Atherosclerosis of Pathophysiology

• Atherosclerosis is a chronic disease characterized by the buildup of lipids, inflammatory cells, and fibrous elements in large arteries.
• This Atherosclerosis process leads to the hardening and narrowing of arterial walls, which can result in serious cardiovascular events.

Below is an overview of atherosclerosis pathophysiology:

1. Endothelial Injury

   • Cause: Damage to the endothelial cells lining arterial walls due to factors like hypertension, smoking, or high cholesterol.
   • Effect: Increased permeability of the endothelium, allowing lipids to enter the arterial wall.

2. Lipid Accumulation

   • LDL Infiltration: Low-density lipoprotein (LDL) particles penetrate the damaged endothelium and accumulate in the intima (inner arterial layer).

3. Inflammatory Response

   • Oxidation of LDL: Accumulated LDL becomes oxidized, triggering an inflammatory reaction.
   • Monocyte Migration: Monocytes adhere to the endothelium, migrate into the intima, and differentiate into macrophages.

4. Foam Cell Formation

   • Engulfing Oxidized LDL: Macrophages ingest oxidized LDL, transforming into foam cells.
   • Fatty Streaks: Aggregation of foam cells forms fatty streaks, the earliest visible atherosclerotic lesions.

5. Fibrous Plaque Formation

   • Smooth Muscle Cell Migration: Smooth muscle cells move from the media (middle arterial layer) to the intima.
   • Extracellular Matrix Production: These cells proliferate and secrete collagen and other matrix components, forming a fibrous cap over the lipid core.

6. Plaque Progression

   • Growth: The plaque enlarges, narrowing the arterial lumen and impeding blood flow.
   • Calcification: Over time, plaques may harden due to calcium deposition.

7. Plaque Rupture and Thrombosis

   • Instability: Thin fibrous caps are prone to rupture.
   • Thrombus Formation: Rupture exposes underlying tissues, leading to blood clot formation that can further obstruct the artery or cause embolism.

Clinical Manifestations of Atherosclerosis:

• Coronary Artery Disease: Leading to angina or heart attacks.
• Stroke: Due to impaired blood flow to the brain.
• Peripheral Artery Disease: Causing pain and mobility issues in limbs.

Key Risk Factors of Atherosclerosis:

• Hyperlipidemia: High LDL and low HDL cholesterol levels.
• Hypertension: Elevated blood pressure damages arterial walls.
• Smoking: Causes oxidative stress and endothelial injury.
• Diabetes: Leads to endothelial dysfunction and promotes inflammation.
• Obesity and Sedentary Lifestyle: Contribute to unfavourable lipid profiles and hypertension.
• Genetic Predisposition: Family history increases risk.

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