Cardio-path- atheroscelosis Flashcards
What is the fundamental basis for the vast majority of vascular disorders.?
Injury to the vessel wall—and in particular to endothelial cells
Blooc vessel Endotherlial Cell injury/dysfunction may contribute to pathologic processes including thrombosis, hypertensive lesions and atherosclerosis.
vascular
Vascular injury leading to Endothelial Cell loss or dysfunction stimulates growth of what?
smooth muscle cells, extra-cellular matrix synthesis, and thickening of the vascular wall.
As a result of vascular injury, smooth muscles cells migrate to the ?
intima -SMCs then proliferate, synthesize ECM, forming a neo-intima covered by an intact EC layer.
Though Smooth muscle cell proliferation and matrix synthesis can help to repair a damaged vessel wall, it can also cause what negative effect?
lead to luminal occlusion.
What ) is characterized by intimal lesions called atheromas (atheromatous/atherosclerotic plaques) that impinge on the vascular lumen, and can rupture to cause sudden occlusion?
atherosclerosis
What pathology underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease, and causes more morbidity and mortality in the Western world than any other disorder!*?
atherosclerosis
Raised lesions composed of soft friable (crumbly) lipid cores covered by fibrous caps:
Atheromatous plaques
Thickness of the intimal lesions also may be sufficient to decrease perfusion of the , leading to ischemia and changes in the ECM caused by subsequent .
media, inflammation.
Subsequent tunica media hypoxia and inflammation from thick intimal atherosclerotoc plaques can weaken the media, and lead to the formation of?
aneurysms
What are constitutional risk factors?
non-modifiable
What is the most important independent risk factor for atherosclerosis?
Family history
Most familial risk is not related to , but related to multifactorial traits, including hypertension, and, diabetes
familial hypercholesterolemia
Familial hypercholesterolemia is a “receptor disease” caused by of-function mutations in the gene encoding the receptor, which is involved in the transport and metabolism of .
loss; LDL; cholesterol.
Describe the LDL receptor disesase familial hypercholesterolemia?
loss-of-function mutations in the gene encoding the LDL receptor
impair the intracellular transport and catabolism of LDL, resulting in accumulation of LDL cholesterol in the plasma.
elevated levels of cholesterol induce premature atherosclerosis and greatly increase the risk of MI.
Atherosclerosis is considered silent until about what age?
middle age or later
Which group of women are protected against atherosclerosis?
premenopausal women
Hyperlipidemial is a major risk factor, why?
The main cholesterol component associated with increased risk is low-density lipoprotein (LDL) cholesterol (“bad cholesterol”); LDL distributes cholesterol to peripheral tissues.
How does the liver get rid of excess cholesterol?
through the bile
HTN can increase the risk of ischemic heart disease by %
60
How does having diabetes affect your risk of MI?
the incidence of myocardial infarction is twice as high in diabetics vs. non-diabetics.
Smoking can the risk of IHD related mortality.
double
What is the response-to-injury hypothesis views atherosclerosis?
chronic inflammatory response of the arterial wall to endothelial injury.
the beginning of the pathogenesis of atherosclerosis begins with endotherial injury, which results in endotherlial - leading to increased , leukocyte , and thrombosis.
dysfunction; permeability; adhesion
What are the 3 suspected triggers of early atheromatous lesions?
HTN, hyperlipidemia, and toxins from cigarette smoke.
What type of lipoprotein accumulates to the vessel wall during plaque formation?
mainly oxidized LDL and cholesterol crystals
Is there platelet adhesion in the pathogenesis of atherosclerosis?
yes
Monocytes also adhere to endothelium in the atherosclerotic process, migrate to the , and differentiate into and then cells.
intima; macrophages, foam
Foam cells (macrophages with stuff inside) accumulate whiich can then release inflammatory .
lipids; cytokines
factors released from activated platelets, macrophages, and vascular wall cells lead to the recruitment of ?
smooth muscle cells to the intima
What contributes to the initiation, progression, and complications of atherosclerotic lesions?
inflammation
Early in atherogenesis dysfunctional express adhesion molecules that promote adhesion, in particular, monocytes and T cells which migrate into the intima under the influence of .
endothelial cells; leukocyte; chemokines
What leads to the “fatty streak” (earliest atherosclerotic lesion) in the vessel?
SMC Proliferation and Matrix Synthesis
What begin as minute yellow, flat macules that coalesce into elongated lesions, 1 cm or more in length?
fatty streaks
note: the fatty streaks are highlighted in red
Fattty streaks are composed of lipid-filled foamy macrophages but are only minimally raised and do/do not cause any significant flow disturbance.
do not
Foamy cells (macs with lipids) in intima
What are the 2 key features of atherosclerotic plaques?
intimal thickening and lipid accumulation
They are white to yellow raised lesions; they range from 0.3 to 1.5 cm in diameter but can coalesce to form larger masses.
Thrombus superimposed on ulcerated plaques gives a red-brown color.
Describe the morphology of an atherosclerotic plaque?
patchy, usually involving only a portion of any given arterial wall.
note: the image is a trichrome stain
blue is fibrosis
C is cholesterol
In descending order of severity, atherosclerosis involves mostly which 5 types of arteries?
- abdominal aorta,
- the coronary arteries,
- the popliteal arteries,
- the internal carotid arteries,
- the vessels of the circle of Willis.
What are the 3 main components of the atherosclerotic plaques?
(1) Cells, including SMCs, macrophages, and T cells;
(2) ECM, including collagen, elastic fibers, and proteoglycans; and
(3) Intracellular and extracellular lipid.
note: the red circles surround cholesterol (lipids)
Atheromas generally over time.
• They also often undergo .
enlarge; calcification
note: calcified plaque
Which vessel has the ulcerated plaque and which is occluded by a clot?
left image- rupture of plaque
right image- clot or thrombus
Which size of arteries are most likely to develop atherosclerosis?
Large elastic arteries (eg, aorta, carotid, and iliac arteries), and large- and mediumsized muscular arteries (eg, coronary, renal, and popliteal arteries) are the vessels most commonly involved.
What are some major consequences of peripheral vascular disease as it concerns the extremities?
gangrene of extremities)
ischemia of the heart, brain, kidneys, and lower extremities. • Myocardial infarction (heart attack), cerebral infarction (stroke), aortic aneurysm, and peripheral vascular disease (gangrene of extremities) are the major clinical consequences of?
atherosclerosis
What is acute plaque change?
plaque rupture causes mechanical obstruction and exposure of substances that promote platelet activation and thrombus generation
What % of a vessel needs to be considered critical stenosis, where tissue demand exceeds supply?
70% occlusion
What is stable angina?
pts have adequate cardiac perfusion, but with exertion, demand exceeds supply, and chest pain develops because of cardiac ischemia due to atherosclerosis
What are some effects of chronic aterial hypoperfusion due to atherosclerosis?
bowel ischemia, sudden cardiac death, chronic IHD, ischemic encephalopathy, and intermittent claudication (ischemic leg pain). -narrowed popliteal arteries
What typically triggers thrombosis?
Acute Plaque Change (plaque erosion or rupture)
Plaques that have a particularly high risk of rupturing, contain large numbers of foam cells and abundant extracellular lipid, have thin fibrous caps containing few smooth muscle cells, and contain clusters of inflammatory cells are considered?
vulnerable plaques
