Pathology Flashcards
What are characteristics of apoptosis?
1) eosinophilic cytoplasm
2) cell / nuclear shrinkage
3) membrane blebbing
4) nuclear fragmentation (karyorrhexis)
5) apoptotic bodies which undergo phagocytosis
what are indicators of apoptosis?
1) DNA laddering. during karyorrhexis (nuclear fragmentation), endonucleases cleave at internucleosomal regions –> 180 bp fragments.
intrinsic pathway specific molecules
1) imbalance of anti- / pro apoptotic factors –> incr. mitochondrial permeability + CYTOCHROME C release.
2) BAX / BAK = pro APOPTOSIS
3) Bcl-2 –> prevents cytochrome C release / Apaf-1 mediated activation of caspases
2 pathways of extrinsic pathway
1) ligand receptor: FasL binding to CD95 [Fas]
2) immune cell mediated: cytotoxic T-cell release of perforin / granzyme B
example of Fas-FasL interaction
thymic medullary negative selection. defective Fas-FasL binding –> autoimmune disorders
differences b/w coagulative + liquefactive necrosis
1) coagulative = proteins denature first, followed by enzymatic degradation
2) liquefactive: lysosomal enzymes released followed by enzymatic degradation
difference b/w red vs. pale infarct
red = hemorrhagic –> loose tissues w/ multiple blood supplies, with injury due to reperfusion injury.
pale infarts = single blood supply –> solid tissues.
pathogenesis of granulomas
Th1 cells secrete y-interferon –> macrophage activation –> TNF-a secretion –> granuloma formation. TEST for LATENT TB before starting anti-TNF therapy as granulomas make breakdown and cause disseminated disease
primary amyloidosis
deposition of proteins from Ig Light chains (plasma cell disorder / multiple myeloma) (affects multiple organ systems)
AA amyloidosis
2ndary due to chronic conditions. fibrils of amyloid A –> multisystem
dialysis related amyloidosis
fibrils of B2-microglobulin w/ ESRD / long-term dialysis –> presents as carpal tunnel syndrome
age-related systemic amyloidosis
normal TTR deposition in myocardium / elsewhere. slow progression to cardiac dysfunction than AL amyloidosis
Alzheimer deposition
amyloid-beta protein from amyloid precursor protein cleaving
diabetes mellitus 2 deposition
islet amyloid polypeptide cdeposition in pancreatic islets
hyperplasia
increase in cell number
dysplasia
abnormal proliferation of cells w/ loss of size, shape, and orientation
carcinoma insitu
1) high N:C ratio
2) clumped chromatin
3) neoplastic cells have not invaded basement membrane
p-glycoprotein
multidrug resistance protein 1 (MDR1): expressed by colon / liver cancer to pump out chemotherapeutic agents
metaplasia
one adult cell type replaced by another, secondary to irritation
desmoplasia
fibrous tissue formation in response to neoplasm
association between tuberous sclerosis and neoplasm
giant cell astroctoma, renal angiomyolipoma, cardiac rhabdomyoma
BRAF
oncogene –. gain of function –> one damaged allele –> incr. cancer risk.
1) serine/threonine kinase
2) associated w/ melanoma
c-kit
Gastrointestinal Stromal Tumor (GIST)
BRCA1/BRCA2
tumor suppressor gene –> both alleles must be lost –> incr. cancer risk –> DNA repair protein
