`
`ANDREOLI
`
`Essentials?
`
`Pharmacosmos v. American Regent - PGR2020-00009
`
`CARPENTER
`
`GRIGGS
`
`LOSCALZO
`
`ee ese ay
`
`Patent Owner Ex. 2014 - Page 1 of 26
`
`

`

`W.B. SAU DERS COMPANY
`A Harcourt Health Sciences Company
`The Curtis Center
`Independence Square West
`Philadelphia, Pennsylvania 19106
`
`Library of Congress Cataloging-in-Publication Data
`
`Cecil essentials of medicine / [edited by] Thomas E. Andreoli, Charles C. J.
`Carpenter, Robert C. Griggs, Joseph Loscalzo.-5th ed.
`
`p. cm.
`
`Includes bibliographical references and index.
`
`ISBN 0-7216-8179-4
`
`1. Internal medicine.
`E.
`Ill. Cecil, Russell L. (Russell La Fayette).
`[DNLM: 1. Internal Medicine. WB 115 C388 2001]
`
`I. Title: Essentials of medicine.
`
`II. Andreoli, Thomas
`
`RC46.C42
`
`2001
`
`616-dc21
`
`99-089413
`
`Senior Developmental Editor: Lynne Gery
`Senior Production Manager: Linda Garber
`Manuscript Editor: Anne Ostroff
`Illustration Specialist: Lisa Lambert
`
`Cecil Essentials of Medicine
`
`ISB. 0- 7216-8179- 4
`
`Copyright © 2001 , 1997, 1993, 1990, 1986 by W.B. Saunders Company
`
`All rights reserved. No part of this publication may be reproduced or transmitted in
`any form or by any means, electronic or mechanical, including photocopy, record(cid:173)
`ing, or any information storage and retrieval system, without permission in writing
`from the publisher.
`
`Printed in the United States of America
`
`Last digit is the print number:
`
`g
`
`8
`
`7
`
`6
`
`5
`
`4
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`3
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`2
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`

`

`EDITOR-I -CHIEF
`Thomas E. Andreoli, M.D., M.A.C.P.
`Professor and The Nolan Chair
`Department of Internal Medicine
`University of Arkansas College of Medicine
`Little Rock, Arkansas
`
`CECIL ESSENTIALS
`OF MEDICINE ~16~~0N
`
`EDITORS
`
`Charles C. J. Carpenter, M.D., M.A.C.P.
`Professor of Medicine
`Director, International Health Institute
`Brown University School of Medicine
`Providence, Rhode Island
`
`Robert C. Griggs, M.D.
`Edward A. and Alma Vollertsen Rykenboer Professor of Neurophysiology
`Chair, Department of Neurology
`University of Rochester School of Medicine and Dentistry
`ew York
`Rochester,
`
`Joseph Loscalzo, M.D., Ph.D.
`Wade Professor and Chair
`Department of Medicine
`Boston University School of Medicine
`Physician-in-Chief
`Boston Medical Center
`Director, Whitaker Cardiovascular Institute
`Boston, Massachusetts
`
`W.B. Saunders Company
`A Harcourt Health Sciences Company
`PH ILADE LPH IA LONDON NEW YORK ST. LOUI S SYDNEY TORONTO
`
`

`

`CONTENTS
`
`SECTION I
`Introduction to Molecular Medicine ... ....... .... 1
`
`I THE MOLECULAR BASIS
`OF HUMAN DISEASE ................................. 3
`Joseph Loscalzo
`Deoxyribonucleic Acid and the Genetic Code 3
`Regulation of Gene Expression 5
`Genetic Variation, Population Diversity, and
`Genetic Polymorphisms 7
`Genes and Human Disease 8
`Gene Mapping 9
`Identifying Mutant Genes 10
`Molecular Diagnostics 11
`Genetic Therapies 12
`Promising Advances 12
`
`SECTION II
`Decision-Making in Medical Practice .. .. ...... 13
`
`2 EVIDENCE-BASED MEDICINE .................... 15
`A wny S. Farajallah • Susan S. Beland
`Searching for Relevant Information 15
`Critica l Appraisal of the Literature 16
`Evaluating Evidence About Diagnostic Tests 16
`Evaluating Evidence About Outcome 17
`Evaluating Evidence About Treatment 17
`Including the Patient in the Decision
`Process 18
`
`SECTION III
`Cardiovascular Disease .................. .. ............. 19
`
`3 STRUCTURE AND FUNCTION
`OF THE NORMAL HEART AND
`BLOOD VESSELS ............... ............. .. ........ 21
`Eric H. Awtry • Joseph Loscalzo
`Microscopic Anatomy 21
`Gross Anatomy 21
`The Circulatory Pathway 22
`The Conduction System 23
`Neural Innervation 24
`Physiology of Contraction 24
`Circulatory Physiology and the Cardiac
`Cycle 24
`Cardiac Performance 25
`Physiology of the Coronary Circulation 27
`
`Physiology of the Systemic Circulation 28
`Physiology of the Pulmonary Circulation 28
`Cardiovascular Response to Exercise 29
`
`4 EVALUATION OF THE PATIENT
`WITH CARDIOVASCULAR DISEASE .......... 30
`Eric H. Awtry• Joseph Loscalzo
`History 30
`Physical Examination 34
`Auscultation 37
`
`5 DIAGNOSTIC TESTS AND
`PROCEDURES IN THE PATIENT
`WITH CARDIOVASCULAR DISEASE .... .... .. 43
`Lisa A. Mendes • Joseph Loscalzo
`Chest Radiography 43
`Electrocardiography 43
`Abnormal ECG Patterns 45
`Long-Term Ambu latory ECG Recording 47
`Stress Testing 48
`Echocardiography 50
`Nuclear Cardiology 52
`Cardiac Catheterization 52
`Right-Sided Heart Catheterization 53
`Other Procedures 53
`Noninvasive Vascular Testing 55
`
`6 HEART FAILURE AND
`CARDIOMYOPA THY .................................. 56
`Lisa A. Mendes • Joseph Loscalzo
`Forms of Heart Failure 56
`Adaptive Mechanisms in Heart Failure 56
`Evaluation and Treatment of Patients w ith Heart
`Failure 57
`Treatment 59
`Refractory Heart Failure 60
`Cardiovascular Assist Devices 61
`Acute Pulmonary Edema 61
`Diastolic Dysfunction 61
`
`7 CONGENITAL HEART DISEASE ................ 63
`Lisa A. Mendes • Joseph Loscalzo
`General Considerations 63
`Fetal and Transitional Circulations 63
`Congenital Aortic Stenosis 63
`
`xiii
`
`

`

`xiv
`
`Contents
`
`Coarctation of the Aorta 64
`Pu lmonic Valve Stenosis 65
`Tetra logy of Fallot 65
`Atrial Septa! Defect 66
`Ventricular Septa! Defect 67
`Patent Ductus Arteriosus 68
`Other Congenital Abnormalities 68
`
`8 ACQUIRED VALVULAR HEART
`DISEASE .... .................. .. ............ ... .... ... .. .. . 69
`Lisa A. Mendes • Joseph Loscalzo
`Aortic Stenosis 69
`Aortic Regurgitation 70
`Mitra! Stenosis 72
`Mitra! Regurgitation 74
`Mitra! Valve Prolapse 74
`Tricuspid Stenosis 75
`Tricuspid Regurgitation 75
`Pulmonic Stenosis and Regurgitation 76
`Multivalvular Disease 76
`Rheumatic Heart Disease 76
`Prosthetic Heart Valves 77
`Endocarditis Prophylaxis 77
`
`9 CORONARY HEART DISEASE ................... 79
`Eric H. Awtry • Joseph Loscalzo
`Epidemiology 79
`Pathophysiology of Atherosclerosis 79
`Risk Factors 80
`Nonatherosclerotic Causes of Cardiac
`\schem ia 81
`Pathophysiology and Consequences of
`Myocardial lschemia 82
`An gina Pectoris 82
`Acute Myocardial Infarction 90
`
`10 CARDIAC ARRHYTHMIAS ....................... 100
`Eric H. Awtry • Joseph Loscalzo
`Mechanisms of Arrhythmogenesis 100
`Approach to the Patient with Suspected
`Arrhythmias 1 03
`Management of Cardiac Arrhythmias 104
`Specific Arrhythmias 111
`Heart Block 120
`Clinical Syndromes 122
`Principles of Cardiopulmonary Resuscitation 125
`
`11 MYOCARDIAL AND PERICARDIAL
`DISEASE ............................ .. ........... ........ 127
`Lisa A. Mendes • Joseph Loscalzo
`Myocarditis 127
`Cardiomyopathy 128
`Amyloidosis 131
`Pericardia\ Disease 132
`
`12 OTHER CARDIAC TOPICS ....................... 137
`Lisa A. Mendes • Joseph Loscalzo
`Cardiac Tumors 137
`Traumatic Heart Disease 138
`Cardiac Surgery 139
`Noncardiac Surgery in the Cardiac Patient 140
`Cardiac Disease in Pregnancy 142
`Specific Cardiac Conditions 142
`
`13 VASCULAR DISEASES AND
`HYPERTENSION ...... ..... ............ .. ............. 145
`Eric H. Awtry • Joseph Loscalzo
`Systemic Vascular Disease 145
`Venous Thromboembolic Disease 152
`Pulmonary Vascular Disease 155
`Hypertension 157
`
`SECTION IV
`Pulmonary and Critical Care Medicine ...... 165
`
`14 APPROACH TO THE PATIENT WITH
`RESPIRATORY DISEASE ...... .. ................. 167
`Bonn ie S. Slavis • Kenneth L. Brigham
`Common Presenting Complaints 167
`Physical Examination 169
`
`15 ANATOMIC AND PHYSIOLOGIC
`CONSIDERATIONS .... .............................. 172
`Bonnie S. Slavis • Kenneth L. Brigham
`Anatomy 172
`Physiology 173
`Abnormalities of Pulmonary Gas Exchange 177
`
`16 DIAGNOSTIC TECHNIQUES AND
`THEIR INDICATIONS ...................... .. ....... 181
`Bonnie S. Slavis • Kenneth L. Brigham
`Imaging Procedures 181
`Evaluation of Lung Function 181
`
`17 OBSTRUCTIVE LUNG DISEASE .............. 185
`Bonnie S. Slavis • Kenneth L. Brigham
`Pathophysiology of Air Flow Obstruction 185
`Asthma 186
`Chronic Obstructive Pulmonary Disease 187
`Bronchiectasis 189
`Cystic Fibrosis 189
`Treatment 190
`
`18
`
`INTERSTITIAL AND INFILTRATIVE
`LUNG DISEASE .............. ..... .. .................. 194
`Bonnie S. Slavis • Kenneth L. Brigham
`Pathophysiology and Clinical
`Manifestations 194
`
`19 DISORDERS OF THE PLEURAL
`SPACE, MEDIASTINUM, AND
`CHEST WALL ........................ .. ................ 201
`Bonnie S. Slavis • Kenneth L. Brigham
`Pleural Disease 201
`Mediastinal Disease 203
`Chest Wall Disease 203
`
`20 NEOPLASTIC DISEASES OF THE
`LUNG ............... .. .......................... ...... ..... 206
`Bonnie S. Slavis • Kenneth L. Brigham
`Risk Factors 206
`Pathology 206
`Clinical Presentation 206
`Diagnosis and Evaluation 207
`Solitary Pulmonary Nodule 208
`Treatment and Prognosis 209
`
`

`

`Diagnostic Work-up of Hypoglycemia 603
`Treatment 603
`
`SECTION XII
`Women's Health ..... .... .... ... .......................... . 605
`
`70 WOMEN'S HEAL TH: GENERAL
`CONCEPTS ........... ...... .... ......................... 607
`Sally L. Hodder • Anne L. Ta ylor
`Gender Differences in the Epidemiology of
`Disease by Age Group 607
`Exercise Across the Fem inine Life
`Cycle 608
`Gender and the Patient-Physician
`Interaction 608
`
`71 HORMONAL INFLUENCES ON
`WOMEN'S HEAL TH ................................. 610
`Sally L. Hodder • Anne L. Ta ylor
`Normal Physiology 610
`Dysmenorrhea and Premenstrual
`Syndrome 610
`Amenorrhea 612
`Abnormal Uterine Bleeding 613
`Hirsutism 616
`Hormone Therapy 616
`
`72 DISEASES COMMON IN WOMEN .......... 620
`Sally L. Hodder • Anne L. Taylor
`Cardiovascular Diseases 620
`Osteoporosis 621
`Breast Cancer and Benign Breast
`Disease 622
`Cancer of the Cervix, Uterus, and Ovary 623
`Sexua lly Transmitted Diseases and Pelvic
`Inflammatory Disease 623
`Urinary Incontinence 625
`Domestic Violence 625
`Disorders of Cogn ition and Affect 626
`
`SECTION XIII
`Diseases of Bone and Bone Mineral
`Metabolism ................................................... 627
`
`73 NORMAL PHYSIOLOGY OF BONE
`AND BONE MINERALS ...................... ..... 629
`F. Richard Bringhurst
`Bone Structure and Metabolism 629
`Calcium Metabolism 630
`Phosphorus Metabolism 632
`Magnesium Metabolism 634
`Vitamin D 636
`Calcitonin 637
`
`74 THE PARATHYROID GLANDS,
`HYPERCALCEMIA,AND
`HYPOCALCEMIA ..................................... 639
`Joel S. Finkelstein
`Normal Physiology 639
`Hypercalcemia 640
`Hypocalcemia 645
`
`75 OSTEOMALACIA AND RICKETS ............. 649
`F. Richard Bringhurst
`
`Contents
`
`xix
`
`Pathogenesis 649
`Specific Causes 649
`Clinical Manifestations 652
`Laboratory and Radiographic Features 652
`Diagnosis 652
`Treatment 652
`
`76 OSTEOPOROSIS ...................................... 654
`Joel S. Finkelstein
`General Considerations 654
`Etiology and Pathogenesis 654
`Cli nical Manifestations 656
`Radiographic Findings 656
`Diagnosis 656
`Treatment 658
`Glucocorticoid-lnduced Bone Loss 660
`
`77 PAGET'S DISEASE OF BONE .................. 662
`Margaret P. Seton
`Incidence and Prevalence 662
`Etiology 662
`Pathology and Pathophysiology 662
`Clinical Picture 662
`Associated Conditions 663
`Laboratory Assessment 663
`Treatment 663
`
`SECTION XIV
`Musculoskeletal and Connective
`Tissue Disease .............................................. 667
`
`78 APPROACH TO THE PATIENT WITH
`RHEUMATIC DISEASE ............................ 669
`Joseph H. Korn
`Musculoskeletal History and Examination 669
`Laboratory Testing 671
`Radiograph ic Studies 672
`
`79
`
`RHEUMATOID ARTHRITIS ...... .. ....... .. ...... 673
`Joseph H. Korn
`Epidemiology and Genetics 673
`Pathology 673
`Pathophysiology 673
`Cli nical Features 674
`Diagnosis 675
`Treatment 675
`Prognosis 677
`
`80 SPONDYLOARTHROPATHIES .................. 678
`Peter A. Merkel
`Epidem iology 678
`Pathogenesis 678
`Clinica l Features 679
`Radiograph ic Features 680
`Treatment 681
`
`81 SYSTEMIC LUPUS
`ERYTHEMATOSUS .................................. 682
`Peter A. Merkel
`Pathogenesis 682
`Clinical Manifestations 682
`Cli nica l Subsets 683
`Treatment 684
`
`

`

`21 DISORDERED BREATHING ...................... 210
`Bonnie S. Slavis • Kenneth L. Brigham
`Sleep Apnea Syndrome 210
`Other Breathing Disorders 211
`
`22 ENVIRONMENTAL AND
`OCCUPATIONAL INJURY ... ....... .. ... ..... .... 213
`Bonnie S. Slavis • Kenneth L. Brigham
`Pneumoconioses 213
`Air Pollution 213
`Noxious Gases and Fumes 214
`Smoke Inhalation 214
`High-Altitude Injury 215
`Drowning and Near-Drowning 215
`
`23 ESSENTIALS OF PULMONARY
`CRITICAL CARE MEDICINE ..................... 216
`Bonnie S. Slavis • Kenneth L. Brigham
`Shock 216
`Acute Respiratory Failure 217
`Oxygen Therapy 217
`Mechanical Ventilation 218
`Complications of Endotracheal Intubation and
`Mechanical Ventilation 219
`Systemic Inflammatory Response Syndrome,
`Sepsis, Multiple Organ Dysfunction
`Syndrome. and Adult Respiratory Distress
`Syndrome 219
`
`SECTION V
`Renal Disease .................... ....... .... ............... . 221
`
`24 ELEMENTS OF RENAL STRUCTURE
`AND FUNCTION .... ....... .. ........... ..... ... ...... 223
`Dinesh K. Chatoth
`Elements of Renal Structure 223
`Elements of Renal Physiology 226
`
`25 APPROACH TO THE PATIENT WITH
`RENAL DISEASE ........................ .... ......... 232
`Yousri M. H. Barri • Sudhir V. Shah
`Assessment of the Patient with Renal
`Disease 232
`The Major Renal Syndromes 234
`Radiologic Imaging of the Urinary Tract 236
`Renal Biopsy 237
`
`26 FLUID AND ELECTROLYTE
`DISORDERS ............. ....... .. ........ .... ... .... ... 238
`Thomas E. Andreoli • Sameh R. Abul-Ezz
`Volume Disorders 238
`Osmolality Disorders 241
`Hyponatremia 242
`Hypernatremia 244
`Disturbances in Potassium Balance 245
`Disturbances in Acid-Base Balance 248
`
`27 GLOMERULAR DISEASES ....................... 253
`Sudhir V. Shah
`The Glomerulus 253
`Mechanisms of Glomerular Injury 253
`Clinical Manifestations of Glomerular
`Disease 253
`
`Contents
`
`XV
`
`Approach to the Patient with Glomerular
`Disease 255
`Acute Nephritic Syndrome 255
`Rapidly Progressive Glomerulonephritis 257
`Nephrotic Syndrome 258
`Asymptomatic Urinary Abnormalities 263
`
`28 MAJOR NONGLOMERULAR
`DISORDERS ..... ...... .... ..... ........................ 266
`Dinesh K. Chatoth
`Tubulointerstitial Nephropathy 266
`Cystic Diseases of the Kidney 269
`Urinary Tract Obstruction 271
`Nephrolithiasis 272
`Renal Neoplasia 275
`
`29 VASCULAR DISORDERS OF THE
`KIDNEY ................ ...... .................. ....... ... . 278
`Yousri M. H. Barri
`Renal Arterial Occlusion 278
`lschemic Renal Disease 278
`Arterioles and Microvasculature 279
`Atheroembolic Diseases of the Kidney 279
`Chronic Hypertensive Nephrosclerosis 280
`Malignant Nephrosclerosis 280
`Scleroderma 280
`Hemolytic-Uremic Syndrome and Thrombotic
`Thrombocytopenic Purpura 281
`Antiphospholipid Syndrome and the Kidney 281
`Renal Vein Thrombosis 282
`
`30 ACUTE RENAL FAILURE ......................... 283
`Sudhir V. Shah
`Definition and Etiology 283
`Differential Diagnosis and Diagnostic Evaluation
`of the Patient 283
`Clinical Presentation, Complications, and
`Management of Acute Tubular Necrosis 287
`Specific Causes of Acute Rena l Failure 288
`
`31 CHRONIC RENAL FAILURE ..... ......... .... ... 291
`Mary Jo Shaver
`Adaptation to Nephron Loss 291
`Conservative Management 292
`Clinical Manifestations 293
`Treatment of End-Stage Renal Failure 296
`
`SECTION VI
`Gastrointestinal Disease ............................ . 301
`
`32 COMMON CLINICAL
`MANIFESTATIONS OF
`GASTROINTESTINAL DISEASE ............... 303
`
`A. Abdominal Pain 303
`Edgar Achkar
`Physiology 303
`Causes of Abdominal Pain 303
`Clinical Features 303
`The Acute Abdomen 305
`Chronic Abdominal Pain 305
`
`

`

`xvi
`
`Contents
`
`B. Gastrointestinal Hemorrhage 306
`Gregory Zuccaro, Jr.
`Acute Gastrointestinal Hemorrhage 306
`Chronic Gastrointestinal Hemorrhage 309
`C. Malabsorption 310
`Edy E. Soffer
`Digestion and Absorption of Fat 310
`Digestion and Absorption of Carbohydrates 31 O
`Digestion and Absorption of Proteins 31 O
`Mechanisms of Malabsorption 310
`Multiple Mechanisms 311
`Clinical Manifestations of Malabsorption 311
`Tests for Malabsorption 312
`Approach to the Patient with Suspected
`Malabsorption 314
`Treatment 314
`D. Diarrhea 316
`Edy E. Soffer
`Definition 316
`Normal Physiology 316
`Pathophysiology 317
`Evaluation of Diarrhea 318
`
`33 ENDOSCOPIC AND RADIOGRAPHIC
`PROCEDURES IN
`GASTROENTEROLOGY ........ .. ............. : ... 321
`John J. Vargo II
`Gastrointestinal Endoscopy 321
`Esophagogastroduodenoscopy and
`Enteroscopy 321
`Endoscopic Retrograde
`Cholangiopancreatography 322
`Endoscopic Ultrasonography 323
`Sigmoidoscopy and Colonoscopy 323
`Radiographic Procedures 323
`
`34 DISEASES OF THE ESOPHAGUS ........ .... 326
`Joel E. Richter
`Normal Esophageal Physiology 326
`Clinical Symptoms of Esophageal Disease 326
`Gastroesophageal Reflux Disease 327
`Motility Disorders of the Oropharynx and
`Esophagus 329
`Other Esophageal Disorders 330
`
`Extraintestinal Manifestations 346
`Other Complications 346
`Colon Cancer 347
`Diagnosis 347
`Differential Diagnosis 347
`Treatment 34 7
`
`37 NEOPLASMS OF THE
`GASTROINTESTINAL TRACT .. .. .... .... ...... 351
`Carol A. Burke
`Esophageal Carcinoma· 351
`Gastric Carcinoma 352
`Colorectal Polyps and Carcinoma 353
`The Polyposis Syndromes 354
`Carcinoid Tumors 355
`
`38 DISEASES OF THE PANCREAS ............... 356
`Darwin L. Conw ell
`Anatomy and Physiology 356
`Acute Pancreatitis 358
`Chronic Pancreatitis 361
`Carcinoma of the Pancreas 362
`
`SECTION Vil
`Diseases of the Liver and Biliary
`System ... .. ...... .. ... , ...... ............ ....... .. ....... .... .... 365
`
`39 LABORATORY TESTS IN LIVER
`DISEASE ................ .. ......... .. ... .... ........ ... .. 367
`Michael 8 . Fallon • Brendan M. M cGuire
`Gary A. Abrams • M iguel R. Arguedas
`Clinical Approach to Liver Disease 367
`Laboratory Tests of Liver Function and
`Disease 367
`Liver Biopsy 370
`
`40 JAUNDICE ... .................... ............. .. ......... 371
`Michael 8. Fallon • Brendan M. M cGuire
`Gary A. Abrams • Miguel R. Arguedas
`Bilirubin Metabolism 371
`Laboratory Tests for Bilirubin 371
`Clinical Classification 372
`Approach to Diagnosis 374
`
`35 DISEASES OF THE STOMACH AND
`DUODENUM ............. .. ................... .... .. .. . 332
`Gary W. Falk
`Gastroduodenal Anatomy 332
`Gastroduodenal Mucosa\ Secretion and
`Protective Factors 332
`Gastroduodenal Motor Physiology 333
`Gastritis 334
`Peptic Ulcer Disease 335
`Zollinger-Ellison Syndrome 341
`Delayed Gastric Emptying 342
`Rapid Gastric Emptying 343
`
`36
`
`INFLAMMATORY BOWEL DISEASE ........ 345
`Aaron Brzezinski
`Etiology 345
`Incidence and Epidemiology 345
`Ulcerative Colitis: Clinical Features 346
`Crohn's Disease: Clinical Features 346
`
`41 ACUTE AND CHRONIC HEPATITIS .... ..... 376
`Michael 8. Fallon • Brendan M . McGuire
`Gary A. Abrams • M iguel R. Arguedas
`Acute Hepatitis 376
`Chronic Hepatitis 383
`
`42 FULMINANT HEPATIC FAILURE ............. 385
`M ichael 8. Fallon • Brendan M. McGuire
`Gary A. Abrams • Miguel R. Arguedas
`Diagnosis 385
`Treatment 385
`Hepatic Transplantation 386
`Prognosis 386
`
`4 3 CIRRHOSIS OF THE LIVER AND ITS
`COMPLICATIONS ......... ......... .. ............... . 387
`M ichael 8 . Fallon • Brendan M. McGuire
`Gary A. Abrams • Miguel R. Arguedas
`Clinical and Laboratory Features 387
`Specific Causes 387
`
`

`

`Major Complications 388
`Hepatic Transplantation 392
`
`44 NEOPLASTIC, INFILTRATIVE, AND
`VASCULAR DISEASES OF THE
`LIVER .. .. ..... ........ .... ........ .... ... ......... ... ... .. . 394
`Michael 8. Fallon • Brendan M. M cGuire
`Gary A. Abrams • Miguel R. Arguedas
`Hepatic Neoplasms 394
`Liver Abscess 395
`Granulomatous Liver Disease 395
`Diagnostic Approach to Hepatic Lesions 396
`Vascular Disease of the Liver 396
`
`45 DISORDERS OF THE GALLBLADDER
`AND BILIARY TRACT .. ... .... .... ...... .. ... ...... 398
`M ichael 8 . Fallon • Brendan M. McGuire
`Gary A. Abrams • M iguel R. Arguedas
`Normal Biliary Physiology 398
`Pathophysiology of Gallstone Formation
`(Cholelithiasis) 398
`Cli nica l Manifestations of Gallstones 399
`
`SECTION VIII
`Hematologic Disease ................................. .. 403
`
`46 HEMATOPOIESIS AND
`HEMATOPOIETIC FAILURE ....... ....... ....... 405
`Eunice S. Wang • Nancy Berliner
`Hematopoietic Tissues 405
`Stem Cell Theory of Hematopoiesis 405
`Hematopoietic Differentia tion Pathw ay 406
`Disorders of Hematopoiesis 408
`
`47 CLONAL DISORDERS OF THE
`HEMATOPOIETIC STEM CELL .. .... ........... 410
`Eunice S. Wang • Nancy Berliner
`Myelodysplastic Disorders 4 1 O
`Myeloproliferative Disord ers 412
`Chron ic Myelogenous Leukemia 414
`Acute Leukemias 415
`
`48 DISORDERS OF RED BLOOD CELLS ....... 419
`Nancy Berliner
`Normal Red Blood Cell Structure and
`Function 419
`Clinical Approach to Anemia 419
`Evaluation of Hypoproliferative Anemia 420
`
`49 CLINICAL DISORDERS OF
`NEUTROPHILS .................. ...................... 431
`Nancy Berliner
`Normal Granulocyte Development, Structure,
`and Function 431
`Determinants of Periphera l Neutrophil
`Number 432
`Eval uation of Leukocytosis (Neutrophilia) 433
`Evaluation of Leukopenia (Neutropenia) 433
`
`50 DISORDERS OF LYMPHOCYTES ............. 435
`Jill Lacy
`Cel ls of the Immune System: Lymphocyte
`Development, Function, and Localization 435
`Neoplasia of Lymphoid Origin 437
`
`Contents
`
`xvii
`
`51 NORMAL HEMOSTASIS ...... ... ....... ........ .. 449
`Henry M. Rinder
`Vascular Wall Physiology 449
`Platelet Physiology 450
`Coagulation Cascade 453
`Endothelial-Associated Fibrinolysis 456
`
`52 DISORDERS OF HEMOSTASIS:
`BLEEDING ........... ................... .. ..... ........ .. 457
`Henry M. Rinder
`Clinical Evaluation of Bleeding 457
`Vascular Causes of Bleeding 457
`Bleeding Caused by Platelet Disorders:
`Thrombocytopenia 459
`Bleeding Caused by Platelet Disorders:
`Qua litative Platelet Defects 465
`Fibrinogen Disorders 468
`Bleeding Caused by Coagulation Factor
`Disorders 469
`Bleeding in Patients with a Normal Laboratory
`Screen 471
`
`53 DISORDERS OF HEMOSTASIS:
`THROMBOSIS ......................................... 473
`Henry M. Rinder
`Clinical Evaluation of Thrombosis 473
`Vascular Causes of Thrombosis 473
`Atherothrombosis 473
`Inherited Risk Factors for Venous
`Thrombosis 475
`Acquired Risk Factors for Venous
`Thrombosis 476
`Hypercoagulability and Platelet Disorders 477
`Laboratory Evaluation of Thrombosis 477
`Therapy for Venous Thromboembolism 478
`Venous Thromboembol ism During
`Pregnancy 480
`Perioperative Anticoagulation 480
`Future Anticoagulant Strategies 481
`
`SECTION IX
`Oncologic Disease ... ........... ... ................. .... . 483
`
`54 CANCER ETIOLOGY: ONCOGENES
`AND ENVIRONMENTAL/TOXIC
`FACTORS .................... .. .. ............ ............ 485
`Christopher E. Desch
`Cancer Phenotype 485
`Cancer Genetics 485
`Etiology 486
`
`55 CANCER EPIDEMIOLOGY AND
`CANCER PREVENTION ...... ...................... 489
`Jennifer J. Griggs
`Cancer Epidemiology 489
`Cancer Preventi on 489
`
`56 SOLID TUMORS ...... .... ......... .... ... ............ 493
`Jennifer J. Griggs • Christopher E. Desch
`Lung Cancer 493
`Gastrointestina l Cancers 495
`Breast Cancer 498
`Genitourinary Cancers 499
`Melanoma 503
`
`

`

`xviii
`
`Contents
`
`57 COMPLICATIONS OF CANCER ................ 505
`Jennifer J. Griggs
`Spinal Cord Compression 505
`Superior Vena Cava Syn drome 506
`Hypercalcemia 506
`Paraneoplastic Syndromes 507
`
`58 PRINCIPLES OF CANCER
`TREATMENT ......................... .. ..... ........... 508
`Christopher E. Desch
`Radiology 508
`Surgery 508
`Radiation Therapy 508
`Chemotherapy 509
`Hormonal Therapy 510
`Supportive Care 511
`Biologic Therapy 511
`Bone Marrow Transplantation 511
`
`SECTION X
`Metabolic Disease .......................... .............. 513
`
`59 EATING DISORDERS ............................... 515
`Peter N. Herbert
`Obesity 515
`Anorexia Nervosa and Bulimia Nervosa 519
`
`60 PRINCIPLES OF NUTRITIONAL
`SUPPORT IN ADULT PATIENTS ............. 522
`Peter N. Herbert
`Nutritional Assessment 522
`Route of Nutritional Support 522
`Water 523
`Calories and Protein 523
`Vitamins and Minerals 524
`Home Nutritional Support 524
`
`61 DISORDERS OF LIPID METABOLISM ...... 526
`Peter N. Herbert
`Plasma Lipoprotein Physiology 526
`Evaluation of Serum Lipoprotein
`Concentrations 527
`Elevated Chylomicrons, VLDL, and IDL 528
`Treatment of Hypertriglyceridemia 529
`Elevated LDL 530
`Treatment of Hypercholesterolemia 530
`Lipids and Vascular Disease 531
`
`62 DISORDERS OF METALS AND
`METALLOPROTEINS ...... .. .. .. ................... 533
`Peter N. Herbert
`Wilson's Disease 533
`Treatment 534
`Hemochromatosis 534
`Porphyrias 536
`
`63
`
`INHERITED DISORDERS OF
`CONNECTIVE TISSUE ............................. 539
`Peter N. Herbert
`Collagen Disorders 539
`Marfan's Syndrome 540
`Pseudoxanthoma Elasticum 541
`
`SECTION XI
`Endocrine Disease .. .. .................................... 543
`
`64 HYPOTHALAMIC-PITUITARY AXIS .......... 545
`Vivien Herman-Bonert
`Anatomy 545
`Anterior Pituitary Hormone Physiology and
`Testing 545
`Neuroradiologic Eva luation of the Pituitary
`Gland 548
`Pituitary and Hypothalamic Disorders 548
`Pituitary Tumors 550
`The Posterior Pituitary Gland 552
`
`65 THE THYROID GLAND .............. .. ............ 555
`Vivien Herman-Bonert • Theodore C.
`Friedman
`Thyroid Hormone Physiology 555
`Thyroid Evaluation 556
`Hyperthyroidism 557
`Graves' Disease 557
`Toxic Adenoma 559
`Toxic Multinodular Goiter 559
`Thyroiditis 559
`Thyrotoxicosis Factitia 560
`Rare Causes of Thyrotoxicosis 560
`Hypothyroidism 560
`Goiter 562
`Sol itary Thyroid Nodules 562
`Thyroid Carcinoma 563
`
`66 THE ADRENAL GLAND ... ....... .. .. .. .......... . 564
`Theodore C. Friedman
`Physiology 564
`Adrenal Insufficiency 565
`Hyporeninemic Hypoaldosteronism 568
`Congenital Adrenal Hyperplasia 568
`Syndromes of Adrenocorticoid
`Hyperfunction 569
`Adrenal Medullary Hyperfunction 574
`
`67 MALE REPRODUCTIVE
`ENDOCRINOLOGY .... .................. ... ......... 575
`Glenn D. Braunstein
`Hypogonadism 575
`Erectile Dysfunction 579
`Gynecomastia 579
`Testicular Tumors 580
`Benign Prostatic Hyperplasia 581
`Carcinoma of the Prostate 581
`
`68 DIABETES MELLITUS ......................... .... . 583
`Philip Barnett • Glenn D. Braunstein
`Definition 583
`Diagnosis 583
`Classification 585
`Pathogenesis 586
`Management 588
`Complications 594
`
`69 HYPOGLYCEMIA ....... ......... ....... .... .......... 599
`Ph ilip Barnett
`Definition 599
`Physiology of Glucose Homeostasis 599
`Clinical Classification of Hypoglycemia 600
`
`

`

`xx
`
`Contents
`
`82 ANTIPHOSPHOLIPID ANTIBODY
`SYNDROME .... .. .................... .. ............. .. . 687
`Peter A. Merkel
`Etiology 687
`Clinical Features 687
`Diagnosis 687
`Treatment 688
`
`83 SYSTEMIC SCLEROSIS
`(SCLERODERMA) .... .. ............ .. .... ...... .. .. .. 689
`Joseph H. Korn
`Epidemiology and Genetics 689
`Pathology and Pathophysiology 689
`Clinical Features 689
`Diagnosis and Differentia l Diagnosis 691
`Treatment 691
`Prognosis 693
`
`84
`
`IDIOPATHIC INFLAMMATORY
`MYOPATHIES ... ....................................... 694
`Robert W. Simms
`Pathology and Pathophysiology 694
`Clinical Presentation 694
`Diagnosis 696
`Differential Diagnosis 696
`Treatment 696
`
`85 SJOGREN 'S SYNDROME .......... .. ............ 698
`Peter A. Merkel
`Clinical Features 698
`Diagnosis 698
`Treatment 700
`
`86 VASCULITIDES ...... ........ .. .... ...... .. ............ 701
`Peter A. Merkel
`Classification 701
`Pathogenesis 701
`Clinical Features 702
`Specific Types of Vasculitis 702
`Diagnosis 704
`Autoantibodies and Vasculitis 705
`Treatment 705
`
`87 CRYSTAL ARTHROPATHIES .. .................. 707
`Joseph H. Korn
`Gout 707
`Calcium Pyrophosphate Deposition Disease 711
`Other Crystal Disorders 711
`
`88 OSTEOARTHRITIS ...................... .. ........... 712
`Robert W. Simms
`Pathology 712
`Cl inical Features and Diagnosis 713
`Treatment 714
`
`89 NONARTICULAR SOFT TISSUE
`DISORDERS .............. .... ........ .. .... ............ 715
`Robert W. Simms
`Etiology and Pathogenesis 715
`Classification of Bursae 715
`Diagnosis of Nonarticular Soft Tissue
`Disorders 716
`Bursitis 716
`Tendinitis 717
`Fibromyalgia Syndrome 717
`
`90 RHEUMATIC MANIFESTATIONS OF
`SYSTEMIC DISORDERS .......................... 720
`Robert W. Simms
`Rheumatic Syndromes Associated with
`Malignancy 720
`Hematologic Disorders 721
`Gastrointestinal Diseases 722
`Endocrine Disorders 723
`Sarcoidosis 724
`
`SECTION XV
`Infectious Disease ... ............ ... .. ......... .. ....... . 725
`
`9 1 ORGANISMS THAT INFECT
`HUMANS .............................. .... ....... ....... 727
`Michael M. Lederman
`Viruses 727
`Chlamydiae 727
`Rickettsiae 728
`Mycoplasma 728
`Bacteria 728
`Fungi 730
`Protozoans 731
`Helminths 732
`
`92 HOST DEFENSES AGAINST
`INFECTION .... ..... ... .................................. 733
`Robert A. Salata
`Local Barriers to Infection 733
`Components of the Immune System 734
`Nonspecific Effector Mechanisms 737
`Resistance to Extracellular Bacteria:
`Encapsulated Organ isms 738
`Resistance to Obligate Intracellular Parasites:
`Viruses 739
`Resistance to Facultative Intracellular Parasites:
`Mycobacterium tuberculosis 740
`
`93 LABORATORY DIAGNOSIS OF
`INFECTIOUS DISEASES .... ...................... 741
`Michael M. Lederman
`Diagnosis by Direct Visualization of the
`Organ ism 741
`Diagnosis by Detection of M icrobial
`Antigens 742
`Diagnosis by Exam ination of Host Immune or
`Inflammatory Responses 742
`Assays that Detect M icrobial Nucleoside
`Sequences 743
`Diagnosis by Isolation of the Organ ism in
`Culture 743
`Vira l Isolation 744
`Isolation of Rickettsia, Chlamydia, and
`Mycoplasma 744
`Bacterial Isolation 744
`Isolation of Fungi and Mycobacteria 744
`
`94 ANTIMICROBIAL THERAPY ..................... 745
`M ichael M. Lederman
`The Pathogen 745
`Site of Infection 745
`Characteristics of the Antimicrobial 746
`Route of Administration 746
`Duration of Therapy 746
`
`

`

`Combinations 749
`Monitoring of Antimicrobial Therapy 749
`Antiviral Agents 749
`Antifunga l Agents 749
`Antimicrobial Resistance Testing 749
`
`95 FEVER AND FEBRILE SYNDROMES .. ...... 750
`Robert A. Salata
`Regulation of Body Temperature 750
`Fever and Hypertherm ia 750
`Acute Febrile Syndromes 752
`Fever of Unknow n Origin 760
`Factitious or Self-Induced Fever 763
`
`96 BACTEREMIA .... .... ... ............ ..... .. ... ......... 765
`Robert A. Salata
`Epidemiology 765
`Pathogenesis 766
`Clinical Manifestations 767
`Diagnosis 769
`Therapy 769
`
`97
`
`98
`
`99
`
`INFECTIONS OF THE NERVOUS
`SYSTEM ..... ... .. ..... ..... .... ............... ........ ... 771
`Robert A. Salata
`Meningitis 772
`Encephal itis 778
`Rabies 779
`Spectrum of Tuberculous, Funga l, and Parasitic
`Infections 779
`
`INFECTIONS OF THE HEAD AND
`NECK ... .... ........ ......... ........ ... ........ ....... ..... 782
`Michael M. Lederman
`Infections of the Ear 782
`Infections of the Nose and Sinuses 782
`Infections of the Mouth and Pharynx 783
`
`INFECTIONS OF THE LOWER
`RESPIRATORY TRACT ..... ............ ........... . 788
`Michael M. Lederman
`Pathogenesis 788
`Epidemiology 789
`Differential Diagnosis 789
`Diagnosis 790
`Specific Pathogenic Organisms 791
`Treatment and Outcome 795
`Prevention 796
`
`100
`
`INFECTIONS OF THE HEART AND
`VESSELS ...... ....................... ... .......... ...... . 798
`Michael M. Lederman
`Infective Endocarditis 798
`Prosthetic Valve Endocarditis 802
`Prophylaxis of Infective Endocarditis 803
`Bacterial Endarteritis and Suppurative
`Ph lebitis 804
`
`101 SKIN AND SOFT TISSUE
`INFECTIONS ....... ............... ..... ........ ........ . 805
`Michael M. Lederman
`Superficia l Infections of the Skin 805
`Deeper Infections of the Skin and Soft
`Tissue 809
`
`Contents
`
`xxi
`
`102
`
`103
`
`104
`
`105
`
`INTRA-ABDOMINAL ABSCESS AND
`PERITONITIS ..... ... .... ............... ................ 811
`Michael M. Lederman
`Intra-Abdominal Abscess 81 1
`Abscesses of Solid Organs 811
`Extraviscera l Abscesses 813
`Peritonitis 813
`
`INFECTIOUS DIARRHEA ..... ............ .. .. .... . 815
`Michael M. Lederman
`Pathogenesis and Pathophysiology: General
`Concepts 815
`Types of Microbial Diarrheal Diseases 815
`General Epidemiologic Considerations 818
`Diagnosis 818
`Management: General Principles of Electrolyte
`Repletion Therapy 818
`
`INFECTIONS INVOLVING BONES
`AND JOINTS ......... ............... .............. ... .. 821
`Michael M. Lederman
`Arthritis 821
`Septic Bursitis 823
`Osteomyelitis 823
`
`INFECTIONS OF THE URINARY
`TRACT ... ... .... .... ... ......... ....... ....... ...... ..... .. 825
`Michael M. Lederman
`Urethritis 825
`Cystitis and Pyelonephritis 825
`Prostatitis 827
`
`106 NOSOCOMIAL INFECTIONS ....... ......... .... 828
`M ichael M. Lederman
`Infection Control 828
`Approach to the Hospita lized Patient with
`Possible Nosocomial Infection 828
`Nosocomial Pneumon ia 829
`lntravascular C