Module 2: Mechanisms

Peripheral artery disease is explained through the process of atherosclerosis and how it leads to symptoms in the limbs. The main mechanism begins with irritation of the arterial lining, especially in medium and large arteries exposed to shear stress. Key contributors include smoking, hypertension, high LDL cholesterol, and diabetes. The summary then follows the progression from endothelial damage to endothelial dysfunction. Once the vessel lining becomes leaky, LDL enters the artery wall, becomes oxidized, and triggers an inflammatory response. Monocytes turn into macrophages, absorb LDL, and form foam cells, while smooth muscle cells migrate and produce a fibrous cap, creating plaque. At the same time, the artery wall becomes harder and less flexible. These changes narrow the vessel, disturb normal blood flow, and reduce oxygen delivery to muscles and other tissues. Symptoms are linked to a supply-demand mismatch, with reduced perfusion causing lactate buildup, acidity, and pain through stimulation of sensory nerve receptors. Later stages can involve hypoxia, tissue damage, ulceration, gangrene, rest pain, and even nerve-related problems such as paralysis. Collateral circulation may reduce or delay symptoms in some patients.