of California, San Francisco, San
Francisco, California
Diseases of the Skin

Stephen J. McPhee, MD
Professor of Medicine, Division of General Internal Medicine, Department of Medicine,
University of California, San Francisco
Disorders of the Adrenal Medulla; Disorders of the Exocrine Pancreas; Thyroid Disease;
Disorders of the Adrenal Cortex; Disorders of the Male Reproductive Tract

Robert O. Messing, MD
Professor of Neurology, University of California San Francisco; Senior Associate Director, Ernest
Gallo Clinic and Research Center, Emeryville, California
Nervous System Disorders

Jason C. Mills, MD, PhD

Assistant Professor, Department of Pathology & Immunology, Washington University School of
Medicine, St. Louis, Missouri
Gastrointestinal Disease

Igor Mitrovic, MD
Associate Professor, Director of Professional School Education, Department of Physiology,
University of California, San Francisco
Cardiovascular Disorders: Vascular Disease

Mark M. Moasser, MD
Associate Professor of Medicine, Helen Diller Family Comprehensive Cancer Center, University
of California, San Francisco
Neoplasia

Tung T. Nguyen, MD
Clinical Professor of Medicine, Division of General Internal Medicine, University of California,
San Francisco
Liver Disease

Dana A. Ohl, MD
Professor of Urology, University of Michigan, Ann Arbor, Michigan
Disorders of the Male Reproductive Tract

Benjamin D. Parker, MD
Division of Nephrology, Department of Medicine, University of California, San Diego, The
Veteran Affairs San Diego Healthcare Systems, San Diego, California
Renal Disease

Thomas J. Prendergast, MD
Associate Professor of Medicine, Pulmonary & Critical Care Medicine, Oregon Health & Science
University, Portland; Staff Physician, Portland Veterans' Affairs Medical Center
Pulmonary Disease

Karen J. Purcell, MD, PhD

Fertility Physicians of Northern California, San Jose, California
Disorders of the Female Reproductive Tract

Antony Rosen, MB, ChB, BSc (Hons)

Mary Betty Stevens Professor of Medicine, Professor of Pathology; Director, Division of
Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Inflammatory Rheumatic Diseases

Stephen J. Ruoss, MD
Associate Professor of Medicine, Pulmonary and Critical Care Medicine, Stanford University
School of Medicine
Pulmonary Disease

Eric J. Seeley, MD
Fellow in Pulmonary and Critical Care, Department of Medicine, University of California, San
Francisco
Pulmonary Disease

Deborah E. Sellmeyer, MD
Department of Medicine/Endocrinology, Johns Hopkins University School of Medicine,
Baltimore, Maryland;
Department of Medicine/Endocrinology, Johns Hopkins Bayview Medical Center, Baltimore,
Maryland
Disorders of the Parathyroids & Calcium & Phosphorus Metabolism

Dolores M. Shoback, MD
Professor of Medicine, University of California, San Francisco; Staff Physician, San Francisco
Department of Veterans Affairs Medical Center
Disorders of the Parathyroids & Calcium & Phosphorus Metabolism

Diane M. Simeone, MD
Lazar J. Greenfield Professor of Surgery and Professor of Molecular and Integrative Physiology;
Chief, Gastrointestinal Surgery, University of Michigan
Disorders of the Exocrine Pancreas

Jens Snksen, MD, PhD

Professor of Urology; Head, Section of Male Infertility and Microsurgery, Department of
Urology, Herlev Hospital, Herlev, Denmark; University of Copenhagen, Copenhagen, Denmark
Disorders of the Male Reproductive Tract

Christopher J. Sonnenday, MD, MHS

Assistant Professor of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan;
Assistant Professor of Health Management & Policy, University of Michigan School of Public
Health, Ann Arbor, Michigan
Disorders of the Exocrine Pancreas

Thaddeus S. Stappenbeck, MD, PhD

Assistant Professor, Department of Pathology & Immunology, Washington University School of
Medicine, St. Louis, Missouri
Gastrointestinal Disease

Robert N. Taylor, MD, PhD

Vice Chair for Research, Department of Gynecology and Obstetrics, Emory University School of
Medicine
Disorders of the Female Reproductive Tract

Sunny Wang, MD
Hematology/Oncology Fellow, University of California, San Francisco
Blood Disorders
Preface
One of Dr. Jack Lange's goals late in life was to add a pathophysiology text to the Lange series
of unique basic and clinical books that have had such a great impact on health science
education all over the world. Pathophysiology of Disease: An Introduction to Clinical Medicine is
the result, and until he died in 1999, Dr. Lange was one of its editors. The goal of this book is
outlined in the introductory chapter (Chapter 1)to introduce students to clinical medicine by
reviewing the pathophysiologic basis of the symptoms and signs of various common diseases.

The book has proved useful as a text for both pathophysiology and introduction to clinical
medicine courses in medical schools, and it has been popular in similar courses in nursing
schools and allied health programs. It is valuable to students early in their medical school
years by highlighting the clinical relevance of their basic science courses and in preparation for
their USMLE Step 1 examinations. The book is also helpful to students engaged in their internal
medicine and surgery clerkships and to house officers as an up-to-date summary of relevant
physiology and a source of key references. Practitioners (both internists and specialists who
provide generalist care) will find it beneficial as a refresher text, designed to update their
knowledge of the mechanisms underlying diseases. Nurses and other allied health practitioners
have found that its concise format and broad scope facilitate their understanding of basic
disease entities.

Pathophysiology of Disease has been translated into Spanish, Italian, Chinese, Japanese,
Greek, Turkish, Albanian, Portuguese, and Indonesian.

In preparation for this sixth edition, the editors and authors reviewed the entire book. There
have been many revisions aimed at updating information, improving clarity, and eliminating
minor errors. References have also been updated, with emphasis on valuable reviews.
Checkpoints, collections of review questions, continue to appear throughout the chapters.

New to This Edition

Sadly, between publication of the fifth edition and start of work on this sixth edition, Dr.
William Fran Ganong, one of the book's editors for the previous 5 editions, died after a
long illness. This sixth edition is dedicated to him (see Dedication). Thus, a major change with
this new edition is the introduction of a new title page editor, Gary D. Hammer, MD, PhD.
While attending on the wards at the University of California, San Francisco, Dr. Stephen
McPhee first met Dr. Hammer when he was a resident in internal medicine there. Dr. Hammer
is now Millie Schembechler Professor of Adrenal Cancer and Director of the Endocrine Oncology
Program at the Comprehensive Cancer Center, and Associate Professor in the Department of
Internal Medicine in the Metabolism, Endocrinology, and Diabetes Section and Associate
Professor, Department of Molecular and Integrative Physiology, at the University of Michigan.
The combination of his expertise in molecular and integrative physiology and his clinical
proficiency in endocrinology and metabolism make him an ideal editor for this text, which is
intended as a bridge between basic science and clinical understanding. Dr. Hammer's energy
and enthusiasm are apparent in the look and feel of this new edition.

With this sixth edition, the authorship of several chapters has evolved and transitionedthe
editors wish to welcome aboard the following new contributors and thank the following past
contributors who are now departing the book:

Sunny Wang, MD, has joined J. Ben Davoren, MD, PhD, as the coauthor of Chapter 6:
Blood Disorders;

Catherine Lomen-Hoerth, MD, PhD, joins Robert O. Messing, MD, for the current
revision of Chapter 7: Nervous System Disorders, and will take over the chapter in
future editions;

Eric J. Seeley, MD, has joined Thomas J. Prendergast, MD, and Stephen J. Ruoss, MD,
as a coauthor for Chapter 9: Pulmonary Disease;

Igor Mitrovic, MD, has taken over revision of Dr. Fran Ganong's Chapter 11:
Cardiovascular Disorders: Vascular Disease;

Tobias Else, MD, and Dr. Hammer, join Dr. McPhee for the current revisions of Chapter
12: Disorders of the Adrenal Medulla, and Chapter 21: Disorders of the Adrenal
Cortex, and will henceforth take over the updating of these chapters;

Jason C. Mills, MD, PhD, and Thaddeus S. Stappenbeck, MD, PhD, have taken on and
revised Chapter 13: Gastrointestinal Disease as Nigel Bunnett, PhD, and Vishwanath
Lingappa, MD, PhD, have retired from the book;

Mandana Khalili, MD, working with Charles E. Liao, MD, produced the current revision
of Chapter 14: Liver Disease by Tung T. Nguyen, MD, who will retire from the book;

Christopher J. Sonnenday, MD, and Diane M. Simeone, MD, join Dr. McPhee for the
current revision of Chapter 15: Disorders of the Exocrine Pancreas, and will henceforth
take over the chapter from him;

Benjamin D. Parker, MD, has joined Joachim H. Ix, MD, as coauthor of Chapter 16:
Renal Disease;

Mikkel Fode, Jens Snksen, MD, PhD, and Dana A. Ohl, MD, join Dr. McPhee for the
current revision of Chapter 23: Disorders of the Male Reproductive Tract, and will
henceforth take over the chapter; and

Stuart M. Levine, MD, joins Allan C. Gelber, MD, MPH, PhD, and Antony Rosen, MB,
ChB, BSc, as a coauthor of Chapter 24: Inflammatory Rheumatic Diseases.
With these transitions, the content of almost half of the book has benefited from the new
contributors' viewpoint and input.

In addition, as with previous editions, each chapter ends with a collection of Case Studies.
These clinical problems give students an opportunity to test their understanding of the
pathophysiology of each clinical entity discussed and to apply their knowledge to exemplar
clinical situations. With this edition, an additional 22 Case Studies have been added by Yeong
Kwok, MD, bringing the total number to 111; in this effort, Dr. Kwok joined his work to that of
Eva M. Aagaard, MD, and Jonathan D. Fuchs, MD, MPH, who prepared the cases for the
previous editions. Drs. Aagaard and Fuchs have now handed on to Dr. Kwok the task of adding
to and maintaining this valuable learning tool. The editors and chapter authors are indebted to
Drs. Aagaard and Fuchs for their work on the previous five editions. As before, detailed
analyses of the cases appear in Chapter 25: Case Study Answers; Dr. Kwok has added answers
to the new Case Studies and updated the existing answers to reflect the changes made by
chapter authors in their revisions.

Finally, the sixth edition of Pathophysiology of Disease: An Introduction to Clinical Medicine

also introduces an attractive new design with four-color illustrations and layout.

With publication of this sixth edition, the editors want to extend special thanks, not only to the
contributors old and new, but also to the students and colleagues who have offered helpful
comments and criticisms for each of the previous editions. The authors and editors continue to
welcome comments and recommendations for future editions, in writing or via electronic mail.
The editors' and authors' institutional and e-mail addresses are given in the Authors section.

Stephen J. McPhee, MD
San Francisco, California

Gary D. Hammer, MD, PhD

Ann Arbor, Michigan
October 2009