Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.
Etiology of PAD:
The principal cause of PAD is atherosclerosis, which results from fatty deposits inside the arterial walls that reduce blood flow. Key risk factors include:
Pathophysiology of PAD:
The pathophysiology of peripheral artery disease (PAD) begins with endothelial dysfunction within the artery walls. Damage to the endothelium is typically caused by risk factors such as hyperlipidemia, hypertension, diabetes mellitus, and nicotine use. Following endothelial damage, low-density lipoprotein (LDL) accumulates within the arterial wall. Over time, these lipids oxidize, forming oxidized LDL, which is particularly harmful.
The presence of oxidized LDL triggers an inflammatory response. White blood cells, notably macrophages, migrate to the affected site, engulf the oxidized LDL, and transform into foam cells. These foam cells, accumulated lipids, and migrating smooth muscle cells contribute to plaque formation. This growing plaque is covered by a fibrous cap, which can either stabilize the plaque or lead to its rupture if the cap is weak.
As the disease progresses, the enlarging plaques harden and further narrow the arterial lumen, a condition known as stenosis. This narrowing reduces blood flow and leads to ischemia, where the tissues receive insufficient oxygen. Initially, this may cause claudication—pain or cramping in the legs during exercise.
When plaques rupture, they can trigger thrombus formation at the site, acutely blocking the artery and causing sudden, severe ischemia and potentially tissue death. However, the body may attempt to compensate for blocked arteries by developing collateral circulation. New blood vessels form around the blockages to improve blood flow, although this is not a cure for PAD.
Several contributory factors, including smoking, diabetes, obesity, a sedentary lifestyle, and high cholesterol, exacerbate the progression and severity of PAD. Each factor can independently accelerate atherosclerosis and exacerbate the symptoms and complications of PAD.
Peripheral artery disease, or PAD, is an atherosclerotic disease that leads to progressive narrowing of the arteries in the upper and lower extremities. It commonly affects the abdominal aorta, iliac, and femoral arteries.
The primary cause of PAD is atherosclerosis. However, it can also result from vascular inflammation, radiation exposure, diabetes, smoking, obesity, hypertension, and hypercholesterolemia.
These factors contribute to endothelial dysfunction, increasing the endothelium's permeability and allowing low-density lipoprotein, or LDL, to penetrate the intima.
Once inside, LDL oxidizes into inflammatory oxidized LDL, attracting macrophages. These macrophages engulf oxidized LDL, forming foam cells.
These cells accumulate to form fatty streaks, which are early signs of atherosclerosis.
As foam cells accumulate and inflammation persists, atherosclerotic plaque develops, comprising cholesterol, foam cells, calcium, and a fibrous cap.
Over time, unstable plaques with thin caps and large necrotic cores may rupture, exposing thrombogenic material, triggering clot formation, and potentially causing acute limb ischemia.
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