1. Necrosis Definition: Causes:

2. Development of Necrosis (2 mechanisms) irreversible damage to mitochondria (failure of ATP generation) ↓ anaerobic respiration ↓ lactic acid accumulation ↓ ↓ pH in intracellalar matrix ( ↑ acidity) ↓ activation of lysosomal enzymes ↓ proteolytic digestion of cell ↓ dead tissue cleaned away damage to cell membrane ↓ loss of phospholipids & damage due to lipid breakdown material ↓ cytoskeleton detached from cell membrane ↓ injury allows enzymes to escape into ECF ↓ Influx of Ca 2+ ions ↓ Ca 2+ causes permanent damage to mitochondria, inhibits cellular enzyme action & denatures protein ↓ characteristic cell changes (coagulative necrosis)

3. Cytoplasmic changes 1- Increased eosinophilia: Increased binding of eosin to the denatured protein Loss of basophilia of RNA 2- Glassy homogenous appearance: due to loss of glycogen particles. 3- Vacuolated cytoplasm: due to enzymatic degradation of the organelles.

4. Nuclear changes Pyknosis – shrinking & condensation Karyorrhexis – rupture of nuclear membrane Karyolysis – basophilia gradually fades

5. Types of Necrosis Coagulative necrosis (Ischaemia Infarction) Colliquative necrosis (Liquefactive necrosis) Caseous necrosis Fat necrosis -Enzymatic fat necrosis -Traumatic fat necrosis Gangrenous necrosis (putrefactive infection)

6. Coagulative necrosis

8. Many nuclei have become pyknotic (shrunken and dark) and have then undergone karorrhexis (fragmentation) and karyolysis (dissolution). The cytoplasm and cell borders are not recognizable.

9. Here is myocardium in which the cells are dying. The nuclei of the myocardial fibers are being lost. The cytoplasm is losing its structure, because no well-defined cross-striations are seen.

11. Liquefactive necrosis The necrotic tissue is rapidly liquefied. It occurs in: 1- Infarctions of the brain: due to high lipid and fluid content. 2- Pyogenic abscess: due to proteolytic enzymes released by pus cells 3- Amoebic abscess: due to liquefactive enzymes released by the parasite

15. Fat Necrosis Enzymatic Fat Necrosis Traumatic Fat Necrosis acute pancreatitis ↓ enzymes escape into surrounding tissue ↓ lipases hydrolyse true fat into glycerol & fatty acids ↓ fatty acids saponify or form soaps (white opaque masses or plaques) ↓ diagnostic of acute pancreatitis ↓ calcification may occur later rupture of cell membrane ↓ release natural fat into tissues ↓ phagocytosed by macrophages ↓ foamy appearance ↓ chronic inflammatory reaction ↓ fibrosis & scarring (no enzymatic fat breakdown)

16. Acute pancreatitis

17. Fat necrosis

18. Caseation necrosis Distinctive type of necrosis in which there is coagulative necrosis with slow liquefaction

19. Caseation necrosis