Atherosclerosis is a disease of the larger arteries. It begins in childhood with localized accumulations of lipid within the arterial intima, termed fatty streaks. By middle age some of these develop into atherosclerotic plaques, focal lesions where the arterial wall is grossly abnormal. Plaques may be several centimetres across, and are most common in the aorta, the coronary and internal carotid arteries, and the circle of Willis. An advanced atherosclerotic plaque, illustrated on the right of Figure 37, demonstrates several features.
1 The arterial wall is focally thickened by intimal smooth muscle cell proliferation and the deposition of fibrous connective tissue, forming a hard fibrous cap. This projects into the vascular lumen, restricting the flow of blood, and often causes ischaemia in the tissue region served by the artery.
2 A soft pool of extracellular lipid and cell debris accumulates beneath the fibrous cap (athera is Greek for ‘gruel’ or ‘porridge’). This weakens the arterial wall, so that the fibrous cap may fissure or tear away. As a result, blood enters the lesions and thrombi (blood clots) are formed. These thrombi, or the material leaking from the ruptured lesion, may be carried to the upstream vascular bed to embolize (plug) smaller vessels. A larger thrombus may totally occlude (block) the artery at the site of the lesion. This causes myocardial infarction or stroke if it occurs in a coronary or cerebral artery, respectively.
3 The endothelium over the lesion is partially or completely lost. This can lead to ongoing formation of thrombi, causing intermittent flow occlusion as in unstable angina.
4 The medial smooth muscle layer under the lesion degenerates. This weakens the vascular wall, which may distend and eventually rupture (an aneurysm). Aneurysms are especially common in the abdominal aorta.
Atherosclerotic arteries may also demonstrate spasms or reduced vasodilatation. This worsens the restriction of the blood flow and promotes thrombus formation (see Chapters 42 and 44).
Pathogenesis of Atherosclerosis
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