Pathoma: Cell Death Flashcards
What is the morphologic hallmark of cell death?
Loss of nucleus
3 ways cell death occurs
pyknosis, karyorrhexis, karyolysis
Pyknosis
shrinking of nucleus
Karyorrhexis
breaking up of nucleus
Karyolysis
nucleus broken down into building blocks
2 mechanisms of cell death
necrosis
apoptosis
Necrosis
death of a large group of cells followed by acute inflammation
Is necrosis pathologic or physiologic?
pathologic only
Coagulative necrosis
necrotic tissue that remains firm
cell shape and organ structure are preserved by coagulation of cellular proteins
Nucleus disappears
What is coagulative necrosis characteristic of?
ischemic infarction of any organ except brain
What is the shape and color of the necrotic tissue?
wedge-shaped and pale
wedge points to the area of occlusion
Red infarction
arises if blood re-enters a loosely organized tissue
testicle during testicular torsion due to the vein being blocked and blood filling testicle
Liquefactive necrosis
necrotic tissue that becomes liquefied
enzymatic lysis of cells and proteins–>liquefaction
What is liquefactive necrosis characteristic of?
brain infarction: because of microglial cells that contain hyrolytic enzymes
Abscess: neutrophils contain hyrolytic enzymes
pancreatitis: pancreatic enzymes activated
Gangrenous necrosis
coagulative necrosis that resembles mummified tissue (dry gangrene)
What is gangrenous necrosis characteristic of?
ischemia of the lower limb and GI tract
if superimposed infection occurs–>liquefactive necrosis ensues (wet gangrene)
Caseous necrosis
soft, friable necrotic tissue with “cottage cheese-like” appearance
coagulative and liquefactive necrosis
What is caseous necrosis characteristic of?
granulomatous inflammation due to TB or fungal infection
Fat necrosis
necrotic adipose tissue with chalky-white appearance due to deposition of Ca2+
Saponification
fat binding with Ca2+
FA released by trauma or lipase joins with Ca2+
example of dystophic calcification
What is fat necrosis characteristic of?
trauma to fat (e.g. breast)–>looks like a mass
pancreatitis-mediated damage of peripancreatic fat
Metastatic calcification
calcification that occurs in multiple tissues due to a high serum Ca2+ or phosphate; not cancerous
Fibrinoid necrosis
necrotic damage to blood vessel wall
leaking of proteins into vessel wall–>bright pink staining
What is fibrinoid necrosis characteristic of?
malignant hypertension or vasculitis
preeclampsia–>fibrinoid necrosis of placenta
Apoptosis
energy-dependent geneticaly programmed cell death
involves single cells or small groups of cells
NOT FOLLOWED BY INFLAMMATION
Physiologic examples of apoptosis
endometrial shedding during menstrual cycle
removal of cells during embryogenesis
CD8+ T cell-mediated killing of virally infected cells
Morphology of apoptosis
dying cell shrinks (becomes eosinophilic)
nucleus condenses and fragments
apoptotic bodies fall from cell and are removed by macrophages
What mediates apoptosis?
Caspases
Caspases
activate proteases (break down cytoskeleton) activate endonucleases (break down DNA)
3 pathways that activate caspases
intrinsic mitochondrial pathway
extrinsic receptor-ligand pathway
cytotoxic CD8+ T cell pathway
Intrinsic mitochondrial pathway
cell injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2
cytochrome c leads from inner mitochondrial membrane–>cytoplasm
Extrinsic receptor-ligand pathway
FAS ligand binds FAS death receptor (CD95) on target cell: negative selection during cell cycle of T cell in thymus
TNF binds TNF receptor on target cell
Cytotoxic CD8+ T cell pathway
perforins create pores in membrane of target cell
granzyme enters pores and activates caspases
