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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 |