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  1. 1. Outcomes of necrosis:-1.Inflammation & resolution occurs if the injury is mild & the tissue has the power to proliferate.2.Inflammation & organization (fibrosis). occurs if the injury is severe &/or the tissuedo not have the power to proliferate.3. Dystrophic calcification- deposition of Ca++salts in necrotic tissue.
  2. 2. Myocardial infarction (Posterolateral pale infarct) 2
  3. 3. Inflammation& fibrosis of severe burn 3
  4. 4. Aortic valve , gross , (calcified aortic stenosis). 4
  5. 5. APOPTOSISApoptosis come from the Greek word which means “falling off”.
  6. 6. Apoptosis• “A programmed active single cell death” that is induced by a tightly regulated intracellular program.Cells actually expend energy in order to die.• Causes of Apoptosis - Physiologic situations - Pathologic conditions
  7. 7. APOPTOSIS• NORMAL (preprogrammed)• PATHOLOGIC (associated with Necrosis)
  8. 8. Apoptosis in Physiologic Situations• Programmed destruction of cell during embryogenesis & development• Hormone-dependent tissue involution - endometrial cells (menstrual cycle)• Cell deletion in proliferating cell population e.g skin• Post-inflammatory clean up- neutrophils.• Cell death induced by cytotoxic T-cells to eliminate harmful cells - viral infected or tumor cells
  9. 9. Apoptosis in Pathologic Conditions• Cell death produced by injurious stimuli – radiation, cytotoxic drug• Cell injury in certain viral diseases – viral hepatitis• Pathologic atrophy• Cell death in tumors .
  10. 10. MORPHOLOGICAL FEATURES OF APOPTOSIS• Cell shrinkage• Chromatin condensation and fragmentation.• Formation of cytoplasmic blebs and apoptotic bodies.• Phagocytosis of apoptotic bodies by adjacent healthy cells or macrophages.• Lack of inflammation.
  11. 11. Morphology of ApoptosisCell shrinkageChromosomecondensationFormation ofcytoplasmic blebsand apoptotic bodiesPhagocytosis ofapoptotic cells or cellbodies
  12. 12. Cellular swelling, Membrane normalcell chromatin cluping damage The sequential ultrastructual changes in necrosis and apoptosisNuclear chromatin Cytoplasmic budding and Phagocytosisi ofcondensation and apoptosisi body apoptosis body fragmentation
  13. 13. Apotosis of hepatocytes
  14. 14. • Fig 1-18
  17. 17. APOPTOSIS BIOCHEMISTRY• Protein Digestion (Caspases)• DNAbreakdown (endonucleases)• Phagocytic Recognition
  18. 18. Comparison of cell death by apoptosis and necrosis
  19. 19. Comparison of cell death by apoptosis and necrosis Feature Necrosis ApoptosisMechanism injurious programmed passive cell death active cell deathCell size Enlarged ReducedExtent single cell group of cellsNucleus Pyknosis / karyorrhexis / karyolysis condensation & Fragmentation (Apoptotic bodies)Plasma membrane Disrupted IntactCellular contents swell& Enzymatic digestion Intact
  20. 20. Comparison of cell death by apoptosis and necrosisBiochemistry impairment & cessation of ion homeostasis Active DNA digestion lysosomes leak lytic enzymes by endonuclease lysosomes intactInflammation usual NoneFate of dead cells phagocytosed by inflammatory phagocytose by cells ( neutrophils & macrophages) macrophagesCause induced by pathologic stimuli induced by physiologic &pathologic stimuli