cell death Flashcards
(22 cards)
cell death in living tissue
membrane damage - lysosomes leaks out - enter cytoplasm - digest the cell - cellular content leaks outside - elicits inflammation
necrosis
- due to ischemic injury (infarct)
- caused by denaturing of proteins within cytoplasm
- loss of the nucleus but preservation of cellular shape
- common in heart, liver and kidney but not brain
nuclear changes: pyknosis, karyorrhesis, karyolysis (loss of nuclear basophilia
coagulative necrosis
cellular destruction by hydrolytic enzymes, leading to autolysis and heterolysis
occurs in abscesses, brain infarcts, and pancreatic necrosis and also connected to bacterial infection
liquefaction necrosis
necrotic parenchymal cells and neutrophils
green color (infection, mito peroxidases)
pus
combination of coagulation and liquefaction necrosis
soft, friable and cheese like appearance
characteristic of granulomatous dz like tuberculosis
caseous necrosis
interaction of T lymphocytes, macrophages and cytokines (gamma interferons)
granulomatous inflammation
action of lipase on adipocytes and is characteristic of acute pancreatitis
chalky white appearance
- dystrophic calcification
1) traumatic - breast
2) enzymatic - acute hemorrhagic pancreatitis
fat necrosis
necrotic connective tissue resembles fibrin; end product of clotting cascade; blood vessels
often due to acute immunologic injury and vascular HTN damage
1) malignant HTN
2) Ag - Ab comely deposits in blood vessels wall
3) polyarteritis nodosa
fibrinoid necrosis
two types dry and wet
gangrenous necrosis
toes in diabetics; line of demarcation
dry gangrene
individual programmed cell death
apoptosis
cells shrink in size and has dense eosinophilic cytoplasm (acidophilic body)
pyknosis and karyorrhexis; cytoplasmic membrane blebs form next, leading to breakdown of the cell into fragments; phagocytosis of apoptotic bodies is by adjacent cells or macrophages
morphologic appearance in apoptosis
pro apoptotic proteins
bax
bak
bim
proteins inhibiting apoptosis
bcl 2
bcl-x
intrinsic apoptosis
1) bcl-2 inhibits cytochrome C release and binds with Apaf-1
2) Apaf-1 activates initiator caspase 9
3) caspase 9 activates caspases 3 and 6 (executioners) = cell death
extrinsic apoptosis
1) death receptors on cell surface - Fas and TNF-1
2) initiator caspase 8 activates caspases 3 and 6 (executioners) = cell death
stimulates apoptosis
elevated by DNA injury and arrests the cell cycle
increases production of pro apoptotic mitochondrial proteins (ex, bax)
p53
failure of cells to undergo apoptosis
1) syndactyly
2) hormone dependent apoptosis prior to menstruation
physiological examples of apoptosis
1) embryogenesis - loss of mullerian structures in male fetuses
2) hormone dependent apoptosis - menstrual cycle
3) thymus - selective death of lymhocytes
4) cell deletion in proliferating cell population - intestinal crypt epithelia)
pathological examples of apoptosis
1) council man bodies in viral (hep B)
2) graft v host
3) cystic fibrosis - duct obstruction and pancreatic atrophy
4) radiation, cytotoxic anticancer drugs
5) accumulation of misfold proteins - degeneration of brain
6) atrophy of parenchymal organs
7) cell death in tumor - cytotoxic CD8 T lymphocytes
necroptosis
part of extrinsic pathway
1) flip prevents apoptosis and virus can survive in the cell
2) release granzymes; dysfunction of mitochondria
3) decrease ATP and increase ROS
4) cell death by necrosis
apoptosis through activation of caspase 8 extrinsic pathway
present on the inner leaflet of the plasma membrane, but in apoptotic cells this phospholipid “flips” out and is expressed on the outer layer of the membrane, where it is recognized by several macrophage receptors
phosphatidylserine
