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| Atherosclerosis |
| Etiology |
•Unknown. Although the role of risk factors
contributing to the pathogenesis is clear, the
problem is that there are a few privileged
individuals and experimental animals that are
resistant when challenged by risk factors.
Knowledge of the resistant factor(s) and their
mechanism(s) of action would lead to a solution
of the etiology. |
| Pathogenesis |
•Hypotheses: Endothelial damage (dysfunction)
with increased permeability, monocyte adhesion,
and endothelial proliferation; hyperlipidemia
with invasion of intima by foamy macrophages;
macrophage derived cytokines (IL-1, TNF) and
growth factors (PDGF, FGF) cause inflammatory
response and proliferation of smooth muscle
with sclerosis; plaque thickened by organization
of superimposed thrombi. |
| Epidemiology |
•Causes 50% of all deaths in
the U.S. due to
coronary, cerebral, peripheral, and mesenteric
vascular disease, and aortic aneurysms. •A disease of Western civilization. Absent in
certain third world ethnic groups. •Major risk factors are high animal fat diets,
hyperlipidemias, hypertension, cigarette
smoking, and diabetes. • Other important risk factors are obesity, male
gender, family history, and physical inactivity. |
| Clinical |
•Important clinical syndromes due to occlusive
disease are ischemic heart disease (angina
pectoris, myocardial infarction, congestive heart
failure), cerebral infarcts, peripheral vascular
disease with gangrene of legs, ischemic bowel
disease with infarction. Ruptured abdominal
aortic aneurysm also a significant cause of death. •Advanced age not an indicator of immunity
to atherosclerosis. Highest death rates by age
are in those over 85 years old:, 50 % or higher. |
| General Gross Description |
•Lesions in childhood appear as "fatty
streaks". •Adult plaques are discrete, yellow white
random elevations, more prominent around ostia
of large branches, abdominal aorta, and coronary,
popliteal, internal carotid, and cerebral arteries. •Plaques may have sclerotic firm surfaces, or
ulcerate with soft exposed grumous material. •Plaques may become confluent with thrombosis. •Severity increases with age, into very old age. |
| General Micro Description |
•An intimal lesion, made up of a deposition of
neutral fats, cholesterol esters, necrotic debris
and foam cells, with a variable chronic fibrotic
inflammatory response forming a superficial
fibrous cap containing smooth muscle and foam
cells and lymphocytes. •Complications are ulcers with thrombi, bleeding
into plaque, embolization of thrombi and/or
atheromas, calcifications, and atrophy of media
with formation of aneurysms. |
| Reference |
• Cotran RS,
Kumar V, Robbins SL. Robbins Pathologic Basis of Disease. 5th edition. Philadelphia, W.B. Saunders, 1994, pp. 473-484.
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