Harrison's Manual of Medicine 20th Ed PDF

HMOM20_FM_pi-pxviii.indd 1 9/6/19 2:26 PM  EDITORS J. Larry Jameson, MD, PhD Robert G. Dunlop Professor of Medicine Dean, Raymond and Ruth Perelman School of Medicine Executive Vice President, University of Pennsylvania for the Health System...

HMOM20_FM_pi-pxviii.indd 1 9/6/19 2:26 PM  EDITORS J. Larry Jameson, MD, PhD Robert G. Dunlop Professor of Medicine Dean, Raymond and Ruth Perelman School of Medicine Executive Vice President, University of Pennsylvania for the Health System Philadelphia, Pennsylvania Anthony S. Fauci, MD Chief, Laboratory of Immunoregulation Director, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland Dennis L. Kasper, MD William Ellery Channing Professor of Medicine Professor of Immunology Department of Immunology Harvard Medical School Boston, Massachusetts Stephen L. Hauser, MD Robert A. Fishman Distinguished Professor Department of Neurology Director, UCSF Weill Institute for Neurosciences University of California, San Francisco San Francisco, California Dan L. Longo, MD Professor of Medicine Harvard Medical School Senior Physician, Brigham and Women’s Hospital Deputy Editor, New England Journal of Medicine Boston, Massachusetts Joseph Loscalzo, MD, PhD Hersey Professor of the Theory and Practice of Medicine Harvard Medical School Chairman, Department of Medicine Physician-in-Chief, Brigham and Women’s Hospital Boston, Massachusetts HMOM20_FM_pi-pxviii.indd 2 9/6/19 2:26 PM  EDITORS J. Larry Jameson, MD, PhD Anthony S. Fauci, MD Dennis L. Kasper, MD Stephen L. Hauser, MD Dan L. Longo, MD Joseph Loscalzo, MD, PhD New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto HMOM20_FM_pi-pxviii.indd 3 9/6/19 2:26 PM Copyright © 2020, 2016, 2013, 2009, 2005, 2002, 1998, 1995, 1991, 1988 by McGraw-Hill Education. All rights reserved. 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McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.  Contents Contributors.............................................................................................................. xiii Preface..........................................................................................................................xv Acknowledgments................................................................................................... xvii SECTION 1   Care of the Hospitalized Patient 1 Electrolytes....................................................................................1 2 Acid-Base Disorders....................................................................16 3 Diagnostic Imaging in Internal Medicine.....................................22 4 Procedures Commonly Performed by Internists............................26 5 Principles of Critical Care Medicine.............................................32 6 Pain and Its Management............................................................35 7 Assessment of Nutritional Status.................................................40 8 Enteral and Parenteral Nutrition..................................................47 9 Transfusion and Pheresis Therapy................................................49 10 Palliative and End-of-Life Care...................................................51 SECTION 2  Medical Emergencies 11 Cardiovascular Collapse and Sudden Death.................................59 12 Shock..........................................................................................62 13 Narcotic Overdose.......................................................................66 14 Sepsis and Septic Shock...............................................................68 15 Acute Pulmonary Edema.............................................................71 16 Acute Respiratory Distress Syndrome..........................................72 17 Respiratory Failure......................................................................75 18 Confusion, Stupor, and Coma......................................................76 19 Stroke..........................................................................................82 20 Subarachnoid Hemorrhage..........................................................91 21 Increased Intracranial Pressure and Head Trauma.........................93 22 Spinal Cord Compression............................................................98 23 Hypoxic-Ischemic Encephalopathy............................................100 24 Status Epilepticus......................................................................101 25 Diabetic Ketoacidosis and Hyperosmolar Coma.........................103 26 Hypoglycemia............................................................................106 27 Oncologic Emergencies.............................................................109 28 Anaphylaxis...............................................................................114 29 Bites, Venoms, Stings, and Marine Poisonings............................115 v HMOM20_FM_pi-pxviii.indd 5 9/6/19 2:26 PM  vi CONTENTS SECTION 3   Common Patient Presentations 30 Fever, Hyperthermia, and Rash..................................................127 31 Generalized Fatigue...................................................................131 32 Unintentional Weight Loss........................................................135 33 Chest Pain.................................................................................137 34 Palpitations...............................................................................141 35 Dyspnea....................................................................................141 36 Cyanosis....................................................................................144 37 Cough and Hemoptysis..............................................................146 38 Edema.......................................................................................149 39 Abdominal Pain.........................................................................153 40 Nausea, Vomiting, and Indigestion.............................................157 41 Dysphagia.................................................................................161 42 Diarrhea, Malabsorption, and Constipation...............................166 43 Gastrointestinal Bleeding...........................................................174 44 Jaundice and Evaluation of Liver Function.................................178 45 Ascites.......................................................................................186 46 Lymphadenopathy and Splenomegaly........................................189 47 Anemia and Polycythemia..........................................................194 48 Azotemia and Urinary Abnormalities.........................................197 49 Pain and Swelling of Joints.........................................................203 50 Back and Neck Pain...................................................................207 51 Headache..................................................................................215 52 Syncope.....................................................................................223 53 Dizziness and Vertigo................................................................227 54 Acute Visual Loss and Double Vision.........................................230 55 Weakness and Paralysis..............................................................234 56 Tremor and Movement Disorders..............................................237 57 Aphasia.....................................................................................240 58 Sleep Disorders..........................................................................242 SECTION 4  Otolaryngology 59 Sore Throat, Earache, and Upper Respiratory Symptoms............247 SECTION 5  Dermatology 60 General Examination of the Skin...............................................255 61 Common Skin Conditions.........................................................258 HMOM20_FM_pi-pxviii.indd 6 9/6/19 2:26 PM  CONTENTS vii SECTION 6   Hematology and Oncology 62 Examination of Blood Smears and Bone Marrow.......................267 63 Red Blood Cell Disorders..........................................................269 64 Leukocytosis and Leukopenia....................................................275 65 Bleeding and Thrombotic Disorders...........................................278 66 Myeloid Leukemias, Myelodysplasia, and Myeloproliferative Syndromes....................................................285 67 Lymphoid Malignancies............................................................296 68 Skin Cancer...............................................................................309 69 Head and Neck Cancer..............................................................312 70 Lung Cancer..............................................................................314 71 Breast Cancer............................................................................320 72 Tumors of the Gastrointestinal Tract..........................................325 73 Genitourinary Tract Cancer.......................................................337 74 Gynecologic Cancer...................................................................343 75 Tumors of the Nervous System...................................................347 76 Prostate Hyperplasia and Carcinoma..........................................352 77 Cancer of Unknown Primary Site...............................................355 78 Paraneoplastic Endocrine Syndromes.........................................359 79 Neurologic Paraneoplastic Syndromes........................................362 SECTION 7  Infectious Diseases 80 Growing Threats in Infectious Disease.......................................367 81 Infections Acquired in Health Care Facilities..............................371 82 Infections in the Immunocompromised Host.............................376 83 Infective Endocarditis................................................................387 84 Intraabdominal Infections..........................................................398 85 Infectious Diarrheas and Bacterial Food Poisoning.....................403 86 Sexually Transmitted and Reproductive Tract Infections.............417 87 Infections of the Skin, Soft Tissues, Joints, and Bones................433 88 Pneumococcal Infections...........................................................440 89 Staphylococcal Infections...........................................................444 90 Streptococcal/Enterococcal Infections, Diphtheria, and Infections Caused by Other Corynebacteria and Related Species..........................................................................453 91 Meningococcal and Listerial Infections......................................463 92 Infections Caused by Haemophilus, Bordetella, Moraxella, and HACEK Group Organisms.................................................467 HMOM20_FM_pi-pxviii.indd 7 9/6/19 2:26 PM  viii CONTENTS 93 Diseases Caused by Gram-Negative Enteric Bacteria and Pseudomonads....................................................................473 94 Infections Caused by Miscellaneous Gram-Negative Bacilli........483 95 Anaerobic Infections..................................................................490 96 Nocardiosis, Actinomycosis, and Whipple’s Disease...................498 97 Tuberculosis and Other Mycobacterial Infections.......................503 98 Lyme Disease and Other Nonsyphilitic Spirochetal Infections..................................................................................515 99 Rickettsial Diseases....................................................................521 100 Mycoplasma pneumoniae, Legionella Species, and Chlamydia pneumoniae....................................................................531 101 Chlamydia trachomatis and Chlamydia psittaci................................535 102 Infections with Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, Epstein-Barr Virus, and Human Herpesvirus Types 6, 7, and 8.........................................537 103 Influenza and Other Viral Respiratory Diseases.........................551 104 Rubeola, Rubella, Mumps, and Parvovirus Infections.................555 105 Enterovirus Infections...............................................................561 106 Insect- and Animal-Borne Viral Infections.................................564 107 HIV Infection and AIDS...........................................................572 108 Pneumocystis Pneumonia, Candidiasis, and Other Fungal Infections.............................................................588 109 Overview of Parasitic Infections.................................................606 110 Malaria, Toxoplasmosis, Babesiosis, and Other Protozoal Infections........................................................610 111 Helminthic Infections and Ectoparasite Infestations..................625 SECTION 8  Cardiology 112 Physical Examination of the Heart.............................................639 113 Electrocardiography...................................................................644 114 Noninvasive Examination of the Heart.......................................648 115 Congenital Heart Disease in the Adult.......................................653 116 Valvular Heart Disease...............................................................658 117 Cardiomyopathies and Myocarditis............................................666 118 Pericardial Disease.....................................................................671 119 Hypertension.............................................................................676 120 Metabolic Syndrome..................................................................682 121 ST-Segment Elevation Myocardial Infarction............................684 122 Unstable Angina and Non-ST-Elevation Myocardial Infarction................................................................694 HMOM20_FM_pi-pxviii.indd 8 9/6/19 2:26 PM  CONTENTS ix 123 Chronic Stable Angina...............................................................698 124 Bradyarrhythmias......................................................................703 125 Tachyarrhythmias......................................................................706 126 Heart Failure and Cor Pulmonale...............................................715 127 Diseases of the Aorta.................................................................721 128 Peripheral Vascular Disease........................................................724 129 Pulmonary Hypertension...........................................................727 SECTION 9  Pulmonology 130 Diagnostic Procedures in Respiratory Disease............................731 131 Asthma......................................................................................734 132 Environmental Lung Diseases....................................................738 133 Chronic Obstructive Pulmonary Disease....................................741 134 Pneumonia, Bronchiectasis, and Lung Abscess...........................745 135 Pulmonary Thromboembolism and Deep-Vein Thrombosis.......754 136 Interstitial Lung Disease............................................................758 137 Diseases of the Pleura................................................................763 138 Diseases of the Mediastinum......................................................766 139 Disorders of Ventilation.............................................................767 140 Sleep Apnea...............................................................................768 SECTION 10   Nephrology 141 Acute Renal Failure...................................................................771 142 Chronic Kidney Disease and Uremia..........................................776 143 Dialysis......................................................................................778 144 Renal Transplantation................................................................781 145 Glomerular Diseases..................................................................784 146 Renal Tubular Disease...............................................................793 147 Dysuria, Urinary Tract Infections, Bladder Pain, and Interstitial Cystitis.....................................................................800 148 Nephrolithiasis..........................................................................805 149 Urinary Tract Obstruction.........................................................807 SECTION 11    Gastroenterology 150 Peptic Ulcer and Related Disorders............................................811 151 Inflammatory Bowel Diseases....................................................817 152 Colonic and Anorectal Diseases.................................................823 153 Cholelithiasis, Cholecystitis, and Cholangitis.............................828 154 Pancreatitis................................................................................835 HMOM20_FM_pi-pxviii.indd 9 9/6/19 2:26 PM  x CONTENTS 155 Acute Hepatitis..........................................................................840 156 Chronic Hepatitis......................................................................847 157 Cirrhosis and Alcoholic Liver Disease........................................855 158 Portal Hypertension...................................................................860 SECTION 12    Allergy, Clinical Immunology, and Rheumatology 159 Diseases of Immediate-Type Hypersensitivity.............................863 160 Primary Immune Deficiency Diseases........................................868 161 Systemic Lupus Erythematosus..................................................871 162 Rheumatoid Arthritis................................................................873 163 The Spondyloarthritides............................................................875 164 Other Connective Tissue Diseases.............................................882 165 Vasculitis...................................................................................885 166 Osteoarthritis............................................................................889 167 Gout, Pseudogout, and Related Diseases....................................891 168 Other Musculoskeletal Disorders...............................................896 169 Sarcoidosis.................................................................................899 170 Amyloidosis...............................................................................901 SECTION 13     Endocrinology and Metabolism 171 Disorders of the Anterior Pituitary and Hypothalamus...............905 172 Diabetes Insipidus and Syndrome of Inappropriate Antidiuretic Hormone.........................................912 173 Thyroid Gland Disorders...........................................................915 174 Adrenal Gland Disorders...........................................................924 175 Obesity......................................................................................930 176 Diabetes Mellitus......................................................................932 177 Disorders of the Male Reproductive System...............................941 178 Disorders of the Female Reproductive System............................946 179 Hypercalcemia and Hypocalcemia..............................................955 180 Osteoporosis and Osteomalacia..................................................961 181 Hypercholesterolemia and Hypertriglyceridemia........................966 182 Hemochromatosis, Porphyrias, and Wilson’s Disease..................972 SECTION 14    Neurology 183 The Neurologic Examination.....................................................979 184 Seizures and Epilepsy.................................................................987 185 Alzheimer’s Disease and Other Dementias.................................999 HMOM20_FM_pi-pxviii.indd 10 9/6/19 2:26 PM  CONTENTS xi 186 Parkinson’s Disease.................................................................. 1007 187 Ataxic Disorders...................................................................... 1014 188 ALS and Other Motor Neuron Diseases.................................. 1017 189 Autonomic Nervous System Disorders..................................... 1020 190 Trigeminal Neuralgia, Bell’s Palsy, and Other Cranial Nerve Disorders................................................ 1027 191 Spinal Cord Diseases............................................................... 1034 192 Multiple Sclerosis.................................................................... 1040 193 Neuromyelitis Optica............................................................... 1048 194 Acute Meningitis and Encephalitis........................................... 1051 195 Chronic and Recurrent Meningitis........................................... 1063 196 Peripheral Neuropathies, Including Guillain-Barré Syndrome................................................................................ 1073 197 Myasthenia Gravis................................................................... 1083 198 Muscle Diseases....................................................................... 1086 SECTION 15    Psychiatry and Substance Abuse 199 Psychiatric Disorders............................................................... 1097 200 Psychiatric Medications........................................................... 1105 201 Eating Disorders...................................................................... 1114 202 Alcohol Use Disorder............................................................... 1116 203 Narcotic Abuse........................................................................ 1120 204 Cocaine and Other Commonly Used Drugs............................. 1122 SECTION 16    Disease Prevention and Health Maintenance 205 Routine Disease Screening....................................................... 1127 206 Vaccines................................................................................... 1131 207 Cardiovascular Disease Prevention........................................... 1133 208 Prevention and Early Detection of Cancer................................ 1137 209 Smoking Cessation.................................................................. 1144 210 Women’s Health...................................................................... 1147 SECTION 17    Adverse Drug Reactions 211 Adverse Drug Reactions.......................................................... 1151 Index 1153 HMOM20_FM_pi-pxviii.indd 11 9/6/19 2:26 PM  NOTICE Medicine is an ever-changing science. As new research and clinical expe- rience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide informa- tion that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the pub- lisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsi- bility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to con- firm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the con- traindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. HMOM20_FM_pi-pxviii.indd 12 9/6/19 2:26 PM  Contributors ASSOCIATE EDITORS S. Andrew Josephson, MD Professor and Chair, Department of Neurology, University of California, San Francisco, San Francisco, California Carol A. Langford, MD, MHS Harold C. Schott Endowed Chair; Director, Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio Leonard S. Lilly, MD Professor of Medicine, Harvard Medical School; Chief, Brigham and Women’s/ Faulkner Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts David B. Mount, MD Assistant Professor of Medicine, Harvard Medical School; Renal Division, Brigham and Women’s Hospital, Renal Division, Boston VA Healthcare System, Boston, Massachusetts Edwin K. Silverman, MD, PhD Professor of Medicine, Harvard Medical School; Chief, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts Neeraj K. Surana, MD, PhD Assistant Professor in Pediatrics, Molecular Genetics and Microbiology, and Immunology, Duke University School of Medicine, Durham, North Carolina Numbers indicate the chapters written or co-written by the contributor. Anthony S. Fauci, MD Chief, Laboratory of Immunoregulation; Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 28, 44, 45, 49, 60, 61, 107, 153–170 Gregory K. Folkers, MPH Chief of Staff, Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 107, 165 Stephen L. Hauser, MD Robert A. Fishman Distinguished Professor, Department of Neurology; Director, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 4, 6, 13, 18–24, 50–58, 75, 79, 183–204, 209 J. Larry Jameson, MD, PhD Robert G. Dunlop Professor of Medicine; Dean, Raymond and Ruth Perelman School of Medicine; Executive Vice President, University of Pennsylvania for the Health System, Philadelphia, Pennsylvania 3, 4, 7, 8, 25, 26, 31, 32, 120, 171–182, 205, 210 xiii HMOM20_FM_pi-pxviii.indd 13 9/6/19 2:26 PM  xiv CONTRIBUTORS S. Andrew Josephson, MD Professor and Chair, Department of Neurology, University of California, San Francisco, San Francisco, California 18-21, 23, 51-54, 57, 183–184, 187, 189, 196–202, 209 Dennis L. Kasper, MD William Ellery Channing Professor of Medicine; Professor of Immunology, Department of Immunology, Harvard Medical School, Boston, Massachusetts 14, 29, 30, 59, 80–106, 108–111, 134, 147, 206 Carol A. Langford, MD Harold C. Schott Endowed Chair; Director, Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio 28, 44, 45, 49, 60, 61, 107, 153–170 Leonard S. Lilly, MD Professor of Medicine, Harvard Medical School; Chief, Brigham and Women’s/ Faulkner Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts 11, 12, 15, 33, 34, 36, 112–119, 121–129, 207 Dan L. Longo, MD Professor of Medicine, Harvard Medical School; Senior Physician, Brigham and Women’s Hospital; Deputy Editor, New England Journal of Medicine, Boston, Massachusetts 9, 10, 27, 39–43, 46, 47, 62–74, 76–78, 150–152, 208 Joseph Loscalzo, MD, PhD Hersey Professor of the Theory and Practice of Medicine, Harvard Medical School; Chairman, Department of Medicine; Physician-in-Chief, Brigham and Women’s Hospital, Boston, Massachusetts 1, 2, 5, 11, 12, 15–17, 33–38, 48, 112–119, 121–146, 148, 149, 207, 211 David B. Mount, MD Assistant Professor of Medicine, Harvard Medical School; Renal Division, Brigham and Women’s Hospital, Renal Division, Boston VA Healthcare System, Boston, Massachusetts 1, 2, 38, 48, 141–146, 148, 149 Edwin K. Silverman, MD, PhD Professor of Medicine, Harvard Medical School; Chief, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 5, 16, 17, 35, 37, 130–133, 135–140 Neeraj K. Surana, MD, PhD Assistant Professor in Pediatrics, Molecular Genetics and Microbiology, and Immunology, Duke University School of Medicine, Durham, North Carolina 14, 29, 30, 59, 80–106, 108–111, 134, 147, 206 HMOM20_FM_pi-pxviii.indd 14 9/6/19 2:26 PM  Preface Harrison’s Principles of Internal Medicine (HPIM), the premier medical textbook for students and clinicians, provides a comprehensive resource for understanding of the biological and clinical aspects of quality patient care. Harrison’s Manual of Medicine aims to fulfill a different need: As a concise, fact-rich resource for point- of-care, the Manual presents clinical information drawn from the 20th edition of HPIM, covering the key features of the diagnosis, clinical manifestations, and treatment of the major diseases that are likely to be encountered on a medical inpatient service and in the clinic. First published 30 years ago, the Manual is well established as a trusted resource for rapid access to clinically practical information. With each edition, it is updated by experts and has become ever more useful with the rapid expan- sion of medical knowledge and the increasing time constraints associated with heavy patient-care responsibilities in modern health care settings. The Manual’s popularity and value reflect its abbreviated format, which has proven extremely useful for initial diagnosis and management in time-restricted clinical settings. In particular, the book’s full-color format allows readers to locate and use infor- mation quickly. In addition, numerous tables and graphics facilitate decisions at the point of care. Although not a substitute for in-depth analysis of clinical problems, the Manual serves as a ready source of informative summaries that will be useful “on the spot” and that will prepare the reader for more in-depth analysis through more extensive reading at a later time. Of note, McGraw-Hill’s Access Medicine website (www.accessmedicine.com) provides online access to both the Manual and Harrison’s Principles of Internal Medicine, making it very easy to seek addi- tional information when needed. The Manual is also available in a variety of eBook and app formats. Like previous editions, this latest edition of the Manual is intended to keep up with the continual evolution of internal medicine practices. To this end, every chapter from the prior edition has been closely reviewed and updated, with substantial revisions and new chapters provided where appropriate. The Editors learned much in the process of updating the Manual and we hope that you will find this edition uniquely valuable as a clinical and educational resource. xv HMOM20_FM_pi-pxviii.indd 15 9/6/19 2:26 PM  This page intentionally left blank HMOM20_FM_pi-pxviii.indd 16  Acknowledgments The Editors and McGraw-Hill wish to thank their editorial staff, whose assistance and patience made this edition come out in a timely manner: From the Editors’ offices: Patricia Duffey; Gregory K. Folkers; Andrew Josephson, MD; H. Clifford Lane, MD; Carol A. Langford, MD; Julie B. McCoy; Anita Ortiz; Elizabeth Robbins, MD; Marie E. Scurti; and Stephanie Tribuna. From McGraw-Hill: James F. Shanahan, Kim J. Davis, and Catherine H. Saggese. The Editors also wish to acknowledge contributors to past editions of this Manual, whose work formed the basis for many of the chapters herein: Tamar F. Barlam, MD; Gerhard P. Baumann, MD; Eugene Braunwald, MD; Punit Chadha, MD; Joseph B. Martin, MD, PhD; Michael Sneller, MD; Kenneth Tyler, MD; Sophia Vinogradov, MD; and Jean Wilson, MD. xvii HMOM20_FM_pi-pxviii.indd 17 9/6/19 2:26 PM  GLOSSARY A2 aortic second sound EBV Epstein-Barr virus ABGs arterial blood gases ECG electrocardiogram ACE angiotensin-converting EEG electroencephalogram enzyme enzyme-linked ELISA  AF atrial fibrillation immunosorbent assay acquired immunodeficiency AIDS  EMG electromyogram syndrome ENT ear, nose, and throat ALS amyotrophic lateral EOM extraocular movement sclerosis ESR  erythrocyte sedimentation ANA antinuclear antibody rate acute respiratory distress ARDS  FDA  U.S. Food and Drug syndrome Administration bid two times daily FEV1  forced expiratory volume in biw twice a week first second bp blood pressure GFR glomerular filtration rate BUN blood urea nitrogen GI gastrointestinal continuous ambulatory CAPD  glucose-6-phosphate G6PD  peritoneal dialysis dehydrogenase CBC complete blood count Hb hemoglobin CF complement fixation Hct hematocrit CHF congestive heart failure HDL high-density lipoprotein CLL chronic lymphocytic HIV human immunodeficiency leukemia virus CML chronic myeloid leukemia hs at bedtime CMV cytomegalovirus HSV herpes simplex virus CNS central nervous system ICU intensive care unit CPK creatine phosphokinase IFN interferon CSF cerebrospinal fluid Ig immunoglobulin CT computed tomography IL interleukin CVP central venous pressure IM intramuscular CXR chest x-ray IP intraperitoneal disseminated intravascular DIC  IV intravenous coagulation IVC inferior vena cava DVT deep-venous thrombosis IVP intravenous pyelogram HMOM20_IFC.indd 1 8/30/19 10:04 AM  GLOSSARY JVP jugular venous pulse PVCs premature ventricular LA left atrium contractions LAD left-axis deviation QAM every morning LBBB left bundle branch block qd every day LDH lactate dehydrogenase qh every hour LDL low-density lipoprotein qhs every bedtime LFT liver function test qid four times daily LLQ left lower quadrant qod every other day LP lumbar puncture RA rheumatoid arthritis LUQ left upper quadrant RBBB right bundle branch block LV left ventricle RBC red blood (cell) count MI myocardial infarction RLQ right lower quadrant MIC minimal inhibitory RR respiratory rate concentration RUQ right upper quadrant MRI  magnetic resonance RV right ventricle imaging S1... S4 heart sounds, 1st to 4th NPO nothing by mouth SARS  severe acute respiratory nonsteroidal NSAIDs  syndrome anti-inflammatory drugs SC subcutaneous P2 pulmonic second sound SL sublingual PaO2  partial pressure of O2 in SLE  systemic lupus arterial blood erythematosus PAO2  partial pressure of O2 in SVC superior vena cava alveolar blood TIA transient ischemic attack PCR polymerase chain reaction tid three times daily PFTs pulmonary function tests tiw thrice a week PMNs  polymorphonuclear cells TLC total lung capacity or leukocytes TNF tumor necrosis factor PO by mouth UA urinalysis PPD  purified protein derivative, skin test for URI  upper respiratory tuberculosis infection prn as needed UTI urinary tract infection pt/pts patient/patients UV ultraviolet PT prothrombin time VDRL test for syphilis PTT  partial thromboplastin VZV varicella-zoster virus time WBC white blood (cell) count HMOM20_IBC.indd 1 8/30/19 10:04 AM  This page intentionally left blank HMOM20_FM_pi-pxviii.indd 18 9/6/19 2:26 PM  Care of the Hospitalized Patient SECTION 1 1 Electrolytes SODIUM Disturbances of sodium concentration [Na+] result in most cases from abnormalities of H2O homeostasis, which change the relative ratio of Na+ to H2O. Disorders of Na+ balance per se are, in contrast, associated with changes in extracellular fluid volume, either hypo- or hypervolemia. Maintenance of “arterial circula- tory integrity” is achieved in large part by changes in urinary sodium excretion and vascular tone, whereas H2O balance is achieved by changes in both H2O intake and urinary H2O excretion (Table 1-1). Confusion can result from the coexistence of defects in both H2O and Na+ balance. For example, a hypovo- lemic pt may have an appropriately low urinary Na+ due to increased renal tubular reabsorption of filtered NaCl; a concomitant increase in circulating arginine vasopressin (AVP)—part of the defense of effective circulating volume (Table 1-1)—will cause the renal retention of ingested H2O and the development of hyponatremia. HYPONATREMIA This is defined as a serum [Na+] 180 mmHg) peristaltic contractions; particularly associated with chest pain or dysphagia, but correlation between symptoms and manometry is inconsistent. Condition may resolve over time or evolve into diffuse spasm; associated with increased fre- quency of depression, anxiety, and somatization. EVALUATION Barium swallow shows corkscrew esophagus, pseudodiverticula, and diffuse spasm. Manometry shows spasm with multiple simultaneous esophageal con- tractions of high amplitude and long duration. In nutcracker esophagus, the contractions are peristaltic and of high amplitude. If heart disease has been ruled out, edrophonium, ergonovine, or bethanechol can be used to provoke spasm. TREATMENT Spastic Disorders Anticholinergics are usually of limited value; nitrates (isosorbide dinitrate, 5–10 mg PO ac) and calcium antagonists (nifedipine, 10–20 mg PO ac) are more effective. Those refractory to medical management may benefit from balloon dilation. Rare pts require surgical intervention: longitudinal myotomy of esoph- ageal circular muscle. Treatment of concomitant depression or other psychologi- cal disturbance may help. SCLERODERMA Atrophy of the esophageal smooth muscle and fibrosis can make the esophagus aperistaltic and lead to an incompetent LES with attendant reflux esophagitis and stricture. Treatment of gastroesophageal reflux disease is discussed in Chap. 40. ESOPHAGEAL INFLAMMATION VIRAL ESOPHAGITIS Herpesviruses I and II, varicella-zoster virus, and CMV can all cause esophagitis; particularly common in immunocompromised pts (e.g., AIDS). Odynophagia, dysphagia, fever, and bleeding are symptoms and signs. Diagnosis is made by endoscopy with biopsy, brush cytology, and culture. TREATMENT Viral Esophagitis Disease is usually self-limited in the immunocompetent person; viscous lido- caine can relieve pain; in immunocompetent pts, herpes and varicella esoph- agitis are treated with acyclovir, 200 mg PO five times a day for 7−10 days; HMOM20_Sec03_p0127-p0246.indd 164 9/6/19 10:30 AM  Dysphagia CHAPTER 41 165 in prolonged cases and in immunocompromised hosts, treatment is with acyclo- vir, 400 mg PO five times a day for 14–21 days, famciclovir, 500 mg PO tid, or valacyclovir 1 g PO tid for 7 days. CMV is treated with ganciclovir, 5 mg/kg IV q12h, until healing occurs, which may take weeks. Oral valganciclovir (900 mg bid) is an effective alternative to parenteral treatment. In nonresponders, foscar- net, 90 mg/kg IV q12h for 21 days, may be effective. CANDIDA ESOPHAGITIS In immunocompromised hosts, or those with malignancy, diabetes, hypo- parathyroidism, hemoglobinopathy, systemic lupus erythematosus, corrosive esophageal injury, candidal esophageal infection may present with odynopha- gia, dysphagia, and oral thrush (50%). Diagnosis is made on endoscopy by iden- tifying yellow-white plaques or nodules on friable red mucosa. Characteristic hyphae are seen on KOH stain. In pts with AIDS, the development of symptoms may prompt an empirical therapeutic trial. TREATMENT Candida Esophagitis In immunocompromised hosts, fluconazole, 200 mg PO on day 1 followed by 100 mg daily for 2–3 weeks, is treatment of choice; alternatives include itracon- azole, 200 mg PO bid, or ketoconazole, 200–400 mg PO daily; long-term main- tenance therapy is often required. Poorly responsive pts or those who cannot swallow may respond to caspofungin 50 mg IV qd for 7–21 days. PILL-RELATED ESOPHAGITIS Doxycycline, tetracycline, aspirin, nonsteroidal anti-inflammatory drugs, KCl, quinidine, ferrous sulfate, clindamycin, alprenolol, and alendronate can induce local inflammation in the esophagus. Predisposing factors include recumbency after swallowing pills with small sips of water and anatomic factors impinging on the esophagus and slowing transit. TREATMENT Pill-Related Esophagitis Withdraw offending drug, use antacids, and dilate any resulting stricture. EOSINOPHILIC ESOPHAGITIS Mucosal inflammation with eosinophils with submucosal fibrosis can be seen especially in pts with food allergies. This diagnosis relies on the presence of symptoms of esophagitis with the appropriate findings on esophageal biopsy. Eotaxin 3, an eosinophil chemokine, has been implicated in its etiology. IL-5 and TARC (thymus and activation-related chemokine) levels may be elevated. Treat- ment involves a 12-week course of swallowed fluticasone (440 µg bid) using a metered-dose inhaler. In 30−50% of pts, proton pump inhibitors can reduce eosinophil infiltrates. OTHER CAUSES OF ESOPHAGITIS IN AIDS Mycobacteria, Cryptosporidium, Pneumocystis, idiopathic esophageal ulcers, and giant ulcers (possible cytopathic effect of HIV) can occur. Ulcers may respond to systemic glucocorticoids. HMOM20_Sec03_p0127-p0246.indd 165 9/6/19 10:30 AM  166 SECTION SECTION12 3 Common Patient Presentations 42 Diarrhea, Malabsorption, and Constipation NORMAL GASTROINTESTINAL FUNCTION ABSORPTION OF FLUID AND ELECTROLYTES Fluid delivery to the GI tract is 8–10 L/d, including 2 L/d ingested; most is absorbed in small bowel. About 2 L/d is delivered to the colon; about 0.2 L/d is excreted in the stool. Colonic absorption is normally 0.05–2 L/d, with capacity for 6 L/d if required. Intestinal water absorption passively follows active trans- port of Na+, Cl–, glucose, and bile salts. Additional transport mechanisms include Cl–/HCO3– exchange, Na+/H+ exchange, H+, K+, Cl–, and HCO3– secretion, Na+- glucose cotransport, and active Na+ transport across the basolateral membrane by Na+,K+-ATPase. NUTRIENT ABSORPTION 1. Proximal small intestine: iron, calcium, folate, fats (after hydrolysis of triglycer- ides to fatty acids by pancreatic lipase and colipase), proteins (after hydrolysis by pancreatic and intestinal peptidases), carbohydrates (after hydrolysis by amylases and disaccharidases); triglycerides absorbed as micelles after solu- bilization by bile salts; amino acids and dipeptides absorbed via specific car- riers; sugars absorbed by active transport 2. Distal small intestine: vitamin B12, bile salts, water 3. Colon: water, electrolytes INTESTINAL MOTILITY Allows propulsion of intestinal contents from stomach to anus and separation of components to facilitate nutrient absorption. Propulsion is controlled by neural, myogenic, and hormonal mechanisms; mediated by migrating motor complex, an organized wave of neuromuscular activity that originates in the distal stomach during fasting and migrates slowly down the small intestine. Colonic motility is mediated by local peristalsis to propel feces. Defecation is effected by relaxation of internal anal sphincter in response to rectal distention, with voluntary control by contraction of external anal sphincter. DIARRHEA PHYSIOLOGY Formally defined as fecal output >200 g/d on low-fiber (western) diet; also fre- quently used to connote loose or watery stools. Considered acute if 4 weeks. Mediated by one or more of the following mechanisms: OSMOTIC DIARRHEA Nonabsorbed solutes increase intraluminal oncotic pressure, causing outpouring of water; usually ceases with fasting; stool osmolal gap >40 (see below). Causes include disaccharidase (e.g., lactase) deficiencies, pancreatic insufficiency, bacte- rial overgrowth, lactulose or sorbitol ingestion, polyvalent laxative abuse, celiac or tropical sprue, and short bowel syndrome. Lactase deficiency can be either primary (more prevalent in blacks and Asians, usually presenting in early adult- hood) or secondary (from viral, bacterial, or protozoal gastroenteritis, celiac or tropical sprue, or kwashiorkor). HMOM20_Sec03_p0127-p0246.indd 166 9/6/19 10:30 AM  Diarrhea, Malabsorption, and Constipation CHAPTER 42 167 SECRETORY DIARRHEA Active ion secretion causes obligatory water loss; diarrhea is usually watery, often profuse, unaffected by fasting; stool Na+ and K+ are elevated with osmolal gap 4 weeks), more insidious course suggests malabsorption, inflamma- tory bowel disease, metabolic or endocrine disturbance, pancreatic insufficiency, laxative abuse, ischemia, neoplasm (hypersecretory state or partial obstruction), or irritable bowel syndrome. Parasitic and certain forms of bacterial enteritis can HMOM20_Sec03_p0127-p0246.indd 167 9/6/19 10:30 AM  168 SECTION SECTION12 3 Common Patient Presentations also produce chronic symptoms. Particularly foul-smelling or oily stool suggests fat malabsorption. Fecal impaction may cause apparent diarrhea because only liquids pass partial obstruction. Several infectious causes of diarrhea are associ- ated with an immunocompromised state. A pathophysiologic mechanism-based list of causes is shown in Table 42-1. TABLE 42-1 Major Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism Secretory Causes Exogenous stimulant laxatives Chronic ethanol ingestion Other drugs and toxins Endogenous laxatives (dihydroxy bile acids) Idiopathic secretory diarrhea or bile acid diarrhea Certain bacterial infections Bowel resection, disease, or fistula (↓ absorption) Partial bowel obstruction or fecal impaction  Hormone-producing tumors (carcinoid, VIPoma, medullary cancer of thyroid, mastocytosis, gastrinoma, colorectal villous adenoma) Addison’s disease Congenital electrolyte absorption defects Osmotic Causes Osmotic laxatives (Mg2+, PO4−3, SO4−2) Lactase and other disaccharide deficiencies Nonabsorbable carbohydrates (sorbitol, lactulose, polyethylene glycol) Gluten and FODMAP intolerance Steatorrheal Causes  Intraluminal maldigestion (pancreatic exocrine insufficiency, bacterial overgrowth, bariatric surgery, liver disease)  Mucosal malabsorption (celiac sprue, Whipple’s disease, infections, abetalipoproteinemia, ischemia, drug-induced enteropathy) Postmucosal obstruction (1° or 2° lymphatic obstruction) Inflammatory Causes Idiopathic inflammatory bowel disease (Crohn’s, chronic ulcerative colitis) Lymphocytic and collagenous colitis  Immune-related mucosal disease (1° or 2° immunodeficiencies, food allergy, eosinophilic gastroenteritis, graft-versus-host disease) Infections (invasive bacteria, viruses, and parasites, Brainerd diarrhea) Radiation injury Gastrointestinal malignancies Dysmotile Causes Irritable bowel syndrome (including postinfectious IBS) Visceral neuromyopathies Hyperthyroidism Drugs (prokinetic agents) Postvagotomy (Continued) HMOM20_Sec03_p0127-p0246.indd 168 9/6/19 10:30 AM  Diarrhea, Malabsorption, and Constipation CHAPTER 42 169 TABLE 42-1 Major Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism (Continued) Factitial Causes Munchausen Eating disorders Iatrogenic Causes Cholecystectomy Ileal resection Bariatric surgery Vagotomy, fundoplication Abbreviation: FODMAP, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. PHYSICAL EXAMINATION Signs of dehydration are often prominent in severe, acute diarrhea. Fever and abdominal tenderness suggest infection or inflammatory disease but are often absent in viral enteritis. Evidence of malnutrition suggests chronic course. Cer- tain signs are frequently associated with specific deficiency states secondary to malabsorption (e.g., cheilosis with riboflavin or iron deficiency, glossitis with B12, folate deficiency). Questions to address in pts with chronic diarrhea are shown in Table 42-2. STOOL EXAMINATION Culture for bacterial pathogens, examination for leukocytes, measurement of C. difficile toxin, and examination for ova and parasites are important compo- nents of evaluation of pts with severe, protracted, or bloody diarrhea. Presence of blood (fecal occult blood test) or leukocytes (Wright’s stain) suggests inflam- mation (e.g., ulcerative colitis, Crohn’s disease, infection, or ischemia). Gram’s stain of stool can be diagnostic of Staphylococcus, Campylobacter, or Candida infec- tion. Steatorrhea (determined with Sudan III stain of stool sample or 72-h quan- titative fecal fat analysis) suggests malabsorption or pancreatic insufficiency. Measurement of Na+ and K+ levels in fecal water helps to distinguish osmotic from other types of diarrhea; osmotic diarrhea is implied by stool osmolal gap > 40, where stool osmolal gap = osmolserum [2 × (Na+ + K+)stool]. LABORATORY STUDIES Complete blood count may indicate anemia (acute or chronic blood loss or malabsorption of iron, folate, or B12), leukocytosis (inflammation), eosinophilia TABLE 42-2 Physical Examination in Pts with Chronic Diarrhea 1. Are there general features to suggest malabsorption or inflammatory bowel disease (IBD) such as anemia, dermatitis herpetiformis, edema, or clubbing? 2. Are there features to suggest underlying autonomic neuropathy or collagen- vascular disease in the pupils, orthostasis, skin, hands, or joints? 3. Is there an abdominal mass or tenderness? 4. Are there any abnormalities of rectal mucosa, rectal defects, or altered anal sphincter functions? 5. Are there any mucocutaneous manifestations of systemic disease such as dermatitis herpetiformis (celiac disease), erythema nodosum (ulcerative colitis), flushing (carcinoid), or oral ulcers for IBD or celiac disease? HMOM20_Sec03_p0127-p0246.indd 169 9/6/19 10:30 AM  170 SECTION SECTION12 3 Common Patient Presentations (parasitic, neoplastic, and inflammatory bowel diseases). Serum levels of cal- cium, albumin, iron, cholesterol, folate, B12, vitamin D, and carotene; serum iron-binding capacity; and prothrombin time can provide evidence of intestinal malabsorption or maldigestion. OTHER STUDIES d-Xylose absorption test is a convenient screen for small-bowel absorptive func- tion. Small-bowel biopsy is especially useful for evaluating intestinal malab- sorption. Specialized studies include Schilling test (B12 malabsorption), lactose H2 breath test (carbohydrate malabsorption), [14C]xylose and lactulose H2 breath tests (bacterial overgrowth), glycocholic breath test (ileal malabsorption), triolein breath test (fat malabsorption), and bentiromide and secretin tests (pancreatic insufficiency). Sigmoidoscopy or colonoscopy with biopsy is useful in the diag- nosis of colitis (esp. pseudomembranous, ischemic, microscopic); it may not allow distinction between infectious and noninfectious (esp. idiopathic ulcer- ative) colitis. Barium contrast x-ray studies may suggest malabsorption (thick- ened bowel folds), inflammatory bowel disease (ileitis or colitis), tuberculosis (ileocecal inflammation), neoplasm, intestinal fistula, or motility disorders. TREATMENT Diarrhea An approach to the management of acute diarrheal illnesses is shown in Fig. 42-1. Symptomatic therapy includes vigorous rehydration (IV or with oral glucose-electrolyte solutions), electrolyte replacement, binders of osmotically active substances (e.g., kaolin-pectin), and opiates to decrease bowel motility (e.g., loperamide, diphenoxylate); opiates may be contraindicated in infectious or inflammatory causes of diarrhea. An approach to the management of chronic diarrhea is shown in Fig. 42-2. MALABSORPTION SYNDROMES Intestinal malabsorption of ingested nutrients may produce osmotic diarrhea, ste- atorrhea, or specific deficiencies (e.g., iron; folate; B12; vitamins A, D, E, and K). Table 42-3 lists common causes of intestinal malabsorption. Protein-losing enter- opathy may result from several causes of malabsorption; it is associated with hypoalbuminemia and can be detected by measuring stool α1-antitrypsin or radiolabeled albumin levels. Therapy is directed at the underlying disease. CONSTIPATION Defined as decrease in frequency of stools to 20 g/day: 14–20 g/day: stool transit bile acid pancreatic search for small fat 100-mL blood required for one melenic stool) usually indicates bleeding proximal to ligament of Treitz but may be as distal as ascending colon; pseudomelena may be caused by inges- tion of iron, bismuth, licorice, beets, blueberries, and charcoal. 3. Hematochezia: Bright red or maroon rectal bleeding usually implies bleed- ing beyond ligament of Treitz but may be due to rapid upper GI bleeding (>1000 mL). 4. Positive fecal occult blood test with or without iron deficiency. 5. Symptoms of blood loss: e.g., light-headedness or shortness of breath. HEMODYNAMIC CHANGES Orthostatic drop in bp >10 mmHg usually indicates >20% reduction in blood volume (± syncope, light-headedness, nausea, sweating, thirst). SHOCK BP 90%; allows visualization of bleeding site and possibility of therapeutic intervention; mandatory for suspected varices, aor- toenteric fistulas; permits identification of “visible vessel” (protruding artery in ulcer crater), which connotes high (∼50%) risk of rebleeding. Upper GI barium radiography: Accuracy ∼80% in identifying a lesion, though does not confirm source of bleeding; acceptable alternative to endoscopy in resolved or chronic low-grade bleeding. Selective mesenteric arteriography: When brisk bleeding precludes identifica- tion of source at endoscopy. Radioisotope scanning (e.g., 99Tc tagged to red blood cells or albumin); used primarily as screening test to confirm bleeding is rapid enough for arteriog- raphy to be of value or when bleeding is intermittent and of unclear origin. LOWER GI BLEEDING CAUSES Anal lesions (hemorrhoids, fissures), rectal trauma, proctitis, colitis (ulcerative colitis, Crohn’s disease, infectious colitis, ischemic colitis, radiation), colonic pol- yps, colonic carcinoma, angiodysplasia (vascular ectasia), diverticulosis, intus- susception, solitary ulcer, blood dyscrasias, vasculitis, connective tissue disease, neurofibroma, amyloidosis, anticoagulation. EVALUATION (SEE BELOW AND FIG. 43-2) History and physical examination. In the presence of hemodynamic changes, perform upper endoscopy followed by colonoscopy. In the absence of hemodynamic changes, perform anoscopy and either flexible sigmoidoscopy or colonoscopy: Exclude hemorrhoids, fis- sure, ulcer, proctitis, neoplasm. Colonoscopy: Often test of choice, but may be impossible if bleeding is massive. Barium enema: No role in active bleeding. Arteriography: When bleeding is severe (requires bleeding rate >0.5 mL/min; may require prestudy radioisotope bleeding scan as above); defines site of bleeding or abnormal vasculature. Surgical exploration (last resort). BLEEDING OF OBSCURE ORIGIN Often small-bowel source. Consider small-bowel enteroclysis x-ray (careful bar- ium radiography via peroral intubation of small bowel), Meckel’s scan, enteros- copy (small-bowel endoscopy), or exploratory laparotomy with intraoperative enteroscopy. TREATMENT Upper and Lower GI Bleeding Venous access with large-bore IV (14–18 gauge); central venous line for major bleed and pts with cardiac disease; monitor vital signs, urine output, Hct (fall may lag). Gastric lavage of unproven benefit but clears stomach before HMOM20_Sec03_p0127-p0246.indd 176 9/6/19 10:30 AM HMOM20_Sec03_p0127-p0246.indd 177 No Hemodynamic Instability Hemodynamic Instability Age