L28 - atherosclerosis Flashcards
describe vascular wall thickening
- what happens
- why?
- injury and normal aging leads to diffuse tunica intima thickening
- recruitment of SMCs int subendothelial compartment from media (SMC) or blood (SMC precursor)
- SMC phenotype = proliferative and synthetic (rather than contractile) leading to elaboration of ECM
define atherosclerosis and explain what happens?
form of arteriosclerosis characterized by fibrofatty lesions (atheromas) in tunica intima
- lesions protrude into vascular lumen
- cause obstruction –> ischemia
- weaken tunica media –> aneurysm
describe fatty streaks and atherosclerotic plaques and atheromas.
- which is worse?
- describe layers of atheromas
- fatty streak = early change in tunica intima
- atheroma precursor
- fatty deposits in subendothelia where there are bifurcations
- thickened subendothelial compartment separates from IEL
- possible foam cells - atherosclerotic plaques become atheromas
- atheromas are worst - irreversible with necrotic center
- inside = cell debris, oxidized LDL, foam cells
- outside = fibrous cap made of ECM components and collagen
# americans that die of IHC annually? increasing or decreasing #s?
500,000
- death rate from IHD/stroke is declining sicne 1963
what are the risk factors for development of atherosclerosis and IHD?
- 2 categories
- NONmodifiable
- age (risk incr. 5x between 40-60)
- sex (men > premenopausal women… women70-80=men)
- fmhx
- genetics (hypercholesterolemia) - Modifiable
- hyperlipidemia/cholestrol
- HTN
- smoking (1+ppd = 2x risk)
- DM (2x incidence of MI, 100x gangrene risk in LE)
- elevated C-reactive protein (inflammatory marker that increases adhesiveness of WBCs)
recommended guidelines for hyperlip and cholesterol?
total 45
TG <150
what is the effect of normal nitric oxide levels?
prevents adhesion of leukocytes and platelets to endothelium
pathogenesis steps of atherosclerosis?
- injury: low NO –> inc. adhesion of leuks/platelets
- accumulation of lipoproteins
- adhesion molecules: monocytes adhere to adhesion molecules and morph into macrophages in subendothelial space
- LDL oxidized: by endothelial cells, SMCs and macrophages ***IMPORTANT STEP - can be inhibited
- foam cells: monocytes and other leuks adhere to endothelium, –> macrophages which engorge lipids to become foam cells
- platelet adhesion (due to low NO)
- growth factors released by platelets, endothelial cells and macros –> recruit SMCs (from media/SMC precursors)
- SMCs change from contractile to proliferative/synthetic –> deposit ECM (+collagen - fibrous cap) –> thickening intima –> reduced patency of lumen
- lipids accumulate: SMCs engulge LDL –> more foam cells (atheroma)
what are the most abundant type of foam cell?
macrophages
- SMCs also have appetite for lipids but macros dominate
what things cause injury to the vascular endothelium?
hyperlip, HTN, smoking, toxins, viruses, immune reactions
which important step of atherosclerosis can be altered to prevent pathogenesis?
oxidization of LDL by endothelial cells/SMCs and macrophages
inhibiting oxidation step is research proven to protect against development of atherosclerosis
what are the 2 main clinical consequences of atherosclerosis?
ischemic heart disease (IHD) and cerebral infarcts
tell me about IHD
- frequency of arteries affected
- which is the widow maker?
- result/consequences
frequency of coronary narrowing:
40-50% = LAD - widow maker
30-40% = RCA
15-20% = circumflex
- arrhythmias
- acute rupture of cardiac wall of IV septum
- rupture of papillary muscles
- ventricular aneurysm
what is the wavefront phenomenon of cell death?
starts with death of INNER wall of myocardium (subendomyocardium) ad
proceeds outward toward subepicardium
- this is bc iner wall wors harder and needs greater nutrient supply (thus dies faster)
what do we use triphenyltetrazolium chloride for?
stain viable vs. nonviable areas
- viable cells contain LDH that ad appears red
- nonviable cells appear white
describe histology of acute MI
- current vs. precious infarct
- ruptures
- viable vs. nonviable cells
- previous infarcted area will appear white due to scar
- current infarct will appear yellow
- well healed MI shows blue collagen and red viable cardiac cells
- ventricular wall rupture appears dark gray/black
tell me about cerebral infarcts
- cause
- early microscopic changes
- later changes
- cause = blockage in cerebral vasculature
- early microscopic change (12-24 hrs post infarct) appears intense eosinophilic
- tissue damage –> infiltration of neutrophils –> clean up damage
- 10 days post infarct shows macrophages in damaged area + glial cells proliferate –> gliosis
what is gliosis?
scar tissue in CNS post CVA
