atherosclerosis Flashcards
what is arteriosclerosis?
hardening of the arteries
thickening and loss of elasticity of arterial walls
what is the pattern of monkeberg medical calcific sclerosis?
pattern of arteriosclerosis
calcific deposits in the muscular arteries
affects persons older than 50
do not encroach the vessel lumen
what does arteriolosclerosis affect (type of vessel)?
small arteries and arterioled
when is arteriolosclerosis common (in what patient populations)?
in hypertension and diabetes mellitus
what is the pathology of arteriolosclerosis?
thickening of the wall with narrowing of the lumen
what types of vessels does atherosclerosis affect?
large arteries
what is the pathology of atherosclerosis?
localized thickening of the wall with lumen thickening
what are the three patterns of arteriosclerosis (list)?
1: monkeberg medical calcific sclerosis
2: arteriolosclerosis
3: atherosclerosis
what type of disease is atherosclerosis? whom does it affect?
chronic inflammatory disease
affects every human being, but progresses with age and will be asymptomatic until a certain stage
what are the six different types of atherosclerosis lesion and what are the histological identifiers for each?
type 1: initial lesion
- isolated macrophage foam cells
type 2: fatty streak lesion
- mainly intracellular lipid accumulation
type 3: intermediate lesion
- type II changes and small extracellular lipid pools
type 4: atheroma lesion
- type II changes and core oc extracellular lipid
type 5: fibroatheroma lesion
- lipid core and fibrotic layer, or multiple lipid cores and fibrotic layers or many calcific layers, or many fibrotic layers
type 6: complicated lesion
- surface defect, hematoma-hemorrhage, thrombus
what is the sequence of progression of the types of atherosclerosis lesion?
two possible pathways:
1 –> 2 –> 3 –> 4 –> 5 –> 6
or
1 –> 2 –> 3 –> 4 –> 6
what is the main growth mechanisms of type 1-4 lesions in atherosclerosis?
growth mainly by lipid accumulation
what is the main growth mechanism of type 5 atherosclerosis lesions?
accelerated smooth muscle and collagen increase
what is the main growth mechanisms of type 6 atherosclerosis lesions?
thrombosis, hematoma
what are fatty streaks? (what population, where in body, precursor to?)
made by foam cells - occur because there's turbulent flow at these sites, and that activates the endothelial cells in children of all populations most prominent in aorta, near ostea reversible probably precursor of atheroma
what are the key processes of atheroma?
intimal thickening
lipid accumulation
what are the features of atheroma? (ie what would you see)
raised focal lesions
initiate into the intima
protrude into and obstruct the vascular lumen
weaken the underlying tunica media
soft grumous core of lipids (cholesterol and CE)
covered by endothelium or a fibrous cap
what is a fibroatheroma?
atheroma plus production of collagen => fibrofatty plaque
encroaches lumen
what are the potential complications of atherosclerosis complicated plaques?
calcification ulceration thrombosis hemorrhage into plaque severe destruction may lead to aneurysm atheroemboli
what is the endothelial injury hypothesis?
possible explaination for the pathogenesis of atherosclerosis
says that atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium
what sustains lesion progression in atherosclerosis (according to the endothelial injury hypothesis)?
interaction between modified (oxidized) lipoproteins, monocyte-derived macrophages, T-lymphocytes, and the normal constituents of arterial walls (endothelial cells, smooth muscle cells, matrix)
what are the steps in the pathogenesis of atherosclerosis as posited by the endothelial injury hypothesis?
1: chronic endothelial injury (due to hyperlipidemia, smoking, hypertension, homocysteine, toxins, viruses, immune reactions)
2: endothelial cell dysfunction (increased permeability, leukocyte adhesion) => monocyte adhesion and emigration
3: smooth muscle emigration from media to intima, macrophage activation
4: macrophages and smooth muscle cells engulf lipid
5: smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid - fibrofatty atheroma is formed
what are the constitutional (non-modifiable) risk factors of atherosclerosis?
age - dominant influene
gender - males more prone
genetic - familial predisposition
what are the modifiable risk factors for atherosclerosis?
hyperlidemia (low ration of HDL:LDL, hypercholesterolemia)
hypertension
cigarette smoking
diabetes mellitus
inflammation
increased blood homocysteine (due to vit B12 and folate deficiency or hypercystinuria (genetic))
metabolic syndrome
lipoprotein (a)
hemostasis imbalance
diet, obesity, lifestyle/stress, exercise
why does hypertension lead to atherosclerosis?
endothelial damage
thickening of vasa vasorum => diminished blood flow to the artery wall
smooth muscle cell proliferation
why does cigarette smoking lead to atherosclerosis?
nicotine is a vasoconstrictor
carbocyhemoglobin increases
nicotine inhibits prostacyclin synthesis
why does diabetes mellitus lead to atherosclerosis?
several deleterious mechanisms:
increased cholsterolemia
endothelial dysfunction
what is metabolic syndrome? how does it contribute to atherosclerosis?
insulin resistance, hypertension and central obesity
thought to be driven by abnormal adipose tissue signaling
mechanism: dyslipidemia –> endothelial dysfunction
what is the hypothetical sequence of cellular interactions according to the endothelial injury hypothesis?
process induced by chronic injury to the endothelium
recruits platelets and monocytes
monocytes migrate in, become macrophages
these uptake lipid - become foam cells
cytokines and growth factors make SMCs move in
these take up fat too, proliferate
can eventually rupture
