BOOK
Robbins & Cotran Pathologic Basis of Disease E-Book
Vinay Kumar | Abul K. Abbas | Jon C. Aster
(2014)
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Book Details
Abstract
Dependable, current, and complete, Robbins and Cotran Pathologic Basis of Disease, 9th Edition is the perennially best-selling text that you’ll use long after your medical student days are behind you. A world-class author team headed by Drs. Vinay Kumar, Abul Abbas, and Jon Aster, delivers the latest, most essential pathology knowledge in a readable, interesting manner, ensuring optimal understanding of the latest basic science and clinical content. High-quality photographs and full-color illustrations highlight new information in molecular biology, disease classifications, new drugs and drug therapies, and much more.
- Rely on uniquely authoritative and readable coverage, ideal for USMLE or specialty board preparation, as well as for course work.
- Simplify your study with an outstanding full-color, highly user-friendly design.
- Stay up to date with the latest information in molecular and genetic testing and mechanisms of disease.
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- Gain a new perspective in key areas thanks to contributions from new authors at the top of their fields.
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Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| IFC_professional | IFC1 | ||
| IFC_regular | IFC2 | ||
| End sheet 3 | IFC3 | ||
| Robbins & Cotran Pathologic Basis of Disease, 9/e | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vii | ||
| Preface: A New Chapter | xi | ||
| Acknowledgments | xiii | ||
| Table Of Contents | xv | ||
| General Pathology | 1 | ||
| 1 The Cell as a Unit of Health and Disease | 1 | ||
| Chapter Contents | 1 | ||
| The Genome | 1 | ||
| Noncoding DNA | 1 | ||
| Histone Organization | 3 | ||
| Micro-RNA and Long Noncoding RNA | 4 | ||
| Micro-RNA (miRNA) | 4 | ||
| Long Noncoding RNA (lncRNA) | 5 | ||
| Cellular Housekeeping | 6 | ||
| Plasma Membrane: Protection and Nutrient Acquisition | 7 | ||
| Passive Membrane Diffusion. | 9 | ||
| Carriers and Channels. | 9 | ||
| Receptor-mediated and fluid-phase uptake (Fig. 1-7). | 9 | ||
| Cytoskeleton and Cell-Cell Interactions | 10 | ||
| Cell-Cell Interactions. | 11 | ||
| Biosynthetic Machinery: Endoplasmic Reticulum and Golgi | 12 | ||
| Waste Disposal: Lysosomes and Proteasomes | 13 | ||
| Cellular Metabolism and Mitochondrial Function | 14 | ||
| Energy Generation. | 14 | ||
| Intermediate metabolism. | 14 | ||
| Cell Death. | 15 | ||
| Cellular Activation | 15 | ||
| Cell Signaling | 15 | ||
| Signal Transduction Pathways | 16 | ||
| Modular Signaling Proteins, Hubs, and Nodes. | 18 | ||
| Transcription Factors. | 18 | ||
| Growth Factors and Receptors | 18 | ||
| Epidermal Growth Factor and Transforming Growth Factor-α. | 19 | ||
| Hepatocyte Growth Factor. | 19 | ||
| Platelet-Derived Growth Factor. | 19 | ||
| Vascular Endothelial Growth Factor. | 20 | ||
| Fibroblast Growth Factor. | 20 | ||
| Transforming Growth Factor-β. | 20 | ||
| Interaction with the Extracellular Matrix | 20 | ||
| Components of the Extracellular Matrix. | 21 | ||
| Collagens. | 23 | ||
| Elastin. | 23 | ||
| Proteoglycans and hyaluronan (Fig. 1-14). | 23 | ||
| Adhesive glycoproteins and adhesion receptors | 24 | ||
| Maintaining Cell Populations | 25 | ||
| Proliferation and the Cell Cycle | 25 | ||
| Stem Cells | 26 | ||
| Regenerative Medicine | 28 | ||
| Concluding Remarks. | 29 | ||
| Suggested Readings | 29 | ||
| Genetics and Epigenetics | 29 | ||
| Cellular Housekeeping | 29 | ||
| Cellular Metabolism and Mitochondrial Function | 29 | ||
| Cellular Activation | 29 | ||
| Maintaining Cell Populations | 29 | ||
| 2 Cellular Responses to Stress and Toxic Insults: | 31 | ||
| Chapter Contents | 31 | ||
| Introduction to Pathology | 31 | ||
| Etiology or Cause. | 32 | ||
| Pathogenesis. | 32 | ||
| Morphologic Changes. | 32 | ||
| Functional Derangements and Clinical Manifestations. | 32 | ||
| Overview: Cellular Responses to Stress and Noxious Stimuli | 32 | ||
| Adaptations of Cellular Growth and Differentiation | 34 | ||
| Hypertrophy | 34 | ||
| Mechanisms of Hypertrophy | 34 | ||
| Hyperplasia | 35 | ||
| Physiologic Hyperplasia | 36 | ||
| Pathologic Hyperplasia | 36 | ||
| Mechanisms of Hyperplasia | 36 | ||
| Atrophy | 36 | ||
| Mechanisms of Atrophy | 37 | ||
| Metaplasia | 37 | ||
| Mechanisms of Metaplasia | 38 | ||
| Overview of Cell Injury and Cell Death | 38 | ||
| Causes of Cell Injury | 39 | ||
| Oxygen Deprivation. | 39 | ||
| Physical Agents. | 39 | ||
| Chemical Agents and Drugs. | 39 | ||
| Infectious Agents. | 39 | ||
| Immunologic Reactions. | 39 | ||
| Genetic Derangements. | 39 | ||
| Nutritional Imbalances. | 40 | ||
| Morphologic Alterations in Cell Injury | 40 | ||
| Reversible Injury | 40 | ||
| Necrosis | 41 | ||
| Patterns of Tissue Necrosis | 43 | ||
| Mechanisms of Cell Injury | 44 | ||
| Depletion of ATP | 45 | ||
| Mitochondrial Damage | 46 | ||
| Influx of Calcium and Loss of Calcium Homeostasis | 46 | ||
| Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) | 47 | ||
| Generation of Free Radicals. | 47 | ||
| Removal of Free Radicals. | 48 | ||
| Pathologic Effects of Free Radicals. | 49 | ||
| Defects in Membrane Permeability | 49 | ||
| Mechanisms of Membrane Damage. | 49 | ||
| Consequences of Membrane Damage. | 49 | ||
| Damage to DNA and Proteins | 50 | ||
| Reversible vs Irreversible Injury. | 50 | ||
| Clinicopathologic Correlations: Selected Examples of Cell Injury and Necrosis | 50 | ||
| Ischemic and Hypoxic Injury | 50 | ||
| Mechanisms of Ischemic Cell Injury | 50 | ||
| Ischemia-Reperfusion Injury | 51 | ||
| Chemical (Toxic) Injury | 51 | ||
| Apoptosis | 52 | ||
| Causes of Apoptosis | 52 | ||
| Apoptosis in Physiologic Situations | 52 | ||
| Apoptosis in Pathologic Conditions | 53 | ||
| Morphologic and Biochemical Changes in Apoptosis | 53 | ||
| Mechanisms of Apoptosis | 53 | ||
| The Intrinsic (Mitochondrial) Pathway of Apoptosis | 53 | ||
| The Extrinsic (Death Receptor-Initiated) Pathway of Apoptosis | 56 | ||
| The Execution Phase of Apoptosis | 56 | ||
| Removal of Dead Cells | 56 | ||
| Clinicopathologic Correlations: Apoptosis in Health and Disease | 57 | ||
| Examples of Apoptosis | 57 | ||
| Growth Factor Deprivation. | 57 | ||
| DNA Damage. | 57 | ||
| Protein Misfolding. | 57 | ||
| Apoptosis Induced by the TNF Receptor Family. | 58 | ||
| Cytotoxic T Lymphocyte-Mediated Apoptosis. | 58 | ||
| Disorders Associated with Dysregulated Apoptosis | 58 | ||
| Necroptosis | 58 | ||
| Autophagy | 60 | ||
| Intracellular Accumulations | 61 | ||
| Lipids | 62 | ||
| Steatosis (Fatty Change) | 62 | ||
| Cholesterol and Cholesterol Esters | 62 | ||
| Proteins | 63 | ||
| Hyaline Change | 63 | ||
| Glycogen | 63 | ||
| Pigments | 64 | ||
| Exogenous Pigments | 64 | ||
| Endogenous Pigments | 64 | ||
| Pathologic Calcification | 65 | ||
| Dystrophic Calcification | 65 | ||
| Metastatic Calcification | 65 | ||
| Cellular Aging | 66 | ||
| DNA Damage. | 66 | ||
| Cellular Senescence. | 67 | ||
| Defective Protein Homeostasis. | 67 | ||
| Deregulated Nutrient Sensing. | 67 | ||
| Suggested Readings | 68 | ||
| Hypertrophy | 68 | ||
| Cell Death | 68 | ||
| Apoptosis | 68 | ||
| Necroptosis | 68 | ||
| Autophagy | 68 | ||
| Aging | 68 | ||
| 3 Inflammation and Repair | 69 | ||
| Chapter Contents | 69 | ||
| Overview of Inflammation: Definitions and General Features | 69 | ||
| Historical Highlights | 71 | ||
| Causes of Inflammation | 71 | ||
| Recognition of Microbes and Damaged Cells | 72 | ||
| Acute Inflammation | 73 | ||
| Reactions of Blood Vessels in Acute Inflammation | 73 | ||
| Changes in Vascular Flow and Caliber | 73 | ||
| Increased Vascular Permeability (Vascular Leakage) | 74 | ||
| Responses of Lymphatic Vessels and Lymph Nodes | 74 | ||
| Leukocyte Recruitment to Sites of Inflammation | 75 | ||
| Leukocyte Adhesion to Endothelium | 75 | ||
| Leukocyte Migration Through Endothelium | 76 | ||
| Chemotaxis of Leukocytes | 77 | ||
| Phagocytosis and Clearance of the Offending Agent | 78 | ||
| Phagocytosis | 78 | ||
| Phagocytic Receptors. | 78 | ||
| Engulfment. | 78 | ||
| Intracellular Destruction of Microbes and Debris | 79 | ||
| Reactive Oxygen Species. | 79 | ||
| Nitric Oxide. | 80 | ||
| Lysosomal Enzymes and Other Lysosomal Proteins. | 80 | ||
| Neutrophil Extracellular Traps | 81 | ||
| Leukocyte-Mediated Tissue Injury | 81 | ||
| Other Functional Responses of Activated Leukocytes | 82 | ||
| Termination of the Acute Inflammatory Response | 82 | ||
| Mediators of Inflammation | 82 | ||
| Vasoactive Amines: Histamine and Serotonin | 83 | ||
| Arachidonic Acid Metabolites | 83 | ||
| Prostaglandins | 84 | ||
| Leukotrienes | 85 | ||
| Lipoxins | 85 | ||
| Pharmacologic Inhibitors of Prostaglandins and Leukotrienes | 85 | ||
| Cytokines and Chemokines | 86 | ||
| Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1) | 86 | ||
| Chemokines | 87 | ||
| Other Cytokines in Acute Inflammation | 88 | ||
| Complement System | 88 | ||
| Other Mediators of Inflammation | 89 | ||
| Platelet-Activating Factor (PAF) | 89 | ||
| Products of Coagulation | 89 | ||
| Kinins | 89 | ||
| Neuropeptides | 89 | ||
| Morphologic Patterns of Acute Inflammation | 90 | ||
| Serous Inflammation | 90 | ||
| Fibrinous Inflammation | 90 | ||
| Purulent (Suppurative) Inflammation, Abscess | 91 | ||
| Ulcers | 91 | ||
| Outcomes of Acute Inflammation | 92 | ||
| Summary of Acute Inflammation | 93 | ||
| Chronic Inflammation | 93 | ||
| Causes of Chronic Inflammation | 93 | ||
| Morphologic Features | 93 | ||
| Cells and Mediators of Chronic Inflammation | 94 | ||
| Role of Macrophages | 94 | ||
| Role of Lymphocytes | 96 | ||
| Other Cells in Chronic Inflammation | 96 | ||
| Granulomatous Inflammation | 97 | ||
| Systemic Effects of Inflammation | 99 | ||
| Tissue Repair | 100 | ||
| Overview of Tissue Repair | 100 | ||
| Cell and Tissue Regeneration | 101 | ||
| Cell Proliferation: Signals and Control Mechanisms | 101 | ||
| Mechanisms of Tissue Regeneration | 101 | ||
| Liver Regeneration | 102 | ||
| Repair by Connective Tissue Deposition | 102 | ||
| Steps in Scar Formation | 103 | ||
| Angiogenesis | 104 | ||
| Deposition of Connective Tissue | 105 | ||
| Remodeling of Connective Tissue | 105 | ||
| Factors That Influence Tissue Repair | 105 | ||
| Selected Clinical Examples of Tissue Repair and Fibrosis | 106 | ||
| Healing of Skin Wounds | 106 | ||
| Healing by First Intention | 106 | ||
| Healing by Second Intention | 107 | ||
| Wound Strength | 108 | ||
| Fibrosis in Parenchymal Organs | 109 | ||
| Abnormalities in Tissue Repair | 109 | ||
| Suggested Readings | 110 | ||
| General Mechanisms of Inflammation | 110 | ||
| Acute Inflammation: Vascular Reactions | 110 | ||
| Acute Inflammation: Role of Leukocytes | 110 | ||
| Mediators of Inflammation | 111 | ||
| Chronic Inflammation: Role of Macrophages and Other Cells | 111 | ||
| Sepsis | 111 | ||
| Tissue Repair: Regeneration and Fibrosis | 111 | ||
| 4 Hemodynamic Disorders, Thromboembolic Disease, and Shock | 113 | ||
| Chapter Contents | 113 | ||
| Edema and Effusions | 113 | ||
| Increased Hydrostatic Pressure | 114 | ||
| Reduced Plasma Osmotic Pressure | 114 | ||
| Sodium and Water Retention | 114 | ||
| Lymphatic Obstruction | 114 | ||
| Clinical Features | 115 | ||
| Hyperemia and Congestion | 115 | ||
| Hemostasis, Hemorrhagic Disorders, and Thrombosis | 116 | ||
| Hemostasis | 116 | ||
| Platelets | 117 | ||
| Coagulation Cascade | 118 | ||
| Factors That Limit Coagulation. | 120 | ||
| Endothelium | 121 | ||
| Hemorrhagic Disorders | 121 | ||
| Thrombosis | 122 | ||
| Endothelial Injury | 122 | ||
| Alternations in Normal Blood Flow | 123 | ||
| Hypercoagulability | 123 | ||
| Heparin-Induced Thrombocytopenia (HIT) Syndrome | 124 | ||
| Antiphospholipid Antibody Syndrome | 124 | ||
| Fate of the Thrombus | 125 | ||
| Clinical Features | 126 | ||
| Venous Thrombosis (Phlebothrombosis). | 126 | ||
| Arterial and Cardiac Thrombosis. | 126 | ||
| Disseminated Intravascular Coagulation | 127 | ||
| Embolism | 127 | ||
| Pulmonary Embolism | 127 | ||
| Systemic Thromboembolism | 127 | ||
| Fat and Marrow Embolism | 128 | ||
| Air Embolism | 128 | ||
| Amniotic Fluid Embolism | 129 | ||
| Infarction | 129 | ||
| Factors That Influence Development of an Infarct. | 130 | ||
| Shock | 131 | ||
| Pathogenesis of Septic Shock | 131 | ||
| Stages of Shock | 133 | ||
| Clinical Consequences. | 134 | ||
| Suggested Readings | 134 | ||
| Fluid Dynamics | 134 | ||
| Hemostasis and Bleeding | 134 | ||
| Thrombosis and Thromboembolism | 135 | ||
| Unusual Forms of Embolic Disease | 135 | ||
| Septic Shock | 135 | ||
| 5 Genetic Disorders | 137 | ||
| Chapter Contents | 137 | ||
| Genes and Human Diseases | 137 | ||
| Mutations | 138 | ||
| Mendelian Disorders | 140 | ||
| Transmission Patterns of Single-Gene Disorders | 140 | ||
| Autosomal Dominant Disorders | 140 | ||
| Autosomal Recessive Disorders | 141 | ||
| X-Linked Disorders | 142 | ||
| Biochemical and Molecular Basis of Single-Gene (Mendelian) Disorders | 142 | ||
| Enzyme Defects and Their Consequences | 142 | ||
| Defects in Receptors and Transport Systems | 143 | ||
| Alterations in Structure, Function, or Quantity of Nonenzyme Proteins | 144 | ||
| Genetically Determined Adverse Reactions to Drugs | 144 | ||
| Disorders Associated with Defects in Structural Proteins | 144 | ||
| Marfan Syndrome | 144 | ||
| Pathogenesis. | 144 | ||
| Clinical Features. | 145 | ||
| Ehlers-Danlos Syndromes (EDS) | 145 | ||
| Disorders Associated with Defects in Receptor Proteins | 147 | ||
| Familial Hypercholesterolemia | 147 | ||
| Normal Process of Cholesterol Metabolism and Transport | 147 | ||
| Disorders Associated with Defects in Enzymes | 149 | ||
| Lysosomal Storage Diseases | 149 | ||
| Tay-Sachs Disease (GM2 Gangliosidosis: Hexosaminidase α-Subunit Deficiency) | 151 | ||
| Clinical Features. | 152 | ||
| Niemann-Pick Disease Types A and B | 152 | ||
| Niemann-Pick Disease Type C | 153 | ||
| Gaucher Disease | 153 | ||
| Clinical Features. | 154 | ||
| Mucopolysaccharidoses (MPS) | 154 | ||
| Clinical Features. | 155 | ||
| Glycogen Storage Diseases (Glycogenoses) | 155 | ||
| Disorders Associated with Defects in Proteins That Regulate Cell Growth | 157 | ||
| Complex Multigenic Disorders | 158 | ||
| Chromosomal Disorders | 158 | ||
| Normal Karyotype | 158 | ||
| Commonly Used Cytogenetic Terminology | 159 | ||
| Structural Abnormalities of Chromosomes | 159 | ||
| Cytogenetic Disorders Involving Autosomes | 161 | ||
| Trisomy 21 (Down Syndrome) | 161 | ||
| Other Trisomies | 163 | ||
| Chromosome 22q11.2 Deletion Syndrome | 163 | ||
| Cytogenetic Disorders Involving Sex Chromosomes | 164 | ||
| Klinefelter Syndrome | 165 | ||
| Turner Syndrome | 166 | ||
| Hermaphroditism and Pseudohermaphroditism | 167 | ||
| Single-Gene Disorders with Nonclassic Inheritance | 168 | ||
| Diseases Caused by Trinucleotide-Repeat Mutations | 168 | ||
| Fragile X Syndrome and Fragile X Tremor/Ataxia | 169 | ||
| Fragile X Tremor/Ataxia. | 171 | ||
| Mutations in Mitochondrial Genes—Leber Hereditary Optic Neuropathy | 171 | ||
| Genomic Imprinting | 172 | ||
| Prader-Willi Syndrome and Angelman Syndrome | 172 | ||
| Gonadal Mosaicism | 174 | ||
| Molecular Genetic Diagnosis | 174 | ||
| Diagnostic Methods and Indications for Testing | 174 | ||
| Laboratory Considerations | 174 | ||
| Indications for Analysis of Inherited Genetic Alterations | 174 | ||
| Indications for Analysis of Acquired Genetic Alterations | 175 | ||
| PCR and Detection of DNA Sequence Alterations | 175 | ||
| Molecular Analysis of Genomic Alterations | 176 | ||
| Fluorescence in Situ Hybridization (FISH) | 177 | ||
| Multiplex Ligation-Dependent Probe Amplification (MLPA) | 177 | ||
| Southern Blotting | 177 | ||
| Cytogenomic Array Technology | 177 | ||
| Array-Based Comparative Genomic Hybridization (Array CGH). | 177 | ||
| SNP Genotyping Arrays. | 178 | ||
| Polymorphic Markers and Molecular Diagnosis | 178 | ||
| Polymorphisms and Genome-Wide Analyses | 179 | ||
| Epigenetic Alterations | 180 | ||
| RNA Analysis | 180 | ||
| Next-Generation Sequencing | 180 | ||
| Bioinformatics | 180 | ||
| Clinical Applications of NGS DNA Sequencing | 181 | ||
| Future Applications | 182 | ||
| Acknowledgment | 182 | ||
| Suggested Reading | 182 | ||
| Molecular Basis of Single Gene Disorders—General | 182 | ||
| Disorders Associated with Defects in Structural Proteins | 182 | ||
| Disorders Associated with Defects in Receptor Proteins | 182 | ||
| Disorders Associated with Defects in Enzymes | 182 | ||
| Cytogenetic Disorders Affecting Autosomes | 182 | ||
| Cytogenetic Disorders Affecting Sex Chromosomes | 182 | ||
| Diseases Caused by Trinucleotide Mutations | 183 | ||
| Diseases Caused by Genomic Imprinting | 183 | ||
| 6 Diseases of the Immune System | 185 | ||
| Chapter Contents | 185 | ||
| The Normal Immune Response | 186 | ||
| Innate Immunity | 186 | ||
| Components of Innate Immunity | 186 | ||
| Cellular Receptors for Microbes, Products of Damaged Cells, and Foreign Substances | 187 | ||
| Toll-Like Receptors. | 187 | ||
| NOD-Like Receptors and the Inflammasome. | 188 | ||
| Other Receptors for Microbial Products. | 188 | ||
| Reactions of Innate Immunity | 188 | ||
| Adaptive Immunity | 188 | ||
| Cells of the Immune System | 189 | ||
| Lymphocyte Diversity | 190 | ||
| T Lymphocytes | 190 | ||
| B Lymphocytes | 191 | ||
| Dendritic Cells | 191 | ||
| Macrophages | 192 | ||
| Natural Killer Cells | 192 | ||
| Innate Lymphoid Cells (ILCs) | 193 | ||
| Tissues of the Immune System | 193 | ||
| Generative Lymphoid Organs | 193 | ||
| Peripheral Lymphoid Organs | 193 | ||
| Lymphocyte Recirculation | 194 | ||
| Major Histocompatibility Complex (MHC) Molecules: The Peptide Display System of Adaptive Immunity | 194 | ||
| Cytokines: Messenger Molecules of the Immune System | 196 | ||
| Overview of Lymphocyte Activation and Immune Responses | 196 | ||
| Display and Recognition of Antigens | 196 | ||
| Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes | 197 | ||
| Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes | 198 | ||
| Decline of Immune Responses and Immunologic Memory | 199 | ||
| Hypersensitivity: Immunologically Mediated Tissue Injury | 200 | ||
| Classification of Hypersensitivity Diseases | 200 | ||
| Immediate (Type I) Hypersensitivity | 201 | ||
| Activation of TH2 Cells and Production of IgE Antibody | 202 | ||
| Sensitization and Activation of Mast Cells | 202 | ||
| Mediators of Immediate Hypersensitivity | 203 | ||
| Preformed Mediators. | 203 | ||
| Lipid Mediators. | 203 | ||
| Cytokines. | 203 | ||
| Late-Phase Reaction | 204 | ||
| Development of Allergies | 204 | ||
| Systemic Anaphylaxis | 204 | ||
| Local Immediate Hypersensitivity Reactions | 205 | ||
| Antibody-Mediated (Type II) Hypersensitivity | 205 | ||
| Opsonization and Phagocytosis | 205 | ||
| Inflammation | 205 | ||
| Cellular Dysfunction | 205 | ||
| Immune Complex–Mediated (Type III) Hypersensitivity | 207 | ||
| Systemic Immune Complex Disease | 207 | ||
| Local Immune Complex Disease (Arthus Reaction) | 208 | ||
| T Cell–Mediated (Type IV) Hypersensitivity | 208 | ||
| CD4+ T Cell–Mediated Inflammation | 208 | ||
| Activation of CD4+ T Cells. | 208 | ||
| Responses of Differentiated Effector T Cells. | 209 | ||
| Clinical Examples of CD4+ T Cell–Mediated Inflammatory Reactions. | 210 | ||
| CD8+ T Cell–Mediated Cytotoxicity | 211 | ||
| Autoimmune Diseases | 211 | ||
| Immunologic Tolerance | 212 | ||
| Central Tolerance | 212 | ||
| Peripheral Tolerance | 213 | ||
| Mechanisms of Autoimmunity: General Principles | 214 | ||
| Role of Susceptibility Genes | 215 | ||
| Association of HLA Alleles with Disease. | 215 | ||
| Association of Non-MHC Genes with Autoimmune Diseases. | 215 | ||
| Role of Infections | 216 | ||
| General Features of Autoimmune Diseases | 217 | ||
| Systemic Lupus Erythematosus (SLE) | 218 | ||
| Spectrum of Autoantibodies in SLE | 218 | ||
| Other Autoantibodies. | 219 | ||
| Etiology and Pathogenesis of SLE | 219 | ||
| Genetic Factors. | 219 | ||
| Immunologic Factors. | 220 | ||
| Environmental Factors. | 221 | ||
| A Model for the Pathogenesis of SLE. | 221 | ||
| Mechanism of Tissue Injury. | 221 | ||
| Clinical Features. | 225 | ||
| Chronic Discoid Lupus Erythematosus. | 225 | ||
| Subacute Cutaneous Lupus Erythematosus. | 226 | ||
| Drug-Induced Lupus Erythematosus | 226 | ||
| Rheumatoid Arthritis | 226 | ||
| Sjögren Syndrome | 226 | ||
| Etiology and Pathogenesis | 226 | ||
| Clinical Features. | 227 | ||
| Systemic Sclerosis (Scleroderma) | 228 | ||
| Etiology and Pathogenesis | 228 | ||
| Clinical Features. | 229 | ||
| Inflammatory Myopathies | 231 | ||
| Mixed Connective Tissue Disease | 231 | ||
| Polyarteritis Nodosa and Other Vasculitides | 231 | ||
| IgG4-Related Disease | 231 | ||
| Rejection of Tissue Transplants | 231 | ||
| Mechanisms of Recognition and Rejection of Allografts | 231 | ||
| Recognition of Graft Alloantigens by T and B Lymphocytes | 231 | ||
| T Cell–Mediated Reactions | 233 | ||
| Antibody-Mediated Reactions | 233 | ||
| Rejection of Kidney Grafts | 233 | ||
| Methods of Increasing Graft Survival | 234 | ||
| Transplantation of Other Solid Organs | 236 | ||
| Transplantation of Hematopoietic Stem Cells | 236 | ||
| Immunodeficiency Syndromes | 237 | ||
| Primary Immunodeficiencies | 237 | ||
| Defects in Innate Immunity | 237 | ||
| Defects in Leukocyte Function | 237 | ||
| Deficiencies Affecting the Complement System | 238 | ||
| Defects in Adaptive Immunity | 238 | ||
| Defects in Lymphocyte Maturation | 238 | ||
| Severe Combined Immunodeficiency | 239 | ||
| X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia) | 240 | ||
| DiGeorge Syndrome (Thymic Hypoplasia) | 241 | ||
| Other Defects in Lymphocyte Maturation | 241 | ||
| Defects in Lymphocyte Activation and Function | 241 | ||
| Hyper-IgM Syndrome | 241 | ||
| Common Variable Immunodeficiency | 241 | ||
| Isolated IgA Deficiency | 242 | ||
| X-Linked Lymphoproliferative Syndrome | 242 | ||
| Other Defects in Lymphocyte Activation | 242 | ||
| Immunodeficiencies Associated with Systemic Diseases | 242 | ||
| Wiskott-Aldrich Syndrome | 242 | ||
| Ataxia Telangiectasia | 242 | ||
| Secondary Immunodeficiencies | 243 | ||
| Acquired Immunodeficiency Syndrome (AIDS) | 243 | ||
| Epidemiology | 244 | ||
| Etiology: The Properties of HIV | 245 | ||
| Structure of HIV | 245 | ||
| Pathogenesis of HIV Infection and AIDS | 245 | ||
| Life Cycle of HIV | 246 | ||
| Infection of Cells by HIV | 246 | ||
| Viral Replication | 247 | ||
| Mechanism of T-Cell Depletion in HIV Infection | 248 | ||
| HIV Infection of Non–T Cells | 249 | ||
| B Cell Function in HIV Infection. | 249 | ||
| Pathogenesis of Central Nervous System Involvement | 250 | ||
| Natural History of HIV Infection | 250 | ||
| Primary Infection, Virus Dissemination, and the Acute Retroviral Syndrome | 250 | ||
| Chronic Infection: Phase of Clinical Latency | 252 | ||
| AIDS | 252 | ||
| Clinical Features of AIDS | 252 | ||
| Opportunistic Infections. | 252 | ||
| Tumors. | 253 | ||
| Kaposi Sarcoma. | 253 | ||
| Lymphomas. | 254 | ||
| Other Tumors. | 255 | ||
| Central Nervous System Disease. | 255 | ||
| Effect of Antiretroviral Drug Therapy on the Clinical Course of HIV Infection. | 255 | ||
| Amyloidosis | 256 | ||
| Properties of Amyloid Proteins | 257 | ||
| Physical Nature of Amyloid. | 257 | ||
| Chemical Nature of Amyloid. | 257 | ||
| Pathogenesis and Classification of Amyloidosis | 258 | ||
| Primary Amyloidosis: Plasma Cell Disorders Associated with Amyloidosis. | 258 | ||
| Reactive Systemic Amyloidosis. | 259 | ||
| Heredofamilial Amyloidosis. | 259 | ||
| Hemodialysis-Associated Amyloidosis. | 260 | ||
| Localized Amyloidosis. | 260 | ||
| Endocrine Amyloid. | 260 | ||
| Amyloid of Aging. | 260 | ||
| Clinical Features. | 262 | ||
| Suggested Readings | 262 | ||
| Innate Immunity | 262 | ||
| Cell-Mediated Immunity | 262 | ||
| Humoral Immunity | 263 | ||
| Immune Regulation | 263 | ||
| Immediate Hypersensitivity, Allergy | 263 | ||
| Other Hypersensitivity Reactions | 263 | ||
| Immunological Tolerance | 263 | ||
| Mechanisms of Autoimmunity: General | 263 | ||
| Systemic Lupus Erythematosus | 263 | ||
| Sjogren Syndrome, Systemic Sclerosis, and Other Systemic Autoimmune Diseases | 264 | ||
| Rejection of Transplants | 264 | ||
| Primary Immunodeficiency Diseases | 264 | ||
| HIV and Aids | 264 | ||
| Amyloidosis | 264 | ||
| 7 Neoplasia | 265 | ||
| Chapter Contents | 265 | ||
| Nomenclature | 266 | ||
| Benign Tumors. | 266 | ||
| Malignant Tumors. | 266 | ||
| Mixed Tumors. | 266 | ||
| Characteristics of Benign and Malignant Neoplasms | 267 | ||
| Differentiation and Anaplasia | 268 | ||
| Metaplasia and Dysplasia. | 270 | ||
| Local Invasion | 271 | ||
| Metastasis | 272 | ||
| Pathways of Spread | 273 | ||
| Seeding of Body Cavities and Surfaces. | 273 | ||
| Lymphatic Spread. | 273 | ||
| Hematogenous Spread. | 274 | ||
| Epidemiology of Cancer | 275 | ||
| The Global Impact of Cancer | 275 | ||
| Environmental Factors | 276 | ||
| Age | 278 | ||
| Acquired Predisposing Conditions | 278 | ||
| Genetic Predisposition and Interactions Between Environmental and Inherited Factors | 279 | ||
| Molecular Basis of Cancer: Role of Genetic and Epigenetic Alterations | 280 | ||
| Cellular and Molecular Hallmarks of Cancer | 282 | ||
| Self-Sufficiency in Growth Signals: Oncogenes | 283 | ||
| Proto-oncogenes, Oncogenes, and Oncoproteins | 284 | ||
| Growth Factors. | 285 | ||
| Growth Factor Receptors. | 285 | ||
| Downstream components of the receptor tyrosine kinase signaling pathway. | 286 | ||
| RAS Mutations. | 286 | ||
| Oncogenic BRAF and PI3K Mutations. | 286 | ||
| Alterations in Nonreceptor Tyrosine Kinases. | 287 | ||
| Transcription Factors. | 288 | ||
| MYC Oncogene. | 288 | ||
| Cyclins and Cyclin-Dependent Kinases. | 288 | ||
| Insensitivity to Growth Inhibition: Tumor Suppressor Genes | 290 | ||
| RB: Governor of Proliferation. | 292 | ||
| TP53: Guardian of the Genome. | 293 | ||
| Other Tumor Suppressor Genes. | 296 | ||
| APC: Gatekeeper of Colonic Neoplasia. | 296 | ||
| E-Cadherin. | 297 | ||
| CDKN2A. | 297 | ||
| TGF-β Pathway. | 298 | ||
| PTEN. | 298 | ||
| NF1. | 298 | ||
| NF2. | 298 | ||
| WT1. | 298 | ||
| PATCHED (PTCH). | 298 | ||
| VHL. | 299 | ||
| STK11. | 299 | ||
| Growth-Promoting Metabolic Alterations: The Warburg Effect | 300 | ||
| Autophagy. | 301 | ||
| Evasion of Programmed Cell Death (Apoptosis) | 301 | ||
| Biochemical Pathways That Lead To Programmed Cell Death. | 302 | ||
| Limitless Replicative Potential: The Stem Cell–Like Properties of Cancer Cells | 303 | ||
| Angiogenesis | 305 | ||
| Invasion and Metastasis | 306 | ||
| Invasion of Extracellular Matrix | 306 | ||
| Vascular Dissemination and Homing of Tumor Cells | 308 | ||
| Molecular Genetics of Metastasis Development | 309 | ||
| Role of Stromal Elements in Metastasis | 309 | ||
| Evasion of Host Defense | 310 | ||
| Tumor Antigens | 310 | ||
| Antitumor Effector Mechanisms | 312 | ||
| Immune Surveillance and Escape | 312 | ||
| Genomic Instability | 314 | ||
| Hereditary Nonpolyposis Colon Cancer Syndrome. | 314 | ||
| Xeroderma Pigmentosum. | 314 | ||
| Diseases with Defects in DNA Repair by Homologous Recombination. | 314 | ||
| Cancers Resulting from Mutations Induced by Regulated Genomic Instability: Lymphoid Neoplasms. | 315 | ||
| Cancer-Enabling Inflammation | 315 | ||
| Dysregulation of Cancer-Associated Genes | 316 | ||
| Chromosomal Changes | 316 | ||
| Chromosomal Translocations. | 316 | ||
| Deletions. | 317 | ||
| Gene Amplification. | 318 | ||
| Chromothrypsis. | 318 | ||
| Epigenetic Changes | 319 | ||
| Noncoding RNAs and Cancer | 320 | ||
| Molecular Basis of Multistep Carcinogenesis | 320 | ||
| Carcinogenic Agents and Their Cellular Interactions | 321 | ||
| Steps Involved in Chemical Carcinogenesis | 322 | ||
| Direct-Acting Carcinogens | 322 | ||
| Indirect-Acting Carcinogens | 323 | ||
| Molecular Targets of Chemical Carcinogens. | 323 | ||
| Promotion of Chemical Carcinogenesis | 324 | ||
| Radiation Carcinogenesis | 324 | ||
| Ultraviolet Rays | 324 | ||
| Ionizing Radiation | 325 | ||
| Microbial Carcinogenesis | 325 | ||
| Oncogenic RNA Viruses | 325 | ||
| Human T-Cell Leukemia Virus Type 1. | 325 | ||
| Oncogenic DNA Viruses | 326 | ||
| Human Papillomavirus. | 326 | ||
| Epstein-Barr Virus. | 327 | ||
| Hepatitis B and C Viruses. | 328 | ||
| Helicobacter pylori | 329 | ||
| Clinical Aspects of Neoplasia | 329 | ||
| Local and Hormonal Effects | 330 | ||
| Cancer Cachexia | 330 | ||
| Paraneoplastic Syndromes | 330 | ||
| Grading and Staging of Tumors | 332 | ||
| Laboratory Diagnosis of Cancer | 332 | ||
| Histologic and Cytologic Methods. | 332 | ||
| Immunohistochemistry. | 334 | ||
| Flow Cytometry. | 334 | ||
| Circulating Tumor Cells. | 334 | ||
| Molecular and Cytogenetic Diagnostics. | 334 | ||
| Molecular Profiles of Tumors: The Future of Cancer Diagnostics | 335 | ||
| Tumor Markers | 337 | ||
| Suggested Readings | 338 | ||
| Cancer Epidemiology | 338 | ||
| Cancer “Evolution” | 338 | ||
| Hallmarks of Cancer | 338 | ||
| Oncogenes | 338 | ||
| Tumor Suppressor Genes | 338 | ||
| Cancer Cell Metabolism | 339 | ||
| Autophagy | 339 | ||
| Evasion of Apoptosis | 339 | ||
| Cancer Stem Cells | 339 | ||
| Angiogenesis | 339 | ||
| Invasion and Metastasis | 339 | ||
| Evasion of Host Defense | 339 | ||
| Cancer Enabling Inflammation | 339 | ||
| Chromosomal Aberrations | 339 | ||
| Epigenetics and Cancer | 339 | ||
| Non-coding RNAs | 339 | ||
| Environmental Carcinogens | 339 | ||
| Microbial Carcinogenesis | 339 | ||
| Cancer Cachexia and Paraneoplastic Syndromes | 340 | ||
| Cancer Diagnostics | 340 | ||
| 8 Infectious Diseases | 341 | ||
| Chapter Contents | 341 | ||
| General Principles of Microbial Pathogenesis | 341 | ||
| How Microorganisms Cause Disease | 342 | ||
| Routes of Entry of Microbes | 342 | ||
| Skin | 342 | ||
| Gastrointestinal Tract | 342 | ||
| Respiratory Tract | 343 | ||
| Urogenital Tract | 343 | ||
| Vertical Transmission | 344 | ||
| Spread and Dissemination of Microbes Within the Body | 344 | ||
| Release from the Body and Transmission of Microbes | 345 | ||
| Host-Pathogen Interactions | 345 | ||
| Host Defenses against Infection | 345 | ||
| Immune Evasion by Microbes | 345 | ||
| Injurious Effects of Host Immunity | 347 | ||
| Infections in People with Immunodeficiencies | 347 | ||
| Host Damage | 348 | ||
| Mechanisms of Viral Injury | 348 | ||
| Mechanisms of Bacterial Injury | 349 | ||
| Bacterial Virulence. | 349 | ||
| Bacterial Adherence to Host Cells. | 349 | ||
| Virulence of Intracellular Bacteria. | 350 | ||
| Bacterial Toxins. | 350 | ||
| Sexually Transmitted Infections | 351 | ||
| Spectrum of Inflammatory Responses to Infection | 351 | ||
| Suppurative (Purulent) Inflammation | 352 | ||
| Mononuclear and Granulomatous Inflammation | 352 | ||
| Cytopathic-Cytoproliferative Reaction | 353 | ||
| Tissue Necrosis | 353 | ||
| Chronic Inflammation and Scarring | 353 | ||
| Special Techniques for Diagnosing Infectious Agents | 353 | ||
| Viral Infections | 354 | ||
| Acute (Transient) Infections | 354 | ||
| Measles | 355 | ||
| Pathogenesis. | 355 | ||
| Mumps | 355 | ||
| Poliovirus Infection | 356 | ||
| West Nile Virus | 356 | ||
| Viral Hemorrhagic Fever | 357 | ||
| Latent Infections (Herpesvirus Infections) | 357 | ||
| Herpes Simplex Viruses | 357 | ||
| Varicella-Zoster Virus (VZV) | 358 | ||
| Cytomegalovirus | 359 | ||
| Congenital Infections. | 359 | ||
| Perinatal Infections. | 360 | ||
| Cytomegalovirus Mononucleosis. | 360 | ||
| CMV in Immunosuppressed Individuals. | 360 | ||
| Chronic Productive Infections | 360 | ||
| Transforming Viral Infections | 360 | ||
| Epstein-Barr Virus (EBV) | 360 | ||
| Pathogenesis. | 360 | ||
| Clinical Features. | 362 | ||
| Bacterial Infections | 362 | ||
| Gram-Positive Bacterial Infections | 362 | ||
| Staphylococcal Infections | 362 | ||
| Pathogenesis. | 362 | ||
| Bacterial Toxins. | 363 | ||
| Streptococcal and Enterococcal Infections | 364 | ||
| Pathogenesis. | 364 | ||
| Diphtheria | 365 | ||
| Listeriosis | 366 | ||
| Anthrax | 366 | ||
| Pathogenesis. | 366 | ||
| Nocardia | 367 | ||
| Gram-Negative Bacterial Infections | 367 | ||
| Neisserial Infections | 368 | ||
| Systemic Pathology: Diseases of Organ Systems | 483 | ||
| 11 Blood Vessels | 483 | ||
| Chapter Contents | 483 | ||
| Vascular Structure and Function | 483 | ||
| Vascular Anomalies | 485 | ||
| Vascular Wall Response to Injury | 485 | ||
| Intimal Thickening: A Stereotyped Response to Vascular Injury | 486 | ||
| Hypertensive Vascular Disease | 487 | ||
| Blood Pressure Regulation | 488 | ||
| Pathogenesis of Hypertension | 490 | ||
| Pathogenesis of Secondary Hypertension. | 490 | ||
| Mechanisms of Essential Hypertension | 490 | ||
| Vascular Pathology in Hypertension | 490 | ||
| Arteriosclerosis | 491 | ||
| Atherosclerosis | 491 | ||
| Epidemiology. | 491 | ||
| Constitutional Risk Factors | 492 | ||
| Modifiable Major Risk Factors | 492 | ||
| Additional Risk Factors | 493 | ||
| Pathogenesis of Atherosclerosis | 494 | ||
| Endothelial Injury. | 494 | ||
| Hemodynamic Disturbances. | 495 | ||
| Lipids. | 495 | ||
| Inflammation. | 496 | ||
| Infection. | 496 | ||
| Smooth Muscle Proliferation and Matrix Synthesis. | 496 | ||
| Overview. | 496 | ||
| Consequences of Atherosclerotic Disease | 499 | ||
| Atherosclerotic Stenosis. | 500 | ||
| Acute Plaque Change. | 500 | ||
| Thrombosis. | 501 | ||
| Vasoconstriction. | 501 | ||
| Aneurysms and Dissection | 501 | ||
| Pathogenesis of Aneurysms. | 501 | ||
| Abdominal Aortic Aneurysm (AAA) | 502 | ||
| Clinical Features. | 503 | ||
| Thoracic Aortic Aneurysm | 503 | ||
| Aortic Dissection | 504 | ||
| Pathogenesis. | 504 | ||
| Clinical Features. | 505 | ||
| Vasculitis | 505 | ||
| Noninfectious Vasculitis | 506 | ||
| Immune Complex-Associated Vasculitis | 506 | ||
| Antineutrophil Cytoplasmic Antibodies | 507 | ||
| Antiendothelial Cell Antibodies | 507 | ||
| Giant Cell (Temporal) Arteritis | 507 | ||
| Pathogenesis. | 508 | ||
| Clinical Features. | 508 | ||
| Takayasu Arteritis | 508 | ||
| Clinical Features. | 509 | ||
| Polyarteritis Nodosa | 509 | ||
| Index | 1345 | ||
| A | 1345 | ||
| B | 1349 | ||
| C | 1351 | ||
| D | 1356 | ||
| E | 1357 | ||
| F | 1360 | ||
| G | 1361 | ||
| H | 1363 | ||
| I | 1366 | ||
| J | 1370 | ||
| K | 1370 | ||
| L | 1370 | ||
| M | 1372 | ||
| N | 1375 | ||
| O | 1377 | ||
| P | 1378 | ||
| Q | 1382 | ||
| R | 1382 | ||
| S | 1383 | ||
| T | 1386 | ||
| U | 1389 | ||
| V | 1389 | ||
| W | 1390 | ||
| X | 1391 | ||
| Y | 1391 | ||
| Z | 1391 | ||
| Inside Back Cover | ibc1 |