Preface

The goal of Pathophysiology of Disease: An Introduction to Clinical Medicine, as outlined in the introductory chapter (Chapter 1), is 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, physician assistants' training programs, and other 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 general internists and specialists who provide generalist care) will find it beneficial as a refresher text, designed to update their knowledge of the mechanisms underlying 132 commonly encountered diseases and disorders. Nurses, nurse-practitioners, physician assistants, and other allied health practitioners have found that its concise format and broad scope facilitate their understanding of these basic disease entities.

Pathophysiology of Disease has been widely adopted in the United States, Canada, and the United Kingdom, and it has been translated into Spanish, Italian, Chinese, Japanese, Greek, and Turkish. Both the text and its Case Study Questions and Answers are also available online at accessmedicine.mhmedical.com, the online version of McGraw-Hill's many medical textbooks (search under "Books, Library, Basic Science" for "Pathophysiology," listed alphabetically).

In preparation for this eighth edition, the editors and authors reviewed the entire book. There have been many text revisions aimed at updating information, improving clarity, and eliminating minor errors. With emphasis on recent pertinent reviews, references have been entirely updated, as have figures and tables. "Checkpoints," collections of review questions, continue to appear throughout the chapters and have been revised.

Examples of Substantive New Content Found in This Eighth Edition

• Update on components and physiology of normal immunity

• Most recent surveillance case definition for HIV infection

• Explication of the concepts of innate immunity and pathogen-associated molecular patterns

• Totally revised chapter on neoplasia, including 19 new figures and 4 new tables

• New figure illustrating iron transport and regulation in the duodenal enterocyte

• New chapter section on urticaria (perivascular dermatitis)

• New chapter section on various forms of spinocerebellar ataxia

• Clarification in text and figures of regional alterations in the overall distribution of ventilation and perfusion referred to as V̇/Q̇ mismatch, including concepts of anatomic versus alveolar (wasted ventilation) dead space and right-to-left shunt

• Update on genetic factors implicated in asthma risk, as well as allergic versus nonallergic asthma

• Newly rewritten section on idiopathic pulmonary fibrosis as a prototypic restrictive (interstitial) lung disease

• Extensive revision of sections on pulmonary edema, adult respiratory distress syndrome (ARDS), and pulmonary venous thromboembolism

• Expanded material on paragangliomas

• New figures on mechanisms leading to nonalcoholic fatty liver disease and to hepatic steatosis

• New table summarizing adverse prognostic signs in acute pancreatitis derived from the Acute Pancreatitis Classification Working Group's 2012 classification, a revision of the Atlanta international consensus classification and definitions of acute pancreatitis

• New table summarizing genetic syndromes associated with pancreatic cancer

• New table summarizing the prevalence of various causes of end-stage renal disease for U.S. Medicare recipients in the 2016 U.S. Renal Data System

• Revised flowchart summarizing the pathogenesis of bone diseases in chronic kidney disease

• Updated information on familial hypocalcuric hypercalcemia, malignant hypercalcemia, autosomal dominant hypocalcemia, and the autoimmune polyendocrine failure syndromes

• The American Diabetes Association's new diagnosis and etiologic classification of diabetes mellitus

• New figure illustrating the amino acid sequence and covalent structure of human proinsulin

• New schematic diagram of glucose-stimulated insulin release from the pancreatic β cell

• New figure showing how pancreatic islet cell secretions of glucagon (from α cells) and insulin (from β cells), which are reciprocally regulated by glucose, play key roles in maintaining glucose homeostasis

• Diagram demonstrating stages in the development of type 1 diabetes mellitus with the appearance of β-cell autoantibodies, followed by dysglycemia, insulinopenia, and then frank hyperglycemia

• Review of mechanisms of the newest classes of pharmacologic agents approved for type 2 diabetes mellitus

• New figure illustrating modifiable cardiovascular risk factors in individuals with diabetes

• New figure illustrating the control of energy homeostasis by arcuate nucleus neurons, both stimulatory and inhibitory neurons with regard to food intake

• Updated information on fine-needle aspiration biopsy of thyroid nodules

• Update on thyroid disorders in pregnancy

• New schematic drawing of the sequence of changes that occur in the alveolar secretory units and duct system of the female breast before, during, and after pregnancy and lactation

• Update of indicators of mild to moderate versus severe preeclampsia-eclampsia

• Incorporation of new International Federation of Gynecology and Obstetrics classification system for pathogenesis of abnormal uterine bleeding

• Update to pathogenesis and pathophysiology of inflammatory myopathies and rheumatoid arthritis

• New chapter section on spondyloarthropathies, including ankylosing spondylitis, reactive arthritis, inflammatory bowel disease–associated arthritis, and psoriatic arthritis

• Updated references throughout the text, including articles mainly from 2015, 2016, and 2017

• Revised and updated figure citations throughout the text

Each chapter ends with a collection of Case Studies. These clinical problems give readers an opportunity to test their understanding of the pathophysiology of each clinical entity discussed and to apply their knowledge to exemplar clinical situations. In this eighth edition, Yeong S. Kwok, MD, of the University of Michigan, has added an additional 12 Case Studies with questions, bringing the total number to 132, or one for each of the clinical entities discussed in the book's 24 chapters. New Case Study topics include:

• Down syndrome as a result of a balanced robertsonian translocation

• Chronic granulomatous disease

• Malignant hypercalcemia

• Cerebellar ataxia

• Urticaria

• Ulcerative colitis

• Type 1 diabetes mellitus

• Subclinical hypothyroidism

• Subclinical hyperthyroidism

• Amenorrhea caused by polycystic ovary syndrome

• Abnormal vaginal bleeding as a result of endometrial cancer

• Spondyloarthropathy as a result of ankylosing spondylitis

As before, detailed analyses of the Cases appear in Chapter 25: Case Study Answers. There, Dr. Kwok has updated the Answers to the existing 120 Case Study Questions to reflect the changes made by chapter authors in their revisions, and he has added Answers to the Questions for the 12 new Case Studies.

With this eighth edition, the authorship of many chapters has evolved and transitioned—this should not be surprising given the book's multiple editions since it was first published in 1992 and given the transition in location of the book's lead editor from the University of California, San Francisco (Stephen J. McPhee, MD), to the University of Michigan (Gary Hammer, MD, PhD). The editors wish to welcome aboard the following new contributors who are joining the book's authors and to thank the following past contributors who are now departing the book:

• Shane C. Quinonez, MD, of the University of Michigan, has taken over the current revision of Chapter 2, Genetic Disease, from Greg Barsh, MD, PhD, of Stanford University; Dr. Barsh, who has been this chapter's author since the book's first edition, will continue as a coauthor for this eighth edition only

• Jennifer J. Chang, MD, and Suzanne M. Donovan, MD, MPH, joined Jeffrey L. Kishiyama, MD, in revising Chapter 3, Disorders of the Immune System. Sadly, Dr. Kishiyama died during the final production process for this edition; please see the In Memoriam below

• Christina T. Fiske, MD, MPH, of Vanderbilt University, has joined Karen C. Bloch, MD, MPH, in revising Chapter 4, Infectious Diseases

• Weiyun Z. Ai, PhD, MD, of UCSF, has assisted chapter author Mark M. Moasser, MD, by revising the hematologic disorders section of Chapter 5, Neoplasia

• J. Ben Davoren, MD, PhD, of UCSF, has replaced Sunny Wang, MD, with Gerald Hsu, MD, PhD, as coauthor of Chapter 6, Blood Disorders; we would like to thank Dr. Wang for her revisions for the sixth and seventh editions

• Vikram G. Shakkottai, MD, PhD, of the University of Michigan, has taken over the current revision of Chapter 7, Nervous System Disorders, from Catherine Lomen-Hoerth, MD, PhD, of UCSF; Dr. Lomen-Hoerth will continue only once more as coauthor for this eighth edition

• Laura B. Pincus, MD, of UCSF, has replaced Melissa M. Meier, MD, as the coauthor, with Timothy H. McCalmont, MD, of Chapter 8, Diseases of the Skin; we would like to thank Dr. Meier for her revisions for the seventh edition

• Thomas H. Sisson, MD, and Dru Claar, MD, of the University of Michigan, have taken over the current revision of Chapter 9, Pulmonary Disease, from Mark S. Chesnutt, MD, and Thomas J. Prendergast, MD, of Oregon Health and Sciences University; Drs. Chesnutt and Prendergast will continue as coauthors for this eighth edition only. We would like to acknowledge Dr. Prendergast for his role in coauthoring the original chapter in the book's first edition and for his revisions for the next seven editions, and Dr. Chesnutt for his assistance with the seventh and eighth editions

• Lauren Fishbein, MD, PhD, of the University of Colorado, is now coauthor of Chapter 12, Disorders of the Adrenal Medulla, with Tobias Else, MD, of the University of Michigan; after the sixth and seventh editions, Gary Hammer, MD, PhD, has now "retired" from coauthorship of this chapter

• Matthew A. Ciorba, MD, of the Washington University at St. Louis, has now joined his colleague Jason C. Mills, MD, PhD, as coauthor of Chapter 13, Gastrointestinal Disease; we are thankful for the past contributions of Thaddeus S. Stappenbeck, MD, PhD, to its revision for the sixth and seventh editions

• Mandana Khalili, MD, MAS, of UCSF, is now working with Nizar A. Mukhtar, MD, of Seattle's Swedish Medical Center in producing the current revision of Chapter 14, Liver Disease; we are grateful to Blaire Burman, MD, of UCSF for assistance with the seventh edition revision

• Timothy L. Frankel, MD, has now joined his University of Michigan colleague Christopher J. Sonnenday, MD, MHS, in producing the current revision of Chapter 15, Disorders of the Exocrine Pancreas

• Joachim H. Ix, MD, has now "retired" from coauthorship of Chapter 16, Renal Disease, which is now coauthored by Rachel Leah Pearlman, MD, and Michael Heung, MD, MS; we thank Dr. Ix for his revisions in the fifth, sixth, and seventh editions

• Deborah E. Sellmeyer, MD, has now "retired" from coauthorship with Dolores M. Shoback, MD, of Chapter 17, Disorders of the Parathyroids & Calcium and Phosphorus Metabolism; we thank Dr. Sellmeyer for her contributions to the fifth, sixth, and seventh editions

• Nazanene H. Esfandiari, MD, of the University of Michigan, has replaced Douglas C. Bauer, MD, of UCSF, as the coauthor, with Stephen J. McPhee, MD, of Chapter 20, Thyroid Disease; we thank Dr. Bauer for his revisions for the second through seventh editions and note that Dr. McPhee, who has been this chapter's author or coauthor for the prior seven editions, will continue as coauthor for this eighth edition only

• Bansari G. Patel, MD, at Wake Forest University, now joins Erika B. Johnston-MacAnanny, MD, now in Richmond, VA, and Robert N. Taylor, MD, PhD, now at the University of Utah, as a coauthor of Chapter 22: Disorders of the Female Reproductive Tract

• Mikkel Fode, MD, PhD, and Jens Sønksen, MD, PhD, of Herlev & Gentofte Hospital of the University of Copenhagen in Herlev, Denmark, and Dana A. Ohl, MD, of the University of Michigan, have assumed authorship of Chapter 23, Disorders of the Male Reproductive Tract; after seven editions, Stephen J. McPhee, MD, has now "retired" from authorship or coauthorship of this chapter

• Allan C. Gelber, MD, MPH, PhD, and Stuart M. Levine, MD, have been joined by a new coauthor, Erika Darrah, PhD, of Johns Hopkins University, for Chapter 24, Inflammatory Rheumatic Diseases; the chapter authors and textbook editors gratefully acknowledge the intellectual contributions of Antony Rosen, MB, ChB, BSc (Hons), to the content of this chapter in the book's third through seventh editions

With these transitions, the content of more than two-thirds of this eighth edition has greatly benefited from the new contributors' viewpoints and inputs (for instance, by including 36 new illustrations in the book's attractive four-color design and layout).

We are saddened to report that, following submission of the revision of Chapter 3, Disorders of the Immune System, for the eighth edition of Pathophysiology of Disease, its lead author, Jeffrey L. Kishiyama, MD, died.

A graduate of Stanford University with a degree in biology and economics, Dr. Kishiyama received his MD from Creighton University School of Medicine. He did his internal medicine residency at Northwestern University, after which he completed a fellowship in allergy and immunology at the University of California, San Francisco (UCSF). Thereafter, Dr. Kishiyama spent many years on the faculties of both UCSF and Stanford University, where he served in a variety of positions, including director of the UCSF Clinical Immunology Laboratory and director of the UCSF Stanford Allergy and Immunology training program. In addition to his academic positions, Dr. Kishiyama maintained an active clinical practice, treating patients at Allergy Asthma Associates of Northern California.

Jeff first joined the authors of Pathophysiology of Disease as a coauthor with Richard Shames, MD, for its third and fourth editions, published in 2000 and 2003. Thereafter, Jeff continued as a solo author for the fifth edition in 2006, the sixth edition in 2010, and the seventh edition in 2014. For the eighth edition, he recruited coauthors Jennifer J. Chang, MD, Fellow in HIV Medicine, and Suzanne M. Donovan, MD, MPH, Clinical Professor of Medicine, Division of Infectious Diseases, of the UCLA School of Medicine.

Jeff was a superb contributor to Pathophysiology, helping to make understandable the increasingly complex field of immunology. Through the years, our readers, particularly our student readers, have been most grateful for his gift in this regard. As one small example, Jeff more than tripled the size of the introductory table of acronyms and abbreviations used throughout both Chapter 3 and the entire book.

We will greatly miss having Jeff as an outstanding (and timely!) contributor to our wonderful book.

With the publication of this eighth 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 email. The editors' and authors' institutional and email addresses are given in the Authors section.