Pathophysiology of Atherosclerosis
*begins with injury to the vascular endothelium and progresses over many years
*initiated by smoking, hypertension, hyperlipidemia, and other factors.
*endothelium undergoes changes and stops producing the normal antithrombotic and vasodilating agents.
*The presence of inflammation attracts inflammatory cells, such as monocytes (macrophages).
*The macrophages ingest lipids, becoming “foam cells” that transport the lipids into the arterial wall.
*Some of the lipid is deposited on the arterial wall, forming fatty streaks.
*Activated macrophages also release biochemical substances that can further damage the endothelium by contributing to the oxidation of low-density lipoprotein (LDL). The oxidized LDL is toxic to the endothelial cells and fuels progression of the atherosclerotic process
*Following the transport of lipid into the arterial wall, smooth muscle cells proliferate and form a fibrous cap over a core filled with lipid and inflammatory infiltrate. These deposits, calledatheromas, or plaques, protrude into the lumen of the vessel, narrowing it and obstructing blood flow
*Plaque may be stable or unstable, depending on the degree of inflammation and thickness of the fibrous cap. If the fibrous cap over the plaque is thick and the lipid pool remains relatively stable, it can resist the stress of blood flow and vessel movement. If the cap is thin and inflammation is ongoing, the lesion becomes what is called vulnerable plaque. At this point, the lipid core may grow, causing the fibrous plaque to rupture.
*A ruptured plaque attracts platelets and causes thrombus formation.
*A thrombus may then obstruct blood flow, leading to acute coronary syndrome (ACS), which may result in an acute myocardial infarction (MI). When an MI occurs, a portion of the heart muscle no longer receives blood flow and becomes necrotic.The anatomic structure of the coronary arteries makes them particularly susceptible to the mechanisms of atherosclerosis.
*Atherosclerotic lesions most often form where the vessels branch, suggesting a hemodynamic component that favors their formation
*Although heart disease is most often caused by atherosclerosis of the coronary arteries, other phenomena may also decrease blood flow to the heart. Examples include vasospasm (sudden constriction or narrowing) of a coronary artery and profound hypotension.