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Cell Injury Dr. Peter Anderson, UAB Pathology

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Cell Injury Atrophy Hypertrophy Hyperplasia Metaplasia

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Cell Injury Conclusion Copyright 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved

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Causes of Cellular Injury Oxygen Deprivation Physical Agents Chemical Agents and Drugs Infectious Agents Immunologic Reactions Genetic Derangements Nutritional Imbalances

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Causes of Cellular Injury Hypoxia Decreased availability of oxygen pneumonia Loss of oxygen carrying capacity of blood anemia Oxygen Deprivation Ischemia Insufficient blood supply Occlusion of artery or vein

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A 65-year-old man comes to the emergency room because of crushing sensation in his chest and pain radiating to his jaw. Case Scenario

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You do a physical exam and draw blood for cardiac work-up. Case Scenario The STAT blood work shows an elevated CK-MB and troponin I. You send him for an emergency cardiac catheterization and possible angioplasty

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Coronary Arteriogram

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Myocardial Infarction

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Morphology of Injured Cells Reversible injury Reversible injury cell swelling leading to hydropic change or vacuolar degeneration Irreversible injury Irreversible injury cell death leading to necrosis nuclear pyknosis followed by karyorrhexis and karyolysis

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Reversible Injury

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Hydropic Degeneration

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Morphology of Injured Cells Reversible injury Reversible injury cell swelling leading to hydropic change or vacuolar degeneration Irreversible injury Irreversible injury necrosis nuclear pyknosis followed by karyorrhexis and karyolysis

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Cell Death (necrosis)

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Cell Death

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Oxygen-Derived Free Radicals Free radicals - chemical species that have a single unpaired electron in an outer orbit: O 2 ; H 2 O 2 ; OH; ONOO Free radicals initiate autocatalytic reactions - propagate chain of damage

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Oxygen-Derived Free Radicals Reactive oxygen species (ROS) are a type of oxygen-derived free radical ROS are produced normally in cells during mitochondrial respiration and energy generation ROS kept in low steady state levels by cellular scavenger systems

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Oxygen-Derived Free Radicals Oxidative Stress ROS production (e.g., inflammation) or a reduction in scavenging systems leads to an excess of free radicals: oxidative stress

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Generation of ROS Oxidation - reduction reactions Absorption of radiant energy Rapid bursts of ROS produced in activated leukocytes during inflammation Enzymatic metabolism of exogenous chemicals or drugs Transition metals - iron and copper Nitric oxide (NO) & peroxynitrite anion (ONOO - )

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Removal of ROS Antioxidants vitamins E, A, C and glutathione Iron and copper binding proteins transferrin, ferritin, lactoferrin, and ceruloplasmin Enzymes Catalase, Superoxide dismutases (SODs), Glutathione peroxidase

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ROS ProductionROS Removal Fe 2+ Vitamins A, C, E Glutathione peroxidase SOD, Catalase Transferrin EQUILIBRIUM

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Pathologic Effects of ROS Lipid peroxidation in membranes. Oxidative modification of proteins. DNA damage

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Cell Injury Conclusion Copyright 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved

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Necrosis & Apoptosis

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Types of Necrosis Coagulative necrosis Liquefaction necrosis Fat necrosis Caseous necrosis Fibrinoid necrosis Gangrenous necrosis

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Coagulative Necrosis Dissolution of nucleus with preservation cellular shape and tissue architecture Coagulation (denaturation) of cell proteins

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Coagulative Necrosis

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Liquefaction Necrosis Hydrolytic enzymes cause autolysis and heterolysis (liquefacation) of cells/tissues Examples: Brain infarct Abscess

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Liquefaction Necrosis

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Fat Necrosis Destruction of adipose tissue due to the action of lipases Examples: Pancreatitis Pancreatic trauma

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Pancreatic Fat Necrosis

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Caseous Necrosis Combination of coagulative and liquefaction necrosis Primarily found in the center of tubercles Inability to digest and remove material from center of granuloma

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Caseous Necrosis - TB

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Fibrinoid Necrosis Necrotic tissue due to immunologic reaction Usually seen in blood vessels with deposition of complement and antibodies in vessel wall

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Fibrinoid Necrosis

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Gangrenous Necrosis Coagulative necrosis with 2 o bacteria infection leading to liquefaction Dry gangrene coagulative necrosis is the predominant pattern Wet gangrene liquefactive process is the dominant pattern

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Gangrenous Necrosis

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Apoptosis

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Programmed cell death

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Apoptosis Physiologic Apoptosis Embryogenesis Hormone-dependent involution menstrual cycle, lactating breast Pathologic Apoptosis Viral diseases leading to cell death Injurious agents anticancer drugs, radiation

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Apoptosis - Mechanisms Activation of endonuclease Cytoskeleton disruption by proteases Cytoplasmic protein cross-linking by transglutaminase Cell surface changes leading to phagocytosis

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Apoptosis General cell shrinkage Chromatin condensation Bleb formation & apoptotic bodies Phagocytosis Lack of an inflammatory reaction Morphologic Characteristics

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Apoptosis

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Copyright 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved

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Apoptosis - Prostate

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The End Cell Injury, Necrosis, & Apoptosis

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The End Case Reviews: Interactive Pathology Laboratory Lab 1b Cellular Injury Cell Injury