Transcript Cell Injury
Cell Injury Dr. Peter Anderson, UAB Pathology Cell Injury Atrophy Hypertrophy Hyperplasia Metaplasia Cell Injury Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved Conclusion Causes of Cellular Injury • • • • • • • Oxygen Deprivation Physical Agents Chemical Agents and Drugs Infectious Agents Immunologic Reactions Genetic Derangements Nutritional Imbalances Causes of Cellular Injury Oxygen Deprivation • Hypoxia – Decreased availability of oxygen • pneumonia – Loss of oxygen carrying capacity of blood • anemia • Ischemia – Insufficient blood supply – Occlusion of artery or vein Case Scenario 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 • You do a physical exam and draw blood for cardiac work-up. • The STAT blood work shows an elevated CK-MB and troponin I. • You send him for an emergency cardiac catheterization and possible angioplasty Coronary Arteriogram Myocardial Infarction Myocardial Infarction Morphology of Injured Cells • Reversible injury – cell swelling leading to hydropic change or vacuolar degeneration • Irreversible injury – cell death leading to necrosis – nuclear pyknosis followed by karyorrhexis and karyolysis Reversible Injury Hydropic Degeneration Morphology of Injured Cells • Reversible injury – cell swelling leading to hydropic change or vacuolar degeneration • Irreversible injury – necrosis – nuclear pyknosis followed by karyorrhexis and karyolysis Cell Death (necrosis) Cell Death Oxygen-Derived Free Radicals • Free radicals - chemical species that have a single unpaired electron in an outer orbit: O2 ; H2O2; ·OH; ONOO • Free radicals initiate autocatalytic reactions - propagate chain of damage 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 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 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-) 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 EQUILIBRIUM Fe2+ Vitamins A , C, E Glutathione peroxidase SOD, Catalase Transferrin ROS Production ROS Removal Pathologic Effects of ROS • Lipid peroxidation in membranes. • Oxidative modification of proteins. • DNA damage Cell Injury Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved Conclusion Necrosis & Apoptosis Types of Necrosis • • • • • • Coagulative necrosis Liquefaction necrosis Fat necrosis Caseous necrosis Fibrinoid necrosis Gangrenous necrosis Coagulative Necrosis • Dissolution of nucleus with preservation cellular shape and tissue architecture • Coagulation (denaturation) of cell proteins Coagulative Necrosis Coagulative Necrosis Liquefaction Necrosis • Hydrolytic enzymes cause autolysis and heterolysis (liquefacation) of cells/tissues • Examples: – Brain infarct – Abscess Liquefaction Necrosis Liquefaction Necrosis Liquefaction Necrosis Fat Necrosis • Destruction of adipose tissue due to the action of lipases • Examples: – Pancreatitis – Pancreatic trauma Pancreatic Fat Necrosis Pancreatic Fat Necrosis Pancreatic Fat Necrosis 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 Caseous Necrosis - TB Caseous Necrosis - TB Fibrinoid Necrosis • Necrotic tissue due to immunologic reaction • Usually seen in blood vessels with deposition of complement and antibodies in vessel wall Fibrinoid Necrosis Gangrenous Necrosis • Coagulative necrosis with 2o bacteria infection leading to liquefaction • Dry gangrene – coagulative necrosis is the predominant pattern • Wet gangrene – liquefactive process is the dominant pattern Gangrenous Necrosis Apoptosis Apoptosis • Programmed cell death Apoptosis • Physiologic Apoptosis – Embryogenesis – Hormone-dependent involution • menstrual cycle, lactating breast • Pathologic Apoptosis – Viral diseases leading to cell death – Injurious agents • anticancer drugs, radiation Apoptosis - Mechanisms • Activation of endonuclease • Cytoskeleton disruption by proteases • Cytoplasmic protein cross-linking by transglutaminase • Cell surface changes leading to phagocytosis Apoptosis Morphologic Characteristics • • • • • General cell shrinkage Chromatin condensation Bleb formation & apoptotic bodies Phagocytosis Lack of an inflammatory reaction Apoptosis Apoptosis Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved Apoptosis - Prostate The End Cell Injury, Necrosis, & Apoptosis The End Cell Injury Case Reviews: Interactive Pathology Laboratory Lab 1b Cellular Injury