Cell Injury Dr. Peter Anderson, UAB Pathology

Cell Injury Atrophy Hypertrophy Hyperplasia Metaplasia

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

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 9

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

EQUILIBRIUM ROS Production ROS Removal 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 Conclusion Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved

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

Morphologic Characteristics 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

Cell Injury, Necrosis, & Apoptosis The End Cell Injury, Necrosis, & Apoptosis

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