Pathophysiology of Intermittent Claudication

Intermittent Claudication

• Pain of intermittent claudication is most often localized to the calf due to superficial femoral and popliteal arteries being commonly affected by atherosclerosis
• Distal aorta and its bifurcation are the next most frequent sites of involvement, which can produce pain in the buttocks, thighs, and legs

Pathogenesis of Atherosclerosis

• Endothelial injury theory:
  • Injury leads to alteration of endothelial properties
  • LDL influx and binding to Glycosaminoglycans (GAG) in sub-endothelium
  • Modified LDL produces inflammatory response
  • Proliferation of smooth muscle cells, thickening of arterial wall, and narrowing of arterial lumen
  • Diffusion of free cholesterol into extracellular spaces, plaque formation, and plaque fracture leading to thrombosis

Clinical Picture

• Symptoms:
  • Asymptomatic arterial insufficiency
  • Symptomatic disease presenting as intermittent claudication (pain that develops with exercise and is relieved with rest)
  • Rest pain that increases at night and decreases with dependency and rubbing
  • Critical leg ischemia, which endangers part or all of the lower extremity
• Conditions associated with lower extremity arterial disease:
  • Arteritis (Thrombangitis obliterance, Rheumatoid arthritis, Systemic lupus erythematosis, Scleroderma, Kawasaki syndrome, Takayasu syndrome)
  • Vasospastic diseases (Reynaud's disease, Reynaud's phenomena)
  • Chronic on top of acute disease

Risk Factors

• Age: incidence of lower extremity arterial disease increases with age
• Male Gender: prevalence of intermittent claudication in women > 50 years is approximately 2.5%
• Diabetes Mellitus and Impaired Glucose Tolerance: diabetics have a sevenfold higher rate of lower extremity amputation
• Smoking: strong risk factor for development of lower extremity arterial disease
• Hypertension: linked to lower extremity arterial disease
• Hyperlipidemia: almost 50% of patients with lower extremity arterial disease have hyperlipidemia

Atherosclerosis

• Most common cause of chronic arterial occlusive disease of the extremities
• Arterial narrowing reduces blood flow to the lower limb >upper limbs
• Intermittent claudication denotes pain that develops in the affected limb with exercise and is relieved with rest

Treatment

• Unfractionated heparin or Low-Molecular-Weight Heparin (LMWH)
• Oral anticoagulation
• Open surgical treatment:
  • Embolectomy/thrombectomy
  • Bypass
• Thrombolysis:
  • Indications: viable or marginally threatened limb, recent acute thrombosis
  • Types: systemic, catheter-directed
  • Agents: streptokinase, urokinase, tissue plasminogen activator (TPA)
  • Contraindications: absolute and relative

Chronic Ischemia of Extremities

• Definition: arterial narrowing or obstruction resulting in reduced blood flow to the limb during exercise or at rest
• Etiology:
  1. Atherosclerosis