Aneurysm formation. Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes structural weakening that can lead to aneurysmal dilation and rupture.
Large elastic arteries (e.g., aorta, carotid, and iliac arteries) and largeand medium-sized muscular arteries (e.g., coronary, renal, and popliteal arteries) are the vessels most commonly involved by atherosclerosis. Accordingly, atherosclerosis is most likely to present with signs and symptoms related to 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.
The natural history, morphologic features, and main pathogenic events are schematized in
Figure 10.15 . The principal pathophysiologic outcome stemming from atherosclerotic lesions vary depending on the size of the affected vessel, the size and stability of the plaques, and the degree to which plaques disrupt the vessel wall. We next describe the features of atherosclerotic lesions that are typically responsible for the clinical manifestations.
At early stages, remodeling of the media tends to preserve the luminal diameter by increasing the overall vessel circumference. Owing to limits on remodeling, however, eventually the expanding atheroma may impinge on blood flow. Although this most commonly happens as a consequence of acute plaque change ( described next), it can also occur gradually, with critical stenosis being the tipping point at which chronic occlusion limits flow so severely
Fig. 10.14 Atheroscleroticplaquerupture.(A)Plaquerupturewithoutsuperimposedthrombus,inapatientwhodiedsuddenly.(B)Acutecoronarythrombosissuperimposedonanatheroscleroticplaquewithfocaldisruptionofthefibrouscap,triggeringfatalmyocardialinfarction.InbothAandB,anarrowpointstothesiteofplaquerupture.(B, Reproduced from Schoen FJ: Interventionalandsurgicalcardiovascularpathology:clinicalcorrelationsandbasicprinciples,Philadelphia, 1989, Saunders, p 61.)
Usually young age Usually middle age to elderly
At lesion-prone areas, and Cell death/degeneration accelerated by risk factors; Inflammation Endothelial dysfunction Plaque growth Monocyte adhesion/emigration Remodeling of plaque
SMC migration to intima and wall ECM SMC proliferation Organization of thrombus ECM elaboration Calcification
Fig. 10.15 Summaryofthenaturalhistory,morphologicfeatures,mainpathogenicevents,andclinicalcomplicationsofatherosclerosis.
that tissue demand exceeds supply. In the coronary artery (and other) circulations, this typically occurs when the vessel is approximately 70% occluded. At rest, affected patients have adequate cardiac perfusion; but with even modest exertion, demand exceeds supply, and chest pain develops because of cardiac ischemia (stable angina) (Chapter 11). The toll of chronic arterial hypoperfusion due to atherosclerosis in various vascular beds includes bowel ischemia, sudden cardiac death, chronic IHD, ischemic encephalopathy, and intermittent claudication (ischemic leg pain).
Plaque erosion or rupture typically triggers thrombosis, leading to partial or complete vascular obstruction and often tissue infarction (
Fig. 10.15 ). Plaque changes fall into three general categories:
Rupture/fissuring, exposing highly thrombogenic plaque constituents
Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood
Hemorrhage into the atheroma, expanding its volume