I General Pathology 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death Key Readings Index E-Glossary 1-1 Glossary of Abbreviations and Terms Basic Terminology The Normal Cell Components of Normal Cells and Their Vulnerabilities Cell Membranes (Cytocavitary System) Second Messenger Systems. Cytosol versus Cytoplasm Nucleus Nucleolus. Rough Endoplasmic Reticulum Ribosomes. Golgi Complex Smooth Endoplasmic Reticulum Mitochondria Oxidative Phosphorylation Vaults Lysosomes and Peroxisomes The Cytoskeleton: Microfilaments, Intermediate Filaments, and Microtubules Cellular Inclusions Intercellular Junctions and the Extracellular Matrix Causes of Cell Injury Oxygen Deficiency Physical Agents Infectious Microbes Nutritional Imbalances Genetic Derangement Workload Imbalance Chemicals, Drugs, and Toxins Immunologic Dysfunction Aging Reversible Cell Injury Acute Cell Swelling Mechanisms of Acute Cell Swelling Acute Cell Swelling Resulting from Hypoxic Injury Acute Cell Swelling Resulting from Specific Types of Cell Membrane Injury Carbon Tetrachloride and Cell Membrane Injury Molecules of the Immune System and Cell Membrane Injury. Morphologic Changes: Their Detection and Evaluation Morphology of Acute Cell Swelling Gross Appearance. Microscopic Appearance. Ultrastructural Appearance. Significance and Fate of Acute Cell Swelling Irreversible Cell Injury and Cell Death Cell Death Cell Death by Oncosis (Oncotic Necrosis) Cell Membrane Injury Leading to Cell Death. Free Radical Injury. Morphologic Appearance of Necrotic Cells and Tissues (Oncotic Necrosis). Gross Appearance of Necrotic Tissue. Histologic Changes in Necrosis (Oncotic Necrosis). Ultrastructure of Necrotic Cells (Oncotic Necrosis). Types of Oncotic Necrosis. Coagulative Necrosis. Caseous Necrosis. Liquefactive Necrosis. Gangrenous Necrosis. Necrosis of Epithelium. Necrosis of Adipose Tissue (Fat Necrosis). Sequelae to Oncotic Necrosis. Morphologic Appearance of Postmortem Changes Cell Death by Apoptosis Triggers of Apoptosis. The Extrinsic (Death Receptor–Initiated) Pathway. The Intrinsic (Mitochondrial) Pathway. The Execution Phase of Apoptosis. Morphologic Appearance of Apoptosis. Chronic Cell Injury and Cell Adaptations Cellular Survival during Sublethal Ischemia or Involution Autophagy Adaptations That Change Cell Size, Number, or Appearance Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia Intracellular Accumulations Lipids Glycogen Proteins Defects in Protein Folding. Other Intracellular Inclusions Autophagic Vacuoles. Crystalline Protein Inclusions. Viral Inclusion Bodies. Lead Inclusions. Extracellular Accumulations Hyaline Substances Amyloid. Classification and Localization of Amyloidosis. Other Extracellular Accumulations Fibrinoid Change. Collagen (Fibrosis). Fatty Infiltration. Gout Pseudogout Cholesterol. Pathologic Calcification Dystrophic Calcification Metastatic Calcification Heterotopic Ossification Pigments Exogenous Pigmented Substances Carbon and Other Dusts. Carotenoid Pigments. Tetracycline. Nonhematogenous Endogenous Pigments Melanin. Lipofuscin and Ceroid. Hematogenous Pigments Hemoglobin. Toxic or Other Metabolic Disorders of Hemoglobin Cyanide. Carbon Monoxide. Nitrite Poisoning. Intravascular Hemolysis (Hemoglobinuria). Hematin. Acid Hematin (Formalin Pigment). Parasitic Hematin. Hemosiderin. Hematoidin. Bilirubin. Porphyria. Cell Cycle Cellular Aging Genetic Basis of Aging Telomeres Cellular Senescence Structural and Biochemical Changes with Cellular Aging Genetic Basis of Disease Types of Diagnoses Chromosome Structure and Function Nuclear Chromosomes Mitochondrial Chromosomes Gene Structure and Function Mechanisms of Genetic Disorders Single-Gene Disorders Single-Gene Disorders of Somatic Cells. Single-Gene Disorders of Germ Cells. Autosomal Dominant Disorders. Autosomal Recessive Disorders. X-Linked Disorders. Single-Gene Disorders of Mitochondria. Chromosomal Disorders. Errors in Cell Division. Numeric Alterations. Structural Alterations. Complex Multigenic Disorders Types of Diagnoses Summary Suggested Readings Suggested Readings 2 Vascular Disorders and Thrombosis Key Readings Index E-Glossary 2-1 Glossary of Abbreviations and Terms Circulatory System Microcirculation, Interstitium, and Cells Fluid Distribution and Homeostasis Abnormal Fluid Distribution Imbalance between Intracellular and Interstitial Compartments Imbalance between Intravascular and Interstitial Compartments (Edema) Mechanisms of Edema Formation Increased Microvascular Permeability Increased Intravascular Hydrostatic Pressure Decreased Intravascular Osmotic Pressure Decreased Lymphatic Drainage Morphologic Characteristics of Edema Hemostasis Hemostatic Process Primary Hemostasis Secondary Hemostasis Thrombolysis and Fibrinolysis Regulation of Hemostasis Coagulation Inhibitors Fibrinolytic Inhibitors Hemostasis and Other Host Responses Disorders of Hemostasis: Hemorrhage and Thrombosis Hemorrhage Thrombosis Normal Blood Flow, Distribution, and Perfusion Alterations in Blood Flow and Perfusion Increased Blood Flow Decreased Blood Flow Decreased Tissue Perfusion Shock Cardiogenic Shock Hypovolemic Shock Blood Maldistribution Stages and Progression of Shock Clinical and Morphologic Features of Shock Suggested Readings Suggested Readings 3 Inflammation and Healing Key Readings Index E-Glossary 3-1 Glossary of Abbreviations and Terms Evolution of the Current Understanding of Inflammation Beneficial and Harmful Aspects of Inflammation Acute Inflammation Substances Inducing the Acute Inflammatory Response Fluidic (Exudative) Phase of the Acute Inflammatory Response Endothelial Cell Dynamics during the Acute Inflammatory Response Formation of Endothelial Cell Gaps Cellular Phase of the Acute Inflammatory Response Leukocyte Adhesion Cascade Leukocyte Adhesion Deficiencies Therapeutic Strategies to Modulate Leukocyte Infiltration Additional Regulation of Inflammation Effector Cells of the Acute Inflammatory Response Vascular Endothelial Cells Mast Cells and Basophils Neutrophils Eosinophils Natural Killer Cells and Natural Killer T Lymphocytes Monocytes and Macrophages Chemical Mediators of the Acute Inflammatory Response Complement Cascade Arachidonic Acid Metabolites Prostaglandin Formation and Inhibition Leukotriene Formation and Inhibition Omega-3 Fatty Acids (Fish Oils) and Inhibition of Eicosanoid Activity Platelet-Activating Factor Cytokine Family Overview in Inflammation and Induction of CD4 TH Subsets Cytokine Receptors and Signaling Inflammatory Proteins Interferons. High Mobility Group Box Protein 1. Chemokines Classification of Chemokines Chemokine Receptors and Signaling Oxygen-Derived Free Radicals and Nitric Oxide Receptors for Exogenous and Endogenous Inflammatory Stimuli and Toll-Like Receptors Antimicrobial Peptides and Collectins Acute Phase Proteins Antiinflammatory Mediators Summary of the Chemical Mediators of Acute Inflammation Reparative Phase of the Acute Inflammatory Response Outcomes of the Acute Inflammatory Response Nomenclature of the Inflammatory Response (Morphologic Diagnoses) Morphologic Classification of Exudates in Acute Inflammatory Lesions Serous Inflammation Catarrhal Inflammation Fibrinous Inflammation Suppurative Inflammation Chronic Inflammation Beneficial and Harmful Aspects of Chronic Inflammation Progression of the Acute Inflammatory Response to Chronic Inflammation, Fibrosis, and Abscess Formation Progression to Chronic/Granulomatous Inflammation Healing by Fibrosis Abscess Formation Granulomatous Inflammation and Granuloma Formation Nodular (Tuberculoid) Granulomas (TH1-Biased Granulomas) Diffuse (Lepromatous) Granulomas (TH2-Biased Granulomas) Sarcoids of Horses Eosinophilic Granulomas Other Chronic Inflammatory/ Granulomatous Conditions Gross and Microscopic Lesions and Nomenclature of the Chronic Inflammatory Response Cellular Mechanisms of Chronic Inflammatory Responses Lymphocytes ?/? T Lymphocytes ?/? T Lymphocytes (CD4/CD8) TH1, TH2, TH17, and T Reg Immunologic Responses Monocytes/Macrophages Epithelium Mononuclear Cell Maturation and Trafficking in the Chronic Inflammatory Response Formation of Epithelioid Macrophages and Multinucleate Giant Cells Dendritic Cells Dendritic Cell Trafficking. B Lymphocytes Plasma Cells Eosinophils Mast Cells Natural Killer Cells Fibroblasts Endothelial Cells Trafficking of Naïve and Activated T and B Lymphocytes Homing of Naïve Lymphocytes via High Endothelial Venules Adherence and Transendothelial Migration of Activated T Lymphocytes Inflammation and the Sensation of Pain The Effect of Inflammation on the Febrile Response and Other Activities Unique Types of Inflammation Septicemia and Endotoxic Shock Septicemia. Septic (Endotoxic) Shock. Wound Healing and Angiogenesis First and Second Intention Healing First Intention Healing Second Intention Healing Impaired Wound Healing Expression of Genes Responsible for Wound Repair Degradation of Cells and Tissue Components in Wounds Degradation of the Extracellular Matrix in Wounds Resynthesis of the Extracellular Matrix with Wound Healing Synthesis of Collagen and Matrix Proteins Collagen Production by Fibroblasts Synthesis of Proteoglycans Fibroblasts and the Mechanistic Basis of Fibrosis Morphology of Granulation Tissue and Fibrous Connective Tissue Granulation Tissue Hypertrophic Scars. Fibrous Connective Tissue Wound Contraction The Scirrhous Reaction Myofibroblasts. Angiogenesis in Wound Repair Initiation of Endothelial Cell Proliferation Endothelial Cell Growth Factors. Endothelial Cell Migration Is Mediated by Integrins. Vascular Remodeling. Regulators/Inhibitors of Endothelial Cell Growth. Epithelialization in Wound Repair Intact Basement Membranes Enhance Reepithelialization Initiation of Cell Proliferation in Epithelia Differentiation of Epithelia Metaplasia in Wound Repair Suggested Readings Suggested Readings Inflammation Healing 4 Mechanisms of Microbial Infections Key Readings Index E-Glossary 4-1 Glossary of Abbreviations and Terms Chronologic Sequence of Steps in Microbial Diseases Portals of Entry Alimentary System (Ingestion) Respiratory System (Inhalation) Urogenital System (Ascending Infection) Skin (Direct Contact and Cutaneous Penetration) Ear and Eye (Direct Contact and Cutaneous Penetration) Target Cells and Substances Epithelial Cells as Microbial Targets Mucosa-Associated Lymphoid Tissues as Microbial Targets Biologic Substances as Microbial Targets Pathways of Spread Mechanisms Used to Colonize Mucosae (or Biologic Substances) at Portals of Entry Colonize Mucus (Goblet Cells) Colonize Cilia (or Microvilli) of Mucosal Epithelial Cells Colonize the Cell (Endocytosis) Mechanisms Used to Cross Mucosae at Portals of Entry M Cell Entry Leukocyte Trojan Horse Entry Dendritic Cell Entry Transcytosis Entry Direct Entry (Motility) Nerve Ending Entry Mechanisms of Adhesion, Colonization, Invasion, and Replication Cell Polarity Transcytosis and Endocytosis/Exocytosis Systemic Spread Defense Mechanisms Barrier Systems Structural (Physical) Barriers Functional (Biologic) Barriers Mucus Layer. Innate and Adaptive Immune Responses Monocyte-Macrophage System Dendritic Cells Phagosome-Lysosome Fusion Genetic Resistance of Animals to Infectious Diseases Disorders of Barrier Systems Disorders of the Innate Immune Response Disorders of the Adaptive Immune Response Bacterial Diseases Pathogenicity Virulence Factors Initial Encounters at Portals of Entry Adhesion, Colonization, Toxigenesis, and Invasiveness Toxigenesis (Toxins) Exotoxins and Lipoteichoic Acid. Endotoxins. A-B Toxin. Other Virulence Factors Secretion Systems. Siderophores. Biofilms/Intracellular Bacterial Communities. Capsules. Role of Bacterial Genes in Susceptibility and/or Resistance to Disease Virulence Factors Antibiotic Resistance Bacterial Transfer of Antibiotic Resistance. Bacterial Gene Transfer Vertical Gene Transfer. Horizontal Gene Transfer. Mechanisms of Genomic Change Bacterial Diseases of Organ Systems Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity Disorders of Domestic Animals Enteric Colibacillosis (Escherichia coli). Enterotoxigenic Escherichia coli. Enteropathogenic Escherichia coli. Enterohemorrhagic Escherichia coli. Enterotoxemic and Septicemic Colibacillosis. Salmonellosis (Salmonella spp.). Enterotoxemia (Clostridium perfringens). Alimentary Anthrax (Bacillus anthracis). Disorders of Horses Rhodococcal Enteritis (Rhodococcus equi). Tyzzer’s Disease (Clostridium piliforme [Bacillus piliformis]). Disorders of Ruminants (Cattle, Sheep, and Goats) Johne’s Disease (Mycobacterium avium ssp. paratuberculosis [MAP]). Bovine Intestinal Tuberculosis (Mycobacterium bovis). Wooden Tongue (Actinobacillus lignieresii). Alimentary Anthrax (Bacillus anthracis). Disorders of Pigs Porcine Proliferative Enteritis/Hemorrhagic Bowel Syndrome (Lawsonia intracellularis). Swine Dysentery (Brachyspira hyodysenteriae). Porcine Polyserositis (Haemophilus suis/parasuis, Actinobacillus suis, Streptococcus suis, or Escherichia coli). Hepatobiliary System and Exocrine Pancreas Disorders of Domestic Animals Hepatic Leptospirosis (Leptospira spp.). Disorders of Horses Tyzzer’s Disease (Clostridium piliforme [Bacillus piliformis]). Disorders of Ruminants (Cattle, Sheep, and Goats) Bacillary Hemoglobinuria (Clostridium haemolyticum). Infectious Necrotic Hepatitis (Clostridium novyi). Disorders of Pigs Porcine Polyserositis (Haemophilus suis/parasuis, Actinobacillus suis, Streptococcus suis, or Escherichia coli). Respiratory System, Mediastinum, and Pleurae Disorders of Domestic Animals Strep Zoo (Streptococcus equi subsp. zooepidemicus). Respiratory Anthrax (Bacillus anthracis). Disorders of Horses Rhodococcal Pneumonia (Rhodococcus equi). Strep Zoo (Streptococcus equi subsp. zooepidemicus). Strangles (Streptococcus equi subsp. equi). Disorders of Ruminants (Cattle, Sheep, and Goats) Bovine Respiratory Disease Complex. Bovine Pneumonic Pasteurellosis/Mannheimiosis (Mannheimia [Pasteurella] haemolytica). Pulmonary Histophilosis (Histophilus somni). Bovine Enzootic Pneumonia (Pasteurella multocida subsp. multocida serogroup A). Contagious Bovine Pleuropneumonia (Mycoplasma mycoides var. mycoides Small Colony). Bovine Tuberculosis (Mycobacterium bovis). Disorders of Pigs Porcine Respiratory Disease Complex. Porcine Pleuropneumonia (Actinobacillus pleuropneumoniae). Atrophic Rhinitis (Bordetella bronchiseptica and Pasteurella multocida). Porcine Enzootic Pneumonia (Mycoplasma hyopneumoniae). Porcine Polyserositis (Haemophilus suis/parasuis, Actinobacillus suis, Streptococcus suis, or Escherichia coli). Disorders of Dogs Acute Tracheobronchitis (Bordetella bronchiseptica). Cardiovascular System and Lymphatic Vessels Disorders of Domestic Animals Embolic Vasculopathy/Vasculitis (Actinobacillus equuli, Escherichia coli, Staphylococcus spp., Streptococcus spp., Fusobacterium necrophorum). Vascular Leptospirosis (Leptospira spp.). Septicemic Anthrax (Bacillus anthracis). Disorders of Horses Glanders (Burkholderia mallei; Farcy, Malleus, Droes). Disorders of Pigs Edema Disease (Escherichia coli). Urinary System Disorders of Domestic Animals Necrohemorrhagic Urocystitis (Escherichia coli, Corynebacterium renale, Pseudomonas spp., Proteus vulgaris, or Klebsiella pneumoniae). Renal Leptospirosis (Leptospira spp.). Disorders of Ruminants (Cattle, Sheep, and Goats) Contagious Bovine Pyelonephritis (Corynebacterium renale, Trueperella pyogenes [formerly Arcanobacterium pyogenes], or Escherichia coli). Pulpy Kidney (Overeating) Disease (Clostridium perfringens). Bone Marrow, Blood Cells, and Lymphatic System Disorders of Domestic Animals Brucellosis (Brucella spp.). Disorders of Horses Strangles (Streptococcus equi subsp. equi). Rhodococcal Mesenteric Lymphadenitis (Rhodococcus equi). Caseous Lymphadenitis (Corynebacterium pseudotuberculosis). Disorders of Ruminants (Cattle, Sheep, and Goats) Caseous Lymphadenitis (Corynebacterium pseudotuberculosis). Brucellosis (Brucella spp.). Disorders of Pigs Rhodococcal Mesenteric Lymphadenitis (Rhodococcus equi). Brucellosis (Brucella spp.). Disorders of Dogs Brucellosis (Brucella spp.). Nervous System Disorders of Domestic Animals Botulism and Tetanus (Clostridium botulinum, Clostridium tetani). Meningitis (Escherichia coli and Other Bacterial Species). Disorders of Ruminants (Cattle, Sheep, and Goats) Listeriosis (Listeria monocytogenes). Thrombotic Meningoencephalitis (Histophilus somni). Focal Symmetric Encephalomalacia (Clostridium perfringens). Mannheimia Meningoencephalitis (Mannheimia haemolytica A1). Disorders of Pigs Edema Disease (Escherichia coli). Muscle Disorders of Ruminants (Cattle, Sheep, and Goats) Blackleg (Clostridium chauvoei). Malignant Edema (Clostridium septicum). Big Head and Black Disease (Clostridium novyi). Bone, Joints, Tendons, and Ligaments Disorders of Ruminants (Cattle, Sheep, and Goats) Lumpy Jaw (Actinomyces bovis). Integumentary System Disorders of Pigs Greasy Pig Disease (Staphylococcus hyicus). Diamond Skin Disease (Erysipelothrix rhusiopathiae). Disorders of Dogs Canine Pyoderma (Staphylococcus intermedius). Female Reproductive System and Mammary Gland Disorders of Domestic Animals Brucellosis (Brucella spp.). Disorders of Ruminants (Cattle, Sheep, and Goats) Bovine Mastitis (Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, and Escherichia coli). Male Reproductive System Disorders of Domestic Animals Brucellosis (Brucella spp.). Viral Diseases Target Cells Viral Pathogenicity and Replication Cycle Virulence Factors Mechanisms of Genomic Change Defense Mechanisms Viral Diseases of Organ Systems Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity Disorders of Domestic Animals Rotavirus Enteritis (Rotavirus, Nonenveloped RNA Virus). Vesicular Stomatitis (Vesiculovirus, Enveloped RNA Virus). Disorders of Ruminants (Cattle, Sheep, and Goats) Bovine Viral Diarrhea–Mucosal Disease (BVD Virus, Pestivirus, Enveloped RNA Virus). Rinderpest (Cattle Plague, Morbillivirus, Enveloped RNA Virus). Contagious Ecthyma (Orf, Sore Mouth, Pustular Dermatitis: Parapoxvirus; Enveloped DNA Virus). Bovine Papular Stomatitis (Parapoxvirus, Enveloped DNA Virus). Foot-and-Mouth Disease (Aphthovirus, Nonenveloped RNA Virus). Disorders of Pigs Transmissible Gastroenteritis (Coronavirus, Enveloped RNA Virus). Porcine Epidemic Diarrhea (Coronavirus, Enveloped RNA Virus). Swine Vesicular Disease (Enterovirus, Nonenveloped RNA Virus). Vesicular Exanthema of Pigs (Calicivirus, Nonenveloped RNA Virus). Foot-and-Mouth Disease (Aphthovirus, Nonenveloped RNA Virus). Disorders of Dogs Parvovirus Enteritis (Parvovirus, Nonenveloped DNA Virus). Canine Enteric Coronavirus (Canine Coronavirus, Enveloped RNA Virus). Canine Distemper (Morbillivirus, Enveloped RNA Virus). Disorders of Cats Feline Infectious Peritonitis (Feline Infectious Peritonitis Virus, Nonenveloped RNA Virus). Parvovirus Enteritis (Parvovirus, Nonenveloped DNA Virus). Hepatobiliary System and Exocrine Pancreas Disorders of Ruminants (Cattle, Sheep, and Goats) Wesselsbron’s Disease (Flavivirus, Enveloped RNA Virus). Rift Valley Fever (Phlebovirus, Enveloped RNA Virus). Disorders of Dogs Infectious Canine Hepatitis (Canine Adenovirus Infection, Canine Adenovirus Type 1, Nonenveloped DNA Virus). Respiratory System, Mediastinum, and Pleurae Disorders of Horses Equine Influenza (Orthomyxovirus, Enveloped RNA Virus). Equine Viral Rhinopneumonitis (Equine Herpesvirus, Alphaherpesvirus, Enveloped DNA Virus). Equine Viral Arteritis (Arterivirus, Enveloped RNA Virus). Disorders of Ruminants (Cattle, Sheep, and Goats) Infectious Bovine Rhinotracheitis (Bovine Herpesvirus, Alphaherpesvirus, Enveloped DNA Virus). Bovine Respiratory Syncytial Virus Pneumonia (Pneumovirus, Enveloped RNA Virus). Bovine Influenza (Orthomyxovirus, Enveloped RNA Virus). Ovine Progressive Pneumonia, (Maedi; Maedi-Visna Virus [Ovine Lentivirus], Enveloped RNA Virus). Caprine Pneumonia (Caprine Arthritis-Encephalitis Virus, Enveloped RNA Virus). Disorders of Pigs Porcine Reproductive and Respiratory Syndrome (Mystery Swine Disease; PRRS Virus, Arterivirus, Enveloped RNA Virus). Swine Influenza (Orthomyxovirus, Enveloped RNA Virus). Inclusion Body Rhinitis–Porcine Cytomegalovirus Infection (Herpesvirus-Cytomegalovirus, Enveloped DNA