pathology Flashcards
(52 cards)
apoptosis
- DNA laddering is a sensitive indicator of apoptosis - 180bp fragments
- radiation therapy causes apoptosis via free radical formation and dsDNA breakage
intrinsic pathway
- inc mitochondrial permeability and cytochorome c release
- Bcl decreased, BAX and BAK increase
- Bcl-2 is anti-apoptotic and inhibts Apaf-1 activation of caspases
extrinsic pathway
- via FasL-Fas (CD95) or immune cell release of perforin and granzyme B
- FasL used in thymic negative selection
- FADD binds caspases and activates them
- defects in FasL are responsible for auto-immune diseases
chromatolysis
- after axonal injury, inc protein synthesis to repair axon
- round cellular swelling, displacement of the nucleus to the periphery, and dispersion of Nissl throughout the cytoplasm
margination and rolling of neutrophils depends on which factors?
- vascular - E and P selectin, GlyCAM-1, CD34
- leukocyte - Sialyl Lewis and L selectin
tight binding of neutrophils depends on which factors?
- vasculature - ICAM and VCAM
- leukocyte - CD11/18 integrins, VLA-4 integrin
transmigration/diapedesis of leukocyte depends on which factors?
- vasculature - PECAM-1
- leukocyte - PECAM-1 (CD31)
chemotactic factors
C5a, IL8 LTB4, kallikrein, platelet activating factor
PDGF
secreted by activated platelets and macrophages, induces vascular remodeling and smooth muscle cell migration
- stimulates fibroblast growth for collagen synthesis
FGF
- stimulates all aspects of angiogenesis
EGF
- stimulates cell growth via tyrosine kinases (EGFR, ERBB2)
TGFbeta
angiogenesis, fibrosis, cell cycle arrest
metalloproteinases
tissue remodeling - secreted by macrophages - important for instability of atherosclerotic plaques
granulomatous diseases
bartonella, berylliosis, Churg-strauss, crohns, fanciesella tularensis, fungal infections (histo, blastomycosis), Wegeners, listeria, M leprae, M tuberculosis, treponema pallidum, sarcoidosis, schistosomiasis
granuloma formation
- macrophages secrete IL 12 that induces Th1 cells
- Th1 cells secrete gamma-interferon, activating macrophages
- TNFa from macrophages induce and maintain granuloma formation (check for TB before starting anti-TNFa)
deceased ESR
sickle cell, polycythemia, CHF
AL amyloidosis
- deposition of Ig Light chains, associated with MM
- nephrotic syndrome, restrictive cardiomyopathy, easy bruising, neuropathy, tongue enlargement
AA amyloidosis
- secondary amyloidosis
- seen with chronic conditions (RA, IBD, protracted infection)
- fibrils composed of serum Amyloid A, often multisystem
dialysis related amyloidosis
- B2 microglobulin deposits, may present as carpal tunnel
- B2 microglobulin provides structural support for MHC1 and is not filtered by dialysate
heritable amyloidosis
- ex: ATTR neuro/cardiac amyloidosis due to transthyretin gene mutation
senile systemic amyloidosis
- deposition of normal TTR in myocardium and other sites
- slow progression to dysfunction, usually asymptomatic
organ-specific amyloidosis
- alzheimers deposition of amyloid beta
- islet amyloid polypeptide (IAPP) in DM
- natriuretic peptide in atrial myocytes
lipofuscin
yellow-brown pigment associated with normal aging formed by oxidation and polymerization of autophagocytosed organellar membranes
- in the heart, liver, kidney, eye and other organs of old people
P glycoprotein
aka multidrug resistant protein (MDR1)
- expressed by some cancer cells to pump out toxins, including chemo
- is an ATP dep efflux pump that esp removes hydrophobic agents like antracyclines
