Flashcards : Atherosclerosis Pathogenesis and Clinical Implications — 35 cartes

Endothelial dysfunction is the initial step caused by risk factors like hypercholesterolemia, hypertension, and smoking, leading to increased permeability and adhesion molecule expression.

Chronic arterial disease with fatty deposits causing stenosis.

It promotes lipid infiltration, especially LDL oxidation, and fosters an inflammatory response that attracts monocytes, setting the stage for plaque formation.

Coronary, carotid, peripheral arteries.

LDL infiltration refers to low-density lipoprotein particles crossing the endothelium into the arterial wall, where they become trapped. Oxidation is the chemical modification of these LDL particles within the arterial wall, which triggers an inflammatory response and foam cell formation.

Endothelial dysfunction from risk factors.

Oxidized LDL promotes inflammation by attracting monocytes that ingested, become foam cells, and contribute to fatty streaks. It also weakens the fibrous cap of plaques, increasing the risk of rupture and thrombosis.

Oxidized LDL promotes inflammation and foam cells.

Foam cells are lipid-laden macrophages that result from monocytes ingesting oxidized LDL within the arterial wall, contributing to plaque formation.

Fatty streaks, fibrous plaques, complicated lesions.

Monocytes are attracted to endothelial injury sites where they migrate into the intima and differentiate into macrophages, which then engulf oxidized LDL to become foam cells.

Stable: collagen-rich; unstable: lipid-rich, rupture-prone.

The initial change is endothelial dysfunction, which allows lipids like LDL to infiltrate the arterial wall, initiating fatty streak formation.

>70-75% causes ischemic symptoms.

Foam cells are macrophages that have ingested oxidized LDL, and their accumulation within the intima leads to the formation of fatty streaks, an early stage of atherosclerotic plaque.

A fibrous plaque is a stage of atherosclerotic plaque characterized by a core of smooth muscle cells, collagen, and extracellular matrix forming a fibrous cap over the lipid core, providing stability to the plaque.

Collagen synthesis in fibrous plaques occurs mainly through smooth muscle cells migrating into the intima, which produce collagen that contributes to the formation of the fibrous cap, stabilizing the plaque and reducing the risk of rupture.

Advanced plaques are characterized by a lipid-rich necrotic core, which is an area of dead cells, lipids, and debris, surrounded by a fibrous cap. The necrotic core results from cellular death and lipid accumulation within the plaque.

The necrotic core makes plaques unstable and vulnerable to rupture, which can trigger thrombus formation and lead to acute ischemic events such as myocardial infarction or stroke.

Plaque stability refers to the likelihood of an atherosclerotic plaque to rupture. Collagen-rich plaques are considered stable because the collagen forms a fibrous cap that prevents rupture, whereas lipid-rich plaques with less collagen are vulnerable and more prone to rupture.

Higher collagen content in a plaque's fibrous cap contributes to its stability and reduces rupture risk, while decreased collagen makes the plaque more vulnerable to rupture, potentially leading to thrombus formation and clinical events.

Critical stenosis refers to the significant narrowing of an artery lumen, typically greater than 70-75%, which can impair blood flow and lead to ischemic symptoms.

Lumen narrowing, or stenosis, indicates the extent of atherosclerotic plaque buildup; when it exceeds a critical threshold (usually >70-75%), it often causes clinical symptoms due to reduced blood supply.

Plaque rupture occurs when the fibrous cap of an unstable atherosclerotic plaque breaks, exposing its lipid core to the bloodstream. This exposure triggers platelet adhesion and activation, leading to thrombus formation that can cause vessel occlusion and acute clinical events.

Thrombus formation at the site of plaque rupture can partially or completely occlude the artery, causing ischemia. In coronary arteries, this can result in myocardial infarction; in cerebral arteries, ischemic stroke; and in peripheral arteries, limb ischemia or gangrene.

Atherosclerosis mainly affects medium to large arteries such as coronary, carotid, and peripheral arteries. In the coronary arteries, it can lead to angina and myocardial infarction; in carotid arteries, it may cause stroke or transient ischemic attack (TIA); and in peripheral arteries, it can result in claudication or gangrene.

Stable plaques are collagen-rich and less prone to rupture, leading to chronic ischemic symptoms like stable angina. Unstable (vulnerable) plaques are lipid-rich and prone to rupture, which can trigger thrombus formation and result in acute events such as myocardial infarction or stroke.

The main modifiable risk factors include hypercholesterolemia, hypertension, smoking, and diabetes, all of which can be controlled or altered through lifestyle changes or medication.

Modifiable causes such as smoking, high cholesterol, and hypertension damage the endothelium, promote lipid infiltration, and stimulate inflammatory responses, thereby accelerating plaque formation and progression.

Many cases are asymptomatic until significant stenosis (>70-75%) causes ischemia. Chronic stable plaques may cause angina, while unstable plaques can rupture, leading to acute events like myocardial infarction, stroke, or limb ischemia.

Early stages are often asymptomatic; as plaques grow, they may cause stable angina or claudication. Rupture or erosion of vulnerable plaques results in acute events like heart attack, stroke, or gangrene, depending on the affected artery.

Progression in atherosclerosis involves the evolution of arterial wall changes from fatty streaks to complex plaques, characterized by lipid accumulation, fibrous cap formation, calcification, and potential rupture. Morphological changes include the development from lipid-laden foam cells to fibrous plaques, and eventually to complicated plaques with necrosis and hemorrhage.

Stable plaques are characterized by a thick, collagen-rich fibrous cap that reduces the risk of rupture, whereas unstable (vulnerable) plaques are lipid-rich with thin caps, making them prone to rupture and thrombosis, which can lead to acute events like myocardial infarction or stroke.

Endothelial dysfunction caused by risk factors such as hypercholesterolemia, hypertension, smoking, or diabetes triggers increased permeability and adhesion molecule expression, initiating lipid infiltration and inflammatory processes in the vessel wall.

Foam cells form when monocytes adhere to and migrate into the intima, where they differentiate into macrophages that engulf oxidized LDL cholesterol, resulting in lipid-laden foam cells that contribute to fatty streak formation.