Atherosclerosis and Intermittent Claudication

Arteritis

• Examples of arteritis include:
• Thrombangitis obliterance (Burger's disease)
• Rheumatoid arthritis
• Systemic lupus erythematosis
• Scleroderma
• Kawasaki syndrome
• Takayasu syndrome

Vasospastic Diseases

• Examples of vasospastic diseases include:
• Reynaud's disease
• Reynaud's phenomena

Risk Factors

• Age: incidence of lower extremity arterial disease increases with age
• Male Gender: higher prevalence of intermittent claudication in men
• Diabetes Mellitus and Impaired Glucose Tolerance: increased risk of lower extremity amputation
• Smoking: strong risk factor for development of lower extremity arterial disease
• Hypertension: linked to lower extremity arterial disease
• Hyperlipidemia: associated with a doubling of the incidence of intermittent claudication

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: pain that develops in the affected limb with exercise and is relieved with rest
• Pain usually occurs distal to the arterial narrowing or obstruction
• Superficial femoral and popliteal arteries are most commonly affected
• Distal aorta and its bifurcation are the next most frequent sites of involvement

Pathogenesis

• Endothelial injury theory:
  • Injury leads to altering of normal homeostatic properties of endothelium
  • LDL influx and binding to Glycosaminoglycans (GAG) in the sub-endothelium
  • Modified form of LDL produces inflammatory response
  • Proliferation of smooth muscle cells → thickening of arterial wall → narrowing of arterial lumen
  • Diffusion of free cholesterol into extracellular spaces
  • Plaque formation and plaque fracture → tissue thromboplastin → thrombosis

Clinical Picture

• Symptoms:
  • Asymptomatic arterial insufficiency
  • Symptomatic disease presenting as intermittent claudication
  • Rest pain increases at night, decreases by dependency and rubbing
  • Critical leg ischemia, which defines the subgroup of patients with symptomatic lower extremity arterial disease in which the ischemic process endangers part or all of the lower extremity

Thrombosis vs Embolism

• Onset:
  • Thrombosis: acute
  • Embolism: sudden
• Site:
  • Thrombosis: on top of a stenosis, calcified
  • Embolism: normal vessels, soft
• Previous complaint:
  • Thrombosis: symptoms of chronic ischemia
  • Embolism: rare
• Findings:
  • Thrombosis: evidence of peripheral arterial disease
  • Embolism: normal pulses
• Multiplicity:
  • Thrombosis: single site
  • Embolism: multiple sites
• Angiography:
  • Thrombosis: diffuse atherosclerosis, tapered and irregular cut off, developed collaterals
  • Embolism: no or minimal ASO, sharp cut off (Fontaine sign), multiple occlusions, no collaterals

Pathophysiology

• Depends on:
  • Degree of obstruction (complete or partial)
  • Site of occlusion
  • Presence of collaterals
  • Affected tissues
• Sluggish circulation distal to the occlusion → secondary thrombosis → occlusion of collaterals
• Different tissues can tolerate ischemia at different rates:
  • Brain and heart: most sensitive
  • Skin, subcutaneous, and muscles: less sensitive
• Nerves: first to be affected (irreversible damage after 6 hours)
• Muscles: more tolerant (up to 6-10 hours)
• Skin: last to show necrosis
• Cellular ischemia:
  • Alteration of cell wall permeability → Na+ and water influx → intra and extracellular edema → compartment syndrome
  • Release of K+ → hyperkalemia → cardiac arrest
  • Release of myoglobin after muscle infarction → precipitate in renal tubules → myoglobinuria and acute renal failure
• Accumulation of acidic products of anaerobic metabolism → metabolic acidosis
• During reperfusion, oxygen free radicals accumulate → cellular insult and necrosis