Peripheral Arteriovascular Disease

Key Concepts

Acute arterial occlusion is a limb-threatening emergency requiring early anticoagulation and Fogarty catheter embolectomy. The clinical diagnosis is based on some variant of the five Ps: pain, pallor, pulselessness, paresthesias, and paralysis. Confirmatory tests are unnecessary and increase the limb’s ischemic time.
Atheroembolism (blue toe syndrome) is associated with cool, painful cyanotic toes in the presence of palpable distal pulses. A proximal source should be localized, most often an atherosclerotic aneurysm in the aorta or the iliac, femoral, or popliteal artery.
Popliteal aneurysms are bilateral in 60% of patients and often coexist with an abdominal aortic aneurysm.
The classic Raynaud attack is triphasic: the fingers become pale, blue, and then red. Raynaud disease has no detectable underlying cause and usually has a benign course. Conversely, Raynaud phenomenon has an underlying disorder, usually connective tissue disease.
The only reliable clinical test for the detection of thoracic outlet syndrome is the elevated arm stress test (EAST).
Partial arterial lacerations continue to bleed, resulting in an expanding hematoma. Complete arterial transections initially have only moderate bleeding but can result in delayed hemorrhage. Blunt arterial injury may produce intimal disruption resulting in dissection, thrombosis, or obstruction. Arterial vasospasm can accompany injuries adjacent to the blood vessel, but spontaneous resolution always occurs in the absence of arterial disruption or intimal injury.
Aneurysms and arterial stenoses are characterized by a systolic murmur. Pseudoaneurysms, associated with prior surgical or trauma sites, are characterized by a loud systolic and possibly a separate, faint diastolic murmur. Arteriovenous fistulae are characterized by a harsh “to and fro” murmur associated with a palpable thrill.
Intra-arterial injection of illicit drugs into the brachial or radial artery is associated with immediate onset of severe, burning pain, and emergency department presentation with patchy blue-purple skin discoloration. Identifying the injection site helps confirm this syndrome, which can be associated with persistent ischemia and tissue loss.

Foundations

Arteries are classified into three categories based on their size and histologic features: (1) large or elastic arteries (the aorta and its immediate proximal, larger branches, including the innominate, subclavian, and common carotid, as well as the pulmonary arteries); (2) medium-sized or muscular arteries (located just distal to elastic arteries, including the common femoral, axillary, and internal carotid arteries); and (3) small arteries (usually <2 mm in diameter) that course in the substance of tissues and organs. This chapter considers diseases of medium and small arteries.

Background

Arterial Anatomy

All arteries possess three layers: the tunica intima, tunica media, and tunica adventitia. As peripheral arteries diminish in caliber, these three layers become progressively indistinct and are no longer identifiable at the level of the arteriole, the precapillary vessel containing smooth muscle.

The tunica intima has an inner lining of endothelial cells surrounded by subendothelial connective tissue. The single layer of continuous endothelium is a unique thromboresistant layer between blood and the potentially thrombogenic subendothelial tissues. The integrity of the endothelium is fundamental for the normal structure and function of the vessel wall. Endothelial injury results in intraluminal thrombosis and contributes to atherosclerosis.

The tunica media is made up primarily of circular or spiral smooth muscle cells arranged in concentric layers. The outer limit of this layer is marked by a well-defined, external elastic membrane. The elastic content of the tunica media gives resilience to medium-sized arteries. With age, elastic fibers deteriorate, replaced by fibrous tissue. This loss of elasticity results in stretching and elongation and accounts for the progressive tortuosity and development of arterial aneurysms with aging. In addition, vascular smooth muscle cells may contribute to lipid accumulation in the vessel wall during atherosclerosis, which precipitates vasoconstriction and dilation.

The tunica adventitia is a layer of connective tissue in which nerve fibers and small, thin-walled nutrient vessels (vasa vasorum) are dispersed. Medium-sized arteries contain more nerve fibers than larger vessels, reflecting their role in the autonomic regulation of blood flow.

The peripheral arterial vascular system can be considered as a single end-organ subject to eight basic pathophysiologic processes: (1) atherosclerosis, (2) aneurysm, (3) embolism, (4) thrombosis, (5) inflammation, (6) trauma, (7) vasospasm, and (8) arteriovenous fistula. Two of these—atherosclerosis and thrombosis—are responsible for most cases of the disease.

Pathophysiology

Atherosclerosis

Atherosclerosis is a disease of large- and medium-sized muscular arteries. The basic lesion, the atheroma, or fibrofatty plaque, is a raised focal plaque within the intima; it has a lipid core covered by a fibrous cap. As the plaques increase in size and number, they progressively encroach on the lumen of the artery and the adjacent media. Atheromas compromise arterial blood flow and weaken the walls of the affected arteries.

The distribution of atherosclerotic plaques is relatively constant. The abdominal aorta typically is susceptible to more atherosclerotic disease than the thoracic aorta, and aortic lesions are much more common and prominent around the ostia of major branches. Other vessels affected by atherosclerosis are the aortoiliac, femoral, and popliteal arteries; the descending thoracic aorta; the coronary arteries; the internal carotid arteries; and the circle of Willis. Upper extremity vessels are usually spared.

As atherosclerosis progresses, atheromas calcify, resulting in hard, brittle vessels. Rupture of the atheromatous plaques discharge debris, producing atheroemboli (cholesterol emboli). Ulcerated lesions produce in situ thrombosis, causing intraluminal occlusion. Hemorrhage into the plaque may further compromise the arterial lumen. Although atherosclerosis primarily affects the intima, in severe cases, the tunica media undergoes pressure atrophy and loss of elastic tissue, with sufficient weakening to create aneurysmal dilation.

Arterial Embolism

An embolus, by definition, is a foreign body, most commonly a blood clot, carried by the blood to a site distant from its point of origin. Most emboli are detached thrombus formations or thromboembolism. Less common emboli include debris from ruptured atherosclerotic plaques, tumor debris, or foreign bodies. Unless otherwise specified, the term embolus in this chapter is defined as thromboembolus.

Thromboembolism

Most arterial emboli (85%) originate from thrombus formation in the heart. Left ventricular thrombus formation resulting from myocardial infarction accounts for 60% to 70% of arterial emboli. Atrial thrombi associated with mitral stenosis and rheumatic heart disease account for only 5% to 10% of arterial emboli. Coexisting atrial fibrillation is present in 60% to 75% of patients with peripheral arterial embolic events because atrial fibrillation predisposes patients to intracardiac clotting.

Acute arterial emboli often cause distal tissue infarction. Clinical outcomes depend on the amount of collateral circulation, the size of the vessel, and the degree of obstruction. Patients with long-standing atherosclerosis have well-developed collateral circulation, whereas sudden occlusion of a normal artery without collateral pathways results in severe ischemia. After acute obstruction, the embolus can propagate proximally or distally, fragment and embolize further to distal vessels, or precipitate venous thrombosis by initiating a localized inflammatory reaction.

Because vessel diameters change abruptly at branch points, embolic occlusion most often occurs at major arterial bifurcations. The common femoral artery bifurcation is the most frequent site, accounting for 35% to 50% of all cases. The smaller femoral and popliteal arteries are involved twice as often as the larger aortic and iliac vessels, reflecting the small size of most emboli.

Arterial emboli, causing arterial occlusion and subsequent ischemia, result in cell death and produce elevated concentrations of potassium, lactic acid, and myoglobin in the extremity distal to the occlusion. Revascularization may result in sudden release, which can produce life-threatening hyperkalemia, metabolic acidosis, and myoglobinuria. This myonephropathic-metabolic syndrome accounts for approximately one-third of the deaths from an arterial embolism after revascularization.

Atheroembolism

Atheroembolism refers to microemboli consisting of cholesterol, calcium, and platelet aggregates dislodged from proximal complicated atherosclerotic plaques that lodge in distal end arteries. In the central nervous system, atheroemboli cause transient ischemic attacks and strokes. In the peripheral vascular system, atheroemboli characteristically cause cool, painful, and cyanotic toes, or the blue toe syndrome.

Atheroemboli are caused by proximally located arterial lesions, usually atherosclerotic plaques or aneurysms. Bilateral distal extremity involvement implies an aortic source, whereas unilateral atheroemboli usually arise from sites distal to the aorta. Distal lesions are most common in the femoropopliteal arteries (60%) and the aortoiliac arteries (40%). Aortic lesions (e.g., aneurysms, polytetrafluoroethylene grafts) are a less common source of microemboli.

Atheroemboli are small (100 to 200 μm in size). Single atheroembolic events seldom result in tissue loss, but atheroemboli tend to cluster. If unrecognized, repeated events ultimately result in the loss of collateral circulation, progressive symptoms, and extensive tissue infarction.

Infectious emboli from bacterial endocarditis can produce septic infarcts that may convert to large abscesses. Rarely, cardiac and noncardiac tumors or foreign bodies may gain access to the arterial circulation and embolize. Primary or metastatic lung neoplasms, malignant melanoma, and bullet emboli have been reported. With cyanotic congenital heart disease (e.g., patent foramen ovale), venous emboli may pass directly to the arterial circulation (paradoxical emboli). Although rare, this possibility should be considered in any patient with simultaneous arterial and venous emboli, particularly if a source of the arterial embolus is not evident.

Arterial Thrombosis

Thrombosis is the in situ formation of a blood clot within the uninterrupted arterial vascular system. Complicated atherosclerotic plaques are usually responsible for the two major factors that cause in situ thrombosis: endothelial injury and alterations in normal blood flow. Less common causes include acute vasculitis and trauma. Thrombosis is rare in normal arteries. Peripheral arterial thrombi are usually occlusive, firmly attached to the damaged arterial wall, and infrequently embolize. Clot propagation intensifies ischemia.

Aneurysms

A true aneurysm is an abnormal localized dilation of the intact vessel wall. With a pseudoaneurysm, the entire wall perforates or ruptures, and the extravasated blood is contained by the surrounding tissues, eventually forming a fibrous sac that communicates with the artery.

Mural and mechanical factors contribute to true aneurysm formation. The major cause of aneurysms is a weakness or defect in the integrity of the arterial wall. The only aneurysms that develop in a normal arterial segment are poststenotic aneurysms, such as with coarctation. Acceleration of flow past a narrow point creates slower flow beyond the stenosis lateral to the jet stream, producing increased lateral pressure. Aneurysmal dilation accelerates, increasing the risk of rupture as diameter increases, as described by Laplace’s law: tension (lateral pressure) in the wall of a hollow viscus varies directly with its radius (tension = pressure × radius).

The most common cause of aneurysms is severe atherosclerosis resulting from thinning and destruction of the tunica media. Atheromatous ulcers covered by mural thrombi are common. Mural thrombi form emboli that then lodge in distal vessels. When an entire aneurysm is filled with thrombus material, arterial occlusion results.

Aneurysms cause clinical symptoms through (1) rupture with subsequent hemorrhage, (2) impingement on adjacent structures, (3) occlusion of a vessel by either direct pressure or mural thrombus formation, (4) embolism from mural thrombus, and (5) a pulsatile mass.

Inflammation

Inflammatory arterial injury can be caused by drugs, irradiation, mechanical trauma, or bacterial invasion. The primary cause of arteritis is noninfectious systemic necrotizing vasculitis. Infectious arteritis is caused by direct invasion of the arterial wall. Septicemia, intravenous drug abuse, or infective endocarditis is most often responsible. Certain fungal infections, particularly aspergillosis and mucormycosis, are frequently associated with vasculitis and thrombosis.

Trauma

Vascular trauma results in characteristic pathologic syndromes. Partial arterial lacerations continue to bleed because the intact portion of the vessel wall prevents retraction and closure of the arterial wound. This may form an expanding hematoma. Complete arterial transection usually has only moderate or insignificant bleeding because of arterial spasm of the transected ends and the formation of a temporary thrombus. Delayed hemorrhage results from relaxation of arterial spasm, liquefaction of the thrombus, or displacement of the thrombus by arterial pressure.

Blunt injury produces intimal disruption. Dissection then leads to progressive obstruction and thrombosis. Vasospasm can accompany injuries adjacent to traumatized blood vessels; spontaneous resolution always occurs in the absence of arterial disruption or intimal injury.

Vasospasm

Vasospastic disorders (Raynaud disease, Raynaud phenomenon, livedo reticularis, acrocyanosis, erythromelalgia) produce an abnormal vasomotor response in distal small arteries. The cause is unknown but may be related to the autonomic innervation of peripheral arterioles. Vasospastic disorders are characterized by the presence of ischemic symptoms and the absence of tissue loss. The arterial wall does not demonstrate any pathology. In contrast, patients with digital ulceration and gangrene always have fixed arterial occlusions in distal extremity arteries.

Arteriovenous Fistulae

Abnormal communication between arteries and veins may result from congenital defects, arterial aneurysm rupture into an adjacent vein, penetrating injuries, and inflammatory necrosis. The artery proximal and veins distal to the fistula become distended, tortuous, and aneurysmal. Proximal and distal veins respond to alterations in hemodynamics with intimal proliferation and fibrosis, followed by a decrease in the internal elastic lamina, resulting in distention, tortuosity, and aneurysm formation. Chronic venous hypertension causes dermatitis and ulceration of overlying skin. The size of the fistula generally increases with time.

Approximately 60% of arteriovenous fistulae are associated with a false aneurysm. False aneurysm formation can occur as part of the fistulous tract or arterial or venous dilation. Increase in cardiac output results in tachycardia, widened pulse pressure, or high-output failure.

Clinical Features

History

Patients with peripheral arterial disease have pain and are at risk for tissue loss (ulceration or gangrene) or a change in sensation or appearance (swelling, discoloration, or temperature change). Related conditions suggest atherosclerosis, including cardiac disease, myocardial infarction, cardiac dysrhythmias (e.g., atrial fibrillation), stroke, transient ischemic attacks, and renal disease. Factors that increase the likelihood of atherosclerosis are cigarette smoking, diabetes, hypercholesterolemia, and hypertension. Intravenous drug use can lead to arterial injury. Risk factors unrelated to atherosclerosis include prior injuries or surgeries, a history of phlebitis or pulmonary embolism, autoimmune disease, arthritis, or coagulation abnormalities.

Physical Examination

A systematic assessment of the peripheral vascular system includes palpation of the pulse volume in the pairs of brachial, radial, femoral, posterior tibial, and dorsalis pedis arteries documented on a scale of 0 to 4+. It is important to note that approximately 10% of the population does not have one of the dorsalis pedis pulses.

The lower extremities should be examined for signs of chronic and advanced ischemia. Muscular atrophy, particularly in the lower extremities, and loss of hair over the toes and feet with thickening of the toenails resulting from the slowness of nail growth are common signs of arterial insufficiency. As ischemia becomes more advanced, the skin becomes shiny, scaly, and “skeletonized” from atrophy of the skin, subcutaneous tissue, and muscle.

Test areas where ischemia is suspected by blanching with finger pressure; a delay in the return of normal color (compared with the unaffected extremity) implies reduced perfusion. Buerger sign provides reliable evidence of severe advanced ischemia. With the patient supine, the legs are elevated to 45 degrees to bring the feet more than 12 inches above the right atrium, and any pallor of the feet is noted. If the color does not change, the patient dorsiflexes the feet five or six times; pallor induced by exercise may also connote inadequate arterial flow. The patient is then moved to the sitting position with the feet hanging down. Within 10 to 15 seconds, color should return, and the veins should fill. Typically in the ischemic foot, the first return of color is cyanosis, transitioning to bright red as reactive hyperemia occurs. If the veins require more than 20 seconds to become distended, advanced ischemia is present. With severely restricted arterial inflow and chronic dilation of the peripheral vascular bed, the foot turns pale on elevation and intensely hyperemic after 1 minute of dependency. Localized pallor or cyanosis associated with poor capillary filling is usually a prelude to ischemic gangrene or ulceration.

Doppler ultrasonography should be used in patients with questionable or absent pulses. The ankle-brachial index (ABI) is made by comparing the systolic blood pressure at the level of the ankle with the brachial systolic pressure. Ankle systolic pressure can be accurately measured with a Doppler probe placed over the dorsalis pedis or posterior tibial artery. This pressure is normally 90% or more of the brachial systolic pressure; with mild arterial insufficiency, it is between 70% and 90%; with moderate insufficiency, between 50% and 70%; and with severe insufficiency, less than 50%.

The Allen test is helpful in assessing the patency of the radial or ulnar artery distal to the wrist. The patient initially opens and closes the hand and then clenches the fist to expel as much blood from the hand as possible; the examiner then compresses the radial and ulnar arteries. When the patient opens the fist, the hand is pale. The examiner then releases pressure from the radial artery but maintains it on the ulnar artery. If the radial artery is patent, the hand becomes pink rapidly; occluded, the hand remains pale. The maneuver is repeated maintaining pressure on the radial artery, releasing the ulnar artery. A comparison can be made with the opposite hand.

Inflammation

Inflammatory vascular disease manifests primarily as skin involvement. Skin lesions typically appear as palpable purpura; other cutaneous manifestations of vasculitis include macules, papules, vesicles, bullae, subcutaneous nodules, ulcers, and recurrent or chronic urticaria. Skin lesions may be pruritic or painful, with a burning or stinging sensation. Lesions are common in dependent areas: lower extremities in ambulatory patients or sacral areas in bedridden patients. Edema and hyperpigmentation occur in areas of recurrent or chronic lesions.

Vasospasm

Vasospastic disorders cause a sharp border between ischemic and normal tissue. Raynaud disease is characterized by intermittent attacks of triphasic color changes: pallor, cyanosis, and then rubor. The most important element is pallor, and during which, the digits turn pale. Attacks last 15 to 60 minutes, and rewarming the hands restores normal color and sensation. Color changes do not occur above the metacarpophalangeal joints and rarely involve the thumb.

Livedo reticularis causes persistent cyanotic mottling of the skin with a typical “fishnet” appearance and may involve all parts of the extremities and trunk. Acrocyanosis, the least common vasospastic disorder, causes persistent, painless, diffuse cyanosis of the fingers, hands, toes, and feet. Cyanosis intensifies with exposure to cold and decreases with warming. The involved parts are cold, exhibit excessive perspiration, and have normal arterial pulses.

Differential Diagnosis

The differential diagnosis related to peripheral arteriovascular diseases is extensive, requiring consideration of dermatologic, neurologic, neurosurgical, orthopedic, cardiac, malignant, diabetic, infectious, and other unrelated diagnoses. The differential diagnosis for specific arteriovascular diseases is reviewed in detail in the following sections.

Diagnostic Testing

An accurate diagnosis of peripheral arterial occlusive disease can be achieved in most patients by careful history and physical examination supplemented by bedside and radiographic testing.

Noninvasive Assessment

Doppler ultrasonography measures blood flow velocity, detecting the frequency shift of sound waves reflected from red blood cells moving toward and away from the transducer. Doppler waveform analysis detects occlusive disease but is less accurate in determining the exact location.

Ultrasound is useful in detecting and evaluating atherosclerotic plaques, mural thrombi, and in sizing aneurysms of the abdominal aorta, iliac, femoral, and popliteal arteries. B-mode ultrasonography is noninvasive, painless, less expensive than other modalities, and universally available. It is the diagnostic procedure of choice for the initial evaluation of the size of peripheral artery aneurysms. Bedside ultrasound can lead to rapid diagnosis of life-threatening conditions and reduce the number of delayed or invasive diagnostic procedures. B-mode duplex ultrasonography combines B-mode ultrasonography images and sophisticated online computer analysis of Doppler waveforms to allow simultaneous acquisition of both the image of a vascular structure and the characteristics of blood flow velocity within it. Duplex scanning permits noninvasive diagnosis of peripheral vascular, cerebrovascular, and venous disease.

Color imaging of blood flow combined with duplex scanning is known as color-coded Doppler, Doppler angiography , or angiodynography. The procedure of choice for most conditions, it allows noninvasive and accurate detection of atherosclerotic plaques and stenoses, their effect on intraluminal blood flow, and the presence of venous thrombosis.

Contrast Arteriography

Angiography is the definitive test of abnormal peripheral artery anatomy. The risk/benefit ratio of this procedure should be considered. Contrast media have direct toxic effects on vascular endothelium and can cause severe idiosyncratic and allergic reactions. The risk of acute kidney injury with contrast media is debated, but it may worsen renal function in patients with a preexisting decrement in the glomerular filtration rate. Catheter-related complications, including embolization, catheter breakage, and vascular disruption, vary with operator skill and anatomic location but average 0.5%. Overall mortality rate from angiography is 0.03%. Emergency angiography may be necessary in the following circumstances: (1) acute arterial embolus or thrombosis if the clinical diagnosis is uncertain, (2) consideration of emergency vascular bypass grafting, and (3) characterization of vascular abnormality before emergency surgical correction. Otherwise, traditional angiography has largely been replaced by computed tomography angiography.

Computed Tomography and Magnetic Resonance Imaging

Computed tomography angiography (CTA) is the most useful test for evaluating the abdominal aorta. In the peripheral arteriovascular system, CTA has replaced invasive arteriography as the diagnostic procedure of choice for assessing peripheral arterial occlusive disease and is also useful for atherosclerotic, infected, and false aneurysms and the cerebral circulation. Magnetic resonance imaging (MRI) with angiography (magnetic resonance angiography) and has been beneficial in delineating cerebrovascular problems (see Chapter 101 ); use has expanded in the evaluation of peripheral vascular disease. MRI detects changes in tissues’ relaxation variables before obvious structural changes, uniquely differentiating blood, thrombus, fat, and fibrosis.

Management

Noninvasive Therapy

Acute Anticoagulation with Heparin

For acute arterial embolism, acute arterial thrombosis, and subclavian vein thrombosis, heparin is indicated at standard intravenous doses (80 units/kg bolus, followed by a maintenance infusion of 18 units/kg/hr). Heparin minimizes clot propagation, which can intensify limb ischemia and jeopardize tissues. Relative contraindications include recent neurosurgery (especially within 2 weeks), major surgery within 48 hours, childbirth within 24 hours, a known bleeding diathesis, thrombocytopenia, a potentially hemorrhagic lesion, and active bleeding.

Fibrinolytic Therapy

Low-dose intra-arterial fibrinolytic therapy is increasingly used for acute arterial occlusion. Patients with limb-threatening ischemia are usually not candidates because they cannot tolerate the time to achieve clot lysis with this approach (6 to 72 hours) without risk of tissue or limb loss. Fibrinolytic therapy is reserved for patients with in situ thrombosis and non-limb-threatening ischemia.

Intra-arterial fibrinolytic agents induce clot lysis in small, distal runoff vessels, decreasing outflow resistance and enabling the native artery to remain open longer. Fibrinolysis often uncovers a critical stenosis that, untreated, may lead to recurrent thrombosis. After successful fibrinolytic therapy, most patients require secondary bypass grafting or angioplasty. Streptokinase, urokinase, and tissue plasminogen activator have all been used successfully. Intravenous administration of a fibrinolytic agent is less effective than direct administration into the clot. Clots more than 30 days old are less likely to achieve successful lysis.

Invasive Therapy

Fogarty Catheter Thrombectomy

Patients with limb-threatening ischemia from embolism should undergo emergency Fogarty catheter embolectomy. Patients with limb-threatening ischemia from in situ thrombosis require direct or Fogarty catheter thrombectomy and vascular bypass grafting. Thrombectomy alone often fails because of recurrent thrombosis. Patients who cannot be bypassed, have irreversible ischemia, or are too ill to tolerate revascularization are treated with primary amputation. The Fogarty catheter is most frequently used for iliac, femoral, and popliteal embolectomy, often with only local anesthesia. Aortic saddle embolus is removed by sequentially passing the Fogarty catheter through bilateral common femoral arteriotomies. Newly formed in situ thrombosis may often be successfully removed with the Fogarty catheter. An older thrombus adheres more firmly to the damaged vessel wall, requiring direct surgical thrombectomy. The Fogarty catheter is not used in the venous system because of valves.

A patient with non-limb-threatening embolism is also treated with Fogarty catheter embolectomy. Non-limb-threatening in situ thrombosis is often aggravated by emergency surgical intervention and is best managed nonoperatively with emergent systemic anticoagulation and consideration of intra-arterial fibrinolytic therapy ( Fig. 73.1 ).

Fig. 73.1, Clinical presentation and management of acute arterial occlusion.

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