092614 path of atherosclerosis Flashcards
examples of large or elastic blood vessels
aorta and major branches (innominate, subclavian, common carotid, iliac) and pulmonary artery
ex of medium sized or muscular arteries
coronary arteries
renal arteries
small arteries and arterioles are found where?
coursing within connective tissue of organs
diff btwn elastic and muscular arteries w respect to the media
in elastic artery, elastic fibers alternate btwn sm muscle cells in media
in muscular artery, the media has primarily sm musc cells; elastic fibers are limited to internal and external elastic lamina
arterioles’ elastic composition?
arterioles have thin internal elastic membrane
terminal arterioles have no elastica
what does medial sm musc contraction in arterioles cause?
adjustment of blood pres and blood flow
arterioles have thin internal elastic membranes and are points of physiologic resistance
size of capillaries in diameter
7-8 microns
what other cells can capillaries by surrounded by other than endothelium
pericytes (smooth musc like cells)
what are the vessels at which leukocytes emigrate in inflam?
venules
characteristics of veins
large lumen, thin wall
endothelial cells can do what
maintain barrier anticoagulant, antithrombotic, fibrinolytic regulators prothrombotic molecules make ECM modulate blood flow regulate inflam regulate cell growth oxidize LDL
how do endothelial cells respond to injury?
two types of response (in terms of timing):
stimulation–is immediate response. rapid and reversible. independent of new protein synthesis. an example would be contraction of endothelial cells in response to histamine
activation–elaboration of gene products with biologic activity requires hours or days to develop
how can endothelial cells be turned into activated state from its basal state?
by factors like turbulent flow, HTN, lipid products, advance glycation end-products, cigarette smoke, etc
what do endothelial cells in the activated state do?
increase expression of procoagulants, adhesion molecules, proinflammatory factors
alter expression of chemokines, cytokines, growth factors
role of vascular sm musc cells
vasoconstriction or dilation
making collagen, elastin, proteoglycans
elaboration of growth factors and cytokines
migration to intima and proliferation in normal vascular repair and pathologic processes such as atherosclerosis
what are pro-growth factors on the vascular sm muscle cells
PDGF, endothelin, thrombin, FGF, IFN-gamma, IL-1
what do sm musc cells do in response to vascular injury
migrate from media into intima
in intima, will undergo mitosis
then will make ECM
intima, as aresult, thickens
intimal sm musc cells are different from normal sm musc cells how?
they cannot contract
arteriosclerosis
hardening of the arteries
types of arteriosclerosis
atherosclerosis-elastic arteries and large/medium muscular arteries
arteriolosclerosis–small arteries and arterioles
Monckeberg medial calcific sclerosis
Monckeberg arteriosclerosis
calcific depositis in media and internal elastic lamina of MEDIUM sized muscular arteries (usually radial and ulnar arteries)
greater than 50 years of age
no obstruction to blood flow
ring shaped (vs eccentric for an atheroma)
usually not clinically significant
two basic types of damage in atherosclerosis
aneurysm formation
stenosis
morphology of fatty streak
multiple yellow, flat dots to streaks. usually in aorta and later in coronaries
may be a precursor of atheroma but not all fatty streaks develop into more advanced lesions
atheroma
fibrofatty plaque
how are lipids incorporated into macrophages?
LDL cholesterol is transported into vessel wall
then endothelial cells and monocytes or macrophages generate free radicals that oxidize the LDL, resulting in lipid peroxidation
oxidized LDL is taken up by macrophages through scavenger receptors
uptake of oxidized LDL activates macrophages and releases proinflammatory cytokines
morphology of fibro fatty plaque
RAISED yellow-white plaque in intima with soft yellow core and white fibrous cap
calcifications in Monckeberg vs fibro fatty plaque
fibro fatty plaques can have calcifications but they would be in the intima. Monckeberg has calcifications in the media
advanced or vulnerable plaques are at risk for
rupture ulceration, erosion, and hemorrhage leading to thrombosis/embolism, progressive luminal narrowing
atheroembolism
aneurysm formation
vulnerable plaque vs stable plaque
vulnerable plaque has a thin fibrous cap, lots of lymphocytes, and thick lipid core
stable cap has a thick fibrous cap, minimal finlam, and small lipid cores
if atherosclerotic plaque ruptures, what forms?
thrombus
what factors contribute to thrombosis
shear stress, high levels of LDL, smoking
aneurysm formation in atherosclerosis is due to
atrophy (due to pressure and or ischemia) of media and destruction of elastic fibers
leading to thinned, wakened wall
pathogenesis of atherosclerosis
chronic inflam response of arterial wall to ENDOTHELIAL INJURY
components: endothelial injury, hemodynamic distrubances, lipid accumulation, inflam, infection (possibly?), sm musc proliferation
strongly suspected causes of chronic endothelial cell injury
hemodynamic disturbances (areas of disturbed flow patterns)
hypercholesterolemia
HTN, smoking toxins, homocysteine, infectious agents
