19. Depletion of ATP Mechanisms of Cell Injury Na + K + ATPase ( Na -pump ) , Ca 2+ Mg 2+ ATPases ( Ca -pump ) Causes Hypoxia, Ischemia Chemical Injury Membrane transport Protein synthesis, Lipogenesis etc ATP
64. HISTOLOGIC FEATURES OF COAGULATIVE NECROSIS Normal cell Reversible cell injury with cytoplasmic & organelle swelling, blebbing & ribosome detachment Irreversible cell injury with rupture of membrane & organelles, & nuclear pyknosis Karyorrhexis Karyolysis
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69. This is an example of coagulative necrosis. This is the typical pattern with ischemia and infarction (loss of blood supply and resultant tissue anoxia). Here, there is a wedge-shaped pale area of coagulative necrosis (infarction) in the renal cortex of the kidney.
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71. Ischemic necrosis of the myocardium A, Normal myocardium. B, Myocardium with coagulation necrosis
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74. Coagulative and liquefactive necrosis A, Kidney infarct exhibiting coagulative necrosis B, A focus of liquefactive necrosis in the kidney Figure 1-19 Coagulative and liquefactive necrosis. A, Kidney infarct exhibiting coagulative necrosis, with loss of nuclei and clumping of cytoplasm but with preservation of basic outlines of glomerular and tubular architecture. B, A focus of liquefactive necrosis in the kidney caused by fungal infection. The focus is filled with white cells and cellular debris, creating a renal abscess that obliterates the normal architecture.
75. The liver shows a small abscess here filled with many neutrophils. This abscess is an example of localized liquefactive necrosis
79. This is the gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy tan to white appearance. Caseous necrosis is really just a combination of coagulative and liquefactive necrosis that is most characteristic of granulomatous inflammation
80. T uberculous granuloma showing an area of central necrosis, epithelioid cells, multiple Langhans-type giant cells, and lymphocytes.
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82. Foci of fat necrosis with saponification in the mesentery
87. Morphology of Apoptosis Cell shrinkage Chromosome condensation Formation of cytoplasmic blebs and apoptotic bodies Phagocytosis of apoptotic cells or cell bodies
91. Labeled (1) are some of the major inducers of apoptosis. These include specific death ligands (tumor necrosis factor [TNF] and Fas ligand), withdrawal of growth factors or hormones, and injurious agents (e.g., radiation). (2) Control and regulation are influenced by members of the Bcl-2 family of proteins, which can either inhibit or promote the cell's death. (3) Executioner caspases activate latent cytoplasmic endonucleases and proteases that degrade nuclear and cytoskeletal proteins. This results in a cascade of intracellular degradation, including fragmentation of nuclear chromatin and breakdown of the cytoskeleton. (4) The end result is formation of apoptotic bodies containing intracellular organelles and other cytosolic components; these bodies also express new ligands for binding and uptake by phagocytic cells.
120. Different cells showdifferent sensitivities/thresholds. Examples: •Brain cells, heart cells susceptible to hypoxiaand ischemia; liver cells susceptible to chemical injury. •Calf muscletolerates 2-3h of ischemia, cardiacmuscle diesin20-30 min. •Highly differentiated surface epithelial cellsof therespiratorytract more susceptible to cigarette smokethan less differentiated basal epithelia. •Nutritional status – glycogen-replete hepatocyte moreresistant to ischemiathan depleted one
121. • Hypoxia - Oxygen deficiency • Ischemia - Impaired blood supply (arterial or venous occlusion) • Infarction - Area of necrosis due to ischemia
123. FOUR VULNERABLE SYSTEMS: • Cell membrane integrity • ATP generation / mitochondrial function • Protein synthesis / enzyme function • Genetic integrity
124. SIX GENERAL MECHANISMS: • ATP depletion (ox/phos or glycolysis) • Oxygen (i) – ischemia/hypoxia • Oxygen (ii) – ROS • Loss of Ca2+ homeostasis • Plasma membrane integrity • Mitochondrial damage
Normal cell has relative narrow range of functions and structure Limited changes in metabolism = homeostasis (increased Glc and TG metabolism in active contracting muscle) Stress = demands in excess of normal homeostatic changes leads to adaptations If stress exceeds adaptive response of cell - injury In addition, a variety of agents can directly injure cells (ie CN, , Hg, pH, temp, etc)
