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  1. 1. Apoptosis Necrosis
  2. 2. Apoptosis• Cell death that is induced by a tightly regulated intracellular program “Programmed Cell Death”• Causes of Apoptosis - Physiologic situations - Pathologic conditions
  3. 3. Morphology of ApoptosisCell shrinkageChromosomecondensationFormation ofcytoplasmic blebs andapoptotic bodiesPhagocytosis ofapoptotic cells or cellbodies
  4. 4. Apoptosis in Physiologic Situations• Programmed destruction of cell during embryogenesis• Hormone-dependent involution - endometrial cells (menstrual cycle)• Cell deletion in proliferating cell population• Death of host cells - neutrophils• Elimination of self reactive lymphocyte• Cell death induced by cytotoxic T-cells - viral infected or tumor cells
  5. 5. 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
  6. 6. Intracellular Accumulations• Manifestation of “metabolic derangements” :intracellular accumulation of abnormal amounts of various substances Fat Protein Glycogen Pigments
  7. 7. Mechanisms ofintracellular accumulations(1) abnormal metabolism(2) alterations in protein folding and transport(3) deficiency of critical enzymes(4) inability to degrade phagocytosed particles
  8. 8. Intracellular Accumulations of Lipids• Accumulation of Lipids - Triglycerides - Cholesterol• Steatosis (fatty change) : abnormal accumulation of triglycerides within parenchymal cells – fatty liver in chronic alcoholism
  9. 9. Lipid circulation Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM) © 2005 Elsevier
  10. 10. Fatty liver Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM) © 2005 Elsevier
  11. 11. Intracellular Accumulations of Lipids• Cholesterol and Cholesterol Esters :Atherosclerosis - accumulation of cholesterol-laden macrophage (foam cell) and smooth muscle cells in the intima of aorta and arteries :Cholesterolosis - accumulation of foam cells in the lamina propria of gallbladder
  12. 12. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM) © 2005 Elsevier
  13. 13. Intracellular Accumulations of Proteins• Accumulation of protein droplets in proximal renal tubule - renal disease with heavy protein leakage across the glomerular filter
  14. 14. Protein reabsorption droplets in the renal tubular epithelium. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM) © 2005 Elsevier
  15. 15. Intracellular Accumulations of Proteins• Defects in protein folding :Defective intracellular transport and secretion :ER stress induced by unfolded and misfolded protein – cell death :Aggregation of abnormal folded protein - amyloidosis
  16. 16. Intracellular Accumulations of Glycogen“Patients with abnormal metabolism of glucose or glycogen”• Diabetes mellitus :disorder of glucose metabolism - glycogen accumulate in epithelial cells of renal tubules, liver cells, beta-cells of the islets of Langerhans and heart muscle cells
  17. 17. Intracellular Accumulations of Glycogen• Glycogen storage disease (Glycogenosis) - genetic diseases - defect of enzymes in the synthesis or breakdown of glycogen accumulation cell injury death
  18. 18. Accumulation of Pigments• Exogenous pigments Carbon ( anthracosis) Coal dust ( pneumoconiosis) Lung: pick up by alveolar macrophages regional lymph nods blackening the tissues of the lungs (anthracosis)
  19. 19. Accumulation of Pigments• Endogenous pigment :Lipofuscin – aging pigment lipid, phospholipid-protein complex (lipid peroxidation) :Melanin – in melanocyte :Hemosiderin – aggregates of ferritin micelles (iron + apoferritin = ferritin)
  20. 20. Pathologic Calcification• Abnormal tissue deposition of Calcium Salts• Two forms 1. Dystrophic calcification 2. Metastatic calcification
  21. 21. Pathologic Calcification Dystrophic Calcification - Area of tissue necrosis - Aging or damage heart valve - Atherosclerosis - Single necrotic cell “psammoma body”
  22. 22. Pathologic Calcification Metastatic Calcification - Occur in normal tissue in“hypercalcemia” Hypercalcemia • Hyperparathyroidism • Destruction of bone tissue • Renal failure
  23. 23. Morphology of Cell Injury and Necrosis• Cell Injury – Reversible – Irreversible• Cell Death – Necrosis – Apoptosis
  24. 24. Morphology of Cell InjuryReversible Injury Cellular swelling Fatty change• Plasma membrane alteration• Mitochondrial Changes• Dilation of Endoplasmic reticulum• Nuclear Alteration
  25. 25. Morphology of Necrotic Cells• Increased Eosinophilia - loss of RNA (basophilia) - denatured cytoplasmic protein• Nuclear Changes - Pyknosis - Karyorrhexis - Karyolysis• Myelin figure – large, whorled phospholipid mass (phospholipid precipitate)
  26. 26. HISTOLOGIC FEATURES OF COAGULATIVE NECROSISNormal cell Karyorrhexis Reversible cell injury with Irreversible cytoplasmic & cell injury Karyolysis organelle with rupture of swelling, blebb membrane & ing & organelles, & ribosome nuclear detachment pyknosis
  27. 27. Morphologic pattern of Necrotic Cell mass• Coagulative necrosis• Liquefactive necrosis• Caseous necrosis• Fat necrosis
  28. 28. Morphologic pattern of Necrotic Cell mass• Coagulative Necrosis :intracellular acidosis – protein denatured – proteolysis inhibited
  29. 29. Ischemic necrosis of the myocardiumA, Normal myocardium.B, Myocardium with coagulation necrosis
  30. 30. Morphologic pattern of Necrotic Cell mass• Liquefactive Necrosis :focal bacterial (or fungal) infections – accumulation of inflammatory cells :hypoxic death of cells within CNS
  31. 31. Coagulative and liquefactive necrosis A, Kidney infarct exhibiting coagulative necrosis B, A focus of liquefactive necrosis in the kidney
  32. 32. Morphologic Pattern of Necrotic Cell Mass• Caseous necrosis :gross appearance :microscopic – granulomatous inflammation
  33. 33. A tuberculous lung with a large area of caseous necrosis
  34. 34. Tuberculous granuloma showing an area of central necrosis, epithelioidcells, multiple Langhans-type giant cells, and lymphocytes.
  35. 35. Foci of fat necrosis with saponification in the mesentery
  36. 36. Ischemic injury
  37. 37. Mechanisms of Cell Injury Ischemic injury
  38. 38. Chemical injury Figure: Sequence of events leading to fatty change and cell necrosis in carbon tetrachloride (CCl4) toxicity. RER, rough endoplasmic reticulum; SER, smoothendoplasmic reticulum.Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:23 PM) © 2005 Elsevier