Robbins Basic Pathology E-Book

Robbins Basic Pathology delivers the pathology knowledge you need, the way you need it, from the name you can trust! This medical textbook’s unbeatable author team helps you efficiently master the core concepts you need to know for your courses and USMLE exams. Get a rich understanding of all essential pathology concepts with expert guidance from an all-star editorial team. Grasp the connections between basic science and clinical medicine with clinicopathologic correlations throughout. Access information anywhere - from the coffee shop to the classroom - with full-text online access at studentconsult.com. Take your learning farther with targeted therapy boxes, clinical cases, virtual microscope slides, and self-assessment questions online! Learn core concepts quickly and efficiently with a highly templated design that highlights pathogenesis and morphology. New interior design with a more modern look Artwork revised and updated for a more modern look and more three-dimensional feel Targeted Therapy boxes included in online text – provides clinical information on appropriate therapy related to the disease under discussion All photomicrographs and gross photos reviewed and improved to ensure excellent quality A trusted title in the world of pathology, Robbins offers easy-to-access information that’s concise and accurate Robbins Basic Pathology, Ninth Edition (2013) 924pp. 978-1-4377-1781-5 Front cover 1 IFC 2 Robbins Basic Pathology 3 Copyright page 6 Dedication 7 Contributors 9 Preface 11 Forty Years of Basic Pathology 11 Acknowledgments 12 Table of Contents 13 Chapter 1 Cell Injury, Cell Death, and Adaptations 15 Chapter Contents 15 Introduction to Pathology 15 Overview of Cellular Responses to Stress and Noxious Stimuli 15 Cellular Adaptations to Stress 17 Hypertrophy 17 Hyperplasia 18 Atrophy 18 Metaplasia 19 Overview of Cell Injury and Cell Death 20 Causes of Cell Injury 20 Oxygen Deprivation 21 Chemical Agents 21 Infectious Agents 21 Immunologic Reactions 21 Genetic Factors 21 Nutritional Imbalances 21 Physical Agents 21 Aging 21 The Morphology of Cell and Tissue Injury 22 Reversible Injury 22 Necrosis 23 Patterns of Tissue Necrosis 23 Mechanisms of Cell Injury 25 Depletion of ATP 26 Mitochondrial Damage and Dysfunction 27 Influx of Calcium 27 Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) 28 Defects in Membrane Permeability 30 Damage to DNA and Proteins 30 Clinicopathologic Correlations: Examples of Cell Injury and Necrosis 30 Ischemic and Hypoxic Injury 31 Ischemia-Reperfusion Injury 31 Chemical (Toxic) Injury 31 Apoptosis 32 Causes of Apoptosis 32 Apoptosis in Physiologic Situations 32 Apoptosis in Pathologic Conditions 32 Mechanisms of Apoptosis 33 The Mitochondrial (Intrinsic) Pathway of Apoptosis 33 The Death Receptor (Extrinsic) Pathway of Apoptosis 33 Activation and Function of Caspases 33 Clearance of Apoptotic Cells 34 Examples of Apoptosis 34 Growth Factor Deprivation 34 DNA Damage 34 Accumulation of Misfolded Proteins: ER Stress 35 Apoptosis of Self-Reactive Lymphocytes 35 Cytotoxic T Lymphocyte鈥揗ediated Apoptosis 36 Autophagy 36 Intracellular Accumulations 37 Fatty Change (Steatosis) 37 Cholesterol and Cholesteryl Esters 37 Proteins 37 Glycogen 38 Pigments 38 Pathologic Calcification 39 Dystrophic Calcification 39 Metastatic Calcification 40 Cellular Aging 40 Bibliography 42 Chapter 2 Inflammation and Repair 43 Chapter Contents 43 Overview of Inflammation and Tissue Repair 43 Acute Inflammation 45 Stimuli for Acute Inflammation 45 Recognition of Microbes, Necrotic Cells, and Foreign Substances 46 Vascular Changes 47 Changes in Vascular Caliber and Flow 47 Increased Vascular Permeability 47 Responses of Lymphatic Vessels 48 Cellular Events: Leukocyte Recruitment and Activation 48 Leukocyte Recruitment 49 Margination and Rolling. 49 Adhesion. 49 Transmigration. 50 Chemotaxis. 50 Leukocyte Activation 51 Phagocytosis. 51 Killing and Degradation of Phagocytosed Microbes. 52 Secretion of Microbicidal Substances. 53 Neutrophil Extracellular Traps (NETs). 53 Leukocyte-Induced Tissue Injury 53 Defects in Leukocyte Function 54 Outcomes of Acute Inflammation 55 Morphologic Patterns of Acute Inflammation 57 Chemical Mediators and Regulators of Inflammation 58 Cell-Derived Mediators 60 Vasoactive Amines 60 Arachidonic Acid Metabolites: Prostaglandins, Leukotrienes, and Lipoxins 60 Anti-inflammatory Drugs That Block Prostaglandin Production. 60 Platelet-Activating Factor 61 Cytokines 62 Tumor Necrosis Factor and Interleukin-1. 62 Chemokines. 62 Reactive Oxygen Species 63 Nitric Oxide 63 Lysosomal Enzymes of Leukocytes 63 Neuropeptides 63 Plasma Protein鈥揇erived Mediators 64 Complement 64 Coagulation and Kinin Systems 65 Anti-inflammatory Mechanisms 66 Chronic Inflammation 67 Chronic Inflammatory Cells and Mediators 67 Macrophages 68 Lymphocytes 69 Other Cells 69 Granulomatous Inflammation 70 Systemic Effects of Inflammation 71 Overview of Tissue Repair 72 Cell and Tissue Regeneration 73 The Control of Cell Proliferation 73 Proliferative Capacities of Tissues 73 Stem Cells 74 Growth Factors 75 Signaling Mechanisms of Growth Factor Receptors 75 Role of the Extracellular Matrix in Tissue Repair 77 Components of the Extracellular Matrix 77 Collagen 77 Elastin 78 Proteoglycans and Hyaluronan 78 Adhesive Glycoproteins and Adhesion Receptors 78 Functions of the Extracellular Matrix 78 Role of Regeneration in Tissue Repair 79 Scar Formation 79 Steps in Scar Formation 79 Angiogenesis 80 Growth Factors Involved in Angiogenesis 81 Activation of Fibroblasts and Deposition of Connective Tissue 82 Growth Factors Involved in ECM Deposition and Scar Formation 82 Remodeling of Connective Tissue 82 Factors That Influence Tissue Repair 83 Selected Clinical Examples of Tissue Repair and Fibrosis 84 Healing of Skin Wounds 84 Healing by First Intention 84 Healing by Second Intention 85 Wound Strength 86 Fibrosis in Parenchymal Organs 86 Bibliography 86 Chapter 3 Hemodynamic Disorders, Thromboembolism, and Shock 89 Chapter Contents 89 Hyperemia and Congestion 89 Edema 90 Increased Hydrostatic Pressure 91 Reduced Plasma Osmotic Pressure 91 Lymphatic Obstruction 91 Sodium and Water Retention 91 Clinical Correlation 92 Hemorrhage 92 Hemostasis and Thrombosis 93 Normal Hemostasis 93 Endothelium 93 Antithrombotic Properties of Normal Endothelium 93 Inhibitory Effects on Platelets. 93 Inhibitory Effects on Coagulation Factors. 94 Fibrinolysis. 94 Prothrombotic Properties of Injured or Activated Endothelium 94 Activation of Platelets. 94 Activation of Clotting Factors. 94 Antifibrinolytic Effects. 94 Platelets 95 Platelet Adhesion 96 Platelet Activation 96 Platelet Aggregation 96 Platelet-Endothelial Interactions 96 Coagulation Cascade 97 Thrombosis 100 Endothelial Injury 100 Abnormal Blood Flow 100 Hypercoagulability 101 Fate of the Thrombus 103 Clinical Correlation 103 Venous Thrombosis (Phlebothrombosis). 103 Disseminated Intravascular Coagulation 104 Embolism 104 Pulmonary Thromboembolism 104 Systemic Thromboembolism 105 Fat Embolism 105 Amniotic Fluid Embolism 105 Air Embolism 105 Infarction 106 Factors That Influence Infarct Development. 107 Shock 108 Pathogenesis of Septic Shock 108 Stages of Shock 110 Clinical Course 111 Bibliography 111 Chapter 4 Diseases of the Immune System 113 Chapter Contents 113 Innate and Adaptive Immunity 113 Cells and Tissues of the Immune System 114 Lymphocytes 114 T Lymphocytes 115 Major Histocompatibility Complex Molecules: The Peptide Display System of Adaptive Immunity 116 B Lymphocytes 117 Natural Killer Cells 118 Antigen-Presenting Cells 118 Dendritic Cells 118 Other Antigen-Presenting Cells 118 Effector Cells 118 Lymphoid Tissues 118 Overview of Normal Immune Responses 119 The Early Innate Immune Response to Microbes 119 The Capture and Display of Microbial Antigens 119 Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Cell-Associated Microbes 119 Cytokines: Messenger Molecules of the Immune System 120 Effector Functions of T Lymphocytes 121 Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes 122 Decline of Immune Responses and Immunologic Memory 123 Hypersensitivity Reactions: Mechanisms of Immune-Mediated Injury 123 Causes of Hypersensitivity Reactions 123 Types of Hypersensitivity Reactions 124 Immediate (Type I) Hypersensitivity 125 Sequence of Events in Immediate Hypersensitivity Reactions 125 Clinical and Pathologic Manifestations 127 Antibody-Mediated Diseases (Type II Hypersensitivity) 128 Mechanisms of Antibody-Mediated Diseases 128 Immune Complex Diseases (Type III Hypersensitivity) 129 Systemic Immune Complex Disease 130 Local Immune Complex Disease 131 T Cell鈥揗ediated (Type IV) Hypersensitivity 131 Inflammatory Reactions Elicited by CD4+ T Cells 132 Delayed-Type Hypersensitivity 133 T Cell鈥揗ediated Cytotoxicity 133 Autoimmune Diseases 134 Immunologic Tolerance 135 Mechanisms of Autoimmunity 136 Genetic Factors in Autoimmunity 137 Role of Infections and Tissue Injury 137 Systemic Lupus Erythematosus 139 Spectrum of Autoantibodies in SLE 141 Mechanisms of Tissue Injury 141 Clinical Manifestations 145 Rheumatoid Arthritis 145 Sj枚gren Syndrome 145 Clinical Course 146 Systemic Sclerosis (Scleroderma) 146 Clinical Course 148 Inflammatory Myopathies 149 Mixed Connective Tissue Disease 149 Polyarteritis Nodosa and Other Vasculitides 149 IgG4-Related Disease 149 Rejection of Transplants 149 Immune Recognition of Allografts 149 Effector Mechanisms of Graft Rejection 151 T Cell鈥揗ediated Rejection 151 Antibody-Mediated Rejection 151 Methods of Improving Graft Survival 152 Transplantation of Hematopoietic Stem Cells 153 Graft-Versus-Host Disease (GVHD). 153 Immune Deficiencies. 153 Immune Deficiency Diseases 153 Primary (Congenital) Immune Deficiencies 153 X-Linked Agammaglobulinemia: Bruton Disease 154 Common Variable Immunodeficiency 155 Isolated IgA Deficiency 155 Hyper-IgM Syndrome 155 Thymic Hypoplasia: DiGeorge Syndrome 155 Severe Combined Immunodeficiency 156 Defects in Lymphocyte Activation 156 Immune Deficiency with Thrombocytopenia and Eczema: Wiskott-Aldrich Syndrome 156 Genetic Deficiencies of Components of Innate Immunity 156 Complement Proteins 156 Phagocytes 157 Other Genetic Disorders of Innate Immunity 157 Secondary (Acquired) Immune Deficiencies 157 Acquired Immunodeficiency Syndrome (AIDS) 157 Epidemiology 157 Sexual Transmission. 158 Parenteral Transmission. 158 Mother-to-Infant Transmission. 158 Etiology and Pathogenesis 158 Structure of HIV 158 Life Cycle of HIV 159 Progression of HIV Infection 160 Mechanisms of T Cell Depletion in HIV Infection 161 Monocytes/Macrophages in HIV Infection 162 DCs in HIV Infection 163 B Cells and Other Lymphocytes in HIV Infection 163 Pathogenesis of CNS Involvement 163 Natural History and Clinical Course 164 Clinical Features 165 Opportunistic Infections. 165 Neoplasms. 165 CNS Involvement. 166 Amyloidosis 167 Classification of Amyloidosis 168 Primary Amyloidosis: Immunocyte Dyscrasias with Amyloidosis 169 Reactive Systemic Amyloidosis 169 Familial (Hereditary) Amyloidosis 169 Localized Amyloidosis 170 Endocrine Amyloid 170 Amyloid of Aging 170 Clinical Course 172 Bibliography 172 Chapter 5 Neoplasia 175 Chapter Contents 175 Nomenclature 176 Benign Tumors 176 Malignant Tumors 176 Characteristics of Benign and Malignant Neoplasms 178 Differentiation and Anaplasia 178 Rate of Growth 180 Cancer Stem Cells and Lineages 180 Local Invasion 181 Metastasis 182 Epidemiology 183 Cancer Incidence 184 Geographic and Environmental Variables 184 Age 185 Heredity 185 Autosomal Dominant Cancer Syndromes 185 Autosomal Recessive Syndromes of Defective DNA Repair 186 Familial Cancers of Uncertain Inheritance 186 Acquired Preneoplastic Lesions 186 Carcinogenesis: The Molecular Basis of Cancer 187 Genetic Lesions in Cancer 187 Karyotypic Changes in Tumors 187 Balanced Translocations 188 Deletions 188 Gene Amplifications 189 Aneuploidy 189 MicroRNAs and Cancer 189 Epigenetic Modifications and Cancer 189 Carcinogenesis: A Multistep Process 191 Hallmarks of Cancer 192 Self-Sufficiency in Growth Signals 192 Growth Factors 192 Growth Factor Receptors and Non-Receptor Tyrosine Kinases 192 Downstream Signal-Transducing Proteins 193 RAS Protein. 193 ABL. 194 Nuclear Transcription Factors 194 Cyclins and Cyclin-Dependent Kinases 194 The Normal Cell Cycle 194 Alterations in Cell Cycle Control Proteins in Cancer Cells 196 Insensitivity to Growth Inhibitory Signals 196 RB Gene: Governor of the Cell Cycle 196 TP53 Gene: Guardian of the Genome 199 Transforming Growth Factor-尾 Pathway 201 Contact Inhibition, NF2, and APC 201 Evasion of Cell Death 203 Autophagy 204 Limitless Replicative Potential 204 Development of Sustained Angiogenesis 205 Ability to Invade and Metastasize 206 Invasion of Extracellular Matrix (ECM) 206 Vascular Dissemination and Homing of Tumor Cells 208 Molecular Genetics of Metastasis 209 Reprogramming Energy Metabolism 209 Evasion of the Immune System 210 Genomic Instability as an Enabler of Malignancy 210 Hereditary Nonpolyposis Colon Cancer Syndrome 210 Xeroderma Pigmentosum 211 Diseases with Defects in DNA Repair by Homologous Recombination 211 Cancers Resulting From Mutations Induced by Regulated Genomic Instability: Lymphoid Neoplasms 211 Tumor-Promoting Inflammation as Enabler of Malignancy 211 Multistep Carcinogenesis and Cancer Progression 212 Etiology of Cancer: Carcinogenic Agents 212 Chemical Carcinogens 213 Direct-Acting Agents 213 Indirect-Acting Agents 213 Mechanisms of Action of Chemical Carcinogens 214 Radiation Carcinogenesis 214 Viral and Microbial Oncogenesis 215 Oncogenic RNA Viruses 215 Oncogenic DNA Viruses 216 Human Papillomavirus 216 Epstein-Barr Virus 216 Hepatitis B and Hepatitis C Viruses 217 Helicobacter pylori 218 Host Defense Against Tumors: Tumor Immunity 218 Tumor Antigens 218 Products of Mutated Oncogenes and Tumor Suppressor Genes 218 Products of Other Mutated Genes 219 Overexpressed or Aberrantly Expressed Cellular Proteins 219 Tumor Antigens Produced by Oncogenic Viruses 220 Oncofetal Antigens 220 Altered Cell Surface Glycolipids and Glycoproteins 220 Cell Type鈥揝pecific Differentiation Antigens 220 Antitumor Effector Mechanisms 220 Cytotoxic T Lymphocytes 220 Natural Killer Cells 220 Macrophages 220 Humoral Mechanisms 220 Immune Surveillance and Immune Evasion by Tumors 221 Clinical Aspects of Neoplasia 221 Effects of Tumor on Host 221 Cancer Cachexia 222 Paraneoplastic Syndromes 222 Grading and Staging of Cancer 222 Laboratory Diagnosis of Cancer 224 Morphologic Methods 224 Tumor Markers 225 Molecular Diagnosis 225 Molecular Profiling of Tumors 225 Expression Profiling 225 Whole Genome Sequencing 226 Bibliography 228 Chapter 6 Genetic and Pediatric Diseases 229 Chapter Contents 229 Genetic Diseases 229 Nature of Genetic Abnormalities Contributing to Human Disease 230 Mutations in Protein-Coding Genes 230 Alterations in Protein-Coding Genes Other Than Mutations 230 Sequence and Copy Number Variations (Polymorphisms) 230 Epigenetic Changes 231 Alterations in Non-Coding RNAs 231 Mendelian Disorders: Diseases Caused by Single-Gene Defects 232 Transmission Patterns of Single-Gene Disorders 233 Disorders of Autosomal Dominant Inheritance 233 Disorders of Autosomal Recessive Inheritance 234 X-Linked Disorders 234 Diseases Caused by Mutations in Genes Encoding Structural Proteins 234 Marfan Syndrome 234 Ehlers-Danlos Syndromes 235 Diseases Caused by Mutations in Genes Encoding Receptor Proteins or Channels 236 Familial Hypercholesterolemia 236 Normal Cholesterol Metabolism. -1 Cystic Fibrosis 237 Clinical Course 240 Diseases Caused by Mutations in Genes Encoding Enzyme Proteins 241 Phenylketonuria 241 Galactosemia 242 Lysosomal Storage Diseases 242 Tay-Sachs Disease (GM2 Gangliosidosis: Deficiency in Hexosaminidase 尾 Subunit) 243 Niemann-Pick Disease Types A and B 244 Niemann-Pick Disease Type C 245 Gaucher Disease 245 Mucopolysaccharidoses 246 Glycogen Storage Diseases (Glycogenoses) 246 Diseases Caused by Mutations in Genes Encoding Proteins That Regulate Cell Growth 247 Complex Multigenic Disorders 248 Cytogenetic Disorders 248 Numeric Abnormalities 249 Structural Abnormalities 249 General Features of Chromosomal Disorders 250 Cytogenetic Disorders Involving Autosomes 251 Trisomy 21 (Down Syndrome) 251 22q11.2 Deletion Syndrome 251 Cytogenetic Disorders Involving Sex Chromosomes 253 Klinefelter Syndrome 253 Turner Syndrome 254 Single-Gene Disorders with Atypical Patterns of Inheritance 255 Triplet Repeat Mutations: Fragile X Syndrome 255 Diseases Caused by Mutations in Mitochondrial Genes 257 Diseases Caused by Alterations of Imprinted Regions: Prader-Willi and Angelman Syndromes 257 Pediatric Diseases 259 Congenital Anomalies 259 Etiology 261 Perinatal Infections 263 Prematurity and Fetal Growth Restriction 263 Respiratory Distress Syndrome of the Newborn 264 Clinical Features 265 Necrotizing Enterocolitis 266 Sudden Infant Death Syndrome 266 Fetal Hydrops 268 Immune Hydrops 268 Nonimmune Hydrops 269 Clinical Course 270 Tumors and Tumor-Like Lesions of Infancy and Childhood 271 Benign Tumors 271 Malignant Tumors 272 Neuroblastoma 272 Clinical Course and Prognosis 273 Retinoblastoma 274 Clinical Features 275 Wilms Tumor 275 Clinical Course 276 Molecular Diagnosis of Mendelian and Complex Disorders 277 Molecular Diagnosis of Copy Number Abnormalities 277 Fluorescence in Situ Hybridization (FISH) 278 Array-Based Genomic Hybridization 278 Direct Detection of DNA Mutations by Polymerase Chain Reaction (PCR) Analysis 278 Linkage Analysis and Genome-Wide Association Studies 280 Indications for Genetic Analysis 281 Bibliography 282 Chapter 7 Environmental and Nutritional Diseases 283 Chapter Contents 283 Health Effects of Climate Change 283 Toxicity of Chemical and Physical Agents 285 Environmental Pollution 286 Air Pollution 286 Outdoor Air Pollution 286 Indoor Air Pollution 287 Metals as Environmental Pollutants 287 Lead 288 Mercury 289 Arsenic 289 Cadmium 290 Industrial and Agricultural Exposures 290 Effects of Tobacco 291 Effects of Alcohol 294 Injury by Therapeutic Drugs and Drugs of Abuse 296 Injury by Therapeutic Drugs: Adverse Drug Reactions 296 Exogenous Estrogens and Oral Contraceptives 296 Exogenous Estrogens. 296 Oral Contraceptives. 297 Acetaminophen 298 Aspirin (Acetylsalicylic Acid) 298 Injury by Nontherapeutic Toxic Agents (Drug Abuse) 298 Cocaine 298 Heroin 299 Marijuana 300 Other Illicit Drugs 301 Injury by Physical Agents 301 Mechanical Trauma 301 Thermal Injury 302 Thermal Burns 302 Hyperthermia 303 Hypothermia 303 Electrical Injury 303 Injury Produced by Ionizing Radiation 303 DNA Damage and Carcinogenesis 304 Fibrosis 304 Effects on Organ Systems 306 Total-Body Irradiation 307 Nutritional Diseases 307 Malnutrition 307 Protein-Energy Malnutrition 308 Marasmus 308 Kwashiorkor 308 Secondary Protein-Energy Malnutrition -1 Anorexia Nervosa and Bulimia 309 Vitamin Deficiencies 310 Vitamin A 310 Function. 310 Deficiency States. 311 Vitamin A Toxicity. 312 Vitamin D 312 Metabolism. 312 Functions. 313 Deficiency States 313 Toxicity. 315 Vitamin C (Ascorbic Acid) 315 Function. 315 Deficiency States. 315 Toxicity. 315 Obesity 316 Leptin 318 Adipose Tissue 318 Gut Hormones 319 Clinical Consequences of Obesity 319 Diet and Systemic Diseases 320 Diet and Cancer 320 Bibliography 320 Chapter 8 General Pathology of Infectious Diseases 323 Chapter Contents 323 General Principles of Microbial Pathogenesis 323 Categories of Infectious Agents 323 Prions 323 Viruses 323 Bacteria 325 Normal Microbiome. 327 Fungi 327 Protozoa 327 Helminths 327 Ectoparasites 328 Special Techniques for Identifying Infectious Agents 328 New and Emerging Infectious Diseases 328 Agents of Bioterrorism 329 Transmission and Dissemination of Microbes 329 Routes of Entry of Microbes 329 Skin 330 Gastrointestinal Tract 330 Respiratory Tract 330 Urogenital Tract 331 Spread and Dissemination of Microbes Within the Body 331 Release from the Body and Transmission of Microbes 332 How Microorganisms Cause Disease 333 Mechanisms of Viral Injury 333 Mechanisms of Bacterial Injury 334 Bacterial Virulence 334 Bacterial Adherence to Host Cells 334 Virulence of Intracellular Bacteria 334 Bacterial Toxins 335 Injurious Effects of Host Immune Responses 335 Immune Evasion by Microbes 336 Spectrum of Inflammatory Responses to Infection 337 Suppurative (Purulent) Inflammation 337 Mononuclear and Granulomatous Inflammation 338 Cytopathic-Cytoproliferative Reaction 338 Tissue Necrosis 338 Chronic Inflammation and Scarring 339 Infections in People with Immunodeficiencies 339 Bibliography 340 Chapter 9 Blood Vessels 341 Chapter Contents 341 Structure and Function of Blood Vessels 341 Vascular Organization 342 Endothelial Cells 343 Vascular Smooth Muscle Cells 344 Congenital Anomalies 344 Blood Pressure Regulation 344 Hypertensive Vascular Disease 346 Epidemiology of Hypertension 346 Vascular Wall Response to Injury 348 Intimal Thickening: A Stereotypical Response to Vascular Injury 348 Arteriosclerosis 349 Atherosclerosis 349 Epidemiology of Atherosclerosis 349 Constitutional Risk Factors 350 Modifiable Major Risk Factors 350 Additional Risk Factors 351 Clinical Consequences of Atherosclerotic Disease 356 Atherosclerotic Stenosis 356 Acute Plaque Change 356 Aneurysms and Dissections 358 Abdominal Aortic Aneurysm 359 Clinical Consequences 360 Thoracic Aortic Aneurysm 360 Aortic Dissection 360 Clinical Consequences 361 Vasculitis 362 Noninfectious Vasculitis 362 Immune Complex鈥揂ssociated Vasculitis. 362 Anti-Neutrophil Cytoplasmic Antibodies. 363 Anti-Endothelial Cell Antibodies. 364 Giant Cell (Temporal) Arteritis 364 Clinical Features of Giant Cell Arteritis 365 Takayasu Arteritis 365 Clinical Features of Takayasu Aortitis 365 Polyarteritis Nodosa 366 Clinical Features of PAN 366 Kawasaki Disease 366 Clinical Features of Kawasaki Disease 366 Microscopic Polyangiitis 366 Clinical Features of Microscopic Polyangiitis 367 Wegener Granulomatosis 367 Clinical Features of Wegener Granulomatosis 368 Churg-Strauss Syndrome 368 Thromboangiitis Obliterans (Buerger Disease) 368 Clinical Features of Buerger Disease 368 Vasculitis Associated with Other Noninfectious Disorders 369 Infectious Vasculitis 369 Disorders of Blood Vessel Hyperreactivity 369 Raynaud Phenomenon 369 Myocardial Vessel Vasospasm 369 Veins and Lymphatics 370 Varicose Veins of the Extremities 370 Clinical Features of Varicose Veins 370 Varicosities of Other Sites 370 Thrombophlebitis and Phlebothrombosis 370 Superior and Inferior Vena Cava Syndromes 370 Lymphangitis and Lymphedema 370 Tumors 371 Benign Tumors and Tumor-Like Conditions 371 Vascular Ectasias 371 Hemangiomas 372 Lymphangiomas 373 Glomus Tumors (Glomangiomas) 373 Bacillary Angiomatosis 373 Intermediate-Grade (Borderline) Tumors 374 Kaposi Sarcoma 374 Clinical Features of KS 374 Hemangioendotheliomas 375 Malignant Tumors 375 Angiosarcomas 375 Hemangiopericytomas 376 Pathology of Vascular Intervention 376 Endovascular Stenting 376 Vascular Replacement 377 Bibliography 377 Chapter 10 Heart 379 Chapter Contents 379 Overview of Heart Disease 379 Heart Failure 379 Left-Sided Heart Failure 381 Clinical Features 381 Right-Sided Heart Failure 382 Clinical Features 382 Congenital Heart Disease 382 Clinical Features 384 Left-to-Right Shunts 384 Atrial Septal Defects and Patent Foramen Ovale 384 Clinical Features 385 Ventricular Septal Defects 385 Clinical Features 385 Patent Ductus Arteriosus 385 Clinical Features 386 Right-to-Left Shunts 386 Tetralogy of Fallot 386 Clinical Features 386 Transposition of the Great Arteries 387 Clinical Features 387 Obstructive Lesions 387 Aortic Coarctation 387 Clinical Features 387 Ischemic Heart Disease 388 Epidemiology 389 Angina Pectoris 390 Myocardial Infarction 391 Infarct Modification by Reperfusion 395 Clinical Features 396 Consequences and Complications of Myocardial Infarction 397 Chronic Ischemic Heart Disease 398 Clinical Features 399 Cardiac Stem Cells 399 Arrhythmias 399 Sudden Cardiac Death 400 Hypertensive Heart Disease 400 Systemic (Left-Sided) Hypertensive Heart Disease 401 Clinical Features 401 Pulmonary Hypertensive Heart Disease鈥擟or Pulmonale 402 Valvular Heart Disease 402 Degenerative Valve Disease 403 Calcific Aortic Stenosis 403 Clinical Features 404 Myxomatous Mitral Valve 404 Clinical Features 404 Rheumatic Valvular Disease 405 Clinical Features 405 Infective Endocarditis 406 Clinical Features 407 Noninfected Vegetations 408 Nonbacterial Thrombotic Endocarditis 408 Libman-Sacks Endocarditis 409 Carcinoid Heart Disease 409 Prosthetic Cardiac Valves 409 Cardiomyopathies 410 Dilated Cardiomyopathy 411 Clinical Features 412 Arrhythmogenic Right Ventricular Cardiomyopathy 413 Hypertrophic Cardiomyopathy 414 Clinical Features 414 Restrictive Cardiomyopathy 415 Myocarditis 415 Clinical Features 417 Pericardial Disease 417 Pericarditis 417 Clinical Features 417 Pericardial Effusions 418 Cardiac Tumors 418 Metastatic Neoplasms 418 Primary Neoplasms 418 Clinical Features 419 Other Cardiac Tumors 419 Cardiac Transplantation 419 Bibliography 420 Chapter 11 Hematopoietic and Lymphoid Systems 421 Chapter Contents 421 Red Cell Disorders 422 Anemia Of Blood Loss: Hemorrhage 423 Hemolytic Anemias 423 Hereditary Spherocytosis 424 Clinical Features 425 Sickle Cell Anemia 425 Incidence 425 Clinical Course 427 Thalassemia 427 Clinical Course 430 Glucose-6-Phosphate Dehydrogenase Deficiency 430 Clinical Features 430 Paroxysmal Nocturnal Hemoglobinuria 431 Immunohemolytic Anemias 431 Warm Antibody Immunohemolytic Anemias 431 Cold Antibody Immunohemolytic Anemias 432 Hemolytic Anemias Resulting from Mechanical Trauma to Red Cells 432 Malaria 432 Clinical Features 433 Anemias of Diminished Erythropoiesis 433 Iron Deficiency Anemia 434 Clinical Features 435 Anemia of Chronic Disease 435 Clinical Features 435 Megaloblastic Anemias 436 Folate (Folic Acid) Deficiency Anemia 436 Clinical Features 437 Vitamin B12 (Cobalamin) Deficiency Anemia (Pernicious Anemia) 437 Clinical Features 437 Aplastic Anemia 438 Clinical Course 438 Myelophthisic Anemia 438 Polycythemia 439 White Cell Disorders 439 Non-Neoplastic Disorders of White Cells 439 Leukopenia 439 Neutropenia/Agranulocytosis 439 Clinical Features 440 Reactive Leukocytosis 440 Infectious Mononucleosis 440 Clinical Features 441 Reactive Lymphadenitis 441 Acute Nonspecific Lymphadenitis 442 Chronic Nonspecific Lymphadenitis 442 Cat-Scratch Disease 442 Neoplastic Proliferations of White Cells 442 Lymphoid Neoplasms 443 Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma 444 Clinical Features of Acute Leukemias 445 Laboratory Findings in Acute Leukemias 445 Genetic Features. 447 Immunophenotypic Features. 447 Prognosis 447 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 447 Immunophenotypic and Genetic Features. 448 Clinical Features 448 Follicular Lymphoma 448 Immunophenotypic Features. 449 Clinical Features 449 Mantle Cell Lymphoma 449 Immunophenotypic and Genetic Features. 449 Clinical Features 449 Diffuse Large B Cell Lymphoma 450 Immunophenotypic Features. 450 Subtypes of Diffuse Large B Cell Lymphoma. 450 Clinical Features 450 Burkitt Lymphoma 450 Immunophenotypic Features 451 Clinical Features 451 Multiple Myeloma and Related Plasma Cell Tumors 451 Multiple Myeloma 451 Solitary Plasmacytoma 451 Monoclonal Gammopathy of Undetermined Significance 452 Lymphoplasmacytic Lymphoma 452 Heavy-Chain Disease. 452 Primary Amyloidosis. 452 Clinical Features 453 Hodgkin Lymphoma 454 Classification. 454 Staging and Clinical Features. 456 Miscellaneous Lymphoid Neoplasms 456 Extranodal Marginal Zone Lymphoma 456 Hairy Cell Leukemia 456 Mycosis Fungoides and S茅zary Syndrome 457 Adult T Cell Leukemia/Lymphoma 457 Peripheral T Cell Lymphomas 457 Myeloid Neoplasms 458 Acute Myeloid Leukemia 458 Classification. 458 Immunophenotype. 459 Prognosis. 459 Myelodysplastic Syndromes 459 Chronic Myeloproliferative Disorders 460 Chronic Myelogenous Leukemia 460 Clinical Features 461 Polycythemia Vera 461 Clinical Course 461 Primary Myelofibrosis 462 Clinical Course 462 Histiocytic Neoplasms 463 Langerhans Cell Histiocytoses 463 Bleeding Disorders 463 Disseminated Intravascular Coagulation 464 Clinical Course 466 Thrombocytopenia 466 Immune Thrombocytopenic Purpura 466 Heparin-Induced Thrombocytopenia 467 Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome 467 Coagulation Disorders 468 Deficiencies of Factor VIII鈥搗on Willebrand Factor Complex 468 von Willebrand Disease 469 Hemophilia A鈥擣actor VIII Deficiency 469 Hemophilia B鈥擣actor IX Deficiency 469 Disorders That Affect The Spleen And Thymus 470 Splenomegaly 470 Disorders of the Thymus 470 Thymic Hyperplasia 471 Thymoma 471 Clinical Features 471 Bibliography 471 Red Cell Disorders 471 White Cell Disorders 471 BLEEDING Disorders 472 Disorders That Affect the Spleen and Thymus 472 Chapter 12 Lung 473 Chapter Contents 473 Atelectasis (Collapse) 474 Acute Lung Injury 474 Acute Respiratory Distress Syndrome 475 Clinical Features 475 Obstructive Versus Restrictive Pulmonary Diseases 476 Obstructive Lung (Airway) Diseases 477 Emphysema 477 Types of Emphysema 478 Centriacinar (Centrilobular) Emphysema 478 Panacinar (Panlobular) Emphysema 478 Distal Acinar (Paraseptal) Emphysema 478 Irregular Emphysema 478 Clinical Features 480 Conditions Related to Emphysema 480 Chronic Bronchitis 481 Clinical Features 481 Asthma 482 Types of Asthma 482 Atopic Asthma 482 Non-Atopic Asthma 482 Drug-Induced Asthma 484 Occupational Asthma 484 Clinical Features 484 Bronchiectasis 484 Clinical Features 486 Chronic Interstitial (Restrictive, Infiltrative) Lung Diseases 486 Fibrosing Diseases 486 Idiopathic Pulmonary Fibrosis 486 Clinical Features 487 Nonspecific Interstitial Pneumonia 487 Cryptogenic Organizing Pneumonia 487 Pulmonary Involvement in Collagen Vascular Diseases 488 Pneumoconioses 488 Coal Worker鈥檚 Pneumoconiosis 489 Clinical Features 489 Silicosis 490 Clinical Features 490 Asbestosis and Asbestos-Related Diseases 491 Clinical Features 491 Drug- and Radiation-Induced Pulmonary Diseases 492 Granulomatous Diseases 492 Sarcoidosis 492 Epidemiology 492 Clinical Features 494 Hypersensitivity Pneumonitis 494 Clinical Features 495 Pulmonary Eosinophilia 495 Smoking-Related Interstitial Diseases 495 Pulmonary Diseases of Vascular Origin 496 Pulmonary Embolism, Hemorrhage, and Infarction 496 Clinical Features 497 Pulmonary Hypertension 498 Clinical Features 498 Diffuse Alveolar Hemorrhage Syndromes 499 Goodpasture Syndrome 499 Idiopathic Pulmonary Hemosiderosis 499 Pulmonary Angiitis and Granulomatosis (Wegener Granulomatosis) 499 Pulmonary Infections 500 Community-Acquired Acute Pneumonias 500 Streptococcus pneumoniae Infections 501 Pneumonias Caused by Other Important Pathogens 502 Haemophilus influenzae 503 Moraxella catarrhalis 503 Staphylococcus aureus 503 Klebsiella pneumoniae 503 Pseudomonas aeruginosa 504 Legionella pneumophila 504 Community-Acquired Atypical Pneumonias 504 Clinical Features 504 Influenza Infections 505 Influenza Virus Type A/H1N1 Infection 505 Hospital-Acquired Pneumonias 505 Aspiration Pneumonia 506 Lu Cell injury, death, and adaptation Inflammation and repair Fluid and hemodynamic disorders / Richard N. Mitchell Diseases of the immune system Neoplasia Genetic and pediatric diseases / Anirban Maitra Environmental diseases General pathology of infectious diseases / Alex McAdam, Arlene Sharpe The blood vessels / Richard N. Mitchell The heart / Richard N. Mitchell The hematopoietic and lymphoid system The lung and upper respiratory tract / Aliya Noor Husain The kidney / Charles E. Alpers The oral cavity and gastrointestinal tract / Jerrold Turner, Mark Lingen The liver and biliary tract / Neil Theise The pancreas / Anirban Maitra The male genital system and lower urinary tract / Jonathan Epstein The female genital system and breast / Husain Sattar The endocrine system / Anirban Maitra Bones, joints, and soft tissue tumors / Andrew Rosenberg Peripheral nervous system and muscle / Peter Pytel The central nervous system and muscle / Matthew P. Frosch Skin / Alexander J.F. Lazar, Wei-Lien Wang.