Irreversible cell injury, apoptosis, necrosis, gangrene, etiology of cell injury, mechanisms of ischemia-induced cell injury, myocardial infarction, lymph/lymphatics, inflammatory cells, course of inflammation and healing

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Colorado State University
Biomedical Science
BMS 460
D.Rao Veeramachaneni

18 September Irreversible Cell Injury: Necrosis and Apoptosis Necrosis – group of cells Exogenous injury Swollen mitochondria and RER, nuclear clumping, ruptured cell membrane Nuclear fragments Pyknosis – clumping, condensation of chromatin Karyorrhexis – break-down Karyolysis Apoptosis – single cell Suicide gene activation Nuclear changes, cytoplasmic fragmentation Apoptotic bodies Events of Apoptosis Can be caused by receptor/ligand, injury, withdrawal of growth factors/hormones, &c. Execution caspases activated Cytoskeleton, &c. broken down Apoptotic bodies Types of Necrosis and Gangrene Necrosis Coagulative necrosis Ischemic cell injury, leading to Loss of plasma membrane’s ability to maintain electrochemical gradients, which results in Influx of Ca ions and dysfunction of mitochondria, and Degradation of plasma membrane and nuclear structures The general tissue architecture of coagulative area is preserved for weeks because of rapid inactivation of cellular hydrolytic enzymes Manifestations of coagulative necrosis are the same regardless of the cause of cell death Liquefactive necrosis Dead cells → acidic pH → activates lysosomal enzymes → liquefaction; occurs most often in the brain When dissolution of dead cells occurs rapidly because of liquefied area of lysosomal enzymes; an abscess or cyst may form Fat necrosis Death of adipose tissue; usually results from trauma or pancreatitis (release of digestive enzymes) Caseous (cheese-like) necrosis Characteristic of lung tissue damaged by tuberculosis Gangrene Dry gangrene is a form of coagulative necrosis characterized by blackened, dry, wrinkled tissue that is separated from adjacent healthy tissue. Wet gangrene results from liquefactive necrosis; typically found in internal organs, appears cold and black; may be foul smelling due to bacterial invasion – gaseous gangrene Cryoglobulinemic vasculitis – blood vessel inflammation, antibodies gather in extremities Associated with Hepatitis C Etiology of Cell Injury Ischemia (↓ blood) and hypoxia (↓ O )2 The most common cause Interruption of blood flow Reperfusion injury, free radicals Sudden onset results in cell death Necrosis When a large area is involved, necrotic tissue is visible in organs macroscopically Infarction Physical and mechanical Chemicals Nutritional Immunological Mechanisms of ischemia-induced cell injury Activated oxygen species: neutrophils Decreased oxygen delivery to the mitochondria causes ATP production to stall + + 2+ and consequently ATP-dependent Na , K , and Ca pumps fail This results in calcium overload Changes in metabolism of phospholipid bilayer and cytoskeletal damage Antioxidants do not produce free radicals Alterations in cell surface induce adhesion and activation of neutrophils These cells release large quantities of activated oxygen species, which then injure the previously ischemic cells Inflammation Post-perfusion injury by oxygen radicals Anoxia Proteolysis due to ischemia Swollen cell Catabolism of ATP, GTP and nucleic acids: abundant purines Reperfusion Necrotic cell Toxic oxygen species are generated not during the period of ischemia itself but rather on restoration of blood flow (oxygen) as accumulated purines get oxidized Proteolysis Xanthene dehydrogenase → Xanthene oxidase Xanthene oxidase and O act2on purines → uric acid + ↑↑ free radicals Myocardial Ischemia: Myocardial Infarction: Heart Attack Normal cardiac tissue consists of branching and anastomosing striated cardiocytes with a central nucleus and intracellular contractile myofilaments. Intercalated disks join individual cardiocytes. Myocardial ischemia caused by occlusion of the coronary artery results within the first 24 hours in the necrosis of cardiocytes. Cardiocytes display an eosinophilic cytoplasm lacking the characteristic intracellular striations detected in the adjacent unaffected cardiocytes. The nuclei are pyknotic (Greek, pyknos, dense, thick; osis, condition) and irregularly shaped. Lactic dehydrogenase-1 and creatine kinase MB-released from dead cardiocytes are detected in serum Creatine kinase (CK) is composed of two dimers, M and B. CK-MM isoenzyme predominates
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