Флашкарти: Atherosclerosis Pathogenesis and Clinical Implications — 35 карти

What is the initiating event in the development of atherosclerosis related to endothelial dysfunction?

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

Atherosclerosis — definition?

Chronic arterial disease with fatty deposits causing stenosis.

How does endothelial dysfunction contribute to the initiation of atherosclerosis?

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

Affected arteries — examples?

Coronary, carotid, peripheral arteries.

What is LDL infiltration and oxidation in the context of atherosclerosis?

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.

Initiates with?

Endothelial dysfunction from risk factors.

Why is oxidized LDL considered a key factor in plaque formation and instability?

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.

Lipid infiltration — key component?

Oxidized LDL promotes inflammation and foam cells.

What are foam cells and how do they form in atherosclerosis?

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

Progressive stages?

Fatty streaks, fibrous plaques, complicated lesions.

What role do monocytes play in foam cell formation during atherosclerosis?

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 vs. unstable plaques — difference?

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

What is the initial cellular change involved in the development of fatty streaks in atherosclerosis?

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

Critical stenosis threshold?

>70-75% causes ischemic symptoms.

How do foam cells contribute to the accumulation of fatty streaks in arteries?

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.

What is a fibrous plaque in atherosclerosis?

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.

How is collagen involved in collagen synthesis within a fibrous 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.

What characterizes advanced plaques in atherosclerosis, and what is the necrotic core?

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.

Why is the necrotic core in advanced plaques clinically significant?

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.

What is plaque stability in atherosclerosis, and how is collagen content related to it?

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.

How does collagen content influence the risk of plaque rupture in atherosclerosis?

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.

What is critical stenosis in the context of lumen narrowing?

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.

How does lumen narrowing relate to the severity of atherosclerotic disease?

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.

What is plaque rupture and how does it contribute to thrombus formation?

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.

How does thrombus formation following plaque rupture lead to clinical consequences?

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.

Which arteries are primarily affected in atherosclerosis and what clinical events can result from involvement of each?

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.

What is the relationship between plaque stability and clinical events in atherosclerosis?

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.

What are the main modifiable risk factors for atherosclerosis?

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

How do modifiable causes contribute to the development of atherosclerosis?

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.

What are the typical symptoms and clinical spectrum of atherosclerosis?

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.

How does the clinical presentation of atherosclerosis vary across different stages or types?

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.

What is the process of progression in atherosclerosis and how do morphological changes occur?

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.

How do the morphological features of plaques influence their stability and risk of clinical events?

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.

What is the initial mechanism in atherogenesis that leads to plaque development?

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.

How do foam cells form during the process of atherogenesis?

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.