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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, Macedonian, 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 transitioned—the 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 Sønksen, 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

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