Robbins and Cotran Pathologic Basis of Disease Professional

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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