Robbins and Cotran Pathologic Basis of Disease Professional

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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. Front Cover IFC_regular End sheet 3 Robbins & Cotran Pathologic Basis of Disease Copyright page Dedication Contributors Preface: A New Chapter Acknowledgments Table of Contents General Pathology 1 The Cell as a Unit of Health and Disease Chapter Contents The Genome Noncoding DNA Histone Organization Micro-RNA and Long Noncoding RNA Micro-RNA (miRNA) Long Noncoding RNA (lncRNA) Cellular Housekeeping Plasma Membrane: Protection and Nutrient Acquisition Passive Membrane Diffusion. Carriers and Channels. Receptor-mediated and fluid-phase uptake (Fig. 1-7). Cytoskeleton and Cell-Cell Interactions Cell-Cell Interactions. Biosynthetic Machinery: Endoplasmic Reticulum and Golgi Waste Disposal: Lysosomes and Proteasomes Cellular Metabolism and Mitochondrial Function Energy Generation. Intermediate metabolism. Cell Death. Cellular Activation Cell Signaling Signal Transduction Pathways Modular Signaling Proteins, Hubs, and Nodes. Transcription Factors. Growth Factors and Receptors Epidermal Growth Factor and Transforming Growth Factor-α. Hepatocyte Growth Factor. Platelet-Derived Growth Factor. Vascular Endothelial Growth Factor. Fibroblast Growth Factor. Transforming Growth Factor-β. Interaction with the Extracellular Matrix Components of the Extracellular Matrix. Collagens. Elastin. Proteoglycans and hyaluronan (Fig. 1-14). Adhesive glycoproteins and adhesion receptors Maintaining Cell Populations Proliferation and the Cell Cycle Stem Cells Regenerative Medicine Concluding Remarks. Suggested Readings Genetics and Epigenetics Cellular Housekeeping Cellular Metabolism and Mitochondrial Function Cellular Activation Maintaining Cell Populations 2 Cellular Responses to Stress and Toxic Insults: Chapter Contents Introduction to Pathology Etiology or Cause. Pathogenesis. Morphologic Changes. Functional Derangements and Clinical Manifestations. Overview: Cellular Responses to Stress and Noxious Stimuli Adaptations of Cellular Growth and Differentiation Hypertrophy Mechanisms of Hypertrophy Hyperplasia Physiologic Hyperplasia Pathologic Hyperplasia Mechanisms of Hyperplasia Atrophy Mechanisms of Atrophy Metaplasia Mechanisms of Metaplasia Overview of Cell Injury and Cell Death Causes of Cell Injury Oxygen Deprivation. Physical Agents. Chemical Agents and Drugs. Infectious Agents. Immunologic Reactions. Genetic Derangements. Nutritional Imbalances. Morphologic Alterations in Cell Injury Reversible Injury Necrosis Patterns of Tissue Necrosis Mechanisms of Cell Injury Depletion of ATP Mitochondrial Damage Influx of Calcium and Loss of Calcium Homeostasis Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) Generation of Free Radicals. Removal of Free Radicals. Pathologic Effects of Free Radicals. Defects in Membrane Permeability Mechanisms of Membrane Damage. Consequences of Membrane Damage. Damage to DNA and Proteins Reversible vs Irreversible Injury. Clinicopathologic Correlations: Selected Examples of Cell Injury and Necrosis Ischemic and Hypoxic Injury Mechanisms of Ischemic Cell Injury Ischemia-Reperfusion Injury Chemical (Toxic) Injury Apoptosis Causes of Apoptosis Apoptosis in Physiologic Situations Apoptosis in Pathologic Conditions Morphologic and Biochemical Changes in Apoptosis Mechanisms of Apoptosis The Intrinsic (Mitochondrial) Pathway of Apoptosis The Extrinsic (Death Receptor-Initiated) Pathway of Apoptosis The Execution Phase of Apoptosis Removal of Dead Cells Clinicopathologic Correlations: Apoptosis in Health and Disease Examples of Apoptosis Growth Factor Deprivation. DNA Damage. Protein Misfolding. Apoptosis Induced by the TNF Receptor Family. Cytotoxic T Lymphocyte-Mediated Apoptosis. Disorders Associated with Dysregulated Apoptosis Necroptosis Autophagy Intracellular Accumulations Lipids Steatosis (Fatty Change) Cholesterol and Cholesterol Esters Proteins Hyaline Change Glycogen Pigments Exogenous Pigments Endogenous Pigments Pathologic Calcification Dystrophic Calcification Metastatic Calcification Cellular Aging DNA Damage. Cellular Senescence. Defective Protein Homeostasis. Deregulated Nutrient Sensing. Suggested Readings Hypertrophy Cell Death Apoptosis Necroptosis Autophagy Aging 3 Inflammation and Repair Chapter Contents Overview of Inflammation: Definitions and General Features Historical Highlights Causes of Inflammation Recognition of Microbes and Damaged Cells Acute Inflammation Reactions of Blood Vessels in Acute Inflammation Changes in Vascular Flow and Caliber Increased Vascular Permeability (Vascular Leakage) Responses of Lymphatic Vessels and Lymph Nodes Leukocyte Recruitment to Sites of Inflammation Leukocyte Adhesion to Endothelium Leukocyte Migration Through Endothelium Chemotaxis of Leukocytes Phagocytosis and Clearance of the Offending Agent Phagocytosis Phagocytic Receptors. Engulfment. Intracellular Destruction of Microbes and Debris Reactive Oxygen Species. Nitric Oxide. Lysosomal Enzymes and Other Lysosomal Proteins. Neutrophil Extracellular Traps Leukocyte-Mediated Tissue Injury Other Functional Responses of Activated Leukocytes Termination of the Acute Inflammatory Response Mediators of Inflammation Vasoactive Amines: Histamine and Serotonin Arachidonic Acid Metabolites Prostaglandins Leukotrienes Lipoxins Pharmacologic Inhibitors of Prostaglandins and Leukotrienes Cytokines and Chemokines Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1) Chemokines Other Cytokines in Acute Inflammation Complement System Other Mediators of Inflammation Platelet-Activating Factor (PAF) Products of Coagulation Kinins Neuropeptides Morphologic Patterns of Acute Inflammation Serous Inflammation Fibrinous Inflammation Purulent (Suppurative) Inflammation, Abscess Ulcers Outcomes of Acute Inflammation Summary of Acute Inflammation Chronic Inflammation Causes of Chronic Inflammation Morphologic Features Cells and Mediators of Chronic Inflammation Role of Macrophages Role of Lymphocytes Other Cells in Chronic Inflammation Granulomatous Inflammation Systemic Effects of Inflammation Tissue Repair Overview of Tissue Repair Cell and Tissue Regeneration Cell Proliferation: Signals and Control Mechanisms Mechanisms of Tissue Regeneration Liver Regeneration Repair by Connective Tissue Deposition Steps in Scar Formation Angiogenesis Deposition of Connective Tissue Remodeling of Connective Tissue Factors That Influence Tissue Repair Selected Clinical Examples of Tissue Repair and Fibrosis Healing of Skin Wounds Healing by First Intention Healing by Second Intention Wound Strength Fibrosis in Parenchymal Organs Abnormalities in Tissue Repair Suggested Readings General Mechanisms of Inflammation Acute Inflammation: Vascular Reactions Acute Inflammation: Role of Leukocytes Mediators of Inflammation Chronic Inflammation: Role of Macrophages and Other Cells Sepsis Tissue Repair: Regeneration and Fibrosis 4 Hemodynamic Disorders, Thromboembolic Disease, and Shock Chapter Contents Edema and Effusions Increased Hydrostatic Pressure Reduced Plasma Osmotic Pressure Sodium and Water Retention Lymphatic Obstruction Clinical Features Hyperemia and Congestion Hemostasis, Hemorrhagic Disorders, and Thrombosis Hemostasis Platelets Coagulation Cascade Factors That Limit Coagulation. Endothelium Hemorrhagic Disorders Thrombosis Endothelial Injury Alternations in Normal Blood Flow Hypercoagulability Heparin-Induced Thrombocytopenia (HIT) Syndrome Antiphospholipid Antibody Syndrome Fate of the Thrombus Clinical Features Venous Thrombosis (Phlebothrombosis). Arterial and Cardiac Thrombosis. Disseminated Intravascular Coagulation Embolism Pulmonary Embolism Systemic Thromboembolism Fat and Marrow Embolism Air Embolism Amniotic Fluid Embolism Infarction Factors That Influence Development of an Infarct. Shock Pathogenesis of Septic Shock Stages of Shock Clinical Consequences. Suggested Readings Fluid Dynamics Hemostasis and Bleeding Thrombosis and Thromboembolism Unusual Forms of Embolic Disease Septic Shock 5 Genetic Disorders Chapter Contents Genes and Human Diseases Mutations Mendelian Disorders Transmission Patterns of Single-Gene Disorders Autosomal Dominant Disorders Autosomal Recessive Disorders X-Linked Disorders Biochemical and Molecular Basis of Single-Gene (Mendelian) Disorders Enzyme Defects and Their Consequences Defects in Receptors and Transport Systems Alterations in Structure, Function, or Quantity of Nonenzyme Proteins Genetically Determined Adverse Reactions to Drugs Disorders Associated with Defects in Structural Proteins Marfan Syndrome Pathogenesis. Clinical Features. Ehlers-Danlos Syndromes (EDS) Disorders Associated with Defects in Receptor Proteins Familial Hypercholesterolemia Normal Process of Cholesterol Metabolism and Transport Disorders Associated with Defects in Enzymes Lysosomal Storage Diseases Tay-Sachs Disease (GM2 Gangliosidosis: Hexosaminidase α-Subunit Deficiency) Clinical Features. Niemann-Pick Disease Types A and B Niemann-Pick Disease Type C Gaucher Disease Clinical Features. Mucopolysaccharidoses (MPS) Clinical Features. Glycogen Storage Diseases (Glycogenoses) Disorders Associated with Defects in Proteins That Regulate Cell Growth Complex Multigenic Disorders Chromosomal Disorders Normal Karyotype Commonly Used Cytogenetic Terminology Structural Abnormalities of Chromosomes Cytogenetic Disorders Involving Autosomes Trisomy 21 (Down Syndrome) Other Trisomies Chromosome 22q11.2 Deletion Syndrome Cytogenetic Disorders Involving Sex Chromosomes Klinefelter Syndrome Turner Syndrome Hermaphroditism and Pseudohermaphroditism Single-Gene Disorders with Nonclassic Inheritance Diseases Caused by Trinucleotide-Repeat Mutations Fragile X Syndrome and Fragile X Tremor/Ataxia Fragile X Tremor/Ataxia. Mutations in Mitochondrial Genes—Leber Hereditary Optic Neuropathy Genomic Imprinting Prader-Willi Syndrome and Angelman Syndrome Gonadal Mosaicism Molecular Genetic Diagnosis Diagnostic Methods and Indications for Testing Laboratory Considerations Indications for Analysis of Inherited Genetic Alterations Indications for Analysis of Acquired Genetic Alterations PCR and Detection of DNA Sequence Alterations Molecular Analysis of Genomic Alterations Fluorescence in Situ Hybridization (FISH) Multiplex Ligation-Dependent Probe Amplification (MLPA) Southern Blotting Cytogenomic Array Technology Array-Based Comparative Genomic Hybridization (Array CGH). SNP Genotyping Arrays. Polymorphic Markers and Molecular Diagnosis Polymorphisms and Genome-Wide Analyses Epigenetic Alterations RNA Analysis Next-Generation Sequencing Bioinformatics Clinical Applications of NGS DNA Sequencing Future Applications Acknowledgment Suggested Reading Molecular Basis of Single Gene Disorders—General Disorders Associated with Defects in Structural Proteins Disorders Associated with Defects in Receptor Proteins Disorders Associated with Defects in Enzymes Cytogenetic Disorders Affecting Autosomes Cytogenetic Disorders Affecting Sex Chromosomes Diseases Caused by Trinucleotide Mutations Diseases Caused by Genomic Imprinting 6 Diseases of the Immune System Chapter Contents The Normal Immune Response Innate Immunity Components of Innate Immunity Cellular Receptors for Microbes, Products of Damaged Cells, and Foreign Substances Toll-Like Receptors. NOD-Like Receptors and the Inflammasome. Other Receptors for Microbial Products. Reactions of Innate Immunity Adaptive Immunity Cells of the Immune System Lymphocyte Diversity T Lymphocytes B Lymphocytes Dendritic Cells Macrophages Natural Killer Cells Innate Lymphoid Cells (ILCs) Tissues of the Immune System Generative Lymphoid Organs Peripheral Lymphoid Organs Lymphocyte Recirculation Major Histocompatibility Complex (MHC) Molecules: The Peptide Display System of Adaptive Immunity Cytokines: Messenger Molecules of the Immune System Overview of Lymphocyte Activation and Immune Responses Display and Recognition of Antigens Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes Decline of Immune Responses and Immunologic Memory Hypersensitivity: Immunologically Mediated Tissue Injury Classification of Hypersensitivity Diseases Immediate (Type I) Hypersensitivity Activation of TH2 Cells and Production of IgE Antibody Sensitization and Activation of Mast Cells Mediators of Immediate Hypersensitivity Preformed Mediators. Lipid Mediators. Cytokines. Late-Phase Reaction Development of Allergies Systemic Anaphylaxis Local Immediate Hypersensitivity Reactions Antibody-Mediated (Type II) Hypersensitivity Opsonization and Phagocytosis Inflammation Cellular Dysfunction Immune Complex–Mediated (Type III) Hypersensitivity Systemic Immune Complex Disease Local Immune Complex Disease (Arthus Reaction) T Cell–Mediated (Type IV) Hypersensitivity CD4+ T Cell–Mediated Inflammation Activation of CD4+ T Cells. Responses of Differentiated Effector T Cells. Clinical Examples of CD4+ T Cell–Mediated Inflammatory Reactions. CD8+ T Cell–Mediated Cytotoxicity Autoimmune Diseases Immunologic Tolerance Central Tolerance Peripheral Tolerance Mechanisms of Autoimmunity: General Principles Role of Susceptibility Genes Association of HLA Alleles with Disease. Association of Non-MHC Genes with Autoimmune Diseases. Role of Infections General Features of Autoimmune Diseases Systemic Lupus Erythematosus (SLE) Spectrum of Autoantibodies in SLE Other Autoantibodies. Etiology and Pathogenesis of SLE Genetic Factors. Immunologic Factors. Environmental Factors. A Model for the Pathogenesis of SLE. Mechanism of Tissue Injury. Clinical Features. Chronic Discoid Lupus Erythematosus. Subacute Cutaneous Lupus Erythematosus. Drug-Induced Lupus Erythematosus Rheumatoid Arthritis Sjögren Syndrome Etiology and Pathogenesis Clinical Features. Systemic Sclerosis (Scleroderma) Etiology and Pathogenesis Clinical Features. Inflammatory Myopathies Mixed Connective Tissue Disease Polyarteritis Nodosa and Other Vasculitides IgG4-Related Disease Rejection of Tissue Transplants Mechanisms of Recognition and Rejection of Allografts Recognition of Graft Alloantigens by T and B Lymphocytes T Cell–Mediated Reactions Antibody-Mediated Reactions Rejection of Kidney Grafts Methods of Increasing Graft Survival Transplantation of Other Solid Organs Transplantation of Hematopoietic Stem Cells Immunodeficiency Syndromes Primary Immunodeficiencies Defects in Innate Immunity Defects in Leukocyte Function Deficiencies Affecting the Complement System Defects in Adaptive Immunity Defects in Lymphocyte Maturation Severe Combined Immunodeficiency X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia) DiGeorge Syndrome (Thymic Hypoplasia) Other Defects in Lymphocyte Maturation Defects in Lymphocyte Activation and Function Hyper-IgM Syndrome Common Variable Immunodeficiency Isolated IgA Deficiency X-Linked Lymphoproliferative Syndrome Other Defects in Lymphocyte Activation Immunodeficiencies Associated with Systemic Diseases Wiskott-Aldrich Syndrome Ataxia Telangiectasia Secondary Immunodeficiencies Acquired Immunodeficiency Syndrome (AIDS) Epidemiology Etiology: The Properties of HIV Structure of HIV Pathogenesis of HIV Infection and AIDS Life Cycle of HIV Infection of Cells by HIV Viral Replication Mechanism of T-Cell Depletion in HIV Infection HIV Infection of Non–T Cells B Cell Function in HIV Infection. Pathogenesis of Central Nervous System Involvement Natural History of HIV Infection Primary Infection, Virus Dissemination, and the Acute Retroviral Syndrome Chronic Infection: Phase of Clinical Latency AIDS Clinical Features of AIDS Opportunistic Infections. Tumors. Kaposi Sarcoma. Lymphomas. Other Tumors. Central Nervous System Disease. Effect of Antiretroviral Drug Therapy on the Clinical Course of HIV Infection. Amyloidosis Properties of Amyloid Proteins Physical Nature of Amyloid. Chemical Nature of Amyloid. Pathogenesis and Classification of Amyloidosis Primary Amyloidosis: Plasma Cell Disorders Associated with Amyloidosis. Reactive Systemic Amyloidosis. Heredofamilial Amyloidosis. Hemodialysis-Associated Amyloidosis. Localized Amyloidosis. Endocrine Amyloid. Amyloid of Aging. Clinical Features. Suggested Readings Innate Immunity Cell-Mediated Immunity Humoral Immunity Immune Regulation Immediate Hypersensitivity, Allergy Other Hypersensitivity Reactions Immunological Tolerance Mechanisms of Autoimmunity: General Systemic Lupus Erythematosus Sjogren Syndrome, Systemic Sclerosis, and Other Systemic Autoimmune Diseases Rejection of Transplants Primary Immunodeficiency Diseases HIV and Aids Amyloidosis 7 Neoplasia Chapter Contents Nomenclature Benign Tumors. Malignant Tumors. Mixed Tumors. Characteristics of Benign and Malignant Neoplasms Differentiation and Anaplasia Metaplasia and Dysplasia. Local Invasion Metastasis Pathways of Spread Seeding of Body Cavities and Surfaces. Lymphatic Spread. Hematogenous Spread. Epidemiology of Cancer The Global Impact of Cancer Environmental Factors Age Acquired Predisposing Conditions Genetic Predisposition and Interactions Between Environmental and Inherited Factors Molecular Basis of Cancer: Role of Genetic and Epigenetic Alterations Cellular and Molecular Hallmarks of Cancer Self-Sufficiency in Growth Signals: Oncogenes Proto-oncogenes, Oncogenes, and Oncoproteins Growth Factors. Growth Factor Receptors. Downstream components of the receptor tyrosine kinase signaling pathway. RAS Mutations. Oncogenic BRAF and PI3K Mutations. Alterations in Nonreceptor Tyrosine Kinases. Transcription Factors. MYC Oncogene. Cyclins and Cyclin-Dependent Kinases. Insensitivity to Growth Inhibition: Tumor Suppressor Genes RB: Governor of Proliferation. TP53: Guardian of the Genome. Other Tumor Suppressor Genes. APC: Gatekeeper of Colonic Neoplasia. E-Cadherin. CDKN2A. TGF-β Pathway. PTEN. NF1. NF2. WT1. PATCHED (PTCH). VHL. STK11. Growth-Promoting Metabolic Alterations: The Warburg Effect Autophagy. Evasion of Programmed Cell Death (Apoptosis) Biochemical Pathways That Lead To Programmed Cell Death. Limitless Replicative Potential: The Stem Cell–Like Properties of Cancer Cells Angiogenesis Invasion and Metastasis Invasion of Extracellular Matrix Vascular Dissemination and Homing of Tumor Cells Molecular Genetics of Metastasis Development Role of Stromal Elements in Metastasis Evasion of Host Defense Tumor Antigens Antitumor Effector Mechanisms Immune Surveillance and Escape Genomic Instability Hereditary Nonpolyposis Colon Cancer Syndrome. Xeroderma Pigmentosum. Diseases with Defects in DNA Repair by Homologous Recombination. Cancers Resulting from Mutations Induced by Regulated Genomic Instability: Lymphoid Neoplasms. Cancer-Enabling Inflammation Dysregulation of Cancer-Associated Genes Chromosomal Changes Chromosomal Translocations. Deletions. Gene Amplification. Chromothrypsis. Epigenetic Changes Noncoding RNAs and Cancer Molecular Basis of Multistep Carcinogenesis Carcinogenic Agents and Their Cellular Interactions Steps Involved in Chemical Carcinogenesis Direct-Acting Carcinogens Indirect-Acting Carcinogens Molecular Targets of Chemical Carcinogens. Promotion of Chemical Carcinogenesis Radiation Carcinogenesis Ultraviolet Rays Ionizing Radiation Microbial Carcinogenesis Oncogenic RNA Viruses Human T-Cell Leukemia Virus Type 1. Oncogenic DNA Viruses Human Papillomavirus. Epstein-Barr Virus. Hepatitis B and C Viruses. Helicobacter pylori Clinical Aspects of Neoplasia Local and Hormonal Effects Cancer Cachexia Paraneoplastic Syndromes Grading and Staging of Tumors Laboratory Diagnosis of Cancer Histologic and Cytologic Methods. Immunohistochemistry. Flow Cytometry. Circulating Tumor Cells. Molecular and Cytogenetic Diagnostics. Molecular Profiles of Tumors: The Future of Cancer Diagnostics Tumor Markers Suggested Readings Cancer Epidemiology Cancer “Evolution” Hallmarks of Cancer Oncogenes Tumor Suppressor Genes Cancer Cell Metabolism Autophagy Evasion of Apoptosis Cancer Stem Cells Angiogenesis Invasion and Metastasis Evasion of Host Defense Cancer Enabling Inflammation Chromosomal Aberrations Epigenetics and Cancer Non-coding RNAs Environmental Carcinogens Microbial Carcinogenesis Cancer Cachexia and Paraneoplastic Syndromes Cancer Diagnostics 8 Infectious Diseases Chapter Contents General Principles of Microbial Pathogenesis How Microorganisms Cause Disease Routes of Entry of Microbes Skin Gastrointestinal Tract Respiratory Tract Urogenital Tract Vertical Transmission Spread and Dissemination of Microbes Within the Body Release from the Body and Transmission of Microbes Host-Pathogen Interactions Host Defenses against Infection Immune Evasion by Microbes Injurious Effects of Host Immunity Infections in People with Immunodeficiencies Host Damage Mechanisms of Viral Injury Mechanisms of Bacterial Injury Bacterial Virulence. Bacterial Adherence to Host Cells. Virulence of Intracellular Bacteria. Bacterial Toxins. Sexually Transmitted Infections Spectrum of Inflammatory Responses to Infection Suppurative (Purulent) Inflammation Mononuclear and Granulomatous Inflammation Cytopathic-Cytoproliferative Reaction Tissue Necrosis Chronic Inflammation and Scarring Special Techniques for Diagnosing Infectious Agents Viral Infections Acute (Transient) Infections Measles Pathogenesis. Mumps Poliovirus Infection West Nile Virus Viral Hemorrhagic Fever Latent Infections (Herpesvirus Infections) Herpes Simplex Viruses Varicella-Zoster Virus (VZV) Cytomegalovirus Congenital Infections. Perinatal Infections. Cytomegalovirus Mononucleosis. CMV in Immunosuppressed Individuals. Chronic Productive Infections Transforming Viral Infections Epstein-Barr Virus (EBV) Pathogenesis. Clinical Features. Bacterial Infections Gram-Positive Bacterial Infections Staphylococcal Infections Pathogenesis. Bacterial Toxins. Streptococcal and Enterococcal Infections Pathogenesis. Diphtheria Listeriosis Anthrax Pathogenesis. Nocardia Gram-Negative Bacterial Infections Neisserial Infections Pathogenesis. Pertussis Pathogenesis. Pseudomonas Infection Pathogenesis. Plague Chancroid (Soft Chancre) Granuloma Inguinale Mycobacteria Tuberculosis Epidemiology. Pathogenesis. Clinical Features. Mycobacterium avium Complex Leprosy Pathogenesis. Spirochetes Syphilis Pathogenesis. Primary Syphilis. Secondary Syphilis. Tertiary Syphilis. Congenital Syphilis. Serologic Tests for Syphilis. Lyme Disease Pathogenesis. Anaerobic Bacteria Abscesses Caused by Anaerobes Clostridial Infections Pathogenesis. Obligate Intracellular Bacteria Chlamydial Infections Rickettsial Infections Pathogenesis. Fungal Infections Yeast Candidiasis Pathogenesis. Cryptococcosis Pathogenesis. Molds Aspergillosis Pathogenesis. Zygomycosis (Mucormycosis) Pathogenesis. Dimorphic Fungi Parasitic Infections Protozoa Malaria Life Cycle and Pathogenesis. Babesiosis Leishmaniasis Pathogenesis. African Trypanosomiasis Pathogenesis. Chagas Disease Pathogenesis. Metazoa Strongyloidiasis Tapeworms (Cestodes): Cysticercosis and Hydatid Disease Trichinosis Schistosomiasis Pathogenesis. Lymphatic Filariasis Pathogenesis. Onchocerciasis Emerging Infectious Diseases Agents of Bioterrorism. Suggested Readings General Principles of Microbial Pathogenesis Virology Bacteriology Fungi Parasitology 9 Environmental and Nutritional Diseases Chapter Contents Environmental Effects on Global Disease Burden Health Effects of Climate Change Toxicity of Chemical and Physical Agents Environmental Pollution Air Pollution Outdoor Air Pollution Indoor Air Pollution Metals as Environmental Pollutants Lead Mercury Arsenic Cadmium Occupational Health Risks: Industrial and Agricultural Exposures Effects of Tobacco Smoking and Lung Cancer. Smoking and Other Diseases. Effects of Alcohol Injury by Therapeutic Drugs and Drugs of Abuse Injury by Therapeutic Drugs (Adverse Drug Reactions) Anticoagulants Menopausal Hormone Therapy (MHT) Oral Contraceptives (OCs) Anabolic Steroids Acetaminophen Aspirin (Acetylsalicylic Acid) Injury by Nontherapeutic Agents (Drug Abuse) Cocaine Opiates Amphetamines and Related Drugs Methamphetamine. MDMA. Marijuana Other Drugs Injury by Physical Agents Mechanical Trauma Thermal Injury Thermal Burns Hyperthermia Hypothermia Electrical Injury Injury Produced by Ionizing Radiation Radiation Units. Main Determinants of the Biologic Effects of Ionizing Radiation. Total-Body Irradiation. Acute Effects on Hematopoietic and Lymphoid Systems. Fibrosis. DNA Damage and Carcinogenesis. Cancer Risks from Exposures to Radiation. Nutritional Diseases Dietary Insufficiency Protein-Energy Malnutrition Marasmus and Kwashiorkor. PEM in the developed world. Cachexia. Anorexia Nervosa and Bulimia Vitamin Deficiencies Vitamin A Function. Vitamin A Deficiency. Vitamin A Toxicity. Vitamin D Metabolism of Vitamin D. Functions. Effects of Vitamin D on Calcium and Phosphorus Homeostasis. Deficiency States. Nonskeletal Effects of Vitamin D. Vitamin D Toxicity. Vitamin C (Ascorbic Acid) Function. Deficiency States. Vitamin C Excess. Obesity Leptin. Adiponectin. Gut Hormones. Actions of Adipocytes. Regulation of adipocyte numbers. Other emerging factors associated with obesity: role of the gut microbiome. General Consequences of Obesity Obesity and Cancer Diet, Cancer, and Atherosclerosis Diet and Cancer Diet and Atherosclerosis Suggested Readings Climate Change and Global Health Environmental Chemicals Air Pollution Toxic Metals Tobacco and Alcohol Radiation Estrogens and Progestins Hormones and Nutritional Disorders Obesity and Metabolic Syndrome 10 Diseases of Infancy and Childhood Chapter Contents Congenital Anomalies Definitions Causes of Anomalies Pathogenesis. Prematurity and Fetal Growth Restriction Fetal Growth Restriction Fetal Abnormalities. Placental Abnormalities. Maternal Abnormalities. Neonatal Respiratory Distress Syndrome Pathogenesis. Clinical Features. Necrotizing Enterocolitis Perinatal Infections Transcervical (Ascending) Infections Transplacental (Hematologic) Infections Sepsis Fetal Hydrops Immune Hydrops Etiology and Pathogenesis. Nonimmune Hydrops Clinical Features. Inborn Errors of Metabolism and Other Genetic Disorders Phenylketonuria Galactosemia Cystic Fibrosis (Mucoviscidosis) Cystic Fibrosis Gene: Normal Structure and Function. Cystic Fibrosis Gene: Mutational Spectra and Genotype-Phenotype Correlation. Genetic and Environmental Modifiers. Clinical Features. Sudden Infant Death Syndrome (SIDS) Epidemiology. Pathogenesis. Tumors and Tumor-like Lesions of Infancy and Childhood Benign Tumors and Tumor-Like Lesions Hemangioma. Lymphatic Tumors. Fibrous Tumors. Teratomas. Malignant Tumors Incidence and Types. Neuroblastic Tumors Clinical Course and Prognostic Features. Wilms Tumor Pathogenesis and Genetics. Clinical Features. Suggested Readings Congenital Anomalies Cytsic Fibrosis and Inborn Errors of Metabolism Diseases of Prematurity and SIDS Tumors of Infancy and Childhood Systemic Pathology: Diseases of Organ Systems 11 Blood Vessels Chapter Contents Vascular Structure and Function Vascular Anomalies Vascular Wall Response to Injury Intimal Thickening: A Stereotyped Response to Vascular Injury Hypertensive Vascular Disease Blood Pressure Regulation Pathogenesis of Hypertension Pathogenesis of Secondary Hypertension. Mechanisms of Essential Hypertension Vascular Pathology in Hypertension Arteriosclerosis Atherosclerosis Epidemiology. Constitutional Risk Factors Modifiable Major Risk Factors Additional Risk Factors Pathogenesis of Atherosclerosis Endothelial Injury. Hemodynamic Disturbances. Lipids. Inflammation. Infection. Smooth Muscle Proliferation and Matrix Synthesis. Overview. Consequences of Atherosclerotic Disease Atherosclerotic Stenosis. Acute Plaque Change. Thrombosis. Vasoconstriction. Aneurysms and Dissection Pathogenesis of Aneurysms. Abdominal Aortic Aneurysm (AAA) Clinical Features. Thoracic Aortic Aneurysm Aortic Dissection Pathogenesis. Clinical Features. Vasculitis Noninfectious Vasculitis Immune Complex-Associated Vasculitis Antineutrophil Cytoplasmic Antibodies Antiendothelial Cell Antibodies Giant Cell (Temporal) Arteritis Pathogenesis. Clinical Features. Takayasu Arteritis Clinical Features. Polyarteritis Nodosa Clinical Features. Kawasaki Disease Clinical Features. Microscopic Polyangiitis Pathogenesis. Clinical Features. Churg-Strauss Syndrome Behçet Disease Granulomatosis with Polyangiitis Pathogenesis. Clinical Features. Thromboangiitis Obliterans (Buerger Disease) Pathogenesis. Clinical Features. Vasculitis Associated with Other Noninfectious Disorders Infectious Vasculitis Disorders of Blood Vessel Hyperreactivity Raynaud Phenomenon Myocardial Vessel Vasospasm Veins and Lymphatics Varicose Veins Clinical Features. Thrombophlebitis and Phlebothrombosis Superior and Inferior Vena Cava Syndromes Lymphangitis and Lymphedema Vascular Tumors Benign Tumors and Tumor-Like Conditions Vascular Ectasias. Hemangioma. Lymphangiomas. Glomus Tumor (Glomangioma). Bacillary Angiomatosis. Intermediate-Grade (Borderline) Tumors Kaposi Sarcoma. Pathogenesis. Clinical Features. Hemangioendothelioma. Malignant Tumors Angiosarcoma. Hemangiopericytoma. Pathology of Vascular Intervention Endovascular Stenting Vascular Replacement Suggested Readings Vascular Structure and Function Vascular Wall Response to Injury Hypertensive Vascular Disease Atherosclerosis Aneurysms and Dissection Vasculitis Veins and Lymphatics Vascular Tumors Pathology of Vascular Intervention 12 The Heart Chapter Contents Cardiac Structure and Specializations Myocardium Valves Conduction System Blood Supply Cardiac Stem Cells Effects of Aging on the Heart Overview of Cardiac Pathophysiology Heart Failure Cardiac Hypertrophy: Pathophysiology and Progression to Heart Failure Left-Sided Heart Failure Right-Sided Heart Failure Congenital Heart Disease Incidence. Cardiac Development. Etiology and Pathogenesis. Clinical Features. Left-to-Right Shunts Atrial Septal Defect Clinical Features. Patent Foramen Ovale. Ventricular Septal Defect Clinical Features. Patent Ductus Arteriosus Right-to-Left Shunts Tetralogy of Fallot Clinical Features. Transposition of the Great Arteries Tricuspid Atresia Obstructive Lesions Coarctation of the Aorta Pulmonary Stenosis and Atresia Aortic Stenosis and Atresia Ischemic Heart Disease Epidemiology. Pathogenesis. Chronic Vascular Occlusion. Acute Plaque Change. Consequences of Myocardial Ischemia. Angina Pectoris Myocardial Infarction Incidence and Risk Factors. Pathogenesis Coronary Arterial Occlusion. Myocardial Response. Patterns of Infarction. Infarct Modification by Reperfusion. Clinical Features. Consequences and Complications of Myocardial Infarction. Chronic Ischemic Heart Disease Arrhythmias Sudden Cardiac Death (SCD) Hypertensive Heart Disease Systemic (Left-Sided) Hypertensive Heart Disease Pulmonary (Right-Sided) Hypertensive Heart Disease (Cor Pulmonale) Valvular Heart Disease Calcific Valvular Degeneration Calcific Aortic Stenosis Clinical Features. Calcific Stenosis of Congenitally Bicuspid Aortic Valve Mitral Annular Calcification Mitral Valve Prolapse (Myxomatous Degeneration of the Mitral Valve) Pathogenesis. Clinical Features. Rheumatic Fever and Rheumatic Heart Disease Pathogenesis. Clinical Features. Infective Endocarditis Pathogenesis. Clinical Features. Noninfected Vegetations Nonbacterial Thrombotic Endocarditis Endocarditis of Systemic Lupus Erythematosus (Libman-Sacks Disease) Carcinoid Heart Disease Pathogenesis. Complications of Prosthetic Valves Cardiomyopathies Dilated Cardiomyopathy Pathogenesis. Clinical Features. Arrhythmogenic Right Ventricular Cardiomyopathy Hypertrophic Cardiomyopathy Pathogenesis. Clinical Features. Restrictive Cardiomyopathy Myocarditis Pathogenesis. Clinical Features. Other Causes of Myocardial Disease Cardiotoxic Drugs. Amyloidosis. Pericardial Disease Pericardial Effusion and Hemopericardium Pericarditis Acute Pericarditis Chronic or Healed Pericarditis. Heart Disease Associated with Rheumatologic Disorders Tumors of the Heart Primary Cardiac Tumors Lipoma. Papillary Fibroelastoma. Rhabdomyoma. Sarcoma. Cardiac Effects of Noncardiac Neoplasms Cardiac Transplantation Suggested Readings General Cardiac Structure and Specializations Heart Failure Congenital Heart Disease Ischemic Heart Disease Arrhythmias Hypertensive Heart Disease Valvular Heart Disease Cardiomyopathies Tumors of the Heart Cardiac Transplantation 13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus Chapter Contents Development and Maintenance of Hematopoietic Tissues Disorders of White Cells Leukopenia Neutropenia, Agranulocytosis Pathogenesis. Clinical Features. Reactive Proliferations of White Cells and Lymph Nodes Leukocytosis Pathogenesis. Lymphadenitis Acute Nonspecific Lymphadenitis Chronic Nonspecific Lymphadenitis Hemophagocytic Lymphohistiocytosis Pathogenesis. Clinical Features. Neoplastic Proliferations of White Cells Etiologic and Pathogenetic Factors in White Cell Neoplasia: Overview Chromosomal Translocations and Other Acquired Mutations. Inherited Genetic Factors. Viruses. Chronic Inflammation. Iatrogenic Factors. Smoking. Lymphoid Neoplasms Definitions and Classifications Precursor B- and T-Cell Neoplasms Acute Lymphoblastic Leukemia/Lymphoma Pathogenesis. Immunophenotype. Clinical Features. Prognosis. Peripheral B-Cell Neoplasms Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma Pathogenesis. Immunophenotype. Clinical Features. Follicular Lymphoma Pathogenesis. Immunophenotype. Clinical Features. Diffuse Large B-Cell Lymphoma Pathogenesis. Immunophenotype. Special Subtypes. Clinical Features. Burkitt Lymphoma Pathogenesis. Immunophenotype. Clinical Features. Plasma Cell Neoplasms and Related Disorders Multiple Myeloma. Pathogenesis. Immunophenotype. Clinical Features. Solitary Myeloma (Plasmacytoma). Smoldering Myeloma. Monoclonal Gammopathy of Uncertain Significance. Lymphoplasmacytic Lymphoma. Pathogenesis. Immunophenotype. Clinical Features. Mantle Cell Lymphoma Pathogenesis. Immunophenotype. Clinical Features. Marginal Zone Lymphomas Hairy Cell Leukemia Pathogenesis. Immunophenotype. Clinical Features. Peripheral T-Cell and NK-Cell Neoplasms Peripheral T-Cell Lymphoma, Unspecified Anaplastic Large-Cell Lymphoma (ALK Positive) Adult T-Cell Leukemia/Lymphoma Mycosis Fungoides/Sézary Syndrome Large Granular Lymphocytic Leukemia Extranodal NK/T-Cell Lymphoma Hodgkin Lymphoma Classification. Pathogenesis. Clinical Features. Myeloid Neoplasms Acute Myeloid Leukemia Classification. Pathogenesis. Immunophenotype. Cytogenetics. Clinical Features. Prognosis. Myelodysplastic Syndromes Pathogenesis. Clinical Features. Myeloproliferative Disorders Chronic Myelogenous Leukemia Pathogenesis. Clinical Features. Polycythemia Vera Pathogenesis. Clinical Features. Essential Thrombocytosis Primary Myelofibrosis Clinical Features. Langerhans Cell Histiocytosis Spleen Splenomegaly Nonspecific Acute Splenitis Congestive Splenomegaly Splenic Infarcts Neoplasms Congenital Anomalies Rupture Thymus Developmental Disorders Thymic Hyperplasia Thymomas Clinical Features. Suggested Readings Hematopoietic Stem Cells White Cell Neoplasms Disorders That Affect the Spleen and Thymus 14 Red Blood Cell and Bleeding Disorders Chapter Contents Anemias Anemias of Blood Loss Acute Blood Loss Chronic Blood Loss Hemolytic Anemias Hereditary Spherocytosis Pathogenesis. Clinical Features. Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase Deficiency Sickle Cell Disease Pathogenesis. Clinical Features Thalassemia Syndromes β-Thalassemias Molecular Pathogenesis. Clinical Syndromes. β-Thalassemia Major. β-Thalassemia Minor. α-Thalassemias Clinical Syndromes. Silent Carrier State. α-Thalassemia Trait. Hemoglobin H Disease. Hydrops Fetalis. Paroxysmal Nocturnal Hemoglobinuria Immunohemolytic Anemias Warm Antibody Type. Cold Agglutinin Type. Cold Hemolysin Type. Hemolytic Anemia Resulting from Trauma to Red Cells Anemias of Diminished Erythropoiesis Megaloblastic Anemias Anemias of Vitamin B12 Deficiency: Pernicious Anemia Normal Vitamin B12 Metabolism. Biochemical Functions of Vitamin B12. Pernicious Anemia Incidence. Pathogenesis. Clinical Features Anemia of Folate Deficiency Etiology. Iron Deficiency Anemia Iron Metabolism. Etiology. Pathogenesis. Clinical Features Anemia of Chronic Disease Aplastic Anemia Etiology. Pathogenesis. Clinical Features Pure Red Cell Aplasia Other Forms of Marrow Failure Polycythemia Bleeding Disorders: Hemorrhagic Diatheses Bleeding Disorders Caused by Vessel Wall Abnormalities Bleeding Related to Reduced Platelet Number: Thrombocytopenia Chronic Immune Thrombocytopenic Purpura (ITP) Pathogenesis. Clinical Features Acute Immune Thrombocytopenic Purpura Drug-Induced Thrombocytopenia HIV-Associated Thrombocytopenia Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS) Bleeding Disorders Related to Defective Platelet Functions Hemorrhagic Diatheses Related to Abnormalities in Clotting Factors The Factor VIII-vWF Complex Von Willebrand Disease Hemophilia A (Factor VIII Deficiency) Hemophilia B (Christmas Disease, Factor IX Deficiency) Disseminated Intravascular Coagulation (DIC) Etiology and Pathogenesis. Clinical Features. Complications of Transfusion Allergic Reactions Hemolytic Reactions Transfusion-Related Acute Lung Injury Infectious Complications Suggested Readings Red Cell Disorders Bleeding Disorders 15 The Lung Chapter Contents Congenital Anomalies Atelectasis (Collapse) Pulmonary Edema Hemodynamic Pulmonary Edema Edema Caused by Microvascular (Alveolar) Injury Acute Lung Injury and Acute Respiratory Distress Syndrome (Diffuse Alveolar Damage) Pathogenesis. Clinical Course. Acute Interstitial Pneumonia Obstructive and Restrictive Lung Diseases Obstructive Lung Diseases Emphysema Pathogenesis. Clinical Course. Other Forms of Emphysema Chronic Bronchitis Pathogenesis. Clinical Features. Asthma Atopic Asthma. Non-Atopic Asthma. Drug-Induced Asthma. Occupational Asthma. Pathogenesis. TH2 Responses, IgE and Inflammation. Genetic Susceptibility. Environmental Factors. Clinical Course. Bronchiectasis Pathogenesis. Clinical Course. Chronic Diffuse Interstitial (Restrictive) Diseases Fibrosing Diseases Idiopathic Pulmonary Fibrosis Pathogenesis. Clinical Course. Nonspecific Interstitial Pneumonia Clinical Course. Cryptogenic Organizing Pneumonia Pulmonary Involvement in Autoimmune Diseases Pneumoconioses Pathogenesis. Coal Workers’ Pneumoconiosis Clinical Course. Silicosis Pathogenesis. Clinical Course. Asbestos-Related Diseases Pathogenesis. Clinical Course. Complications of Therapies Drug-Induced Lung Diseases. Radiation-Induced Lung Diseases. Granulomatous Diseases Sarcoidosis Pathogenesis. Immunologic Factors. Genetic Factors. Clinical Course. Hypersensitivity Pneumonitis Clinical Features. Pulmonary Eosinophilia Smoking-Related Interstitial Diseases Desquamative Interstitial Pneumonia Respiratory Bronchiolitis-Associated Interstitial Lung Disease Pulmonary Langerhans Cell Histiocytosis Pulmonary Alveolar Proteinosis Surfactant Dysfunction Disorders Diseases of Vascular Origin Pulmonary Embolism and Infarction Pathogenesis. Clinical Course. Pulmonary Hypertension Pathogenesis. Clinical Course. Diffuse Pulmonary Hemorrhage Syndromes Goodpasture Syndrome Pathogenesis. Clinical Features. Idiopathic Pulmonary Hemosiderosis Polyangiitis With Granulomatosis Pulmonary Infections Community-Acquired Bacterial Pneumonias Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Staphylococcus aureus Klebsiella pneumoniae Pseudomonas aeruginosa Legionella pneumophila Mycoplasma pneumoniae Clinical Course. Community-Acquired Viral Pneumonia Influenza Infections Human Metapneumovirus Severe Acute Respiratory Syndrome Clinical Course. Health Care-Associated Pneumonia Hospital-Acquired Pneumonia Aspiration Pneumonia Lung Abscess Etiology and Pathogenesis. Clinical Course. Chronic Pneumonia Histoplasmosis Blastomycosis Coccidioidomycosis Pneumonia in the Immunocompromised Host Pulmonary Disease in Human Immunodeficiency Virus Infection Lung Transplantation Tumors Carcinomas Etiology and Pathogenesis. Tobacco Smoking. Industrial Hazards. Air Pollution. Molecular Genetics. Lung Cancer in Never Smokers. Precursor (Preinvasive) Lesions. Classification. Staging. Clinical Course. Paraneoplastic Syndromes. Neuroendocrine Proliferations and Tumors Carcinoid Tumors Clinical Features. Miscellaneous Tumors Metastatic Tumors Pleura Pleural Effusion Inflammatory Pleural Effusions Noninflammatory Pleural Effusions Pneumothorax Pleural Tumors Solitary Fibrous Tumor Malignant Mesothelioma Clinical Course. Suggested Readings Acute Lung Injury Obstructive Pulmonary Diseases Emphysema Chronic Bronchitis Asthma Bronchiectasis Idiopathic pulmonary fibrosis Nonspecific Interstitial Pneumonia Organizing Pneumonia Pneumoconiosis Radiation Pneumonitis Sarcoidosis Hypersensitivity Pneumonia Eosinophilic Lung Diseases Smoking-related Interstitial Diseases Pulmonary alveolar proteinosis Surfactant Dysfunction Disorders Pulmonary Hypertension Pulmonary hemorrhage Syndromes Pneumonia Lung Transplantation Lung Cancer Pleura 16 Head and Neck Chapter Contents Oral Cavity Diseases of Teeth and Supporting Structures Caries (Tooth Decay) Gingivitis Periodontitis Inflammatory/Reactive Lesions Aphthous Ulcers (Canker Sores) Fibrous Proliferative Lesions Infections Herpes Simplex Virus Infections Oral Candidiasis (Thrush) Deep Fungal Infections Oral Manifestations of Systemic Disease Hairy Leukoplakia Precancerous and Cancerous Lesions Leukoplakia and Erythroplakia Squamous Cell Carcinoma Molecular Biology of Squamous Cell Carcinoma. Odontogenic Cysts and Tumors Upper Airways Nose Inflammations Infectious Rhinitis. Allergic Rhinitis. Nasal Polyps. Chronic Rhinitis. Sinusitis. Necrotizing Lesions of the Nose and Upper Airways Nasopharynx Inflammations Tumors of the Nose, Sinuses, and Nasopharynx Nasopharyngeal Angiofibroma. Sinonasal (Schneiderian) Papilloma. Olfactory Neuroblastoma (Esthesioneuroblastoma). NUT Midline Carcinoma. Nasopharyngeal Carcinoma. Larynx Inflammations Reactive Nodules (Vocal Cord Nodules and Polyps) Squamous Papilloma and Papillomatosis Carcinoma of the Larynx Sequence of Hyperplasia-Dysplasia-Carcinoma. Ears Inflammatory Lesions Otosclerosis Tumors Neck Branchial Cyst (Cervical Lymphoepithelial Cyst) Thyroglossal Duct Cyst Paraganglioma (Carotid Body Tumor) Salivary Glands Xerostomia Inflammation (Sialadenitis) Mucocele. Sialolithiasis and Nonspecific Sialadenitis. Neoplasms Pleomorphic Adenoma Clinical Features. Warthin Tumor (Papillary Cystadenoma Lymphomatosum) Mucoepidermoid Carcinoma Other Salivary Gland Tumors Suggested Readings 17 The Gastrointestinal Tract Chapter Contents Congenital Abnormalities Atresia, Fistulae, and Duplications Diaphragmatic Hernia, Omphalocele, and Gastroschisis Ectopia Meckel Diverticulum Pyloric Stenosis Hirschsprung Disease Pathogenesis. Clinical Features. Esophagus Esophageal Obstruction Achalasia Esophagitis Lacerations Chemical and Infectious Esophagitis Reflux Esophagitis Pathogenesis. Clinical Features. Eosinophilic Esophagitis Esophageal Varices Pathogenesis. Clinical Features. Barrett Esophagus Clinical Features. Esophageal Tumors Adenocarcinoma Pathogenesis. Clinical Features. Squamous Cell Carcinoma Pathogenesis. Clinical Features. Stomach Gastropathy and Acute Gastritis Pathogenesis. Clinical Features. Stress-Related Mucosal Disease Pathogenesis. Clinical Features. Chronic Gastritis Helicobacter pylori Gastritis Epidemiology. Pathogenesis. Clinical Features. Autoimmune Gastritis Pathogenesis. Clinical Features. Uncommon Forms of Gastritis Eosinophilic Gastritis. Lymphocytic Gastritis. Granulomatous Gastritis. Complications of Chronic Gastritis Peptic Ulcer Disease Pathogenesis. Clinical Features. Mucosal Atrophy and Intestinal Metaplasia Dysplasia Gastritis Cystica Hypertrophic Gastropathies Ménétrier Disease Zollinger-Ellison Syndrome Gastric Polyps and Tumors Inflammatory and Hyperplastic Polyps Fundic Gland Polyps Gastric Adenoma Gastric Adenocarcinoma Epidemiology. Pathogenesis. Clinical Features. Lymphoma Pathogenesis. Clinical Features. Carcinoid Tumor Clinical Features. Gastrointestinal Stromal Tumor Epidemiology. Pathogenesis. Clinical Features. Small Intestine and Colon Intestinal Obstruction Hernias Adhesions Volvulus Intussusception Ischemic Bowel Disease Pathogenesis. Clinical Features. Angiodysplasia Malabsorption and Diarrhea Cystic Fibrosis Celiac Disease Pathogenesis. Clinical Features. Environmental Enteropathy Autoimmune Enteropathy Lactase (Disaccharidase) Deficiency Abetalipoproteinemia Infectious Enterocolitis Cholera Pathogenesis. Clinical Features. Campylobacter Enterocolitis Pathogenesis. Clinical Features. Shigellosis Pathogenesis. Clinical Features. Salmonella Pathogenesis. Clinical Features. Typhoid Fever Pathogenesis. Clinical Features. Yersinia Pathogenesis. Clinical Features. Escherichia coli Enterotoxigenic E. coli. Enteropathogenic E. coli. Enterohemorrhagic E. coli. Enteroinvasive E. coli. Enteroaggregative E. coli. Pseudomembranous Colitis Pathogenesis. Clinical Features. Whipple Disease Pathogenesis. Viral Gastroenteritis Norovirus. Rotavirus. Adenovirus. Parasitic Enterocolitis Ascaris lumbricoides. Strongyloides. Necator duodenale and Ancylostoma duodenale. Enterobius vermicularis. Trichuris trichiura. Schistosomiasis. Intestinal Cestodes. Entamoeba histolytica. Giardia lamblia. Cryptosporidium. Irritable Bowel Syndrome Pathogenesis. Clinical Features. Inflammatory Bowel Disease Epidemiology. Pathogenesis. Crohn Disease Clinical Features. Ulcerative Colitis Clinical Features. Indeterminate Colitis Colitis-Associated Neoplasia Other Causes of Chronic Colitis Diversion Colitis Microscopic Colitis Graft-Versus-Host Disease Sigmoid Diverticular Disease Pathogenesis. Clinical Features. Polyps Hyperplastic Polyps Inflammatory Polyps Hamartomatous Polyps Juvenile Polyps Peutz-Jeghers Syndrome Pathogenesis. Clinical Features. Neoplastic Polyps Adenomatous Polyposis Hereditary Non-Polyposis Colorectal Cancer Adenocarcinoma Epidemiology. Pathogenesis. Clinical Features. Tumors of the Anal Canal Hemorrhoids Acute Appendicitis Pathogenesis. Clinical Features. Tumors of the Appendix Peritoneal Cavity Inflammatory Disease Peritoneal Infection Sclerosing Retroperitonitis Tumors Suggested Readings Congenital Abnormalities Esophagus Esophagitis Barrett Esophagus Esophageal Tumors Stomach Chronic Gastritis Complications of Chronic Gastritis Hypertrophic Gastropathies Gastric Polyps and Tumors Small Intestine and Colon Ischemic Bowel Disease and Angiodysplasia Malabsorption and Diarrhea Infectious Enterocolitis Irritable Bowel Syndrome Inflammatory Bowel Disease Other Causes of Colitis Sigmoid Diverticulitis Polyps Adenocarcinoma Hemorrhoids Acute Appendicitis and Tumors of the Appendix Peritoneal Cavity 18 Liver and Gallbladder Chapter Contents The Liver and Bile Ducts General Features of Liver Disease Mechanisms of Injury and Repair Hepatocyte and Parenchymal Responses Scar Formation and Regression Inflammation and Immunity Liver Failure Acute Liver Failure Clinical Course. Chronic Liver Failure and Cirrhosis Clinical Features. Portal Hypertension Ascites. Portosystemic Shunts. Splenomegaly. Acute-on-Chronic Liver Failure Infectious Disorders Viral Hepatitis Hepatitis A Virus Hepatitis B Virus Hepatitis C Virus Hepatitis D Virus Hepatitis E Virus Clinicopathologic Syndromes of Viral Hepatitis Acute Asymptomatic Infection with Recovery. Acute Symptomatic Infection with Recovery. Acute Liver Failure. Chronic Hepatitis. The Carrier State. HIV and Chronic Viral Hepatitis. Bacterial, Parasitic, and Helminthic Infections Autoimmune Hepatitis Clinicopathologic Features. Drug- and Toxin-Induced Liver Injury Alcoholic Liver Disease Pathogenesis. Clinical Features. Metabolic Liver Disease Nonalcoholic Fatty Liver Disease (NAFLD) Pathogenesis. Clinical Features. Hemochromatosis Pathogenesis. Clinical Features. Wilson Disease Pathogenesis. Clinical Features. α1-Antitrypsin Deficiency Pathogenesis. Clinical Features. Cholestatic Diseases Bilirubin and Bile Formation Pathophysiology of Jaundice Neonatal Jaundice. Hereditary Hyperbilirubinemias. Cholestasis Large Bile Duct Obstruction Cholestasis of Sepsis Primary Hepatolithiasis Clinical Features. Neonatal Cholestasis Biliary Atresia Pathogenesis. Clinical Features. Autoimmune Cholangiopathies Primary Biliary Cirrhosis (PBC) Pathogenesis. Clinical Features. Primary Sclerosing Cholangitis (PSC) Pathogenesis. Clinical Features. Structural Anomalies of the Biliary Tree Choledochal Cysts Fibropolycystic Disease Circulatory Disorders Impaired Blood Flow into the Liver Hepatic Artery Compromise Portal Vein Obstruction and Thrombosis Impaired Blood Flow Through the Liver Hepatic Venous Outflow Obstruction Hepatic Vein Thrombosis Sinusoidal Obstruction Syndrome Pathogenesis. Passive Congestion and Centrilobular Necrosis Hepatic Complications of Organ or Hematopoietic Stem Cell Transplantation Graft-Versus-Host Disease and Liver Graft Rejection Hepatic Disease Associated with Pregnancy Preeclampsia and Eclampsia Acute Fatty Liver of Pregnancy Intrahepatic Cholestasis of Pregnancy Nodules and Tumors Nodular Hyperplasias Benign Neoplasms Hepatocellular Adenomas Pathogenesis. Malignant Tumors Hepatoblastoma Hepatocellular Carcinoma (HCC) Pathogenesis. Precursor Lesions of HCC Clinical Features. Cholangiocarcinoma (CCA) Other Primary Hepatic Malignant Tumors Metastasis Gallbladder Congenital Anomalies Cholelithiasis (Gallstones) Prevalence and Risk Factors. Pathogenesis of Cholesterol Stones. Pathogenesis of Pigment Stones. Clinical Features. Cholecystitis Acute Cholecystitis Pathogenesis. Clinical Features. Chronic Cholecystitis Clinical Features. Carcinoma Pathogenesis. Clinical Features. Suggested Readings Mechanisms of Liver Injury and Repair Acute, Chronic, Acute-On-Chronic Liver Failure Viral Hepatitis Autoimmune Liver Diseases Drug- and Toxin-Induced Liver Injury Metabolic Liver Diseases Cholestatic Syndromes Benign and Malignant Liver Tumors 19 The Pancreas Chapter Contents Congenital Anomalies Pancreas Divisum. Annular Pancreas. Ectopic Pancreas. Agenesis. Pancreatitis Acute Pancreatitis Pathogenesis. Clinical Features. Chronic Pancreatitis Pathogenesis. Clinical Features. Nonneoplastic Cysts Congenital Cysts Pseudocysts Neoplasms Cystic Neoplasms Pancreatic Carcinoma Precursors to Pancreatic Cancer Pathogenesis KRAS. CDKN2A. SMAD4. TP53. Other Genes. DNA Methylation Abnormalities. Gene Expression. Epidemiology and Inheritance. Clinical Features. Acinar Cell Carcinoma Pancreatoblastoma Suggested Readings Congenital Anomalies Acute Pancreatitis Chronic Pancreatitis Pseudocysts Cystic Neoplasms Pancreatic Carcinoma 20 The Kidney Chapter Contents Clinical Manifestations of Renal Diseases Glomerular Diseases Structure of the Glomerulus Pathologic Responses of the Glomerulus to Injury Hypercellularity. Basement Membrane Thickening. Hyalinosis and Sclerosis. Pathogenesis of Glomerular Injury Diseases Caused by In Situ Formation of Immune Complexes Antibodies Against Planted Antigens Disease Caused by Antibodies Directed Against Normal Components of the Glomerular Basement Membrane Glomerulonephritis Resulting from Deposition of Circulating Immune Complexes Mechanisms of Glomerular Injury Following Immune Complex Formation Cell-Mediated Immunity in Glomerulonephritis Activation of Alternative Complement Pathway Mediators of Glomerular Injury Cells Soluble Mediators Epithelial Cell Injury Mechanisms of Progression in Glomerular Diseases Focal Segmental Glomerulosclerosis (FSGS). Tubulointerstitial Fibrosis. Nephritic Syndrome Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis Poststreptococcal Glomerulonephritis Etiology and Pathogenesis. Clinical Course. Nonstreptococcal Acute Glomerulonephritis (Postinfectious Glomerulonephritis) Rapidly Progressive (Crescentic) Glomerulonephritis Classification and Pathogenesis. Clinical Course. Nephrotic Syndrome Pathophysiology. Causes. Membranous Nephropathy Pathogenesis. Clinical Features. Minimal-Change Disease Etiology and Pathogenesis. Clinical Features. Focal Segmental Glomerulosclerosis (FSGS) Classification and Types. Pathogenesis. Clinical Course. HIV-Associated Nephropathy Membranoproliferative Glomerulonephritis (MPGN) Pathogenesis. Clinical Features. Secondary MPGN Dense Deposit Disease Clinical Features. Isolated Glomerular Abnormalities IgA Nephropathy (Berger Disease) Pathogenesis. Clinical Features. Hereditary Nephritis Alport Syndrome Pathogenesis. Clinical Features. Thin Basement Membrane Lesion (Benign Familial Hematuria) Chronic Glomerulonephritis Clinical Course. Glomerular Lesions Associated with Systemic Diseases Lupus Nephritis Henoch-Schönlein Purpura Glomerulonephritis Associated with Bacterial Endocarditis and Other Systemic Infections Diabetic Nephropathy Fibrillary Glomerulonephritis Other Systemic Disorders Tubular and Interstitial Diseases Acute Tubular Injury/Necrosis Pathogenesis. Clinical Course. Tubulointerstitial Nephritis Pyelonephritis and Urinary Tract Infection Etiology and Pathogenesis. Acute Pyelonephritis Clinical Features. Chronic Pyelonephritis and Reflux Nephropathy Clinical Features. Tubulointerstitial Nephritis Induced by Drugs and Toxins Acute Drug-Induced Interstitial Nephritis Pathogenesis. Clinical Features. Nephropathy Associated with NSAIDs Other Tubulointerstitial Diseases Urate Nephropathy Hypercalcemia and Nephrocalcinosis Acute Phosphate Nephropathy Light-Chain Cast Nephropathy (“Myeloma Kidney”) Clinical Features. Bile Cast Nephropathy Vascular Diseases Nephrosclerosis Pathogenesis. Clinical Features. Malignant Nephrosclerosis Pathogenesis. Clinical Features. Renal Artery Stenosis Pathogenesis. Clinical Course. Thrombotic Microangiopathies Pathogenesis. Thrombotic Thrombocytopenic Purpura. Other Vascular Disorders Atherosclerotic Ischemic Renal Disease Atheroembolic Renal Disease Sickle-Cell Nephropathy Diffuse Cortical Necrosis Renal Infarcts Congenital and Developmental Anomalies Agenesis of the Kidney. Hypoplasia. Ectopic Kidneys. Horseshoe Kidneys. Cystic Diseases of the Kidney Autosomal Dominant (Adult) Polycystic Kidney Disease Genetics and Pathogenesis. Clinical Features. Autosomal Recessive (Childhood) Polycystic Kidney Disease Genetics and Pathogenesis. Cystic Diseases of Renal Medulla Medullary Sponge Kidney Nephronophthisis and Adult-Onset Medullary Cystic Disease Genetics and Pathogenesis. Multicystic Renal Dysplasia Acquired (Dialysis-Associated) Cystic Disease Simple Cysts Urinary Tract Obstruction (Obstructive Uropathy) Clinical Features. Urolithiasis (Renal Calculi, Stones) Etiology and Pathogenesis. Clinical Features. Neoplasms of the Kidney Benign Neoplasms Renal Papillary Adenoma Angiomyolipoma Oncocytoma Malignant Neoplasms Renal Cell Carcinoma Epidemiology. Classification of renal cell carcinoma: histology, cytogenetics, and genetics. Clinical Features. Urothelial Carcinoma of the Renal Pelvis Suggested Readings Pathogenesis of Immune-Mediated Glomerular Injury Mechanisms of Progression in Glomerular Diseases Nephrotic Syndrome Nephritic Syndrome Rapidly Progressive (Crescentic) Glomerulonephritis Isolated Urinary Abnormalities Acute Tubular Injury/Necrosis Tubulointerstitial Nephritis Vascular Diseases Cystic Diseases of the Kidney Neoplasms of the Kidney 21 The Lower Urinary Tract and Male Genital System Chapter Contents The Lower Urinary Tract Ureters Congenital Anomalies Inflammation Tumors and Tumor-like Lesions Obstructive Lesions Sclerosing Retroperitoneal Fibrosis. Urinary Bladder Congenital Anomalies Inflammation Acute and Chronic Cystitis Special Forms of Cystitis Interstitial Cystitis (Chronic Pelvic Pain Syndrome). Malakoplakia. Polypoid Cystitis. Metaplastic Lesions Neoplasms Urothelial Tumors Epidemiology and Pathogenesis. Variants of Urothelial Carcinoma. Other Epithelial Bladder Tumors. Clinical Course of Bladder Cancer. Mesenchymal Tumors Benign Tumors. Sarcomas. Secondary Tumors Obstruction Urethra Inflammation Tumors and Tumor-like Lesions The Male Genital Tract Penis Congenital Anomalies Hypospadias and Epispadias Phimosis Inflammation Tumors Benign Tumors Condyloma Acuminatum Peyronie Disease Malignant Tumors Carcinoma in Situ (CIS) Invasive Carcinoma Clinical Features. Testis and Epididymis Congenital Anomalies Cryptorchidism Regressive Changes Atrophy and Decreased Fertility Inflammation Nonspecific Epididymitis and Orchitis Granulomatous (Autoimmune) Orchitis Specific Inflammations Gonorrhea Mumps Tuberculosis Syphilis Vascular Disorders Torsion Spermatic Cord and Paratesticular Tumors Testicular Tumors Germ Cell Tumors Environmental Factors. Genetic Factors. Classification. Pathogenesis. Seminoma Spermatocytic Seminoma Embryonal Carcinoma Yolk Sac Tumor Choriocarcinoma Teratoma Mixed Tumors Clinical Features of Testicular Germ Cell Tumors. Biomarkers. Tumors of Sex Cord-Gonadal Stroma Leydig Cell Tumors Sertoli Cell Tumors Gonadoblastoma Testicular Lymphoma Miscellaneous Lesions of Tunica Vaginalis Prostate Inflammation Benign Enlargement Benign Prostatic Hyperplasia or Nodular Hyperplasia Incidence. Etiology and Pathogenesis. Clinical Features. Tumors Adenocarcinoma Incidence. Etiology and Pathogenesis. Grading and Staging. Clinical Course. Miscellaneous Tumors and Tumor-like Conditions Suggested Readings Penile Disorders Testicular Disorders Bladder Disorders Prostatic Disorders 22 The Female Genital Tract Chapter Contents Infections Infections of the Lower Genital Tract Herpes Simplex Virus. Other Lower Female Genital Tract Infections. Infections Involving the Lower and Upper Genital Tract Pelvic Inflammatory Disease Vulva Bartholin Cyst Nonneoplastic Epithelial Disorders Lichen Sclerosus Squamous Cell Hyperplasia Benign Exophytic Lesions Condyloma Acuminatum Squamous Neoplastic Lesions Vulvar Intraepithelial Neoplasia and Vulvar Carcinoma Glandular Neoplastic Lesions Papillary Hidradenoma Extramammary Paget Disease Vagina Developmental Anomalies Premalignant and Malignant Neoplasms of the Vagina Vaginal Intraepithelial Neoplasia and Squamous Cell Carcinoma Embryonal Rhabdomyosarcoma Cervix Inflammations Acute and Chronic Cervicitis Endocervical Polyps Premalignant and Malignant Neoplasms of the Cervix Pathogenesis. Cervical Intraepithelial Neoplasia (Squamous Intraepithelial Lesions) Cervical Carcinoma Clinical Features. Cervical Cancer Screening and Prevention Body of Uterus and Endometrium Endometrial Histology in the Menstrual Cycle Functional Endometrial Disorders (Dysfunctional Uterine Bleeding) Anovulatory Cycle Inadequate Luteal Phase Inflammatory Disorders Acute Endometritis Chronic Endometritis Endometriosis and Adenomyosis Pathogenesis. Clinical Features. Endometrial Polyps Endometrial Hyperplasia Malignant Tumors of the Endometrium Carcinoma of the Endometrium Pathogenesis. Type I (Endometrial) Carcinoma. Type II (Serous) Carcinoma. Clinical Features. Malignant Mixed Müllerian Tumors Tumors of Endometrial Stroma Adenosarcomas Stromal Tumors Tumors of the Myometrium Leiomyomas Leiomyosarcomas Fallopian Tubes Inflammations Tumors and Cysts Ovaries Nonneoplastic and Functional Cysts Follicle and Luteal Cysts Polycystic Ovaries and Stromal Hyperthecosis Ovarian Tumors Classification. Epithelial Tumors Serous Tumors Pathogenesis. Mucinous Tumors Pathogenesis. Endometrioid Ovarian Tumors Pathogenesis. Clear Cell Carcinoma Cystadenofibroma Transitional Cell Tumors Clinical Course, Detection, and Prevention of Ovarian Epithelial Tumors Germ Cell Tumors Teratomas Mature (Benign) Teratomas. Monodermal or Specialized Teratomas. Immature Malignant Teratomas. Dysgerminoma Yolk Sac Tumor Choriocarcinoma Other Germ Cell Tumors Sex Cord-Stromal Tumors Granulosa Cell Tumors Fibromas, Thecomas, and Fibrothecomas Sertoli-Leydig Cell Tumors Other Sex Cord-Stromal Tumors Metastatic Tumors Gestational and Placental Disorders Disorders of Early Pregnancy Spontaneous Abortion Ectopic Pregnancy Clinical Features. Disorders of Late Pregnancy Twin Placentas Abnormalities of Placental Implantation Placental Infections Preeclampsia and Eclampsia Pathogenesis. Clinical Features. Gestational Trophoblastic Disease Hydatidiform Mole Complete Mole Partial Mole Clinical Features. Invasive Mole Choriocarcinoma Incidence. Clinical Features. Placental Site Trophoblastic Tumor (PSTT) Suggested Readings Infectious Diseases of Lower Genital Tract Vulva Vagina Cervix Uterus and Endometrium Ovary Placenta 23 The Breast Chapter Contents Disorders of Development Milk Line Remnants Accessory Axillary Breast Tissue Congenital Nipple Inversion Clinical Presentations of Breast Disease Inflammatory Disorders Acute Mastitis Squamous Metaplasia of Lactiferous Ducts Duct Ectasia Fat Necrosis Lymphocytic Mastopathy (Sclerosing Lymphocytic Lobulitis) Granulomatous Mastitis Benign Epithelial Lesions Nonproliferative Breast Changes (Fibrocystic Changes) Proliferative Breast Disease Without Atypia Gynecomastia Proliferative Breast Disease with Atypia Clinical Significance of Benign Epithelial Changes Carcinoma of the Breast Incidence and Epidemiology Risk Factors. Etiology and Pathogenesis Familial Breast Cancer Sporadic Breast Cancer Molecular Mechanisms of Carcinogenesis and Tumor Progression Types of Breast Carcinoma Carcinoma in Situ Ductal Carcinoma in Situ (DCIS) Lobular Carcinoma in Situ Invasive (Infiltrating) Carcinoma Special Histologic Types of Invasive Carcinoma Male Breast Cancer Prognostic and Predictive Factors Stromal Tumors Fibroadenoma Phyllodes Tumor Lesions of Interlobular Stroma Malignant Tumors of Interlobular Stroma Other Malignant Tumors of the Breast Suggested Readings Benign Breast Disease Risk Factors for Developing Carcinoma Biology of Breast Carcinoma Breast Cancer Classification Clinical Aspects of Breast Carcinoma Other Tumors 24 The Endocrine System Chapter Contents Pituitary Gland Clinical Manifestations of Pituitary Disease Pituitary Adenomas and Hyperpituitarism Clinical Course. Lactotroph Adenoma Clinical Course. Somatotroph Adenomas Clinical Course. Corticotroph Adenomas Clinical Course. Other Anterior Pituitary Adenomas Hypopituitarism Posterior Pituitary Syndromes Hypothalamic Suprasellar Tumors Thyroid Gland Hyperthyroidism Clinical Course. Hypothyroidism Congenital hypothyroidism. Autoimmune hypothyroidism. Iatrogenic hypothyroidism. Cretinism Myxedema Thyroiditis Hashimoto Thyroiditis Pathogenesis. Clinical Course. Subacute Lymphocytic (Painless) Thyroiditis Clinical Course. Granulomatous Thyroiditis Pathogenesis. Clinical Course. Graves Disease Pathogenesis. Clinical Course. Diffuse and Multinodular Goiters Diffuse Nontoxic (Simple) Goiter Clinical Course. Multinodular Goiter Clinical Course. Neoplasms of the Thyroid Adenomas Pathogenesis. Clinical Features. Carcinomas Pathogenesis Genetic Factors. Papillary Carcinomas. Follicular Carcinomas. Anaplastic (Undifferentiated) Carcinomas. Medullary Thyroid Carcinomas. Environmental Factors. Papillary Carcinoma Clinical Course. Follicular Carcinoma Clinical Course. Anaplastic (Undifferentiated) Carcinoma Clinical Course. Medullary Carcinoma Clinical Course. Congenital Anomalies Parathyroid Glands Hyperparathyroidism Primary Hyperparathyroidism Clinical Course. Asymptomatic Hyperparathyroidism. Symptomatic Primary Hyperparathyroidism. Secondary Hyperparathyroidism Clinical Course. Hypoparathyroidism Clinical Features. Pseudohypoparathyroidism The Endocrine Pancreas Diabetes Mellitus Diagnosis Classification Glucose Homeostasis Regulation of Insulin Release Insulin Action and Insulin Signaling Pathways Pathogenesis of Type 1 Diabetes Mellitus Genetic Susceptibility Environmental Factors Mechanisms of β Cell Destruction Pathogenesis of Type 2 Diabetes Mellitus Genetic Factors Environmental Factors Metabolic Defects in Diabetes Insulin Resistance β-Cell Dysfunction Monogenic Forms of Diabetes Genetic Defects in β-Cell Function. Genetic Defects that Impair Tissue Response to Insulin. Diabetes and Pregnancy Clinical Features of Diabetes The Classic Triad of Diabetes Acute Metabolic Complications of Diabetes Chronic Complications of Diabetes Pathogenesis of Chronic Complications. Formation of Advanced Glycation End Products. Activation of Protein Kinase C. Oxidative Stress and Disturbances in Polyol Pathways. Hexosamine Pathways and Generation of Fructose-6-Phosphate. Morphology and Clinical Features of Chronic Complications of Diabetes Clinical Manifestations of Chronic Diabetes Pancreatic Neuroendocrine Tumors Hyperinsulinism (Insulinoma) Clinical Features. Zollinger-Ellison Syndrome (Gastrinomas) Clinical Features. Other Rare Pancreatic Endocrine Neoplasms Adrenal Glands Adrenal Cortex Adrenocortical Hyperfunction (Hyperadrenalism) Hypercortisolism (Cushing Syndrome) Pathogenesis. Clinical Course. Primary Hyperaldosteronism Clinical Course. Adrenogenital Syndromes Clinical Course. Adrenocortical Insufficiency Primary Acute Adrenocortical Insufficiency Waterhouse-Friderichsen Syndrome Primary Chronic Adrenocortical Insufficiency (Addison Disease) Pathogenesis. Clinical Course. Secondary Adrenocortical Insufficiency Adrenocortical Neoplasms Other Adrenal Lesions Adrenal Medulla Pheochromocytoma Clinical Course. Multiple Endocrine Neoplasia Syndromes Multiple Endocrine Neoplasia, Type 1 Multiple Endocrine Neoplasia, Type 2 Pineal Gland Pinealomas Suggested Readings Pituitary Thyroid Parathyroid Pancreas—Diabetes Pancreas—Neuroendocrine Tumors Adrenal Cortex Adrenal Medulla Multiple Endocrine Neoplasia 25 The Skin Chapter Contents The Skin: More Than a Mechanical Barrier Disorders of Pigmentation and Melanocytes Freckle (Ephelis) Lentigo Melanocytic Nevus (Pigmented Nevus, Mole) Pathogenesis. Dysplastic Nevi Pathogenesis. Melanoma Pathogenesis. Prognostic Factors. Clinical Features. Benign Epithelial Tumors Seborrheic Keratoses Pathogenesis. Acanthosis Nigricans Pathogenesis. Fibroepithelial Polyp Epithelial or Follicular Inclusion Cyst (Wen) Adnexal (Appendage) Tumors Premalignant and Malignant Epidermal Tumors Actinic Keratosis Squamous Cell Carcinoma Pathogenesis. Basal Cell Carcinoma Pathogenesis. Tumors of the Dermis Benign Fibrous Histiocytoma (Dermatofibroma) Dermatofibrosarcoma Protuberans Pathogenesis. Tumors of Cellular Migrants to the Skin Mycosis Fungoides (Cutaneous T-Cell Lymphoma) Mastocytosis Pathogenesis. Disorders of Epidermal Maturation Ichthyosis Pathogenesis. Acute Inflammatory Dermatoses Urticaria Pathogenesis. Acute Eczematous Dermatitis Pathogenesis. Erythema Multiforme Pathogenesis. Chronic Inflammatory Dermatoses Psoriasis Pathogenesis. Seborrheic Dermatitis Pathogenesis. Lichen Planus Pathogenesis. Blistering (Bullous) Diseases Inflammatory Blistering Disorders Pemphigus Pathogenesis. Bullous Pemphigoid Pathogenesis. Dermatitis Herpetiformis Pathogenesis. Noninflammatory Blistering Disorders Epidermolysis Bullosa and Porphyria Epidermolysis Bullosa. Porphyria. Disorders of Epidermal Appendages Acne Vulgaris Pathogenesis. Rosacea Pathogenesis. Panniculitis Erythema Nodosum and Erythema Induratum Infection Verrucae (Warts) Pathogenesis. Molluscum Contagiosum Impetigo Pathogenesis. Superficial Fungal Infections Suggested Readings Melanoma and Dysplastic Nevi Epidermal Skin Tumors Mastocytosis and Cutaneous T Cell Lymphoma Autoimmune and Inflammatory Skin Disorders Blistering Disorders Disorders of Skin Appendages and Subcutis 26 Bones, Joints, and Soft Tissue Tumors Chapter Contents Bone Basic Structure and Function of Bone Matrix Cells Development Homeostasis and Remodeling Developmental Disorders of Bone and Cartilage Defects in Nuclear Proteins and Transcription Factors Defects in Hormones and Signal Transduction Proteins Defects in Extracellular Structural Proteins Type 1 Collagen Diseases (Osteogenesis Imperfecta) Diseases Associated with Mutations of Types II, IX, X, and XI Collagen Defects in Metabolic Pathways (Enzymes, Ion Channels, and Transporters) Osteopetrosis Pathogenesis. Clinical Features. Diseases Associated with Defects in Degradation of Macromolecules Mucopolysaccharidoses Acquired Disorders of Bone and Cartilage Osteopenia and Osteoporosis Pathogenesis. Clinical Course. Paget Disease (Osteitis Deformans) Pathogenesis. Clinical Course. Rickets and Osteomalacia Hyperparathyroidism Renal Osteodystrophy Pathogenesis. Fractures Healing of Fractures Osteonecrosis (Avascular Necrosis) Clinical Course. Osteomyelitis Pyogenic Osteomyelitis Clinical Course. Mycobacterial Osteomyelitis Skeletal Syphilis Bone Tumors and Tumor-Like Lesions Bone-Forming Tumors Osteoid Osteoma and Osteoblastoma Osteosarcoma Pathogenesis. Clinical Course. Cartilage-Forming Tumors Osteochondroma Pathogenesis. Clinical Course. Chondromas Pathogenesis. Clinical Course. Chondrosarcoma Clinical Course. Tumors of Unknown Origin Ewing Sarcoma Family Tumors Pathogenesis. Clinical Course. Giant Cell Tumor Pathogenesis. Clinical Course. Aneurysmal Bone Cyst Pathogenesis. Clinical Course. Lesions Simulating Primary Neoplasms Fibrous Cortical Defect and Nonossifying Fibroma Fibrous Dysplasia Pathogenesis. Clinical Course. Metastatic Tumors Joints Osteoarthritis Pathogenesis. Clinical Course. Rheumatoid Arthritis Pathogenesis. Clinical Course. Juvenile Idiopathic Arthritis Seronegative Spondyloarthropathies Ankylosing Spondylitis Reactive Arthritis Enteritis Associated Arthritis Psoriatic Arthritis Infectious Arthritis Suppurative Arthritis Mycobacterial Arthritis Lyme Arthritis Viral Arthritis Crystal-Induced Arthritis Gout Pathogenesis. Clinical Course. Calcium Pyrophosphate Crystal Deposition Disease (Pseudo-Gout) Pathophysiology. Joint Tumors and Tumor-Like Conditions Ganglion and Synovial Cysts Tenosynovial Giant Cell Tumor Pathogenesis. Clinical Features. Soft Tissue Pathogenesis. Tumors of Adipose Tissue Lipoma Liposarcoma Fibrous Tumors Nodular Fasciitis Fibromatoses Superficial Fibromatosis Deep Fibromatosis (Desmoid Tumors) Skeletal Muscle Tumors Rhabdomyosarcoma Smooth Muscle Tumors Leiomyoma Leiomyosarcoma Tumors of Uncertain Origin Synovial Sarcoma Undifferentiated Pleomorphic Sarcoma Acknowledgement Suggested Readings Basic Structure and Biology of Bone Skeletal Dysplasias Osteoporosis Paget Disease Metabolic Bone Diseases Osteogenic Tumors Chondrogenic Tumors Ewing Sarcoma Giant Cell Tumor of Bone Aneurysmal Bone Cyst Fibrous Dysplasia Osteoarthritis Rheumatoid Arthritis and Related Conditions Infectious Arthritis Gout and Pseudogout Tenosynovial Giant Cell Tumor Soft Tissue Sarcomas 27 Peripheral Nerves and Skeletal Muscles Chapter Contents Diseases of Peripheral Nerves General Types of Peripheral Nerve Injury Axonal Neuropathies Demyelinating Neuropathies Neuronopathies Anatomic Patterns of Peripheral Neuropathies Specific Peripheral Neuropathies Inflammatory Neuropathies Guillain-Barré Syndrome (Acute Inflammatory Demyelinating Polyneuropathy) Pathogenesis. Clinical Features. Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy Pathogenesis. Neuropathy Associated with Systemic Autoimmune Diseases Neuropathy Associated with Vasculitis Infectious Neuropathies Leprosy (Hansen Disease) Lyme Disease HIV/AIDS Diphtheria Varicella-Zoster Virus Metabolic, Hormonal, and Nutritional Neuropathies Diabetes Pathogenesis. Clinical Features. Other Metabolic, Hormonal, and Nutritional Neuropathies Toxic Neuropathies Neuropathies Associated with Malignancy Neuropathies Caused by Physical Forces Inherited Peripheral Neuropathies Hereditary motor and sensory neuropathies/Charcot-Marie-Tooth (CMT) disease Hereditary sensory neuropathies with or without autonomic neuropathy Hereditary neuropathy with pressure palsy Familial amyloid polyneuropathies Peripheral neuropathy accompanying inherited metabolic disorders Diseases of the Neuromuscular Junction Antibody-Mediated Diseases of the Neuromuscular Junction Myasthenia Gravis Pathogenesis. Clinical Features. Lambert-Eaton Myasthenic Syndrome Congenital Myasthenic Syndromes Disorders Caused by Toxins Diseases of Skeletal Muscle Skeletal Muscle Atrophy Neurogenic and Myopathic Changes in Skeletal Muscle Inflammatory Myopathies Dermatomyositis Pathogenesis. Clinical Features. Polymyositis Pathogenesis. Inclusion Body Myositis Treatment of Inflammatory Myopathies Toxic Myopathies Inherited Diseases of Skeletal Muscle Muscular Dystrophies X-Linked Muscular Dystrophy with Dystrophin Mutation/Duchenne and Becker Muscular Dystrophy Pathogenesis. Clinical Features. Myotonic Dystrophy Pathogenesis. Emery-Dreifuss Muscular Dystrophy Fascioscapulohumeral Dystrophy Pathogenesis. Limb-Girdle Muscular Dystrophy Diseases of Lipid or Glycogen Metabolism Mitochondrial Myopathies Clinical Features. Spinal Muscular Atrophy and the Differential Diagnosis of a Hypotonic Infant Ion Channel Myopathies (Channelopathies) Peripheral Nerve Sheath Tumors Schwannomas Clinical Features. Neurofibromas Malignant Peripheral Nerve Sheath Tumors (MPNST) Neurofibromatosis Type 1 and Type 2 Neurofibromatosis Type 1 Neurofibromatosis Type 2 Suggested Readings Neuropathies and Other Non-Neoplastic Disorders of Peripheral Nerves Muscular Dystrophies and Other Disorders of Muscle Tumors of Peripheral Nerves 28 The Central Nervous System Chapter Contents Cellular Pathology of the Central Nervous System Reactions of Neurons to Injury Reactions of Astrocytes to Injury Reactions of Microglia to Injury Reactions of Other Glial Cells to Injury Cerebral Edema, Hydrocephalus, and Raised Intracranial Pressure and Herniation Cerebral Edema Hydrocephalus Raised Intracranial Pressure and Herniation Malformations and Developmental Disorders Neural Tube Defects Forebrain Anomalies Posterior Fossa Anomalies Syringomyelia and Hydromyelia Perinatal Brain Injury Trauma Skull Fractures Parenchymal Injuries Concussion Direct Parenchymal Injury Diffuse Axonal Injury Traumatic Vascular Injury Epidural Hematoma Subdural Hematoma Clinical Features. Sequelae of Brain Trauma Spinal Cord Injury Cerebrovascular Disease Hypoxia, Ischemia, and Infarction Global Cerebral Ischemia Focal Cerebral Ischemia Clinical Features. Hypertensive Cerebrovascular Disease Lacunar Infarcts Slit Hemorrhages Hypertensive Encephalopathy Intracranial Hemorrhage Intraparenchymal Hemorrhage Clinical Features. Subarachnoid Hemorrhage and Ruptured Saccular Aneurysms Pathogenesis. Clinical Features. Vascular Malformations Clinical Features. Infections Acute Meningitis Acute Pyogenic (Bacterial) Meningitis Acute Aseptic (Viral) Meningitis Acute Focal Suppurative Infections Brain Abscess Subdural Empyema Extradural Abscess Chronic Bacterial Meningoencephalitis Tuberculosis Clinical Features. Neurosyphilis Neuroborreliosis (Lyme Disease) Viral Meningoencephalitis Arthropod-Borne Viral Encephalitis Herpes Simplex Virus Type 1 Herpes Simplex Virus Type 2 Varicella-Zoster Virus (Herpes Zoster) Cytomegalovirus Poliomyelitis Clinical Features. Rabies Clinical Features. Human Immunodeficiency Virus Progressive Multifocal Leukoencephalopathy Subacute Sclerosing Panencephalitis Fungal Meningoencephalitis Other Infectious Diseases of the Nervous System Prion Diseases Pathogenesis and Molecular Genetics. Creutzfeldt-Jakob Disease (CJD) Variant Creutzfeldt-Jakob Disease Fatal Familial Insomnia (FFI) Demyelinating Diseases Multiple Sclerosis Pathogenesis. Clinical Features. Neuromyelitis Optica Acute Disseminated Encephalomyelitis and Acute Necrotizing Hemorrhagic Encephalomyelitis Central Pontine Myelinolysis Neurodegenerative Diseases Alzheimer Disease Molecular Genetics and Pathogenesis. Clinical Features. Frontotemporal Lobar Degenerations (FTLDs) FTLD-Tau Molecular Genetics and Pathogenesis. FTLD-TDP Molecular Genetics and Pathogenesis. Parkinson Disease (PD) Molecular Genetics and Pathogenesis. Dementia with Lewy Bodies Atypical Parkinsonism Syndromes Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD) Multiple System Atrophy (MSA) Pathogenesis. Huntington Disease Molecular Genetics and Pathogenesis. Clinical Features. Spinocerebellar Degenerations Spinocerebellar Ataxias Molecular Genetics. Friedreich Ataxia Ataxia-Telangiectasia Clinical Features. Amyotrophic Lateral Sclerosis (ALS) Molecular Genetics and Pathogenesis. Clinical Features. Other Motor Neuron Diseases Spinal and Bulbar Muscular Atrophy (Kennedy Disease) Spinal Muscular Atrophy Genetic Metabolic Diseases Neuronal Storage Diseases Leukodystrophies Mitochondrial Encephalomyopathies Toxic and Acquired Metabolic Diseases Vitamin Deficiencies Thiamine (Vitamin B1) Deficiency Vitamin B12 Deficiency Neurologic Sequelae of Metabolic Disturbances Hypoglycemia Hyperglycemia Hepatic Encephalopathy Toxic Disorders Carbon Monoxide Methanol Ethanol Radiation Tumors Gliomas Astrocytoma Infiltrating Astrocytomas Molecular Genetics. Clinical Features. Pilocytic Astrocytoma Pleomorphic Xanthoastrocytoma Brainstem Glioma Oligodendroglioma Molecular Genetics. Clinical Features. Ependymoma and Related Paraventricular Mass Lesions Molecular Genetics. Clinical Features. Neuronal Tumors Poorly Differentiated Neoplasms Medulloblastoma Molecular Genetics. Clinical Features. Atypical Teratoid/Rhabdoid Tumor Molecular Genetics. Clinical Features. Other Parenchymal Tumors Primary CNS Lymphoma Germ Cell Tumors Pineal Parenchymal Tumors Meningiomas Molecular Genetics. Clinical Features. Metastatic Tumors Paraneoplastic Syndromes Familial Tumor Syndromes Tuberous Sclerosis Complex Von Hippel-Lindau Disease Neurofibromatosis Suggested Readings General Malformations and Developmental Diseases Perinatal Brain Injury Trauma Cerebrovascular Disease Infections Prion Disease Demyelinating Diseases Neurodegenerative Diseases Genetic Metabolic Diseases Tumors 29 The Eye Chapter Contents Orbit Functional Anatomy and Proptosis Thyroid Ophthalmopathy (Graves Disease) Other Orbital Inflammatory Conditions Neoplasms Eyelid Functional Anatomy Neoplasms Conjunctiva Functional Anatomy Conjunctival Scarring Pinguecula and Pterygium Neoplasms Sclera Cornea Functional Anatomy Keratitis and Ulcers Corneal Degenerations and Dystrophies Band Keratopathies Keratoconus Fuchs Endothelial Dystrophy Stromal Dystrophies Anterior Segment Functional Anatomy Cataract The Anterior Segment and Glaucoma Endophthalmitis and Panophthalmitis Uvea Uveitis Neoplasms Uveal Nevi and Melanomas Retina and Vitreous Functional Anatomy Retinal Detachment Retinal Vascular Disease Hypertension Diabetes Mellitus Retinopathy of Prematurity (Retrolental Fibroplasia) Sickle Retinopathy, Retinal Vasculitis, Radiation Retinopathy Retinal Artery and Vein Occlusions Age-Related Macular Degeneration (AMD) Other Retinal Degenerations Retinitis Pigmentosa Retinitis Retinal Neoplasms Retinoblastoma Retinal Lymphoma Optic Nerve Anterior Ischemic Optic Neuropathy Papilledema Glaucomatous Optic Nerve Damage Other Optic Neuropathies Optic Neuritis The End-Stage Eye: Phthisis Bulbi Suggested Readings The Orbit The Eyelid and Conjunctiva The Cornea Glaucoma The Uvea The Retina The Optic Nerve Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Inside back cover