Contents

1 Fundamentals of Pathology

Pathology ...... 2 Signs of Death ...... 5 Methods Equivocal Signs of Death Brain Death Disease ...... 5 Unequivocal Signs of Death Etiology Causal Pathogenesis Statistics ...... 5 Formal Pathogenesis Clinical Course Autopsy ...... 5

2 Cellular Pathology

Nuclear Lesions ...... 6 Inclusions ...... 12 Forms of Nuclei Amorphous inclusions Chromosomes Crystalline inclusions Particulate inclusions DNA Repair Defects ...... 6 Xeroderma pigmentosum Oncofetal Lesion ...... 12 Ribosome-lamellae complexes Chromosome Abnormalities ...... 6 Annulated lamellae layers Change in the Size of the Nucleus ...... 8 Mitochondria-lamellar-layer complexes Relation of Nucleus to Cytoplasm Nuclear Euploidy Lesions of the Smooth Endoplasmic Nuclear Polyploidy Nuclear Aneuploidy Reticulum (SER) ...... 14 Chromatin Change ...... 8 Quantitative Change ...... 14 Heterochromatin Condensation Proliferation of SER Dyskaryosis Atrophy of the SER Perinuclear Hyperchromatosis Morphologic Change ...... 14 Karyolysis Formation of Vesicles in the SER Inclusions ...... 8 „Cytoplasmic Nuclei“ Cytoplasmic inclusions Inclusions ...... 14 Paraplasmic inclusions Change in the Number of Nuclei ...... 10 Golgi Lesions ...... 16 Polynuclear Cells Anuclear Cells Atrophy of the Golgi Apparatus ...... 16 Antinuclear Autoantibodies ...... 10 Hypertrophy of the Golgi Apparatus ..... 16 Nucleolar Change ...... 10 Golgi-associated disorders ...... 16 Inflammatory nucleoli Cholestasis Tumor nucleoli Fatty Liver Giant nucleoli Achondroplasia Alveolar Proteinosis Lesions of the Rough Endoplasmic Reticulum (RER) ...... 12 Mitochondrial Lesions ...... 18 Quantitative Change ...... 12 Quantitative Change ...... 18 Increase in the number of cisterns Mitochondrial Proliferation Decrease in the number of cisterns Mitochondrial Depletion Morphologic Change ...... 12 Morphologic Change ...... 18 Fragmentation of the RER Megamitochondria Formation of vacuoles in the RER Mitochondrial Swelling Swelling of the RER RER cistern collapse Structural Change in Mitochondrial DNA .. 20 XII Contents

Mitochondrial DNA Mutations ...... 20 Lysosomal Phase ...... 28 Congenital Forms Heterophagy Acquired Forms Autophagy Changes in the Mitochondrial Cristae .... 20 Post-lysosomal Phase ...... 28 Membrane proliferation Lysosomal Lipid Pigments Membrane loss Lysosomal Diseases ...... 30 Inclusions ...... 20 Delayed Enzyme Release Matrix inclusions Increased Enzyme Release Crista inclusions Lysosomal Enzyme Deficiency Grana inclusions Cytomembrane Lesions ...... 32 Mitochondrial Disorders ...... 22 Apical Cell Edema Disrupted Communication Mitochondrial Myopathies ...... 22 Hypoxia ...... 22 Receptor Lesions ...... 32 Receptor dysfunction Hypoxemic Hypoxia Ischemic Hypoxia Cytoskeletal Lesions ...... 34 Hyperglycemic Hypoxia Histotoxic Hypoxia Microtubular Lesions ...... 34 Polymerization Block Mitochondrial Autoantibodies ...... 22 Microfilament Lesions Peroxisomal Lesions ...... 24 Intermediate Filament Lesions ...... 34 Peroxisomal Diseases ...... 24 Actin Bodies Mallory Bodies Acatalasemia Refsum Disease Cerebrohepatorenal Syndrome Adrenoleukodystrophy Systemic Carnitine Deficiency Lysosomal Lesions ...... 26 Prelysosomal Phase ...... 26 Heterophagy Autophagy

3 Connective Tissue Lesions

Collagen Lesions ...... 36 Structure of Amyloid ...... 50 Types of Amyloid ...... 50 Types of Collagen ...... 36 AL Amyloid Biosynthesis Disorders ...... 38 AA Amyloid Ehlers-Danlos Syndrome (EDS) AF Amyloid Scurvy AE Amyloid Osteogenesis Imperfecta AS Amyloid Classification of Amyloidoses ...... 52 Fibrosis ...... 40 Systemic Amyloidosis Sequelae of Fibrosis ...... 40 Localized Amyloidosis Pulmonary Fibrosis Sequelae of Fibrosis ...... 42 Elastin Lesions ...... 54 Cirrhosis of the Liver Biosynthesis Disorders ...... 54 Collagenolysis Disorders ...... 44 Restrictive Dermopathy a1-Antitrypsin Deficiency Senile Elastosis Fibrinoid Necrosis Trichopoliodystrophy Collagen Hyalinization Type V Ehlers-Danlos Syndrome Elastosis ...... 56 Collagen Vascular Diseases ...... 46 Actinic Elastosis Microfibril Lesions ...... 48 Pseudoxanthoma Elasticum Marfan’s Syndrome Fibroelastosis ...... 56 Sequelae of Fibroelastosis ...... 56 Amyloidosis ...... 48 Intimal Fibroelastosis General Definitions ...... 48 Endocardial Fibroelastosis Contents XIII

Elastin Lysis Disorders ...... 58 Sequelae of Mucoid Degeneration ...... 62 Sequelae of Elastin Lysis Disorders ...... 58 Proteoglycan Secretion Disorders ...... 64 Polyarteritis nodosa Temporal Arteritis Cystic Fibrosis ...... 64 Syphilitic Aortitis Sequelae of Cystic Fibrosis ...... 64 Bronchiectasis Proteoglycan Lesions ...... 60 Cystic fibrosis of the pancreas Meconium ileus Proteoglycan Complexing Disorders ...... 60 Liver cirrhosis Mucoid Degeneration Sequelae of Mucoid Degeneration ...... 60 Proteoglycan Lysis Deficiencies ...... 66 Mucoid Meniscopathy Mucopolysaccharidoses ...... 66 Ganglion Hurler’s Syndrome Cystic Vascular Degeneration Hunter’s Syndrome Mitral Valve Prolapse Syndrome Mucolipidoses ...... 66

4 Errors of Metabolism: Inorganic Compounds

Oxygen ...... 68 Iron ...... 72 Acute Generalized Hypoxia ...... 68 Iron Deficiency ...... 72 Absolute Iron Deficiency Acute Local Hypoxia ...... 69 Relative Iron Deficiency Chronic Hypoxia ...... 69 Iron Overload ...... 72 Fatty Degeneration Hemochromatosis Organ Atrophy Secondary Siderosis Interstitial Fibrosis Copper ...... 74 Calcium ...... 70 Copper Deficiency ...... 74 Hypocalcemia ...... 70 Chronic Copper Deficiency Hypercalcemia ...... 70 Trichopoliodystrophy Copper Overload ...... 74 Wilson’s Disease

5 Errors of Metabolism: Organic Compounds

Carbohydrates ...... 76 Malabsorption Syndromes ...... 82 Disorders Associated with Malabsorption ... 82 Gluten Enteropathy Glycogenoses ...... 76 Whipple Disease Type I Glycogenosis Type II Glycogenosis Fatty Degeneration ...... 84 Type III Glycogenosis Dietary Steatosis Transport Steatosis Carbohydrate Malabsorption ...... 78 Absorptive Steatosis Lactose Intolerance Retention Steatosis Saccharose-Isomaltose Intolerance Disorders of Fat Catabolism ...... 84 Glucose Synthesis Disorders ...... 78 Starvation Fructose-1,6-Diphosphatase Deficiency Obesity Hereditary Fructose Intolerance Ketonemia Deficient Carbohydrate Metabolism ...... 78 Phytanic Acid Storage Disease Propionic Acidemia Diabetes Mellitus ...... 78 Methylmalonic Aciduria Type I Diabetes mellitus Type II Diabetes mellitus Hypolipoproteinemia Disorders ...... 86 Sequelae ...... 80 Abetalipoproteinemia Galactosemia ...... 80 Analphalipoproteinemia Lipids ...... 82 Hyperlipoproteinemia Disorders ...... 88 Type I Hyperlipoproteinemia Fat Uptake Disorders ...... 82 Type II Hyperlipoproteinemia XIV Contents

Type III Hyperlipoproteinemia Disorders of Amino Acid Metabolism ..... 96 Type IV Hyperlipoproteinemia Phenylketonuria Type V Hyperlipoproteinemia Albinism Familial LCAT Deficiency Alkaptonuria1 Sequelae of Hyperlipoproteinemia ...... 90 Maple Syrup Urine Disease Atherosclerosis Primary Hyperoxaluria Xanthoma Type I Homocystinuria Cystinuria Sphingolipidoses ...... 92 Cystinosis Gaucher’s Disease Sphingomyelin Lipidosis Urea Synthesis Disorders ...... 100 Krabbe’s Disease Metachromatic Leukodystrophy Nucleotides ...... 102 Fabry Disease Hyperuricemia ...... 102 Type I GM Gangliosidosis 2 Primary Gout GM Gangliosidosis 1 Sequelae of Adult Gout Proteins ...... 96 Secondary Gout Defective Serum Proteins ...... 96

6 Pigment Lesions

Exogenous Pigments ...... 104 Defective Bilirubin Conjugation Defective Bilirubin Excretion Cosmetic Pigments ...... 104 Tyrosine-Derivative Pigments ...... 112 Occupational Toxin Pigments ...... 104 Cutaneous Melanin ...... 112 Anthracosis Vitiligo Plumbism Albinism Chalcosis Hemochromatosis Iatrogenic Pigments ...... 104 Addison’s Disease Argyria Phenylketonuria Amalgam Melasma Tetracycline Neuromelanin ...... 114 Carotene Parkinson’s Disease Non-Melanin Pigments ...... 114 Endogenous Pigments ...... 106 Brown Colon Alkaptonuria Hematogenous Pigments ...... 106 Porphyria ...... 106 Lipogenic Pigments ...... 114 Congenital Erythropoietic Porphyria Hemoglobin Breakdown Pigments ...... 106 Hyperbilirubinemia ...... 108 Excessive Bilirubin Production Defective Bilirubin Uptake

7 Sublethal Cell Damage

Hypertrophy ...... 116 Hyperplasia of the Adrenal Cortex ...... 122 Types of Hypertrophy ...... 116 Adrenal Cortex Hyperfunction Syndrome .. 122 Diseases Associated with Hypertrophy .....116 Hyperaldosteronism Hypertrophic Cardiomyopathy Hypercortisolism Congenital Hypertrophic Pyloric Stenosis Adrenogenital Syndrome Atrophy ...... 124 Hyperplasia ...... 118 Types of Atrophy ...... 124 Types of Hyperplasia ...... 118 Disorders Associated with Generalized Atrophy 124 Diseases Associated with Hyperplasia ...... 118 Senile Atrophy Endometrial Hyperplasia Atrophy Due to Inanition (Cachexia) Prostatic Hyperplasia Disorders Associated with Organ Atrophy .126 Endocrinal Hyperplasia ...... 120 Osteoporosis Thyroid Hyperplasia Alzheimer’s Disease Parathyroid Hyperplasia Pick’s Disease Contents XV

8 Lethal Cell Injury

Apoptosis ...... 128 Coagulative Necrosis ...... 130 Special Forms of Coagulative Necrosis .... 130 Programmed Cell Death ...... 128 Commitment phase Liquefactive Necrosis ...... 132 Executive phase Special Forms of Liquefactive Necrosis .... 132 Accidental Cell Death ...... 130 Shrinking Necrosis ...... 132 Necrosis ...... 130 Autolysis ...... 132 Focal Cytoplasmic Necrosis ...... 130

9 Calcification and Stone Disorders

Calcification ...... 134 Metastatic Calcification ...... 136 Disorders Associated with Metastatic Dystrophic Calcification ...... 134 Calcification ...... 136 Degenerative Calcification ...... 134 Pulmonary calcinosis Disorders Associated with Degenerative Renal calcinosis Calcification ...... 134 Gastric calcinosis Calcinosis cutis Myocardial calcinosis Myositis ossificans Valvular calcific degeneration Stone Disorders ...... 138 Mo¨nckeberg medial calcific sclerosis Urolithiasis Necrotic Calcification ...... 136 Cholelithiasis

10 Chemical Cell Injury

Drug-Induced Disorders ...... 140 Anemia Erythrocyte disease Drug-Induced Damage to Blood Cells ... 140 Lead nephropathy Drug-Induced Skin Disease ...... 140 Lead encephalopathy Polyneuropathy Drug-Induced Liver Disease ...... 141 Asbestosis ...... 142 Drug-Induced Kidney Disease ...... 141 Sequelae ...... 142 Pneumoconiosis (asbestos lung) Drug-Induced Lung Disease ...... 141 Pleural plaques Drug-Induced Neurologic Disorders ...... 141 Malignant mesotheliomas Diseases from Environmental Factors 142 Disease from Alimentary Factors ..... 144 a-Amanitine Poisoning Carbon Monoxide Poisoning ...... 142 Alcoholism Sequelae ...... 142 Sequelae of Alcoholism ...... 144 Severe carbon monoxide poisoning Alcoholic Fatty Degeneration of the Liver Acute carbon monoxide poisoning Alcoholic Hepatitis Alcoholic Liver Cirrhosis Lead Poisoning ...... 142 Megaloblastic Anemia Sequelae ...... 142 Wernicke-Korsakoff Syndrome Metaphyseal lead lines Cardiomyopathy Acquired porphyria

11 Physical Cell Injury

Thermal Injury ...... 146 Cold-Induced Injuries ...... 148 Hypothermia Heat-Induced Injuries ...... 146 Frostbite Heat Stroke Sequelae of Cold Injuries ...... 148 Burns Endangiitis obliterans Raynaud Syndrome ...... 148 XVI Contents

Electrical Injuries ...... 150 Laser Radiation ...... 150 Radiation Injury ...... 150 Ionizing Radiation ...... 152 Sequelae of Radiation ...... 152 Microwaves and Infrared Radiation ..... 150 Radiation Vasculitis Visible Light and Ultraviolet Radiation ... 150 Radiation Dermatitis Radiation Enteritis Sequelae of Light Radiation ...... 150 Radiation Bone Necrosis Acute photodermatosis Radiation-Induced Leukocyte Disease Chronic photodermatosis Radiation Therapy ...... 154

12 Immune Pathology

Antigen ...... 156 Contact Allergy Tuberculin Reaction Antigen Neutralization ...... 156 Granulomatous Hypersensitivity Reaction Immune Organs ...... 157 Transplantation Pathology ...... 178 Central Immune Organs ...... 157 Transplant Allergy Graft-Versus-Host Disease Thymus Bursa of Fabricius and Bone Marrow Autoimmune Disorders ...... 180 Peripheral Immune Organs ...... 157 Systemic Autoimmune Disorders ...... 180 Lymph Nodes Systemic Lupus Erythematosus Spleen Progressive systemic sclerosis MALT Dermatomyositis SALT Goodpasture’s Syndrome Cell-Mediated Immunity ...... 158 Wegener’s Granulomatosis Rheumatoid Arthritis TLymphocytes ...... 158 Sjo¨gren’s Syndrome Initial Immune Response ...... 158 Autoimmune Disorders Organ specific .... 186 Effector Mechanisms Hashimoto Thyroiditis Secondary Immune Response Autoimmune Adrenalitis Humoral Immunity ...... 160 Type I Diabetes Mellitus BLymphocytes ...... 160 Myasthenia Gravis Autoimmune Gastritis Initial Immune Response ...... 160 Multiple Sclerosis Effector Mechanisms Secondary Immune Response ...... 162 Immunodeficiency Disorders ...... 188 Primary Immunodeficiency Disorders ..... 188 Immune-Regulating Antigens ...... 164 X-Linked Agammaglobulinemia Classification of the HLA Genes ...... 164 Transient Hypogammaglobulinemia Function of the HLA Antigens ...... 164 Heavy-Chain Defect HLA-Associated Disorders ...... 164 j Chain Defect IgG Subclass Defect Pathogenic Immune Reactions ...... 166 Hyper IgM Syndrome Hypersensitivity Reactions ...... 166 Isolated IgA Deficiency Type I Hypersensitivity Reactions ...... 166 Common Variable Immunodeficiency Local Anaphylaxis Primary Immunodeficiency Syndromes: Systemic Anaphylaxis T-Cell Defects ...... 189 Atopic Reaction DiGeorge Syndrome Disorders Associated with Type I Nezelof Syndrome Hypersensitivity Reaction ...... 168 Chronic Myocutaneous Candidiasis Bronchial Asthma Primary Immunodeficiency Syndromes: Allergic Rhinosinusitis B-Cell and T-Cell Defects ...... 190 Type II Hypersensitivity Reactions ...... 170 Severe combined immunodeficiency (= SCID) Type III Hypersensitivity Reactions ...... 170 Ataxia Telangiectasia Serum Disease Wiskott-Aldrich Syndrome Disorders Associated with Serum Disease .172 Secondary Immunodeficiency Syndromes .190 Immune Complex Vasculitis Monoclonal Gammopathy Immune Complex Nephritis Acquired Immunodeficiency Syndrome (AIDS) Local Immune Complex Disease Sequelae of AIDS ...... 192 Disorders Associated with Local Immune HIV Lymphadenopathy Complex Disease ...... 174 Kaposi’s Sarcoma Extrinsic Allergic Alveolitis HIV-Associated Pneumopathy Type IV Hypersensitivity Reaction ...... 174 HIV Encephalitis Cutaneous Basophilic Hypersensitivity Reaction Contents XVII

13 Pathology of Inflammation ...... 194

Definition of Inflammation ...... 194 Influenzal Pneumonia Disorders Associated with Enterohemorrhagic E. Coli Etiology of Inflammation ...... 194 Hemorrhagic Viral Urocystitis Spread of Inflammation ...... 194 Anthrax Viral Hemorrhagic Fever Local inflammation Acute Pancreatitis Metastatic inflammation Generalized infection Necrotizing Inflammation ...... 218 Symptoms of Inflammation ...... 194 Ulcerous Necrotizing Inflammation ...... 218 Acute Necrotizing Ulcerous Gingivitis Exudative Inflammatory Reaction ...... 196 Peptic Gastroduodenal Ulcer Changes in Microcirculation ...... 196 Ulcerous Colitis Increased Permeability ...... 198 Diffuse Necrotizing Inflammation ...... 218 Leukocyte Transmigration ...... 200 Necrotizing Fasciitis Biologic Role of Inflammatory Cells ...... 200 A reactive Necrotizing Inflammation ...... 220 Inflammation Mediators ...... 202 Gangrenous Inflammation ...... 220 Cell-Derived Mediators Lymphocytic Inflammation ...... 220 Plasma-Derived Mediators Fetal Inflammation ...... 220 Acute Exudative Inflammations ...... 204 Courses of Acute Inflammation ...... 222 Serous Inflammation ...... 204 Dissolution of the exudate Seromucous Inflammation ...... 204 Regeneration Secondary postinfectious disorders Associated Disorder ...... 204 Chronic inflammation Acute Rhinitis Hematogenous Dissemination Fibrinous Inflammation ...... 206 Chronic Inflammation ...... 224 Fibrinous Parenchymal Inflammation ..... 206 Fibrinous Serosal Inflammation ...... 206 Chronic Nonsuppurative Inflammation .. 224 Associated Disorders ...... 206 Associated Disorder ...... 224 Fibrinous Pleuritis Chronic Bronchitis Fibrinous Pericarditis Chronic Suppurative Inflammation ...... 224 Fibrinous Peritonitis Fibrinous Mucosal Inflammation ...... 208 Chronic Mucopurulent Inflammation ..... 224 Pseudomembranous Croupous Form Influenza Type Granulating Inflammations ...... 226 Pseudomembranous Necrotizing Form Demarcation of Necrosis (Diphtheria Type) Chronic Abscess Fibrinous Suppurative Inflammation .... 210 Chronic Fistula Associated Disorder ...... 210 Chronic Ulcer Lobar Pneumonia Granulomatous Inflammations ...... 228 Suppurative Inflammation ...... 212 Granuloma Cells ...... 228 Mucopurulent Inflammation ...... 212 Histogenesis of Granulomas ...... 228 Empyema ...... 212 Epithelioid granulomas Phlegmon ...... 212 Histiocytic Granulomas Morphology of Granulomas ...... 229 Abscess-Forming Inflammation ...... 212 Sarcoid Granulomas Appendicitis Sarcoidosis Acute Pyogenic Pyelonephritis Crohn’s Disease Acute Pyogenic Meningitis Tuberculous Granuloma Hemorrhagic Inflammation ...... 216 Pseudotuberculous Granuloma Scarlet Fever Rheumatic Granuloma Waterhouse-Friderichsen Syndrome Rheumatoid Granuloma Plague Foreign-Body Granuloma

14 Viral Infection

Uncoated Single-Stranded RNA Viruses 238 Uncoated Double-Stranded RNA Viruses 240 Picornaviridae ...... 238 Reoviridae ...... 240 Poliomyelitis Virus ...... 238 Rotavirus Hepatitis A Virus (HAV) ...... 240 Rhinoviruses ...... 240 XVIII Contents

Coated Single-Strand RNA Viruses .... 240 Varicella Zoster Virus Togaviridae ...... 240 Cytomegalovirus (CMV) Alpha virus Epstein-Barr Virus (EBV) Rubivirus Coated Single-Stranded DNA Viruses .248 Flaviviridae ...... 240 Hepadnaviridae ...... 248 Orthomyxoviridae ...... 242 Hepatitis B Virus (HBV) Influenza Virus Paramyxoviridae ...... 242 Uncoated Double-Stranded DNAViruses 250 Parainfluenza Virus Adenoviridae Mumps Virus Papovaviridae Respiratory Syncytial Virus (RSV) Miopapovaviridae Measles Virus Arenaviridae ...... 242 Uncoated Single-Stranded DNA Viruses 250 Rhabdoviridae ...... 244 Parvoviridae ...... 250 Rabies Virus Parvovirus B19 Retroviridae ...... 244 Prion Diseases ...... 252 Oncornaviruses Human Immunodeficiency Virus (HIV) Disorders Associated with Prions ...... 252 Creutzfeldt-Jakob Disease Coated Double-Stranded RNA Viruses 246 Gerstmann’s Hereditary Senile Ataxia Poxviridae ...... 246 Kuru Variola Virus Scrapie Molluscum Contagiosum Virus Bovine Spongiform Encephalopathy Herpesviridae ...... 246 Herpes Simplex Virus (HSV)

15 Bacterial Infection

Gram-Positive Cocci ...... 254 Enterobacteriaceae ...... 260 Staphylococci ...... 254 DisordersAssociatedwithEnterobacteriaceae 260 Staphylococcus epidermidis Typhoid Fever Staphylococcus aureus Salmonella Enteritis Streptococci ...... 254 Short-Curved Gram-Negative Streptococcus pyogenes Rod-shaped Bacteria ...... 262 Vibrio cholerae Gram-Negative Cocci ...... 256 Campylobacter jejuni coli Neisseriaceae ...... 256 Helicobacter pylori Neisseria gonorrhoeae Neisseria meningitidis Flexible Spiral Gram-Negative Bacteria .. 262 Borrelia burgdorferi Gram-Positive Rods ...... 256 Treponema pallidum Corynebacterium diphtheriae Listeria monocytogenes Mycobacteria (Acid-Resistant Rods) ..... 264 Actinomyces israelii Tuberculosis Bacteria Bacillus anthracis Mycobacterium leprae Clostridia ...... 258 Obligatory Intracellular Bacteria ...... 266 Clostridia – associated Disorders ...... 258 Rickettsia prowazekii Clostridial Gas Calymmatobacterium granulomatis Tetanus Chlamydia Botulism Antibiotic associated Enterocolitis Bacteria Without a Cell Wall ...... 266 Mycoplasma pneumoniae Gram-Negative Rod-shaped Bacteria .... 260 Contents XIX

16 Mycotic Infection

Skin Mycoses (Superficial Mycoses) ...... 268 Molds ...... 272 Dermatophytoses ...... 268 Aspergillus Fungi Subcutaneous and Mucosal Mycoses ..... 268 Mucor (Zygomycetes) Organ and Systemic Mycoses ...... 268 Dimorphic Fungi ...... 272 Yeasts ...... 270 Histoplasma capsulatum Coccidioides immitis Candida albicans Rhinosporidium seeberi Cryptococcus neoformans

17 Protozoan Infection

Zoomastigophora ...... 274 Sporozoa ...... 276 Trypanosoma cruzi Toxoplasma gondii Leishmania Plasmodia Trichomonas vaginalis Giardia lamblia Mycoid Parasites ...... 278 Lobosea ...... 276 Pneumocystis carinii Entamoeba histolytica

18 Helminthic Infection

Trematodes ...... 280 Nematodes ...... 284 Schistosomes Enterobius vermicularis Cestodes ...... 280 Wuchereria bancrofti Taenia saginata Trichinella spiralis Taenia solium Echinococcus granulosus Echinococcus multilocularis

19 Hereditary Disorders

Chromosomal Disorders ...... 287 Chromosome Breakage Syndromes ..... 290 Autosomal Aberrations ...... 287 Single-Gene Disorders ...... 292 Numeric Autosomal Aberrations ...... 288 Autosomal Dominant Inheritance ...... 292 Triploidy Autosomal Recessive Inheritance ...... 292 Trisomy 21 (Down Syndrome) X-Linked Dominant Inheritance ...... 292 Trisomy 18 (Edwards Syndrome) Trisomy 13 (Patau Syndrome) X-Linked Recessive Inheritance ...... 292 Structural Autosomal Aberrations ...... 288 Multifactorial Hereditary Disorders .. 293 Deletion Syndrome Microdeletion Syndromes Mitochondrial Hereditary Disorders .. 293 Sex Chromosome Aberrations ...... 290 Klinefelter’s Syndrome XYY Syndrome Turner’s Syndrome XX Contents

20 Congenital Malformations

Basic Teratologic Terminology ...... 294 Failures of dorsal Fusion (Dysraphia) Malformation Failures of ventral Fusion Anomalies Agenesis Dysplasia Aplasia Hypoplasia General Etiology ...... 295 Atresia Genetic causes Stenosis Exogenous causes Vestige General Causal Pathogenesis ...... 295 Hamartia Chorista Cell Proliferation ...... 295 Cysts Cell Contact Mechanisms Atavism Proliferation Stimulators Multiple Malformations ...... 302 Proliferation Inhibitors Field Defects Proliferation Modulators Sequence Cell Determination and Differentiation .... 296 Syndrome Cell Determination Congenital disorder Cell Differentiation Cell Migration ...... 296 Etiologic Forms of Embryopathy ...... 302 Apoptosis (Cell Death) ...... 296 Radiation Embryopathy Diabetic Embryopathy Blastopathies ...... 298 Thalidomide Embryopathy Congenital Rubella Syndrome Conjoined Twins-Malformations ...... 298 Embryofetal Alcohol Syndrome Complete Symmetrical Double Malformations Amniotic Band Syndrome Incomplete Symmetrical Double Teratogenesis and Tumorigenesis Malformations Multifactorial Malformations „Parasitic“ Asymmetrical Double Malformations Fetopathies ...... 306 Feto-fetal Transfusion Syndrome ...... 298 Diabetic Fetopathy Cytomegalovirus Fetopathy Embryopathies ...... 300 Listerial Fetopathy Morphogenetic Forms of Embryopathy .. 300 Fetal Toxoplasmosis Isolated (Single) Malformations ...... 300 Congenital Syphilis Supernumerary Malformations Fusion Malformations

21 Tissue Repair

Tissue Repair ...... 308 Wound Healing in Internal Organs ...... 314 Regulatory Mechanisms ...... 309 Reversibly Postmitotic Cells Irreversibly Postmitotic Cells Physiologic Regeneration ...... 309 Wound Healing in the Central Nervous System 316 Solitary regeneration Open Brain Injuries Cyclical regeneration Closed Brain Injuries Permanent regeneration ...... 309 Wound Healing in Peripheral Nerves Pathologic Regeneration ...... 310 Metaplasia ...... 318 Epithelial Metaplasia ...... 318 Complete Regeneration ...... 310 Squamous Metaplasia Incomplete Regeneration ...... 310 Intestinal Metaplasia Urothelial Metaplasia Wound Healing ...... 310 Mesenchymal Metaplasia ...... 318 Healing of a Skin Wound ...... 310 Types of Wound Healing Heteroplasia ...... 318 Phases of Wound Healing Heterotopia ...... 318 Fracture Healing ...... 314 Tissue Displacement ...... 318 Healing by First Intention Healing by Second Intention Contents XXI

22 Tumor Pathology

General Definition of „Tumor“ ...... 320 Formal Tumorigenesis ...... 340 Benign Tumors ...... 320 Precursors and Early Stages ...... 340 Malignant Tumors ...... 320 Precancerous Conditions ...... 340 Tumors of Limited Malignancy ...... 320 Intra epithelial Neoplasia Tumor-like Lesions ...... 320 Leukoplakia Causal Tumorigenesis ...... 321 Carcinoma in Situ ...... 340 Disturbed DNA repair ...... 321 Early Invasive Carcinoma ...... 340 Disturbed Cellular Communication ...... 321 Cellular and Nuclear Changes ...... 342 Proliferation Disinhibition ...... 321 Cellular Changes ...... 342 Growth Factors Anaplasia Proto-oncogenes Biochemical Convergence Tumor Suppressor Genes Nuclear Changes ...... 342 Tumor Immunology ...... 326 DNA Content of Tumor Cells Chromosome Aberrations Tumor Antigens ...... 326 Oncofetal Antigens Tumor Angiogenesis ...... 344 Differentiation Antigens Tumor Dissemination ...... 344 Tumor Immunity ...... 326 Metastasis ...... 346 Chemical Tumorigenesis ...... 328 Lymphatic Metastasis Stages of Carcinogenesis ...... 328 Hematogenous Metastasis Initiation Cavitary Metastasis Promotion Canalicular Metastasis Latency Inoculated Metastases Progression Tumor Regression ...... 350 Metastasis Sequelae of Tumor Regression ...... 350 Metabolic Carcinogen Activation ...... 330 Remission Organ and Species Specificity ...... 330 Complete remission Viral Tumorigenesis ...... 332 Spontaneous remission DNA Tumor Viruses ...... 332 Recurrence Human papilloma viruses Tumor Complications ...... 352 Adenoviruses Local Complications ...... 352 Epstein-Barr Virus Stenosis Hepatitis B Virus Circulatory Disruption RNA Tumor Viruses Tumor Necrosis Physical Tumorigenesis ...... 334 Disruption of Organ Function Ionizing Radiation Systemic Complications ...... 352 Ultraviolet Radiation Tumor Metastases Foreign Bodies Cancer Cachexia Tumor Anemia Human Tumorigenesis ...... 336 Paraneoplastic Syndromes Predisposition ...... 336 Hormonal Factors ...... 336 Tumor Classification ...... 355 Age ...... 336 Nonepithelial Tumors ...... 355 Senile tumors General Definitions ...... 355 Childhood tumors Benign Nonepithelial Tumors Nutritional Factors and Drug Use ...... 336 Malignant Nonepithelial Tumors Nutritional Fats Fibrous Tumors ...... 356 High Nutritional Fiber Intake Fibroma Alcohol Abuse Fibrosarcoma Cigarette Smoke Muscle Tumors ...... 356 Environmental Factors ...... 336 Leiomyomas Genetic Changes ...... 338 Leiomyosarcoma Susceptibility Genes Rhabdomyoma Tumor Promotion Rhabdomyosarcoma Oncogene Activation Tumors of Fatty Tissue ...... 356 Defective Apoptosis Lipoma Defects in Differentiation Genes Liposarcoma Defects in Metastasis-Suppressor Genes Cartilage Tumors ...... 358 Defective Immune Surveillance Chondroma Resistance to Therapy XXII Contents

Chondrosarcoma Adenocarcinoma ...... 372 Bone Tumors ...... 358 Highly Differentiated Forms Osteoma Moderately Differentiated Forms Osteosarcoma Mucigenous Carcinomas Leukemias ...... 358 Urothelial Carcinoma ...... 372 Acute Myelogenous Leukemia Papillary Urothelial Carcinomas Chronic Myelogenous Leukemia (CML) Solid Urothelial Carcinomas Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia (CLL) Carcinomas of Specific Organs ...... 374 Malignant Lymphoma ...... 362 Prostatic Carcinomas Carcinoma of the Breast Hodgkin’s Lymphomas Lung Carcinoma Non-Hodgkin’s Lymphomas Colorectal Carcinoma Melanocytic Tumors ...... 366 Melanocytic Nevi Dysontogenetic Tumors ...... 382 Malignant Melanoma Teratoma ...... 382 Brain Tumors ...... 366 Mature Teratoma Gliomas Immature Teratoma Nerve Sheath Tumors Embryonal Tumors (Blastomas) ...... 382 Meningioma Neuroblastoma Benign Epithelial Tumors ...... 370 Medulloblastoma Retinoblastoma Papillomas ...... 370 Nephroblastoma Basal Cell Papilloma Embryonal Tumors Arising from Vestigial Mucosal Papilloma Papilloma of Glandular Excretory Ducts Tissue ...... 382 Urothelial Papilloma Ameloblastoma Adenomas ...... 370 Craniopharyngioma Chordoma Solid Adenoma Mesodermal Mixed Tumor Tubular Adenoma Villous Adenoma Semimalignant Tumors ...... 384 Cystadenoma Basal Cell Carcinoma Fibroadenoma Carcinoid Appendix Malignant Epithelial Tumors ...... 372 Ameloblastoma Chordoma Squamous Cell Carcinoma ...... 372 Craniopharyngioma Highly Differentiated Forms Undifferentiated Forms

23 Generalized Circulatory Disorders

Arterial Hypertension ...... 386 Portal Hypertension ...... 392 Essential Hypertension ...... 386 Sequelae of Portal Hypertension ...... 392 Renal Hypertension ...... 386 Development of Collateral Circulation Renovascular Hypertension Congenitive Splenomegaly Renoparenchymal Hypertension Ascites Endocrinal Hypertension ...... 388 Shock ...... 394 Cardiovascular Hypertension ...... 388 Neurologic Hypertension ...... 388 Pathogenetic Forms of Shock ...... 394 Sequelae of Arterial Hypertension ...... 388 Cardiogenic Shock Hypertensive Cardiac Hypertrophy Hypovolemic Shock Hypertensive Arteriopathy Septic Shock Anaphylactic Shock Pulmonary Hypertension ...... 390 Endocrine Shock Primary Pulmonary Hypertension Neurogenic Shock Secondary Pulmonary Hypertension Hemodynamic Forms of Shock ...... 394 Sequelae of Pulmonary Hypertension ..... 390 Hyperdynamic Shock Syndrome Chronic Cor Pulmonale Hypodynamic Shock Syndrome Hypertensive Pulmonary Vascular Disease Contents XXIII

Sequelae of Shock ...... 396 Hemorrhage 398 Shock Lung Bleeding Through Ruptures ...... 398 Shock Kidney Weakening of the Vessel Wall Shock Hepatopathy Over-Stretching of Vascular Structures Shock Pancreatopathy Diapedesis Bleeding ...... 398 Shock Endocarditis Hemorrhagic Diathesis ...... 400 Shock Enteropathy Osler-Weber-Rendu Disease Shock Encephalopathy Thrombocytopenic Forms Shock Endocrinopathy Thrombasthenic Forms Coagulopathic Forms

24 Localized Circulatory Disorders

Thrombosis ...... 404 Air Embolism ...... 412 Causal Pathogenesis ...... 404 Cholesterol Embolism ...... 412 Endothelial Lesion („wall factor“) Amniotic Fluid Embolism ...... 412 Hemodynamic Abnormality („flow factor“) Parasite Embolism ...... 412 Hypercoagulability („blood factor“) Forms of Thrombi ...... 406 Arterial Circulatory Disorders ...... 414 Laminated Thrombus (depository Thrombus) Red Thrombus (stagnation thrombus) Absolute Persistent ...... 414 Mixed Thrombus Anemic Infarct Hyaline Thrombus Forms of Thrombosis ...... 408 Absolute Temporary Ischemia ...... 416 Venous Thrombosis Relative Ischemia ...... 416 Arterial Thrombosis Acute Temporary Relative Ischemia Cardiac Thrombosis Chronic Relative Ischemia Sequelae of Thrombosis ...... 408 Disorders Associated with Absolute Recurrent Thrombus Persistent Ischemia ...... 418 Obliteration of the Vessel Myocardial Post-thrombotic Syndrome Anemic Splenic Infarct Puriform Thrombolysis Anemic Thrombus Calcification Anemic Renal Infarct Thromboembolism Venous Hemodynamic Disorders ..... 422 Embolism ...... 410 Thromboembolism ...... 410 Venous Stasis ...... 422 Venous Thromboembolism Associated Disorders ...... 422 Arterial Thromboembolism Hepatic Congestion Fat Embolism ...... 412 Hemorrhagic Infarct ...... 422 Traumatic Fat Embolism Associated Disorders ...... 422 Fat Emboli Syndrome Hemorrhagic Cerebral Infarction Mesenteric Infarction

25 Edema

Hydrostatic Edema ...... 424 Seguclae of Edema ...... 426 Cardiac Edema Sclerosis Portal Edema Dermatopathy Venous Edema Recurrent Erysipelas Osmotic Edema Nodal Vascular Sinus Transformation Stewart-Treves Syndrome Oncotic Edema ...... 426 Cerebral Edema ...... 428 Vascular Edema ...... 426 Vasogenic Cerebral Edema Lymphedema ...... 426 Cytotoxic Cerebral Edema Interstitial Cerebral Edema Hyposmotic Cerebral Edema

Index ...... 431