Peripheral Arterial Disease

PAD is not a leg disease that happens to involve arteries — it is systemic atherosclerosis wearing a leg. Lipoproteins accumulate in the arterial wall, macrophages swallow them and become foam cells, a fibrous plaque forms, and the lumen narrows. Early on the artery dilates outward (positive remodeling) and preserves flow; as narrowing progresses, blood is diverted around the block through collateral vessels. Plaque accumulation is the cause in almost every case — vasculitis, arterial injury, and radiation are uncommon alternatives — and the vessels involved are, in order, the aortoiliac, femoropopliteal, and infrapopliteal segments. Peripheral vascular disease is the umbrella term; it includes this arterial disease and venous disease, two arms with opposite positioning and compression rules.

The exertional pattern is pure supply-and-demand. Resting blood flow in PAD is similar to a healthy adult’s — but during walking, blood cannot flow past the obstruction fast enough, so fixed oxygen delivery cannot match rising muscle oxygen demand and the muscle hurts. Rest lowers demand, and the pain resolves. Collaterals can maintain an asymptomatic state despite significant stenosis; claudication appears when the patient reaches the point at which collateral blood flow is maximized and cannot provide any additional perfusion. That collateral ceiling also explains why a prescribed walking program works: repeated walking to the point of pain promotes new collateral circulation, and the ceiling rises.

Where the pain lands tells you where the block is: the affected muscle group is one joint distal to the level of occlusion. Aortoiliac disease → buttock, hip, or thigh pain (aortoiliac occlusion can produce Leriche syndrome: buttock claudication, erectile dysfunction, and absent femoral pulses); femoropopliteal (superficial femoral) disease → calf pain; infrapopliteal/tibial disease → foot pain. Because the same plaque process is running in the coronary and cerebral beds, PAD carries an increased risk of myocardial infarction, stroke, and cardiovascular death — about one-third of PAD patients have concomitant coronary disease, and each additional diseased vascular bed raises the risk of major cardiovascular events stepwise.

The 2024 ACC/AHA guideline sorts PAD into four clinical subsets: asymptomatic PAD (20–59% of patients with proven PAD report no leg symptoms — many simply shrink their activity to stay below the ischemic threshold, and they carry functional impairment and cardiovascular risk comparable to claudicants); chronic symptomatic PAD, which includes claudication; chronic limb-threatening ischemia (CLTI); and acute limb ischemia (ALI). The guideline definition of claudication is worth memorizing verbatim: "fatigue, cramping, aching, pain, or other discomfort of vascular origin in the muscles of the lower extremities that is consistently induced by walking and consistently relieved by rest (usually within approximately 10 min)." Only about one-third of PAD patients have this textbook pattern — most have atypical exertional leg symptoms (pain both at rest and with exertion, or pain lasting longer than 10 minutes after stopping).

Two older staging systems still appear on exams. Fontaine: I asymptomatic · II intermittent claudication · III ischemic rest pain · IV tissue necrosis/gangrene. Rutherford (chronic): 0 asymptomatic · 1 mild, 2 moderate, 3 severe claudication · 4 ischemic rest pain · 5 minor tissue loss · 6 major tissue loss. Rest pain marks the moment atherosclerotic narrowing is so severe that flow cannot meet the resting metabolic demand of the limb: pain in the toes, dorsum of the foot, or ankle, worse at night and aggravated by lying supine. Wounds then open on the toes or distal forefoot, where perfusion is most compromised. CLTI is defined as chronic (more than 2 weeks) ischemic rest pain, non-healing wounds or ulcers, or gangrene attributable to proven arterial occlusive disease — and it requires urgent intervention. Reassuringly, most claudication is stable: only 1–3% per year progress to limb-threatening ischemia, and nearly 80% remain stable over 5 years.

Gravity explains the positioning rules and the classic exam finding together. With the artery nearly closed, perfusion pressure at the foot is barely enough — so raising the leg turns it pale (elevation pallor) while dangling it turns it red (dependent rubor) as gravity pulls blood through. Rest pain "usually resolves when the limb is placed in a dependent position, … which improves perfusion through gravity." That is why the ischemic patient hangs the foot over the side of the bed at 3 a.m., why the arterial ulcer is not elevated, and why relief of rest pain by dependency — not elevation — distinguishes arterial from venous insufficiency.

Every cell of the comparison table follows from one difference: arterial disease is too little blood arriving; venous disease is blood that cannot leave. Pain: arterial claudication comes with walking and eases with rest within about 10 minutes, and rest pain is nocturnal, worse supine or elevated, and relieved by dangling; venous pain is a throbbing, cramping ache or heaviness that worsens with prolonged standing and toward the end of the day, improves with rest and leg elevation, and has no association with exercise — that last feature is the discriminator. Pulses: arterial — diminished or absent, sometimes found only with Doppler; venous — pulses remain normal. Temperature: arterial — cool, one foot colder than the other; venous — skin feels warm. Skin color: arterial — pale when elevated, dusky or red when lowered, cyanotic or mottled; venous — dark, discolored, brown hemosiderin staining from pooled blood leaking iron into the skin, stasis dermatitis, lipodermatosclerosis.

Hair, nails, texture: arterial — hair loss, thickened brittle nails, shiny, tight, dry skin, calf muscle atrophy; venous — dry, rough, scaly skin with enlarged tortuous varicosities. Edema: arterial — not a feature (arterial wounds lack stasis changes); venous — ankle and lower-leg swelling that worsens through the day. Capillary refill: arterial — prolonged beyond 3 seconds. Ulcers: arterial ulcers sit on the toes, feet, heels, foot dorsum, and anterior leg, look "punched out" with well-defined borders, have a dry base with a pale or necrotic (black) center, and are usually painful unless coexisting neuropathy blunts it; venous ulcers sit on the medial lower leg over the medial malleolus (the gaiter area), are shallow and irregular with edges macerated by exudate, sit in a field of edema and hyperpigmentation, and cause mild-to-aching pain. Position and therapy: arterial — dangle, do not elevate, no compression (an ABI below 0.5 is an absolute contraindication to compression); venous — elevate above the heart at least 30 minutes three times a day, graduated compression is the main conservative component, plus calf-muscle exercise.

Chronic PAD can turn acute in minutes. Acute limb ischemia is acute (14 days or less) hypoperfusion of the limb from sudden arterial occlusion — in-situ thrombosis of a stenosed artery or bypass graft (graft occlusion within 14 days of surgery is a recognized scenario), or a cardiac embolus. The limb becomes ischemic, cold, painful, and numb: the 6 Ps — Pain, Pallor, Pulselessness, Poikilothermia (coldness), Paresthesia, Paralysis. The clock is set by muscle: skeletal muscle tolerates ischemia for about 4 to 6 hours, and the longer the symptoms are present, the less likely limb salvage becomes. ALI is diagnosed clinically, at the bedside, without waiting for imaging, using a handheld continuous-wave Doppler because pulse palpation is unreliable here: loss of the arterial Doppler signal means the limb is threatened; loss of both arterial and venous signals means it may be irreversibly damaged.

The Rutherford ALI classes tell you which limb can still be saved — and they read as a progression. I Viable: no sensory or motor loss, audible arterial and venous Doppler. IIa Marginally threatened: mild sensory loss limited to the toes, no motor loss, arterial Doppler often inaudible. IIb Immediately threatened: sensory loss beyond the toes plus motor weakness — requires immediate revascularization if salvage is to be accomplished. III Irreversible: complete anesthesia and paralysis with no venous Doppler — nonsalvageable. The teaching point: sensory loss precedes motor loss, so paralysis and complete numbness are the late, limb-lost signs, not the first cues.

Restoring flow has its own cost. Reperfusion releases oxygen free radicals that make capillaries leaky; fluid floods the closed osteofascial compartments of the lower leg (by far the most common site), venous outflow is compressed first, venous pressure climbs, and eventually arterial inflow falls — compartment syndrome, more likely after prolonged and more severe ischemia. Its earliest cue is pain out of proportion, often present only on passive stretch; paresthesia, pallor, pulselessness, and paralysis are late, and their absence does not exclude it. The ideal window for fasciotomy is within 6 hours, and it is not recommended after 36 hours. Reperfusion also washes muscle breakdown products into the circulation, so creatine kinase, renal function, and urine output are monitored alongside the leg.