general Flashcards
end pathway of apoptosis?
activation of cytostolic caspases –> cellular breakdown
** ATP required
histologic features of apoptosis?
eosinophilic cytoplasm cell and nuclear shrinkage (pyknosis) basophilia membrane blebbing nuclear fragmentation (karyorrhexis) apoptotic body formation
what is DNA laddering?
sensitive indicator of apoptosis
endonucleases cleave DNA during karyorrhexis –> fragments in multiples of 180bp
radiation therapy effects on tumor cells?
apoptosis of tumors and surroudning tissue
free radical formation
dsDNA breakage
intrinsic pathway of apoptosis?
when regulating factor is withdrawn
increase in BAX and BAK (proapoptotic), decrease in Bcl-2 (antiapoptotic)
increased mito permeability and cytochrome c release
Bcl-2 function?
binds and inhibits Apaf-1 –> prevent cytochrome c release
Apaf-1 normally induces caspase activation
what happens with overexpression of Bcl-2?
Apaf-1 overly inhibited
decreased caspase activation
tumorigenesis
** e.g. follicular lymphoma
extrinsic pathway of apoptosis?
1) FasL binds Fas (CD95) –> multiple Fas molecules coalesce –> binding site for FADD –> binds/activates caspases
2) cytotoxic T cell –> perforin and granzyme B
defects in Fas-FasL cause what?
autoimmune disorders (needed for thymic medullary negative selection)
cell outlines preserved, increased cytoplasmic acidophilia?
coagulative necrosis
ischemia/infarcts in most tissues
** proteins denature –> enzymatic degradation
cellular debris and macrophages –> cystic spaces and cavitation?
liquefactive necrosis
bacterial abscesses, brain infarcts
** enzymatic degradation (lysosomal enzyme from neutrophils) –> proteins denature
fragmented cells and debris surrounded by lymphocytes and macrophages?
caseous necrosis
TB, systemic fungi
** macrophages wall off –> granular debris
outlines of dead fat cells without peripheral nuclei, dark blue on H&E?
fat necrosis
enzymatic (pancreatitis), nonenzymatic (breast trauma)
** cells –> lipase –> FAs in cell membranes broken down
thick and pink vessel walls?
fibrinoid necrosis
immune rxns in vessels
** immune complexes + fibrin –> vessell wall damage
types of gangrene?
ischemia –> dry gangrene – coagulative
superinfection –> wet – liquefactive
irreversible types of cell injury?
nuclear pyknosis, karyorrhexis, karyolysis
plasma membrane damage
lysosomal rupture
mitochondrial permeability/vacuolization
reversible types of cell injury?
cellular/mitochondrial swelling nuclear chromatin clumping decreased glycogen fatty change ribosomal/polysomal detachment membrane blebbing
area of brain susceptible to ischemia?
ACA/MCA/PCA boundary - watershed
area of heart susceptible to ischemia?
subendocardium (LV)
areas of kidney susceptible to ischemia?
straight segment of prox tubule
thick ascending limb
area of liver susceptible to ischemia?
zone III - around central vein
area of colon susceptible to ischemia?
splenic flexure, rectum - watershed
vascular component of inflammation?
increased vascular permeability
vasodilation
endothelial injury
cellular component of acute inflammation?
neutrophil
eosinophil
antibody