Robbins & Cotran Pathologic Basis of Disease

Description

Readable and highly illustrated, Robbins and Cotran Pathologic Basis of Disease, 10th Edition presents an in-depth, state-of-the-art overview of human diseases and their cellular and molecular basis. This best-selling text delivers the latest, most essential pathology knowledge in a readable, interesting manner, ensuring optimal understanding of the latest basic science and clinical content. More than 1,000 high-quality photographs and full-color illustrations highlight new information in molecular biology, disease classifications, new drugs and drug therapies, and much more. This superb learning package also includes an enhanced eBook with a full complement of ancillary content on Student Consult. Endsheet Robbins & Cotran Pathologic Basis of Disease Copyright Page Dedication Contributors Preface Acknowledgments Table Of Contents 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 Long Noncoding RNA Gene Editing Cellular Housekeeping Plasma Membrane: Protection and Nutrient Acquisition Membrane Transport Passive Diffusion. Carriers and Channels (Fig. 1.8). Receptor-Mediated and Fluid-Phase Uptake (see Fig. 1.8) Cytoskeleton Cell-Cell Interactions Biosynthetic Machinery: Endoplasmic Reticulum and Golgi Apparatus Waste Disposal: Lysosomes and Proteasomes Cellular Metabolism and Mitochondrial Function Cellular Activation Cell Signaling Signal Transduction Pathways Modular Signaling Proteins, Hubs, and Nodes Transcription Factors Growth Factors and Receptors Epidermal Growth Factor (EGF) and Transforming Growth Factor-α (TGF-α). Hepatocyte Growth Factor (HGF). Platelet-derived Growth Factor (PDGF). Vascular Endothelial Growth Factor (VEGF). Fibroblast Growth Factor (FGF). Transforming Growth Factor β (TGF-β). Extracellular Matrix Components of the Extracellular Matrix (Fig. 1.15) Collagens. Elastin. Proteoglycans and Hyaluronan (see Fig. 1.15B). 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 Cell Injury, Cell Death, and Adaptations Chapter Contents Introduction to Pathology Overview of Cellular Responses to Stress and Noxious Stimuli Causes of Cell Injury Oxygen Deprivation Physical Agents Chemical Agents and Drugs Infectious Agents Immunologic Reactions Genetic Abnormalities Nutritional Imbalances The Progression of Cell Injury and Death Reversible Cell Injury Cell Death Necrosis Patterns of Tissue Necrosis Apoptosis Causes of Apoptosis Apoptosis in Physiologic Situations Apoptosis in Pathologic Conditions Morphologic and Biochemical Changes in Apoptosis Mechanisms of Apoptosis The Mitochondrial (Intrinsic) Pathway of Apoptosis The Extrinsic (Death Receptor–Initiated) Pathway of Apoptosis The Execution Phase of Apoptosis Removal of Dead Cells Other Mechanisms of Cell Death Autophagy Mechanisms of Cell Injury General Mechanisms of Cell Injury and Intracellular Targets of Injurious Stimuli Mitochondrial Damage Membrane Damage Damage to DNA Oxidative Stress: Accumulation of Oxygen-Derived Free Radicals Generation of Free Radicals Removal of Free Radicals Pathologic Effects of Free Radicals Disturbance in Calcium Homeostasis Endoplasmic Reticulum Stress: the Unfolded Protein Response Clinicopathologic Correlations: Selected Examples of Cell Injury and DEATH Hypoxia and Ischemia Mechanisms of Ischemic Cell Injury Ischemia-Reperfusion Injury Chemical (Toxic) Injury Adaptations of Cellular Growth and Differentiation Hypertrophy Mechanisms of Hypertrophy Hyperplasia Mechanisms of Hyperplasia Atrophy Mechanisms of Atrophy Metaplasia Mechanisms of Metaplasia 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. Dysregulated Nutrient Sensing. Suggested Readings Mechanisms of Cell Injury Cell Death Apoptosis Necroptosis and Pyroptosis Autophagy Adaptations 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 and Interleukin-1 Chemokines Other Cytokines in Acute Inflammation Complement System Other Mediators of Inflammation Platelet-Activating Factor Products of Coagulation Kinins Neuropeptides Morphologic Patterns of Acute Inflammation Serous Inflammation Fibrinous Inflammation Purulent (Suppurative) Inflammation and 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 Mechanisms of Angiogenesis. Deposition of Connective Tissue Remodeling of Connective Tissue Factors That Influence Tissue Repair 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 Defects in Healing: Chronic Wounds Excessive Scarring Suggested Readings General Mechanisms of Inflammation Sensors of Inflammatory Stimuli Acute Inflammation: Vascular Reactions Acute Inflammation: Role of Neutrophils 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 Normal Hemostasis Platelets Coagulation Cascade Factors That Limit Coagulation Endothelium Hemorrhagic Disorders Thrombosis Endothelial Injury Alterations in Normal Blood Flow Hypercoagulability Heparin-Induced Thrombocytopenia (HIT) Syndrome Antiphospholipid Antibody Syndrome (APS) Fate of the Thrombus Clinical Features Venous Thrombosis (Phlebothrombosis). Arterial and Cardiac Thrombosis. Disseminated Intravascular Coagulation (DIC) Embolism Pulmonary Embolism (PE) Systemic Thromboembolism Fat Embolism Air Embolism Amniotic Fluid Embolism Infarction Factors That Influence Development of an Infarct. Shock Pathogenesis of Septic Shock Stages of Shock Clinical Features 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 (EDSs) Disorders Associated With Defects in Receptor Proteins Familial Hypercholesterolemia Normal Cholesterol Metabolism and Transport Disorders Associated With Enzyme Defects 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 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 (FXS) Fragile X–Associated Tremor/Ataxia Syndrome and Fragile X–Associated Primary Ovarian Failure 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) Cytogenomic Array Technology Polymorphic Markers and Molecular Diagnosis Epigenetic Alterations RNA Analysis Next-Generation Sequencing (NGS) Bioinformatics Clinical Applications of Next-Generation DNA Sequencing Future Applications Acknowledgment Suggested Readings Molecular Basis of Single-Gene Disorders—General Disorders Associated With Defects in Structural Proteins Disorders Associated With Defects in Receptor Proteins Lysosomal Storage Disorders 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 Natural Killer Cells Reactions of Innate Immunity Adaptive Immunity Cells of the Adaptive Immune System Lymphocyte Diversity T Lymphocytes B Lymphocytes Dendritic Cells (DCs) Macrophages Tissues of the Immune System Primary Lymphoid Organs. Secondary Lymphoid Organs. Lymphocyte Recirculation Major Histocompatibility Complex 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 Reactions Immediate (Type I) Hypersensitivity Activation of Th2 Cells and Production of IgE Antibody Sensitization and Activation of Mast Cells Mediators of Immediate Hypersensitivity 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 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 and Other Environmental Factors General Features of Autoimmune Diseases Systemic Lupus Erythematosus (SLE) Spectrum of Autoantibodies in Systemic Lupus Erythematosus Pathogenesis Genetic Factors. Immunologic Factors. Environmental Factors. A Model for the Pathogenesis of SLE. Mechanisms of Tissue Injury. Clinical Features Chronic Discoid Lupus Erythematosus Subacute Cutaneous Lupus Erythematosus Drug-Induced Lupus Erythematosus Rheumatoid Arthritis Sjögren Syndrome Pathogenesis Clinical Features Systemic Sclerosis (Scleroderma) 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 Patterns and Mechanisms of Graft Rejection Methods of Increasing Graft Survival Transplantation of Hematopoietic Stem Cells (HSCs) Immunodeficiency Diseases Primary Immunodeficiencies Defects in Innate Immunity Defects in Leukocyte Function Deficiencies Affecting the Complement System Defects in Adaptive Immunity Severe Combined Immunodeficiency X-linked SCID. Autosomal Recessive SCID. X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia) DiGeorge Syndrome (Thymic Hypoplasia) Other Defects in Lymphocyte Maturation Hyper-IgM Syndrome Common Variable Immunodeficiency Isolated IgA Deficiency X-Linked Lymphoproliferative Disease 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 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 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, Dysplasia, and Carcinoma In Situ 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 Oncoproteins and Cell Growth Growth Factors. Growth Factor Receptors. Downstream Components of the Receptor Tyrosine Kinase Signaling Pathway. Nonreceptor Tyrosine Kinases. Transcription Factors. MYC. 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. VHL. STK11. Growth-Promoting Metabolic Alterations: The Warburg Effect Autophagy. Oncometabolism. Evasion of Cell Death Limitless Replicative Potential: The Stem Cell–Like Properties of Cancer Cells Angiogenesis Invasion and Metastasis Invasion of Extracellular Matrix Vascular Dissemination, Homing, and Colonization Evasion of Immune Surveillance Tumor Antigens Antitumor Effector Mechanisms Mechanisms of Immune Evasion by Cancers Genomic Instability DNA Mismatch Repair Factors. Nucleotide Excision Repair Factors. Homologous Recombination Repair Factors. DNA Polymerase. Regulated Genomic Instability in Lymphoid Cells. Cancer-Enabling Inflammation Dysregulation of Cancer-Associated Genes Chromosomal Changes Chromosomal Translocations. Deletions. Gene Amplification. Complex Chromosomal Rearrangements. Epigenetic Changes Noncoding RNAs and Cancer Molecular Basis of Multistep Carcinogenesis Carcinogenic Agents and Their Cellular Interactions Chemical Carcinogenesis Direct-Acting Carcinogens Indirect-Acting Carcinogens Molecular Targets of Chemical Carcinogens. 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 Clinical Manifestations 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 Diagnostics and Cytogenetics. Molecular Profiles of Tumors: The Future of Cancer Diagnostics Tumor Markers Suggested Readings Cancer Epidemiology Cancer Evolution and Genomics 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 Noncoding 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 Immune Evasion by Microbes Injurious Effects of Host Immunity Infections in People With Immunodeficiencies Host Damage by Microbes Mechanisms of Viral Injury Mechanisms of Bacterial Injury Bacterial Virulence. Bacterial Adherence to Host Cells. Intracellular Bacteria. Bacterial Toxins. Spectrum of Inflammatory Responses to Infection Suppurative (Purulent) Inflammation Mononuclear and Granulomatous Inflammation Cytopathic-Cytoproliferative Reaction Tissue Necrosis Chronic Inflammation and Scarring Viral Infections Acute (Transient) Infections Measles Pathogenesis Mumps Poliomyelitis West Nile Virus Infections Viral Hemorrhagic Fever Zika Virus Infections Dengue Novel Coronavirus SARS-CoV-2 (COVID-19) Latent Infections (Herpesvirus Infections) Herpes Simplex Virus (HSV) Infections Varicella-Zoster Virus (VZV) Infections Cytomegalovirus (CMV) Infections Congenital Infections. Perinatal Infections. CMV Mononucleosis. CMV in Immunosuppressed Individuals. Chronic Productive Infections Transforming Viral Infections Epstein-Barr Virus (EBV) Infections Pathogenesis Clinical Features Bacterial Infections Gram-Positive Bacterial Infections Staphylococcal Infections Pathogenesis S. aureus Toxins. Streptococcal and Enterococcal Infections Pathogenesis Diphtheria Listeriosis Anthrax Pathogenesis Nocardial Infections Gram-Negative Bacterial Infections Neisserial Infections Pathogenesis Pertussis Pathogenesis Pseudomonal Infections Pathogenesis Plague Chancroid (Soft Chancre) Granuloma Inguinale Mycobacterial Infections Tuberculosis Epidemiology Pathogenesis Clinical Features Nontuberculous Mycobacterial Infections Leprosy Pathogenesis Spirochete Infections Syphilis Pathogenesis Primary Syphilis. Secondary Syphilis. Tertiary Syphilis. Congenital Syphilis. Serologic Tests for Syphilis. Lyme Disease Pathogenesis Anaerobic Bacterial Infections Abscesses Clostridial Infections Pathogenesis Obligate Intracellular Bacterial Infections Chlamydial Infections Infections Caused by Other Intracellular Bacteria Pathogenesis Fungal Infections Yeast Infections Candidiasis Pathogenesis Candida auris Infections Cryptococcosis Pathogenesis Pneumocystis Infections Mold Infections Aspergillosis Pathogenesis Mucormycosis (Zygomycosis) Pathogenesis Parasitic Infections Protozoal Infections Malaria Pathogenesis Babesiosis Leishmaniasis Pathogenesis African Trypanosomiasis Pathogenesis Chagas Disease Pathogenesis Toxoplasmosis Pathogenesis Metazoal Infections Strongyloidiasis Cysticercosis and Hydatid Disease (Tapeworm Infections) Trichinosis Pathogenesis Schistosomiasis Pathogenesis Lymphatic Filariasis Pathogenesis Onchocerciasis Sexually Transmitted Infections Emerging Infectious Diseases Agents of Bioterrorism. Special Techniques for Diagnosing Infectious Agents Suggested Readings General Principles of Microbial Pathogenesis Virology Bacteriology Fungi Parasitology 9 Environmental and Nutritional Diseases Chapter Contents 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 Oral Contraceptives Acetaminophen Aspirin (Acetylsalicylic Acid) Injury by Nontherapeutic Agents (Drug Abuse) Cocaine Opioids and Opiates Amphetamines and Related Drugs Methamphetamine. 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 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 Severe Acute Malnutrition Marasmus. Kwashiorkor. Malnutrition in the Upper Income 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. Adipose Tissue. Role of the Gut Microbiome. Clinical Consequences of Obesity Obesity and Cancer Diet and Cancer Diet and Systemic Diseases Suggested Readings Climate Change Air Pollution Heavy Metal Poisoning Effects of Alcohol and Tobacco Menopausal Hormone Therapy and Oral Contraceptives Drugs of Abuse and Radiation Injury Malnutrition Vitamins Obesity 10 Diseases of Infancy and Childhood Chapter Contents Congenital Anomalies Definitions Causes of Anomalies Pathogenesis Prematurity and Fetal Growth Restriction Fetal Growth Restriction Maternal Abnormalities Fetal Abnormalities Placental 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 Spectrum and Genotype-Phenotype Correlation Genetic and Environmental Modifiers Clinical Features Sudden Infant Death Syndrome Epidemiology Pathogenesis Tumors and Tumorlike Lesions of Infancy and Childhood Benign Tumors and Tumorlike Lesions Hemangioma Fibrous Tumors Teratomas Malignant Tumors Incidence and Types Neuroblastic Tumors Clinical Course and Prognostic Features (Table 10.7) Wilms Tumor Pathogenesis and Genetics Clinical Features Suggested Readings Congenital Anomalies, Hydrops, and Infections Cystic Fibrosis and Inborn Errors of Metabolism Diseases of Prematurity and SIDS Tumors of Infancy and Childhood 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 Mechanisms of Secondary Hypertension. Mechanisms of Essential Hypertension. Vascular Pathology in Hypertension Arteriosclerosis Atherosclerosis Epidemiology. Risk Factors Constitutional Risk Factors Modifiable Major Risk Factors Additional Risk Factors Pathogenesis of Atherosclerosis Endothelial Injury. Hemodynamic Disturbances. Hypercholesterolemia. Inflammation. Infection. Smooth Muscle Proliferation and Matrix Synthesis. Overview. Consequences of Atherosclerotic Disease Atherosclerotic Stenosis. Acute Plaque Change. Aneurysms and Dissection Pathogenesis Abdominal Aortic Aneurysm Clinical Features Thoracic Aortic Aneurysm Aortic Dissection Pathogenesis Clinical Features Vasculitis Noninfectious Vasculitis Immune Complex–Associated Vasculitis Antineutrophil Cytoplasmic Antibodies Anti–Endothelial Cell Antibodies Giant Cell (Temporal) Arteritis Pathogenesis Clinical Features Takayasu Arteritis Clinical Features Polyarteritis Nodosa (PAN) Clinical Features Kawasaki Disease Clinical Features Microscopic Polyangiitis Pathogenesis Clinical Features Granulomatosis With Polyangiitis (GPA) Pathogenesis Clinical Features Churg-Strauss Syndrome 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 Caval Syndromes Lymphangitis and Lymphedema Vascular Tumors Benign Tumors and Tumor-Like Conditions Vascular Ectasias. Hemangiomas. Lymphangiomas. Glomus Tumor (Glomangioma). Bacillary Angiomatosis. Intermediate-Grade (Borderline) Tumors Kaposi Sarcoma. Pathogenesis Clinical Features Hemangioendothelioma. Malignant Tumors Angiosarcoma. 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 Disorders of Blood Vessel Hyperreactivity 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 Regeneration 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 Cardiac Development Congenital Heart Disease Incidence 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 Clinical Features 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 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 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 (IE) Pathogenesis Clinical Features Noninfected Vegetations Nonbacterial Thrombotic Endocarditis (NBTE) Endocarditis of Systemic Lupus Erythematosus (Libman-Sacks Disease) Carcinoid Heart Disease Pathogenesis Complications of Prosthetic Valves Cardiomyopathies Dilated Cardiomyopathy (DCM) Pathogenesis Clinical Features Arrhythmogenic Cardiomyopathy Hypertrophic Cardiomyopathy Pathogenesis Clinical Features Restrictive Cardiomyopathy Amyloidosis Myocarditis Pathogenesis Clinical Features Other Causes of Myocardial Disease Cardiotoxic Drugs Radiation Pericardial Disease Pericardial Effusion and Hemopericardium Pericarditis Acute Pericarditis Chronic or Healed Pericarditis Tumors of the Heart Primary Cardiac Tumors Metastatic Neoplasms Cardiac Transplantation Cardiac Devices Ventricular Assist Devices 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 Normal Hematopoiesis 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: Overview Etiologic and Pathogenetic Factors in White Cell Neoplasia 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 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 Mantle Cell Lymphoma Pathogenesis Immunophenotype. Clinical Features Marginal Zone Lymphomas Hairy Cell Leukemia Pathogenesis Immunophenotype. Clinical Features Peripheral T- 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 Plasma Cell Neoplasms and Related Disorders Multiple Myeloma Pathogenesis Immunophenotype. Clinical Features Smoldering Myeloma Solitary Osseous Plasmacytoma Monoclonal Gammopathy of Undetermined Significance Lymphoplasmacytic Lymphoma Pathogenesis Immunophenotype. Clinical Features Hodgkin Lymphoma Classification. Pathogenesis Clinical Features Pathogenic Lessons From Lymphoid Neoplasms Myeloid Neoplasms Acute Myeloid Leukemia Classification. Pathogenesis Immunophenotype. Cytogenetics. Clinical Features Myelodysplastic Syndrome Pathogenesis Clinical Features Myeloproliferative Neoplasms Chronic Myeloid Leukemia Pathogenesis Clinical Features Polycythemia Vera Pathogenesis Clinical Features Essential Thrombocytosis Pathogenesis Clinical Features Primary Myelofibrosis Pathogenesis Clinical Features Langerhans Cell Histiocytosis Pathogenesis Clinical Features Spleen Splenomegaly Nonspecific Acute Splenitis Congestive Splenomegaly Splenic Infarcts Neoplasms Congenital Anomalies Rupture Thymus Developmental Disorders Thymic Hyperplasia Thymoma Clinical Features Suggested Readings Hematopoietic Stem Cells White Cell Neoplasms 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 β-Thalassemia Molecular Pathogenesis Clinical Syndromes β-Thalassemia Major. β-Thalassemia Minor. α-Thalassemia Clinical Syndromes Silent Carrier State. α-Thalassemia Trait. Hemoglobin H (HbH) Disease. Hydrops Fetalis. Paroxysmal Nocturnal Hemoglobinuria Immunohemolytic Anemia Warm Antibody Type. Cold Agglutinin Type. Cold Hemolysin Type. Hemolytic Anemia Resulting From Trauma to Red Cells Anemias of Diminished Erythropoiesis Megaloblastic Anemia Vitamin B12 Deficiency Anemia: 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 Inflammation 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 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 Function Hemorrhagic Diatheses Related to Abnormalities in Clotting Factors 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 Features Obstructive and Restrictive Lung Diseases Obstructive Lung Diseases Chronic Obstructive Pulmonary Disease Emphysema Pathogenesis Chronic Bronchitis Pathogenesis Clinical Features of COPD Other Forms of Emphysema Asthma Atopic Asthma. Non-Atopic Asthma. Drug-Induced Asthma. Occupational Asthma. Pathogenesis Th2 Responses, IgE, and Inflammation. Genetic Susceptibility. Environmental Factors. Clinical Features Bronchiectasis Pathogenesis Clinical Features Chronic Diffuse Interstitial (Restrictive) Diseases Fibrosing Diseases Idiopathic Pulmonary Fibrosis Pathogenesis Clinical Features Nonspecific Interstitial Pneumonia Clinical Features Cryptogenic Organizing Pneumonia Pulmonary Involvement in Autoimmune Diseases Pneumoconioses Pathogenesis Coal Workers’ Pneumoconiosis Clinical Features Silicosis Pathogenesis Clinical Features Asbestos-Related Diseases Pathogenesis Clinical Features Complications of Therapies Drug-Induced Lung Diseases. Radiation-Induced Lung Diseases. Granulomatous Diseases Sarcoidosis Pathogenesis Clinical Features 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 Clinical Features Surfactant Dysfunction Disorders Diseases of Vascular Origin Pulmonary Embolism and Infarction Pathogenesis Clinical Features Pulmonary Hypertension Pathogenesis Clinical Features Diffuse Pulmonary Hemorrhage Syndromes Idiopathic Pulmonary Hemosiderosis Goodpasture Syndrome (Anti–Glomerular Basement Membrane Antibody Disease With Pulmonary Involvement) Pathogenesis Clinical Features 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 Features Community-Acquired Viral Pneumonia Influenza Human Metapneumovirus Human Coronaviruses Clinical Features Health Care–Associated Pneumonia Hospital-Acquired Pneumonia Aspiration Pneumonia Lung Abscess Etiology and Pathogenesis Clinical Features 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. Acquired Mutations. Lung Cancer in Never-Smokers. Precursor (Preinvasive) Lesions. Classification Staging. Clinical Features 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 Features 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 Langerhans Cell Histiocytosis 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 Inflammatory Lesions Infectious Rhinitis. Allergic Rhinitis. Nasal Polyps. Chronic Rhinitis. Sinusitis. Necrotizing Lesions of the Nose and Upper Airways Nasopharynx Inflammatory Lesions Tumors of the Nose, Sinuses, and Nasopharynx Nasopharyngeal Angiofibroma. Sinonasal (Schneiderian) Papilloma. Olfactory Neuroblastoma (Esthesioneuroblastoma). NUT Midline Carcinoma. Nasopharyngeal Carcinoma. Larynx Inflammatory Lesions Reactive Nodules (Vocal Cord Nodules and Polyps) Squamous Papilloma and Papillomatosis Carcinoma of the Larynx Hyperplasia-Dysplasia-Carcinoma Sequence. 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 Warthin Tumor (Papillary Cystadenoma Lymphomatosum) Mucoepidermoid Carcinoma Other Salivary Gland Tumors Adenoid cystic carcinomas. Acinic cell carcinomas. 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 and Related Disorders 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 Stress-Related Mucosal Disease Pathogenesis Clinical Features Chronic Gastritis and its Complications Helicobacter pylori Gastritis Epidemiology. Pathogenesis Clinical Features Autoimmune Atrophic Gastritis Pathogenesis Clinical Features Uncommon Forms of Gastritis Eosinophilic Gastritis. Lymphocytic Gastritis. Granulomatous Gastritis. Peptic Ulcer Disease Epidemiology. Pathogenesis Clinical Features Other Complications of Chronic Gastritis 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 Neuroendocrine Neoplasms 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 Enteric Dysfunction Autoimmune Enteropathy Lactase (Disaccharidase) Deficiency Microvillus Inclusion Disease 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 Escherichia coli. Enteropathogenic Escherichia coli. Enterohemorrhagic Escherichia coli. Enteroinvasive Escherichia coli. Enteroaggregative Escherichia coli. Pseudomembranous Colitis Pathogenesis Clinical Features Whipple Disease Pathogenesis Viral Gastroenteritis Norovirus. Rotavirus. Adenovirus. Parasitic Enterocolitis Ascaris lumbricoides. Strongyloides. Necator duodenale and Ancylostoma duodenale. Trichuris trichiura. Enterobius vermicularis and Enterobius gregorii. Schistosomiasis. Intestinal Cestodes. Entamoeba histolytica. Giardia lamblia. Cryptosporidium. Irritable Bowel Syndrome Pathogenesis Clinical Features Inflammatory Bowel Disease (IBD) 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 Familial Adenomatous Polyposis Hereditary Non-Polyposis Colorectal Cancer (HNPCC) 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 Esophageal Obstruction Esophagitis Barrett Esophagus Esophageal Tumors Stomach Gastropathy and Acute Gastritis Chronic Gastritis Hypertrophic Gastropathies Gastric Polyps and Tumors Small Intestine and Colon Intestinal Obstruction Ischemic Bowel Disease and Angiodysplasia Malabsorption and Diarrhea Infectious Enterocolitis Irritable Bowel Syndrome Inflammatory Bowel Disease Other Causes of Colitis 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 Liver Failure Acute Liver Failure Clinical Features Chronic Liver Failure and Cirrhosis Clinical Features Portal Hypertension Ascites Portosystemic Shunts Splenomegaly Pulmonary Complications of Liver Failure and Portal Hypertension. Acute-on-Chronic Liver Failure Infectious Disorders Viral Hepatitis Hepatitis A Virus Epidemiology Pathogenesis Clinical Features Hepatitis B Virus Epidemiology Pathogenesis Clinical Features Hepatitis C Virus Epidemiology Pathogenesis Clinical Features Hepatitis D Virus Epidemiology Pathogenesis Clinical Features Hepatitis E Virus Epidemiology Pathogenesis Clinical Features Clinicopathologic Syndromes of Viral Hepatitis Bacterial, Fungal, and Parasitic Infections Autoimmune Hepatitis Pathogenesis Clinical Features Drug- and Toxin-Induced Liver Injury Pathogenesis Clinical Features Fatty Liver Disease Alcoholic Liver Disease Pathogenesis Clinical Features Nonalcoholic Fatty Liver Disease (NAFLD) Pathogenesis Clinical Features Inherited Liver Disease Hemochromatosis Pathogenesis Clinical Features Wilson Disease Pathogenesis Clinical Features α1-Antitrypsin Deficiency Pathogenesis Clinical Features Cholestatic Disease Bile Formation and Secretion Pathophysiology of Hyperbilirubinemia Clinical Features Physiologic Jaundice of the Newborn Hereditary Hyperbilirubinemia Large Bile Duct Obstruction Cholestasis of Sepsis Primary Hepatolithiasis Neonatal Cholestasis Extrahepatic Biliary Atresia Clinical Features Nonobstructive Neonatal Cholestasis Autoimmune Cholangiopathies Primary Biliary Cholangitis (PBC) Pathogenesis Clinical Features Primary Sclerosing Cholangitis (PSC) Pathogenesis Clinical Features Structural Anomalies of the Biliary Tree Choledochal Cyst 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 Clinical Features Sinusoidal Obstruction Syndrome Pathogenesis Clinical Features Passive Congestion and Centrilobular Necrosis Hepatic Disease Associated With Pregnancy Preeclampsia and Eclampsia Clinical Features Acute Fatty Liver of Pregnancy Pathogenesis Clinical Features Intrahepatic Cholestasis of Pregnancy Nodules and Tumors Non-Neoplastic Mass Lesions Focal Nodular Hyperplasia Pathogenesis Clinical Features Other Non-Neoplastic Mass Lesions Benign Neoplasms Cavernous Hemangioma Hepatocellular Adenoma Pathogenesis Clinical Features Primary Malignant Neoplasms Hepatoblastoma Clinical Features Hepatocellular Carcinoma (HCC) Pathogenesis Clinical Features Malignant Biliary Tumors Pathogenesis Clinical Features Other Primary Hepatic Malignant Tumors Metastasis Gallbladder Congenital Anomalies Cholelithiasis (Gallstones) Epidemiology Pathogenesis of Cholesterol Stones Pathogenesis of Pigment Stones Clinical Features Cholecystitis Acute Cholecystitis Pathogenesis Clinical Features Chronic Cholecystitis Clinical Features Gallbladder 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 Fatty Liver Disease Inherited Liver Diseases Cholestatic Syndromes Circulatory Disorders 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 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 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 Glomerulosclerosis Tubular Injury and Interstitial Fibrosis Nephritic Syndrome Acute Proliferative (Postinfectious and Infection-Associated) Glomerulonephritis Pathogenesis Clinical Features Crescentic (Rapidly Progressive) Glomerulonephritis Pathogenesis Clinical Features Nephrotic Syndrome Pathophysiology Pathogenesis Membranous Nephropathy Pathogenesis Clinical Features Minimal Change Disease Pathogenesis Clinical Features Focal Segmental Glomerulosclerosis Classification and Types Pathogenesis Clinical Features HIV-Associated Nephropathy Membranoproliferative Glomerulonephritis Pathogenesis Clinical Features Secondary Membranoproliferative Glomerulonephritis Dense Deposit Disease Clinical Features Fibrillary Glomerulonephritis Other Glomerular Diseases IgA Nephropathy (Berger Disease) Pathogenesis Clinical Features Hereditary Nephritis Alport Syndrome Pathogenesis Clinical Features Thin Basement Membrane Nephropathy (Benign Familial Hematuria) Glomerular Lesions Associated With Systemic Diseases Lupus Nephritis Henoch-Schönlein Purpura Diabetic Nephropathy Other Systemic Disorders Tubular and Interstitial Diseases Acute Tubular Injury/Necrosis Pathogenesis Clinical Features Tubulointerstitial Nephritis Pyelonephritis and Urinary Tract Infection 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 Autosomal Dominant Tubulointerstitial Kidney Disease Light-Chain Cast Nephropathy (“Myeloma Kidney”) Clinical Features Bile Cast Nephropathy Vascular Diseases Nephrosclerosis Pathogenesis Clinical Features Renal Artery Stenosis Pathogenesis Clinical Features Thrombotic Microangiopathies Pathogenesis Endothelial Injury. Platelet Aggregation. Typical (Epidemic, Classic, Diarrhea-Positive) Hemolytic Uremic Syndrome Atypical (Non-Epidemic, Diarrhea-Negative) Hemolytic Uremic Syndrome Thrombotic Thrombocytopenic Purpura Other Vascular Disorders Atherosclerotic Ischemic Renal Disease Atheroembolic Renal Disease Sickle Cell Nephropathy 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 the Renal Medulla Medullary Sponge Kidney Nephronophthisis Genetics and Pathogenesis Multicystic Renal Dysplasia Acquired 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 Tumors and Tumor-Like Lesions Obstructive Lesions Sclerosing Retroperitoneal Fibrosis Urinary Bladder Congenital Anomalies Inflammation Acute and Chronic Cystitis Clinical Features Special Forms of Cystitis Interstitial Cystitis (Chronic Pelvic Pain Syndrome). Malakoplakia. Polypoid Cystitis. Metaplastic Lesions Neoplasms Urothelial Neoplasms Epidemiology. Pathogenesis Clinical Features Other Epithelial Bladder Tumors 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 and Tumor-Like Conditions Condyloma Acuminatum Peyronie Disease Malignant Tumors Squamous Carcinoma in situ/Penile Intraepithelial Neoplasia Invasive Squamous Cell Carcinoma Pathogenesis Clinical Features Testis and Epididymis Congenital Anomalies Cryptorchidism Clinical Features Regressive Changes Atrophy and Decreased Fertility Inflammation and Infections Nonspecific Epididymitis and Orchitis Granulomatous (Autoimmune) Orchitis Infections Gonorrhea Mumps Tuberculosis Syphilis Other Infections Vascular Disorders Torsion Spermatic Cord and Paratesticular Tumors Testicular Tumors Germ Cell Tumors Pathogenesis Environmental Factors. Genetic Factors. Steps in the Development of Germ Cell Tumors. Classification. Seminoma Spermatocytic Tumor Embryonal Carcinoma Yolk Sac Tumor Choriocarcinoma Teratoma Mixed Tumors Clinical Features of Testicular Germ Cell Tumors. Serum Biomarkers in Germ Cell Tumors. Tumors of Sex Cord–Gonadal Stroma Leydig Cell Tumors Sertoli Cell Tumors Gonadoblastoma Testicular Lymphoma Lesions of Tunica Vaginalis Prostate Inflammation Benign Enlargement Benign Prostatic Hyperplasia Etiology and Pathogenesis Clinical Features Neoplasms Adenocarcinoma Epidemiology and Pathogenesis. Environmental Factors. Inherited Genetic Factors. Androgens. Acquired Genetic and Epigenetic Alterations. Precursor Lesions. Grading and Staging. Clinical Features Miscellaneous Tumors 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 (PID) Vulva Bartholin Cyst Non-Neoplastic 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 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 Endometrioid Endometrial Carcinoma Serous Endometrial Carcinoma Pathogenesis Clinical Features Carcinosarcoma (Malignant Mixed Müllerian Tumors) Tumors of Endometrial Stroma Adenosarcoma Stromal Tumors Tumors of the Myometrium Leiomyoma Leiomyosarcoma Fallopian Tubes Inflammations Tumors and Cysts Ovaries Non-Neoplastic 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 Teratoma Mature (Benign) Teratomas Monodermal or Specialized Teratomas Immature Malignant Teratomas Dysgerminoma Yolk Sac Tumors 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 Clinical Features Placental Site Trophoblastic Tumors 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 Molecular Classification and Pathogenesis Pathogenesis of Familial Breast Cancer Pathogenesis of Sporadic Breast Cancer Types of Breast Carcinoma Carcinoma in Situ Ductal Carcinoma in Situ. Clinical Features Lobular Carcinoma in Situ. Invasive (Infiltrating) Carcinoma Special Histologic Types of Invasive Carcinoma Prognostic and Predictive Factors for Invasive Carcinoma Male Breast Cancer Stromal Tumors Fibroadenoma Clinical Features Phyllodes Tumor Clinical Features Lesions of Interlobular Stroma Malignant Tumors of Interlobular Stroma Other Malignant Tumors of the Breast Suggested Readings The Social, Historical, and Political Significance of Breast Cancer General Sources of Information About Breast Cancer Large Internet Breast Cancer Datasets Breast Cancer Biology Resources for Classification, Staging, Reporting, and Treating Breast Cancer 24 The Endocrine System Chapter Contents Pituitary Gland Clinical Manifestations of Pituitary Disease Pituitary Adenomas and Hyperpituitarism Pathogenesis Clinical Features Lactotroph Adenoma Clinical Features Somatotroph Adenoma Clinical Features Corticotroph Adenoma Clinical Features Other Anterior Pituitary Tumors Hypopituitarism Posterior Pituitary Syndromes Hypothalamic Suprasellar Tumors Thyroid Gland Hyperthyroidism Clinical Features Hypothyroidism Cretinism Myxedema Thyroiditis Hashimoto Thyroiditis Pathogenesis Clinical Features Subacute Lymphocytic (Painless) Thyroiditis Clinical Features Granulomatous Thyroiditis Pathogenesis Clinical Features Graves Disease Pathogenesis Clinical Features Diffuse and Multinodular Goiter Diffuse Nontoxic (Simple) Goiter Clinical Features Multinodular Goiter Pathogenesis Clinical Features Neoplasms of the Thyroid Thyroid Adenomas Pathogenesis Clinical Features Thyroid Carcinomas Pathogenesis Driver Mutations. Environmental Factors. Papillary Carcinoma and Follicular Variants, Including Invasive Encapsulated Follicular Variant of PTC and Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features Clinical Features Follicular Carcinoma Clinical Features Poorly Differentiated and Anaplastic (Undifferentiated) Carcinoma Clinical Features Medullary Carcinoma Clinical Features Congenital Anomalies Parathyroid Glands Hyperparathyroidism Primary Hyperparathyroidism Clinical Features Secondary Hyperparathyroidism Clinical Features 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 Genetic Susceptibility Environmental Factors Mechanisms of β-Cell Destruction Pathogenesis of Type 2 Diabetes Genetic Factors Environmental Factors Metabolic Defects in Type 2 Diabetes Insulin Resistance Obesity 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 Morphology of Chronic Complications of Diabetes Diabetic Macrovascular Disease Diabetic Microangiopathy Diabetic Nephropathy Capillary Basement Membrane Thickening. Diffuse Mesangial Sclerosis. Nodular Glomerulosclerosis. Diabetic Ocular Complications Diabetic Neuropathy Clinical Manifestations of Chronic Diabetes Pancreatic Neuroendocrine Tumors Pathogenesis Hyperinsulinism (Insulinoma) Clinical Features Zollinger-Ellison Syndrome (Gastrinoma) Clinical Features Other Rare Pancreatic Endocrine Neoplasms Adrenal Glands Adrenal Cortex Adrenocortical Hyperfunction (Hyperadrenalism) Hypercortisolism (Cushing Syndrome) Pathogenesis Clinical Features Primary Hyperaldosteronism Clinical Features Adrenogenital Syndromes Clinical Features Adrenocortical Insufficiency Primary Acute Adrenocortical Insufficiency Waterhouse-Friderichsen Syndrome Primary Chronic Adrenocortical Insufficiency (Addison Disease) Pathogenesis Clinical Features Secondary Adrenocortical Insufficiency Adrenocortical Neoplasms Other Adrenal Lesions Adrenal Medulla Pheochromocytoma Clinical Features Multiple Endocrine Neoplasia Syndromes Multiple Endocrine Neoplasia, Type 1 Multiple Endocrine Neoplasia, Type 2 Pineal Gland Pinealoma 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 Clinical Features Benign Epithelial Tumors Seborrheic Keratosis 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 Other Types of Panniculitis 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) Defects in Metabolic Pathways (Enzymes, Ion Channels, and Transporters) Osteopetrosis Pathogenesis Clinical Features Diseases Associated With Defects in Degradation of Macromolecules Mucopolysaccharidoses Metabolic Diseases of Bone Osteopenia and Osteoporosis Pathogenesis Clinical Features Osteomalacia and Rickets Hyperparathyroidism Renal Osteodystrophy Pathogenesis Paget Disease (Osteitis Deformans) Pathogenesis Clinical Features Fractures Healing of Fractures Osteonecrosis (Avascular Necrosis) Clinical Features Osteomyelitis Pyogenic Osteomyelitis Clinical Features Mycobacterial Osteomyelitis Skeletal Syphilis Bone Tumors and Tumor-Like Lesions Bone-Forming Tumors Osteoid Osteoma and Osteoblastoma Osteosarcoma Pathogenesis Clinical Features Cartilage-Forming Tumors Osteochondroma Pathogenesis Clinical Features Chondroma Pathogenesis Clinical Features Chondrosarcoma Pathogenesis Clinical Features Tumors of Unknown Origin Ewing Sarcoma Pathogenesis Clinical Features Giant Cell Tumor Pathogenesis Clinical Features Aneurysmal Bone Cyst Pathogenesis Clinical Features Lesions Simulating Primary Neoplasms Fibrous Cortical Defect and Nonossifying Fibroma Clinical Features Fibrous Dysplasia Pathogenesis Clinical Features Metastatic Tumors Joints Arthritis Osteoarthritis Pathogenesis Clinical Features Rheumatoid Arthritis Pathogenesis Clinical Features Juvenile Idiopathic Arthritis Seronegative Spondyloarthropathies Ankylosing Spondylitis Reactive Arthritis Infectious Arthritis Suppurative Arthritis Mycobacterial Arthritis Viral Arthritis Lyme Arthritis Crystal-Induced Arthritis Gout Pathogenesis Clinical Features Calcium Pyrophosphate Crystal Deposition Disease (Pseudogout) Pathogenesis Clinical Features Joint Tumors and Tumor-Like Conditions Ganglion and Synovial Cysts Tenosynovial Giant Cell Tumor Pathogenesis Clinical Features Soft Tissue Tumors Pathogenesis Tumors of Adipose Tissue Lipoma Liposarcoma Pathogenesis Clinical Features Fibrous Tumors Nodular Fasciitis Fibromatoses Superficial Fibromatosis Deep Fibromatosis (Desmoid Tumors) Clinical Features Skeletal Muscle Tumors Rhabdomyosarcoma Clinical Features Smooth Muscle Tumors Leiomyoma Leiomyosarcoma Clinical Features Tumors of Uncertain Origin Synovial Sarcoma Clinical Features Undifferentiated Pleomorphic Sarcoma Clinical Features Acknowledgment Suggested Readings Basic Structure and Biology of Bone Skeletal Dysplasias Osteoporosis Hyperparathyroidism Paget Disease Osteonecrosis Osteosarcoma Chondrogenic Tumors Ewing Sarcoma Giant Cell Tumor of Bone Aneurysmal Bone Cyst Fibrous Dysplasia Osteoarthritis Rheumatoid Arthritis and Related Conditions Lyme Disease 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 Disease Hereditary Sensory Neuropathies With or Without Autonomic Neuropathy Familial Amyloid Polyneuropathies 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 Immune-Mediated Necrotizing Myopathy (IMNM) Polymyositis Pathogenesis Inclusion Body Myositis Toxic Myopathies Inherited Diseases of Skeletal Muscle Muscular Dystrophies X-Linked Muscular Dystrophy With Dystrophin Mutation Including Duchenne and Becker Muscular Dystrophy Pathogenesis Clinical Features Limb-Girdle Muscular Dystrophy Myotonic Dystrophy Pathogenesis Emery-Dreifuss Muscular Dystrophy (EMD) Fascioscapulohumeral Dystrophy Pathogenesis Diseases of Lipid or Glycogen Metabolism Mitochondrial Myopathies Clinical Features Spinal Muscular Atrophy and Differential Diagnosis of a Hypotonic Infant Ion Channel Myopathies (Channelopathies) Peripheral Nerve Sheath Tumors Schwannomas Clinical Features Neurofibromas Pathogenesis Malignant Peripheral Nerve Sheath Tumors 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, Raised Intracranial Pressure, and Herniation Cerebral Edema Hydrocephalus Raised Intracranial Pressure and Herniation Malformations and Developmental Disorders Neural Tube Defects Clinical Features 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 and Ischemia Focal Cerebral Ischemia Lacunar Infarcts Clinical Features Global Cerebral Hypoxia/Ischemia Intracranial Hemorrhage Intraparenchymal Hemorrhage Clinical Features Subarachnoid Hemorrhage and Ruptured Saccular Aneurysm Pathogenesis Clinical Features Vascular Malformations Clinical Features Vascular Dementia Infections Acute Meningitis Acute Pyogenic (Bacterial) Meningitis Acute Aseptic (Viral) Meningitis Acute Focal Suppurative Infections Brain Abscess Clinical Features 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 Cytomegalovirus Poliomyelitis Clinical Features Rabies Clinical Features Human Immunodeficiency Virus Clinical Features Progressive Multifocal Leukoencephalopathy Fungal Meningoencephalitis Other Infectious Diseases of the Nervous System Demyelinating Diseases Multiple Sclerosis (MS) Pathogenesis Clinical Features Neuromyelitis Optica Acute Disseminated Encephalomyelitis and Acute Necrotizing Hemorrhagic Encephalomyelitis Central Pontine Myelinolysis Neurodegenerative Diseases Prion Diseases Pathogenesis Creutzfeldt-Jakob Disease (CJD) Variant Creutzfeldt-Jakob Disease Alzheimer Disease (AD) Pathogenesis Clinical Features Frontotemporal Lobar Degenerations (FTLDs) FTLD-tau Pathogenesis FTLD-TDP Pathogenesis Parkinson Disease (PD) Pathogenesis Dementia With Lewy Bodies Atypical Parkinsonian Syndromes Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD) Multiple System Atrophy (MSA) Pathogenesis Huntington Disease (HD) Pathogenesis Clinical Features Spinocerebellar Degenerations Spinocerebellar Ataxias (SCA) Pathogenesis Friedreich Ataxia Ataxia-Telangiectasia Clinical Features Amyotrophic Lateral Sclerosis (ALS) Pathogenesis Clinical Features Other Motor Neuron Diseases Spinal and Bulbar Muscular Atrophy (Kennedy Disease) Spinal Muscular Atrophy (SMA) 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 Ethanol Radiation Tumors Gliomas Astrocytoma Infiltrating Astrocytomas (WHO Grades II to IV) Pathogenesis Clinical Features Oligodendroglioma Pathogenesis Clinical Features Pilocytic Astrocytoma Ependymoma Pathogenesis Clinical Features Choroid Plexus Tumors Neuronal and Glioneuronal Tumors Embryonal Neoplasms Medulloblastoma Pathogenesis Clinical Features Primary CNS Lymphoma Meningiomas Pathogenesis Clinical Features Metastatic Tumors Paraneoplastic Syndromes Familial Tumor Syndromes Neurofibromatoses and Schwannomatosis Tuberous Sclerosis Complex Von Hippel-Lindau Disease Acknowledgment Suggested Readings General Response to Injury Malformations and Developmental Diseases Trauma Cerebrovascular Disease Infections Demyelinating Diseases Prion 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 Anterior Segment Functional Anatomy Cataract Anterior Segment and Glaucoma Endophthalmitis and Panophthalmitis Uvea Uveitis Neoplasms Uveal Nevi and Melanomas Epidemiology and Pathogenesis Clinical Features Retina and Vitreous Functional Anatomy Retinal Detachment Retinal Vascular Disease Hypertension Diabetes Mellitus Retinopathy of Prematurity (Retrolental Fibroplasia) Sickle Retinopathy, Retinal Vasculitis, and 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 Orbit Eyelid and Conjunctiva Cornea Glaucoma Uvea Retina Optic Nerve