Menu Expand
Sleisenger and Fordtran's Gastrointestinal and Liver Disease E-Book

Sleisenger and Fordtran's Gastrointestinal and Liver Disease E-Book

Mark Feldman | Lawrence S. Friedman | Lawrence J. Brandt

(2015)

Additional Information

Book Details

Abstract

  • Consult this title on your favorite e-reader.
  • Get the essential gastroenterology information you need from one authoritative source with an outstanding global reputation for excellence.
  • Zero in on the key information you need to know with a consistent, full-color chapter design.
  • Stay up to date with emerging and challenging topics: enteric microbiota and probiotics; fecal microbiota transplantation; Clostridium difficile colitis; and factitious gastrointestinal diseases.
  • Incorporate the latest findings and improvements in care for liver disease patients—from diagnosis and treatment through post-treatment strategies and management of complications.
  • Expert Consult eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, references, and videos from the book on a variety of devices.

Table of Contents

Section Title Page Action Price
Vol-1 Vol-1-Cover
Front cover Vol-1-Cover
IFC_Vol.1 IBC2
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease Vol-1-iii
Copyright page Vol-1-iv
Dedication Vol-1-v
Contributors Vol-1-vii
Foreword Vol-1-xix
Preface Vol-1-xxi
Table of Contents Vol-1-xxiii
Video Contents Vol-1-xxix
Abbreviation List Vol-1-xxxi
I Biology of the Gastrointestinal Tract 1
1 Cellular Growth and Neoplasia 3
Chapter Outline 3
Mechanisms of Normal Cell Homeostasis 3
Cellular Proliferation 3
Apoptosis 4
Senescence 4
Signaling Pathways That Regulate Cellular Growth 4
Intestinal Tumor Development 6
Multistep Formation 6
Clonal Expansion 8
Cancer Stem Cells 8
Neoplasia-Associated Genes 8
Oncogenes 8
Peptide Growth Factor Oncogenes 8
Protein Kinase–Related Oncogenes 8
Signal Transduction–Related Oncogenes (Membrane-Associated G Proteins) 8
Nuclear Oncogenes 9
Tumor Suppressor Genes 9
Tumor Suppressor Gene Inactivation 10
Adenomatous Polyposis Coli Gene 10
TP53 Gene 10
SMAD4 Gene 10
DNA Repair Genes 10
Oncogenic Signaling Pathways 11
Noncoding RNAs 11
Epigenetics 12
Tumor Metabolism 12
Environmental and Microenvironmental Influences 12
Chemical Carcinogenesis 12
Dietary Factors 12
Microbiome 13
Inflammation and Cancer 13
Biological Features of Tumor Metastasis 13
Epithelial-Mesenchymal Transition 13
Angiogenesis and Lymphangiogenesis 14
Molecular Medicine: Current and Future Approaches in Gastrointestinal Oncology 14
Molecular Diagnostics 14
Genome-wide Association Studies 14
Whole Genome Sequencing and Exome Sequencing 15
Key References 15
References 15.e1
2 Mucosal Immunology and Inflammation* 16
Chapter Outline 16
Immune Responses in Gut-Associated Lymphoid Tissue 16
Controlled/Physiologic Inflammation 16
Oral Tolerance 17
Unusual Immunoglobulins of Gut-Associated Lymphoid Tissue 18
Physiology of Gut-Associated Lymphoid Tissue and the Intestinal Barrier 20
Functional Anatomy of Gut-Associated Lymphoid Tissue 20
Peyer’s Patches and M Cells 20
Intestinal Epithelial Cells 21
Antigen Trafficking Across the Epithelium 21
Recognition of Pathogen-Associated Molecular Patterns by Pattern Recognition Receptors 21
Antigen Presentation in the Gut 22
Intestinal Mononuclear Cells 22
Intraepithelial Lymphocytes 22
Lamina Propria Mononuclear Cells 24
T Cell Differentiation 24
Innate Lymphoid Cells 25
Dendritic Cells 25
Gut-Associated Lymphoid Tissue–Relevant Chemokines 25
Key References 26
References 27.e1
3 The Enteric Microbiota 28
Chapter Outline 28
Life without Microbes 28
Primer on Terminology 28
Methodologies Used to Study the Microbiota 29
Next-Generation Sequencing 29
HITChip 30
Metagenomics 30
Characteristics of the Human Gastrointestinal Microbiota 30
Host-Microbe Spatial Relationships 30
Host-Microbe Age-Sensitive Relationships 31
Microbe-Microbe Signaling 31
Language of Host-Microbe Dialogue 32
Microbes, Immunity, and Metabolic Health 33
Microbiota Composition and Disease Associations 33
Microbes and Drugs 33
Therapeutic Manipulation of the Microbiota 34
Intestinal Virome 34
Future Directions 35
Key References 35
References 35.e1
4 Gastrointestinal Hormones and Neurotransmitters 36
Chapter Outline 36
Hormones and Neurotransmitters 36
Definitions 36
Modes of Transmitter Release 37
Endocrine 37
Paracrine 37
Autocrine 37
Neurotransmission 37
Transducing Signals From the Gastrointestinal Lumen 38
Recognizing Signals Through Cell Surface Receptors 40
G Protein–Coupled Receptors 40
Signaling Through Cyclic Adenosine Monophosphate 40
Signaling Through Calcium 40
Enzyme–Coupled Receptors 40
Ion Channel–Coupled Receptors 41
Nutrient Chemosensing 41
Lipids 41
Proteins and Amino Acids 41
Tastants 42
Sensing the Microbiome 42
Other Factors That Stimulate Transmitter Release 42
The Transmitters 42
Gut Neuropeptides 43
Gastrin 43
Cholecystokinin 44
Secretin 44
Vasoactive Intestinal Polypeptide 44
Glucagon 45
Glucose-Dependent Insulinotropic Polypeptide 45
Pancreatic Polypeptide Family 46
Substance P and the Tachykinins 46
Somatostatin 46
Motilin 47
Leptin 47
Ghrelin 47
Neurotransmitters 47
Acetylcholine 47
Catecholamines 48
Dopamine 48
Serotonin 48
Histamine 48
Nitric Oxide 49
Cannabinoids and Other Chemical Transmitters 49
Cannabinoids 49
Adenosine 50
Cytokines 50
The Importance of Hormones and Neurotransmitters 50
Growth and Abnormal Growth of the Gastrointestinal Mucosa 50
Growth Factor Receptors 51
Epidermal Growth Factor 51
Transforming Growth Factor-α 51
Transforming Growth Factor-β 51
Insulin-like Growth Factors 51
Fibroblast Growth Factor and Platelet-Derived Growth Factor 51
Trefoil Factors 52
Diabetes Mellitus and the Gastrointestinal Tract 52
Gastrointestinal Regulation of Appetite 53
Key References 53
References 54.e1
II Nutrition in Gastroenterology 55
5 Nutritional Principles and Assessment of the Gastroenterology Patient 57
Chapter Outline 57
Basic Nutritional Concepts 57
Energy Stores 57
Energy Metabolism 57
Resting Energy Expenditure 57
Energy Expenditure of Physical Activity 58
Thermic Effect of Feeding 58
Recommended Energy Intake in Hospitalized Patients 58
Methods Incorporating Metabolic Stress Factors 59
Method without a Stress Factor 59
Caloric Delivery and Avoidance of Hyperglycemia 59
Protein 61
Nitrogen Balance 61
Carbohydrate 62
Lipids 62
Essential Fatty Acids 62
Major Minerals 62
Micronutrients 62
Vitamins 63
Trace Minerals 63
Physiologic and Pathophysiologic Factors Affecting Micronutrient Requirements 70
Age 70
Malabsorption and Maldigestion 70
Starvation 71
Malnutrition 72
Protein-Energy Malnutrition 72
Primary versus Secondary Protein-Energy Malnutrition: A Body Compartment Perspective 73
Protein-Energy Malnutrition in Children 73
Kwashiorkor 74
Marasmus 74
Nutritional Dwarfism 74
Physiologic Impairments Caused by Protein-Energy Malnutrition 75
System Effects 75
Gastrointestinal Tract 75
Cardiovascular System 75
Immune System 75
Respiratory System 75
Endocrine System 75
Other Effects 75
Wound Healing 75
Skin 76
Hair 76
Kidneys 76
Bone Marrow 76
Nutritional Assessment Techniques 76
History 76
Weight Loss 76
Food Intake 76
Evidence of Malabsorption 77
Evidence of Specific Nutrient Deficiencies 77
Influence of Disease on Nutrient Requirements 77
Functional Status 77
Physical Examination 77
Hydration Status 77
Tissue Depletion 77
Muscle Function 77
Specific Nutrient Deficiencies 77
Anthropometry 77
Functional Measures of Protein-Calorie Status 79
Biochemical Measures of Protein-Calorie Status 79
Serum Proteins 79
Creatinine-Height Index 79
Discriminant Analyses of Protein-Calorie Status 79
Rapid Screening Tools for Assessment of Targeted Populations 80
Subjective Global Assessment 80
Mini-Nutritional Assessment 80
Aggressive Nutritional Support in the Hospitalized Patient 81
Malnourished Patients Undergoing Major Surgery 81
Patients Hospitalized with Decompensated Alcoholic Liver Disease 82
Patients Undergoing Radiation Therapy 82
Key References 82
References 82.e1
6 Nutritional Management 83
Chapter Outline 83
Nutrition in Specific Disease States 83
Intestinal Failure (Short Bowel Syndrome) 83
Pancreatitis 84
Crohn’s Disease 84
Liver Disease 85
Diverticular Disease 86
Dumping Syndrome 86
Cancer 86
Obesity 86
Critical Illness 87
Nutritional Therapy 88
Parenteral Nutrition 88
Central Parenteral Nutrition Formulation 88
Peripheral Parenteral Nutrition Formulation 89
Administration 89
Laboratory Testing 89
Metabolic Complications 90
Vascular Access Devices 90
Central Venous Catheter Complications 91
Enteral Nutrition 91
Nasoenteric Tube Access 91
Percutaneous Endoscopic Enteral Access 93
Percutaneous Endoscopic Gastrostomy 93
Indications. 93
Cancer. 93
Stroke. 93
Dementia. 93
Disabling Neurologic Conditions. 94
Procedure. 94
Percutaneous Endoscopic Gastrojejunostomy 96
Direct Percutaneous Jejunostomy 97
Surgical Enteral Access 98
Fluoroscopic Percutaneous Enteral Access 98
Enteral Feeding 98
Water Requirements 98
Advancement of Tube Feedings 99
Enteral Formulations 99
Blenderized Formulations. 99
Standard Polymeric Formulations. 99
Predigested Formulations. 99
Specialty Formulations. 99
Immune-Modulating Formulas. 99
Renal Formulas. 99
Enteral Feeding Complications 99
Oral Diet Therapy 100
Clear Liquid Diets 100
Full Liquid Diets 100
Soft Diets 100
Fiber- and Residue-Restricted Diets 100
High-Fiber Diets 100
Post-gastrectomy and Anti-dumping Diets 100
Low-Fat Diets 100
Acknowledgment 101
Key References 101
References 101.e1
7 Obesity 102
Chapter Outline 102
Definitions 103
Body Mass Index 103
Central Adiposity 103
Prevalence and Costs 103
Causes 104
Energy Imbalance 104
Environmental Agents 104
Intrauterine Factors 104
Neonatal Environment 104
Adiposity Rebound 104
Drug-Induced Weight Gain 104
Diet 105
Physical Inactivity 105
Smoking 105
Viruses 105
Microbiome 105
Host Agents 105
Genetic Causes 105
Neurophysiologic Factors 105
Pathology and Pathophysiology 106
Fat Cell as an Endocrine Cell 106
Brown Adipose Tissue 106
Visceral and Ectopic Fat 106
Complications and Consequences 106
Diseases and Disorders 106
Disorders Related to Enlarged and Visceral Fat Cells 106
Diabetes 106
Lipid Derangements 106
Cardiovascular Diseases 107
Hypertension 107
Kidney Disease 107
Gallbladder Disease 107
Liver Disease 107
Gastroesophageal Reflux Disease 107
Cancer 107
Endocrine Effects 108
Pneumonia 108
Disorders Associated with Increased Fat Mass 108
Obstructive Sleep Apnea 108
Diseases of the Bones, Joints, Muscles, Connective Tissue, and Skin 108
Psychosocial Dysfunction 109
Death 109
Benefits of Weight Loss 109
Evaluation 109
History 109
Physical Examination 110
Laboratory Studies 111
Prevention 111
Treatment 111
Diets 111
Popular Diets 112
Low-Fat Diets 112
Low Energy Density Diets 112
Low-Carbohydrate Diets 112
Very Low-Calorie Diets 112
Commercial Programs 113
Lifestyle Modification 113
Exercise 113
Pharmacotherapy 113
Mechanisms of Drug Action 114
FDA-Approved Medications 114
Orlistat 114
Sympathomimetic Amines 115
Lorcaserin 115
Topiramate and Phentermine Extended Release 115
Bupropion and Naltrexone 116
Drugs Approved for an Indication Other than Obesity 116
Metformin 116
Bupropion 116
Glucagon-like Peptide-1 Agonists 117
Exenatide 117
Liraglutide 117
Pramlintide 117
Pramlintide and Phentermine 118
Zonisamide 118
Surgery 118
Key References 118
References 118.e1
8 Surgical and Endoscopic Treatment of Obesity 119
Chapter Outline 119
Evaluation and Selection of Bariatric Surgery Candidates 120
Surgical Techniques 120
Surgical Complications 122
Nutritional Deficiencies 123
Outcomes 123
Endoscopic Management of Bariatric Surgical Complications 124
Ulceration 124
Postoperative Gastrointestinal Bleeding 124
Stenosis 125
Foreign Body Complications 125
Leaks and Fistulae 126
Pancreaticobiliary Disease 127
Weight Regain and Dilated Gastrojejunal Anastomosis 127
Endoscopic Treatments for Obesity 127
Key References 129
References 129.e1
9 Feeding and Eating Disorders 130
Chapter Outline 130
Epidemiology 130
Causative Factors 131
Satiety 131
Appetite 131
Energy Storage 131
Onset and Course 132
Evaluation 132
Diagnosis of Specific Disorders 132
Anorexia Nervosa 133
Binge Eating Disorder 134
Other Specified Feeding or Eating Disorder and Unspecified Feeding or Eating Disorder 134
Avoidant/Restrictive Food Intake Disorder (ARFID) 134
Pica 135
Rumination Disorder 135
Differential Diagnosis 135
Nutritional, Medical, and Laboratory Evaluation 136
Nutritional Evaluation 136
Medical Evaluation 137
Laboratory Evaluation 138
Gastrointestinal Abnormalities Associated with Eating Disorders 138
Management of Eating Disorders in the Adult 142
Psychiatric Treatment 142
Psychotherapy 143
Pharmacotherapy 144
Weight Management 144
Medical Management of GI Symptoms 145
Key References 147
References 147.e1
10 Food Allergies 148
Chapter Outline 148
Definitions and Prevalence 148
Definitions 148
Prevalence 148
Pathogenesis 149
Clinical Features 151
IgE-Mediated Disorders 152
Pollen-Food Allergy Syndrome 152
Gastrointestinal Allergy 152
Infantile Colic 152
Mixed IgE- and Non–IgE-Mediated Disorders 152
Eosinophilic Esophagitis 153
Eosinophilic Gastroenteritis 153
Allergic Eosinophilic Proctocolitis 153
Non–IgE-Mediated Disorders 154
Food Protein-Induced Enterocolitis Syndrome 154
Dietary Protein-Induced Enteropathy 154
Celiac Disease 154
Dermatitis Herpetiformis 155
Other Gastrointestinal Disorders 155
Diagnosis 155
Treatment and Natural History 155
Key References 157
References 157.e1
III Symptoms, Signs, and Biopsychosocial Issues 159
11 Acute Abdominal Pain 161
Chapter Outline 161
Anatomy 161
Visceral Pain 161
Somatic-Parietal Pain 164
Referred Pain 164
Evaluation 164
Approach to Acute Care 165
History 165
Chronology 165
Location 166
Intensity and Character 166
Aggravating and Alleviating Factors 166
Associated Symptoms 166
Past Medical History 166
Physical Examination 166
Abdominal Examination 167
Genital, Rectal, and Pelvic Examinations 167
Laboratory Data 167
Imaging Studies 167
CT 167
US 167
Other Diagnostic Tests 168
Causes 168
Acute Appendicitis 168
Acute Biliary Disease 169
Small Bowel Obstruction 169
Acute Diverticulitis 170
Acute Pancreatitis 170
Perforated Peptic Ulcer 170
Acute Mesenteric Ischemia 171
Abdominal Aortic Aneurysm 171
Abdominal Compartment Syndrome 171
Other Intra-abdominal Causes 172
Extra-abdominal and Systemic Causes 172
Special Circumstances 172
Extremes of Age 172
Pregnancy 173
Immunocompromised Hosts 173
Pharmacologic Management 174
Key References 174
References 174.e1
12 Chronic Abdominal Pain 175
Chapter Outline 175
Definition and Clinical Approach 175
Abdominal Wall Pain 176
Anterior Cutaneous Nerve Entrapment and Myofascial Pain Syndromes 176
Slipping Rib Syndrome 177
Thoracic Nerve Radiculopathy 177
Functional Abdominal Pain Syndrome 177
Epidemiology 177
Pathophysiology 178
Ascending Visceral Pain Transmission 178
Descending Modulation of Pain 179
Visceral Sensitization 179
Biochemical Mechanisms of Sensitization 179
Role of the Central Nervous System 179
Clinical Implications 180
Clinical Features 180
History 180
Patient Behavior 180
Physical Examination 181
Diagnosis and Differential Diagnosis 181
Treatment 181
Establishing a Successful Patient-Physician Relationship 181
Instituting a Treatment Plan 182
Pharmacotherapy 182
Mental Health Referral and Psychological Treatments 183
Role of Laparoscopy with Lysis of Adhesions 183
Narcotic Bowel Syndrome 183
Key References 184
References 184.e1
13 Symptoms of Esophageal Disease 185
Chapter Outline 185
Dysphagia 185
Pathophysiology 185
Differential Diagnosis and Approach 186
Oropharyngeal Dysphagia 186
Esophageal Dysphagia 186
Odynophagia 188
Globus Sensation 189
Pathophysiology 189
Approach 189
Hiccups 189
Chest Pain of Esophageal Origin 189
Pathophysiology 190
Approach 190
Heartburn and Regurgitation 191
Pathophysiology 191
Approach 192
Extraesophageal Symptoms of GERD 192
Key References 193
References 193.e1
14 Dyspepsia 194
Chapter Outline 194
Definition 194
Organic Causes of Dyspepsia 194
Intolerance to Food or Drugs 195
PUD 195
GERD 195
Gastric and Esophageal Cancer 195
Pancreatic and Biliary Tract Disorders 195
Other GI or Systemic Disorders 196
Functional Dyspepsia 196
Dyspepsia Symptom Complex 196
Pattern and Heterogeneity 196
Subgroups 196
Overlap with Heartburn and IBS 197
Epidemiology 198
Pathophysiology 198
Delayed Gastric Emptying 198
Impaired Gastric Accommodation to a Meal 198
Hypersensitivity to Gastric Distension 198
Altered Duodenal Sensitivity to Lipids or Acid 199
Other Mechanisms 199
Pathogenic Factors 199
Genetic Predisposition 199
Infection 199
Hp Infection 199
Postinfection Functional Dyspepsia 199
Psychosocial Factors 199
Approach to Uninvestigated Dyspepsia 200
History and Physical Examination 200
Laboratory Testing 200
Initial Management Strategies 200
Prompt Endoscopy and Directed Treatment 200
Test and Treat for Hp Infection 201
Empirical Antisecretory Drug Therapy 201
Recommendations 201
Additional Investigations 202
Treatment of Functional Dyspepsia 202
General Measures 202
Pharmacologic Treatment 202
Acid-Suppressive Drugs 202
Eradication of Hp Infection 202
Prokinetic Agents 202
Antidepressants 203
Other Pharmacotherapeutic Approaches 203
New Drug Development 203
Psychological Interventions 204
Recommendations 205
Key References 206
References 206.e1
15 Nausea and Vomiting 207
Chapter Outline 207
Pathophysiology 207
Clinical Characteristics 208
Causes 208
Acute Vomiting 209
Acute Intestinal Obstruction 209
Gastric Outlet Obstruction 209
Intestinal Infarction 210
Extraintestinal Causes 210
Toxins and Drugs 210
Metabolic Causes 210
Infectious Causes 210
Neurologic Causes 210
Postoperative Nausea and Vomiting 211
Chronic or Relapsing Vomiting 211
Partial Intestinal Obstruction 211
Gastric Outlet Obstruction 211
GI Motility Disorders 211
Neurologic Disorders 211
Nausea and Vomiting During Pregnancy 212
Functional Vomiting 212
Cyclic Vomiting Syndrome 213
Superior Mesenteric Artery Syndrome 213
Rumination Syndrome 214
Evaluation 214
Acute Vomiting 214
Basic Tests 214
Imaging 214
Additional Tests 215
Chronic Vomiting 215
Esophageal Manometry 216
Measurement of Gastric Emptying 216
Cutaneous Electrogastrography 216
GI Manometry 216
Autonomic Function Tests 216
Histopathologic Studies 216
Complications 216
Emetic Injuries to the Esophagus and Stomach 216
Spasm of the Glottis and Aspiration Pneumonia 217
Fluid, Electrolyte, and Metabolic Alterations 217
Nutritional Deficiencies 217
Treatment 217
Correction of Metabolic Complications 217
Pharmacologic Treatment 217
Central Antiemetic Agents 217
Dopamine D2 Receptor Antagonists 217
Benzamides. 217
Benzimidazole Derivatives. 217
Phenothiazines and Butyrophenones 218
Antihistamines and Antimuscarinic Agents 218
Serotonin Antagonists 218
Glucocorticoids 218
Cannabinoids 218
Neurokinin-1 Receptor Antagonists 218
Adjuvant Agents and Therapies 218
Gastric Prokinetic Agents 219
Serotonin 5-HT4 Receptor Agonists 219
Motilin Receptor Agonists 219
Gastric Electrical Stimulation 219
Key References 219
References 220.e1
16 Diarrhea 221
Chapter Outline 221
Definition 221
Pathophysiology 222
Osmotic Diarrhea 222
Secretory Diarrhea 223
Complex Diarrhea 224
Clinical Classification 226
Acute versus Chronic Diarrhea 226
Large-Volume versus Small-Volume Diarrhea 226
Osmotic versus Secretory Diarrhea 226
Watery versus Fatty versus Inflammatory Diarrhea 226
Epidemiologic Features 226
Differential Diagnosis 227
Evaluation 229
History 229
Physical Examination 229
Further Evaluation of Acute Diarrhea 230
Further Evaluation of Chronic Diarrhea 231
Chronic Watery Diarrhea 232
Chronic Inflammatory Diarrhea 234
Chronic Fatty Diarrhea 234
Treatment 235
Empirical Therapy of Acute Diarrhea 235
Empirical Therapy of Chronic Diarrhea 235
Selected Diarrheal Syndromes 236
IBS and Functional Diarrhea 236
Microscopic Colitis 237
Postsurgical Diarrhea 237
Diarrhea after Gastric Surgery 237
Diarrhea after Bowel Resection 238
Ileostomy Diarrhea 238
Postcholecystectomy Diarrhea 238
Bile Acid–Induced Diarrhea 238
Diarrhea in Hospitalized Patients 238
Factitious Diarrhea 239
Idiopathic Secretory Diarrhea 240
Diarrhea of Obscure Origin 240
Key References 240
References 241.e1
17 Intestinal Gas 242
Chapter Outline 242
Composition and Volume of GI Gas 242
Gas Metabolism and Excretion 242
Diffusion of Gas Between the Intestinal Lumen and Blood 242
Mouth to Stomach 243
Small Intestine 243
Colon 243
Passage of Fermentable Products into the Colon 244
Metabolic Activity of Colonic Microflora 245
Odoriferous Gases 245
Anal Gas Evacuation 245
Intestinal Propulsion, Accommodation, and Tolerance to Gas 246
Clinical Gas Problems 246
Repetitive Eructation 247
Vol-2 Vol-2-Cover
Front cover Vol-2-Cover
IFC_Vol.2 Vol-2-IFC2
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease Vol-2-iii
Copyright page Vol-2-iv
Dedication Vol-2-v
Contributors Vol-2-vii
Foreword Vol-2-xix
Preface Vol-2-xxi
Table of Contents Vol-2-xxiii
Video Contents Vol-2-xxix
Abbreviation List Vol-2-xxxi
IX Liver 1215
71 Embryology, Anatomy, Histology, and Developmental Anomalies of the Liver 1217
Chapter Outline 1217
Embryology 1217
Hepatic Stem Cells and Maturational Lineages 1218
Vascular Development 1219
Anatomy 1219
Nerves 1220
Lymphatics 1220
Histology 1220
Organization of the Liver Parenchyma 1221
Developmental Anomalies (See Chapter 62) 1222
Riedel’s Lobe 1222
Abernethy Malformation 1222
Key References 1222
References 1222.e1
72 Liver Physiology and Energy Metabolism 1223
Chapter Outline 1223
Liver Cell Types and Organization 1223
Parenchymal Cells 1223
Hepatocytes 1223
Plasma Membranes 1223
Cell Junctions. 1224
Cytoskeleton 1224
Nucleus 1224
Transport between the Nucleus and Cytoplasm. 1224
Endoplasmic Reticulum 1225
Golgi Complex 1225
Lysosomes 1225
Mitochondria 1225
Peroxisomes 1225
Exocytosis and Endocytosis 1225
Bile Duct Epithelial Cells 1226
Sinusoidal Cells 1226
Hepatic Sinusoidal Endothelial Cells 1226
Kupffer Cells 1227
Perisinusoidal Cells 1227
Hepatic Stellate Cells 1227
Pit Cells 1227
Integration of the Functions of the Different Cell Types 1227
Cell-Matrix Interactions 1228
Components of the Extracellular Matrix 1228
Regeneration and Apoptosis of Liver Cells 1228
Regeneration 1228
Gene Expression During Regeneration 1228
Immediate Early Genes 1229
Delayed Early Genes 1229
Cell Cycle Genes 1230
Integration of Cytokine and Growth Factors in Regeneration 1230
Apoptosis 1230
Autophagy 1231
Protein Synthesis and Degradation in the Liver 1232
Hepatic Gene Expression 1232
Nuclear Receptors 1232
Protein Folding 1232
Protein Catabolism 1233
Hepatic Nutrient Metabolism 1234
Carbohydrate 1234
Regulation of Glucose Uptake and Efflux from the Hepatocyte 1234
Formation of Glucose-6-Phosphate 1234
Conversion of Glucose-6-Phosphate to Glucose 1235
Hepatic Metabolism of Galactose and Fructose 1236
Glycogen Formation 1236
Regulation of Glycolytic-Gluconeogenic Pathways 1236
Carbohydrate Metabolism in Cirrhosis 1237
Lipid 1237
Fatty Acid Synthesis 1237
Beta Oxidation of Fatty Acids 1237
Mitochondrial Beta Oxidation 1237
Peroxisomal Beta Oxidation 1238
Lipoproteins 1238
Types 1238
Apolipoproteins 1239
Lipolytic Enzymes and Lipid Transport Proteins 1239
Intestinal and Hepatic Lipid Transport 1239
Transport of ApoB-Containing Lipoproteins 1240
Transport of ApoA-Containing High-Density Lipoproteins 1241
Lipoprotein Receptors 1241
Low-Density Lipoprotein Receptor 1241
Very-Low-Density Lipoprotein Receptor 1241
Chylomicron Remnant Receptor 1241
Low-Density Lipoprotein Scavenger Receptor 1241
High-Density Lipoprotein Receptor 1241
Derangement of Lipid Metabolism in Liver Disease 1242
Key References 1242
References 1242.e1
73 Liver Chemistry and Function Tests 1243
Chapter Outline 1243
Bilirubin (See Chapter 21) 1243
Metabolism 1243
Measurement 1244
Approach to the Patient with an Elevated Level 1244
Aminotransferases 1245
Approach to the Patient with an Elevated Level 1246
Alkaline Phosphatase 1247
GGTP 1247
5′-Nucleotidase 1248
Approach to the Patient with an Elevated Level 1248
Tests of Hepatic Synthetic Function 1249
Albumin 1249
Prothrombin Time 1250
Tests to Detect Hepatic Fibrosis 1250
Quantitative Liver Function Tests 1251
Indocyanine Green Clearance 1251
Galactose Elimination Capacity 1251
Caffeine Clearance 1251
Lidocaine Metabolite Formation 1251
Aminopyrine Breath Test 1251
Bile Acids 1252
Specific Applications of Liver Biochemical Testing 1252
Drug-Induced Liver Injury 1252
Surgical Candidacy and Organ Allocation 1252
Key References 1253
References 1253.e1
74 Overview of Cirrhosis 1254
Chapter Outline 1254
Pathogenesis 1254
Diagnosis 1254
Natural History 1257
Prognosis 1259
Treatment 1259
Reversal of Fibrosis 1260
Key References 1260
References 1260.e1
75 Hemochromatosis 1261
Chapter Outline 1261
Causes of Iron Overload 1261
Pathophysiology 1262
Intestinal Iron Absorption 1262
Hepcidin 1262
HFE Protein 1263
Iron-Induced Tissue Injury and Fibrosis 1264
Clinical Features 1264
Diagnosis 1265
Treatment and Prognosis 1268
Family Screening 1269
Key References 1269
References 1269.e1
76 Wilson Disease 1270
Chapter Outline 1270
Copper Metabolism 1270
Molecular Pathogenesis 1270
Pathology 1272
Clinical Features 1272
Hepatic Presentation 1273
Neurologic Presentation 1273
Psychiatric Presentation 1273
Ocular Signs 1273
Involvement of Other Systems 1273
Diagnosis 1274
Tests 1274
Approach 1275
Mutation Analysis 1275
Presymptomatic Diagnosis of First-Degree Relatives 1276
Treatment 1276
Prognosis 1278
Key References 1278
References 1279.e1
77 Other Inherited Metabolic Disorders of the Liver 1280
Chapter Outline 1280
Clinical Features of Metabolic Liver Disease 1280
α1-Antitrypsin Deficiency 1281
Pathophysiology 1281
Clinical Features 1281
Histopathology 1282
Diagnosis 1282
Treatment 1282
Glycogen Storage Diseases 1283
Type I 1283
Clinical Features 1283
Hepatic Involvement 1284
Diagnosis 1284
Treatment 1284
Type III 1285
Clinical Features 1285
Treatment 1285
Type IV 1285
Congenital Disorders of Glycosylation 1285
Porphyrias 1287
Pathophysiology 1287
Acute Porphyrias 1287
Cutaneous Porphyrias 1288
Hepatic Involvement 1289
Diagnosis 1289
Treatment 1290
Tyrosinemia 1290
Pathophysiology 1290
Clinical and Pathologic Features 1291
Diagnosis 1291
Treatment 1292
Urea Cycle Defects 1292
Pathophysiology 1292
Clinical Features 1293
Diagnosis 1294
Treatment 1294
Arginase Deficiency 1295
Bile Acid Synthesis and Transport Defects 1295
Bile Acid Synthesis Defects 1296
Diagnosis 1296
Disorders of Enzymes Involved in Modification of the Steroid Ring 1296
Disorders of Enzymes Involved in Side-Chain Modification 1297
Peroxisomal Disorders 1297
Bile Acid Transport Defects 1298
Treatment 1299
CF 1299
Clinical and Pathologic Features 1299
Pathophysiology 1299
Diagnosis 1300
Treatment 1300
Mitochondrial Liver Diseases 1300
Key References 1301
References 1301.e1
78 Hepatitis A 1302
Chapter Outline 1302
Virology 1302
Epidemiology 1303
Pathogenesis 1304
Clinical Features 1304
Fulminant Hepatitis A 1305
Extrahepatic Manifestations 1305
Autoimmune Hepatitis after Acute Hepatitis A 1305
Diagnosis 1305
Prevention and Treatment 1306
Immunization against Hepatitis A Virus in Patients with Chronic Illnesses 1307
Key References 1308
References 1308.e1
79 Hepatitis B 1309
Chapter Outline 1309
Epidemiology 1309
Geographic Distribution and Sources of Infection 1309
Infectivity 1310
Prevalence 1310
Clinical Outcomes 1310
Acute Hepatitis B 1310
Chronic Hepatitis B 1311
Virology 1311
Viral Replication 1311
Genotypes 1311
Mutations 1312
Hepatitis B Surface Antigen Gene 1312
Precore, Basal Core Promoter, and Core Genes 1314
HBV DNA Polymerase 1314
Pathogenesis 1314
Natural History 1315
Serum ALT as a Surrogate Marker for Disease Activity 1316
HBV DNA Level and Long-Term Complications 1316
Clinical and Pathologic Features 1317
Acute Hepatitis B 1317
Chronic Hepatitis B 1317
Extrahepatic Manifestations 1317
Arthritis-Dermatitis 1317
Polyarteritis Nodosa 1317
Glomerulonephritis 1317
Cryoglobulinemia 1318
Histopathologic Features 1318
Acute Flares 1318
Spontaneous Flares 1318
Immunosuppressive Therapy–Induced Flares 1319
Antiviral Therapy–Induced Flares 1320
During Interferon Therapy. 1320
During Nucleos(t)ide Analog Therapy. 1321
After Withdrawal of Nucleos(t)ide Analog. 1321
During Antiretroviral Therapy. 1321
Flares Associated with Genotypic Variation 1321
Flares Caused by Infection with Other Viruses 1321
Diagnosis 1321
Treatment 1322
Goals 1322
Cultural Barriers 1323
Choice of Agent 1323
Definitions of Response 1323
Nucleoside and Nucleotide Analogs 1324
Lamivudine 1324
Adefovir Dipivoxil 1325
Entecavir 1325
Telbivudine 1325
Tenofovir Disoproxil Fumarate 1325
Emtricitabine 1325
HBV DNA Monitoring 1325
Drug Failure 1326
Interferon 1326
Combination Interferon and Nucleos(t)ide Analog Therapy 1326
Guidelines 1326
Special Populations 1327
Pregnant Women 1327
Severe Acute Hepatitis 1327
Cirrhosis 1328
HBV-HIV Coinfection 1328
HBV-HCV Coinfection 1328
Urgent Treatment 1328
Prevention 1329
Hepatitis B Immune Globulin 1329
Hepatitis B Vaccine 1329
Vaccination Schedule 1329
Postexposure and Perinatal Prophylaxis 1329
Bivalent Vaccine 1330
Recommendations 1330
Key References 1330
References 1331.e1
80 Hepatitis C* 1332
Chapter Outline 1332
Virology 1332
Structure 1332
Genomic Organization 1333
Viral Replication and Life Cycle 1333
Virus Protein Function 1334
Genotypes and Quasispecies 1335
Epidemiology 1336
Incidence and Prevalence 1336
Transmission 1336
Percutaneous Transmission 1336
Nonpercutaneous Transmission 1337
Sporadic HCV Infection 1337
Pathogenesis 1337
Viral Mechanisms 1337
Immune-Mediated Mechanisms 1337
Clinical Features 1338
Acute Hepatitis C 1338
Chronic Hepatitis C 1339
Extrahepatic Manifestations 1339
Diagnosis 1340
Indirect Assays 1340
Direct Assays 1340
HCV Genotype 1340
Selection of Serologic and Virologic Tests 1341
Liver Biopsy and Noninvasive Assessment of Fibrosis 1341
Natural History 1343
Factors Associated with Progression 1343
Hepatocellular Carcinoma 1344
Treatment 1344
Goals 1345
Virologic Response 1345
Drugs 1345
Interferons 1345
Ribavirin 1345
Direct-Acting Antiviral Agents 1346
Acute Hepatitis C 1346
Chronic Hepatitis C 1346
Pegylated Interferon and Ribavirin 1346
Pegylated Interferon, Ribavirin, and a First-Generation Protease Inhibitor 1347
Pegylated Interferon, Ribavirin, and Other Direct-Acting Antiviral Agents 1348
Interferon-Free Therapies 1349
Indications and Contraindications 1349
Monitoring and Safety 1350
HCV-HIV Coinfection 1351
Liver Transplant Recipients 1351
Key References 1352
References 1352.e1
81 Hepatitis D 1353
Chapter Outline 1353
Epidemiology 1353
Virology 1354
Pathogenesis 1355
Diagnosis 1355
HDV RNA 1355
Hepatitis D Antigen 1356
Antibody to HDV 1356
Natural History 1357
Clinical Features 1357
Treatment 1358
Interferon 1358
Combination Antiviral Therapy 1358
Novel Drugs 1359
Prevention 1359
Key References 1359
References 1359.e1
82 Hepatitis E 1360
Chapter Outline 1360
Virology 1360
Epidemiology 1360
Genotypes 1 and 2 1361
Genotypes 3 and 4 1362
Pathogenesis 1362
Clinical Features 1364
Acute Hepatitis E 1364
Chronic Hepatitis E 1364
Diagnosis 1364
Treatment and Prevention 1365
Key References 1365
References 1365.e1
83 Hepatitis Caused by Other Viruses 1366
Chapter Outline 1366
Hepatitis G and GB Agent Infection 1366
Virology 1366
Epidemiology 1367
Clinical Features 1367
Diagnosis 1367
GB Virus Type C and HIV 1367
Treatment 1368
TT Virus Infection 1368
Virology 1368
Epidemiology 1369
Clinical Features 1369
Treatment 1369
Sanban, Yonban, and SEN Virus and TTV-like Minivirus Infections 1369
Systemic Viral Infections That May Involve the Liver 1369
EBV 1369
Cytomegalovirus 1370
HSV 1371
Varicella-Zoster Virus 1372
Other Viruses 1372
Key References 1372
References 1373.e1
84 Bacterial, Parasitic, and Fungal Infections of the Liver, Including Liver Abscesses 1374
Chapter Outline 1374
Bacterial Infections Involving or Affecting the Liver 1374
Gram-Positive and Gram-Negative Bacteria 1374
Toxic Shock Syndrome: Staphylococcus aureus or Group A Streptococci 1374
Clostridium perfringens 1374
Actinomyces 1375
Listeria 1375
Shigella and Salmonella 1375
Yersinia 1375
Gonococci 1375
Legionella 1375
Burkholderia pseudomallei (Melioidosis) 1376
Brucella 1376
Coxiella burnetii (Q Fever) 1376
Bartonella (Oroya Fever) 1376
Bacillary Angiomatosis and AIDS 1376
Bacterial Sepsis and Jaundice 1376
Chlamydia 1376
Fitz-Hugh–Curtis Syndrome 1376
Rickettsiae 1376
Rocky Mountain Spotted Fever 1376
Ehrlichiae 1377
Spirochetes 1377
Leptospirosis 1377
Syphilis 1377
Secondary Syphilis 1377
Tertiary (Late) Syphilis 1377
Lyme Disease 1377
TB and Other Mycobacteria 1378
Parasites (Tables 84-1 and 84-2) 1378
Protozoa (see also Chapter 113) 1378
Malaria 1378
The Plasmodium Life Cycle 1378
Histopathologic Features 1378