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 (mainly cholesterol, usually complexed to proteins and cholesterol esters) 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 rather constant. The abdominal aorta has 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. Vessels of the upper extremities are usually spared.

As atherosclerosis progresses, atheromas almost always calcify, resulting in hard, brittle vessels. Ulceration of the luminal surface and rupture of the atheromatous plaques discharge debris, producing atheroemboli (cholesterol emboli). Fissured or ulcerated lesions can produce in situ thrombosis, causing acute 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.

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.¹ 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 predicted 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 within an aneurysm. Such mural thrombi can form emboli that 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) presentation as a pulsatile mass.

Arterial Embolism: An embolus is a blood clot or other foreign body that is carried by the blood to a site distant from its point of origin. Most emboli are the result of detached thrombus formation (thromboembolism). Less common sources include debris from ruptured atherosclerotic plaques, tumor debris, or foreign bodies. Unless otherwise specified, the term embolus in this chapter is defined as thromboembolus.

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.⁶

Peripheral arterial thrombi are usually occlusive, although they may be limited to one wall (mural) in larger vessels. Peripheral arterial thrombi are usually firmly attached to the damaged arterial wall and infrequently embolize. The clot may propagate proximally and distally, which intensifies ischemia.

Inflammation: Inflammatory arterial injury can be caused by drugs, irradiation, mechanical trauma, or bacterial invasion. The major cause of arteritis is noninfectious systemic necrotizing vasculitis. Most cases of infectious arteritis are 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: Different types of vascular injury result 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, causing progressive deformity, pain, and nerve compression. Complete arterial transection usually has only moderate or insignificant bleeding because of arterial spasm of the transected ends of the artery and the formation of a temporary thrombus. Delayed hemorrhage in completely transected arteries may result from relaxation of arterial spasm, eventual liquefaction of the thrombus, or displacement of the thrombus by arterial pressure. Blunt injury may produce partial or complete intimal disruption. Dissection of the distal intima can lead to progressive obstruction and thrombosis. Complete occlusion may not occur for hours or days after injury. Vasospasm can accompany injuries that are adjacent to blood vessels; spontaneous resolution always occurs in the absence of arterial disruption or intimal injury.

Vasospasm: Vasospastic disorders (Raynaud’s disease, Raynaud’s phenomenon, livedo reticularis, acrocyanosis, erythromelalgia) produce an abnormal vasomotor response in distal small arteries. The cause of these disorders is unknown but may be related to the autonomic innervation of the peripheral arterioles. The vasospastic disorders are characterized by the presence of ischemic symptoms and the absence of tissue loss. True organic changes within the arterial wall are absent. In contrast, patients with digital ulceration and gangrene always have fixed arterial occlusions in the distal extremity arteries.

Arteriovenous Fistulae: Abnormal communication between arteries and veins may result from congenital defects, rupture of an arterial aneurysm into an adjacent vein, penetrating injuries, and inflammatory necrosis associated with neoplasms or infection. Arteriovenous fistulae can occur in any region of the body. The artery proximal to the fistula becomes distended, tortuous, and aneurysmal. Similar changes occur in the venous side of the fistula. 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. The resultant chronic venous hypertension may cause 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.⁷ False aneurysm formation can occur as part of the fistulous tract or as the result of arterial or venous dilation.⁷

The increase in cardiac output that occurs when blood switches from the arterial to the venous system can result in a widened pulse pressure or high-output cardiac failure.

Acute Arterial Occlusion: The patient with acute arterial occlusion usually exhibits some variant of the five Ps: pain, pallor, pulselessness, paresthesias, and paralysis. Paresthesias and paralysis indicate limb-threatening ischemia that requires emergency surgical intervention regardless of the cause. In patients with non–limb-threatening ischemia, accurate differentiation between embolism and in situ thrombosis as the cause of acute arterial occlusion determines management. Arterial embolism is best managed by emergency Fogarty catheter embolectomy. Non–limb-threatening ischemia from in situ thrombosis is often aggravated by emergency surgical intervention and is therefore initially best managed nonoperatively, if possible (Fig. 87-1). Because acute arterial embolism usually occurs in patients without significant peripheral atherosclerosis and without well-developed collateral circulation, it usually manifests as sudden limb-threatening ischemia. Patients describe a sensation of the leg’s being “struck” by a severe shocking pain. Often the patient has to sit or fall to the ground during the sudden event.

In situ thrombosis usually occurs in patients who have long-standing significant peripheral atherosclerosis and well-developed collateral circulation and is often seen subacutely with non–limb-threatening ischemia. A history of claudication is common with in situ thrombosis and rare in patients with arterial embolism.

Chronic Arterial Insufficiency: Chronic arterial insufficiency causes two characteristic types of pain: intermittent claudication and ischemic pain at rest. The location of arterial occlusion determines the location of claudication. Calf claudication is associated with femoral and popliteal disease, typically a cramping pain, reliably reproduced by the same degree of exercise and completely relieved by rest (usually 1-5 minutes). Aortoiliac occlusive disease causes claudication in the buttocks and hips, as well as the calves. The calf pain in aortoiliac disease is generally more severe than the buttock and thigh pain, which is more often described as an aching, discomfort, or weakness. Some patients deny pain, complaining only that the thigh or hip “gives out” with exercise. Aortoiliac occlusive disease severe enough to produce bilateral claudication is almost always associated with impotence in men (Leriche’s syndrome). Even in the absence of impotency, bilateral hip or thigh pain in a man should indicate the possibility of aortoiliac occlusive disease.

Chronic arterial insufficiency may progress so that ischemic pain occurs at rest. Rest pain often begins in the feet and typically involves the foot distal to the metatarsals, awakening the patient from sleep. Ischemic rest pain is a severe, unrelenting pain aggravated by elevation and unrelieved by analgesics, but patients have prompt relief with any activity that involves a standing position. Patients often sleep with the leg dangling over the side of the bed or sleep in a chair to improve perfusion pressure to the distal tissues.

Arterial Embolism: The physical examination can differentiate arterial embolism from in situ thrombosis. The sudden loss of a pulse is the hallmark of arterial embolism but may be difficult to recognize if the prior pulse status is unknown or is abnormal as the result of associated atherosclerosis. A bounding pulse may be felt initially at the location of an embolus from transmitted pulsations through the fresh clot. In general, patients with arterial embolism have few physical findings suggestive of long-standing peripheral vascular disease with normal proximal and contralateral limb pulses. Tenderness to palpation may occur at the site of an embolic occlusion.

If arterial embolism is suspected, the physical examination should be directed toward identifying its source, most commonly a left ventricular mural thrombus secondary to a prior myocardial infarction and a left atrial thrombus in a patient with mitral valve disease. Coexistent atrial fibrillation is common.

The limb distal to an embolic occlusion is initially chalk white. Because of absence of blood from the venules of the subcapillary layer, the demarcation between ischemic and nonischemic tissue is sharp. With time, cyanosis may appear, indicating desaturation of blood with continued ongoing ischemia. Paresthesia or paralysis indicates limb-threatening ischemia. The presence of sensitivity to light touch is often the best guide to viability of the tissue. Complete anesthesia demands immediate surgical intervention. Paralysis represents severe skeletal muscle and neural ischemia, which may be irreversible. Involuntary muscle contracture with woody hardness represents irreversible ischemia.

Arterial Thrombosis: Physical findings of in situ thrombosis are often accompanied by evidence of atherosclerotic occlusive disease. Proximal or contralateral limb pulses are usually diminished or absent. An embolic source, such as mitral valve disease or atrial fibrillation, is usually absent. Because of collateral circulation, demarcation of limb ischemia is less well defined in these patients (Table 87-1).

Carotid, renal, and femoral arteries may have bruits, and there may be an abdominal aortic aneurysm. If an occlusion of the upper extremity vessels is suggested, the subclavian artery should be evaluated by palpating for thrills and listening for bruits in the supraclavicular fossa.

A funduscopic examination may yield evidence of arteriosclerosis or hypertension. Hollenhorst plaques (atheromatous emboli containing cholesterol crystals in the retinal arterioles) may be detected. Roth’s spots (round or oval white spots seen near the optic disk) may be present in patients with infective endocarditis.

Embolic phenomena can cause diverse end-organ damage: hemiplegia from cerebral emboli, flank pain with hematuria from renal emboli, left upper quadrant abdominal pain from splenic infarcts, and pleuritic pain with hemoptysis from pulmonary emboli. Septic pulmonary embolism from right-sided endocarditis may be confused with pneumonia.

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. The skin lesions may be pruritic or even painful, with a burning or stinging sensation. Lesions are more common in dependent areas: in the lower extremities in ambulatory patients or in the sacral area in bedridden patients. Edema accompanies some lesions, and hyperpigmentation occurs in areas of recurrent or chronic lesions.

Vasospasm: Vasospastic disorders cause a sharp border between ischemic and normal tissue. Raynaud’s disease is characterized by intermittent attacks of triphasic color changes: pallor, cyanosis, and then rubor.⁹ The most important element is pallor, during which the digits turn chalk white. 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 is characterized by a persistent cyanotic mottling of the skin that has a typical “fishnet” appearance and may involve all parts of the extremities and trunk. Acrocyanosis, the least common vasospastic disorder, is characterized by persistent, painless, diffuse cyanosis of the fingers, hands, toes, and feet. Cyanosis usually intensifies with exposure to cold and decreases with warming. The involved parts are nearly always cold, exhibit excessive perspiration, and have normal arterial pulses.

Arteriovenous Fistulae: Arteriovenous malformations and fistulae, although rare, must be distinguished from vascular bruits or aneurysms. True aneurysms and arterial stenoses are associated with a systolic murmur. Pseudoaneurysms generally have a loud systolic and sometimes a separate faint diastolic murmur. Arteriovenous fistulae have a constant systolic and diastolic (to-and-fro) murmur heard best directly over the lesion and often associated with a palpable thrill, precisely analogous to the findings of a therapeutic dialysis arteriovenous fistula. Unless congenital, arteriovenous fistulae occur at prior operative or trauma sites. The skin overlying the lesion may be warm, but distally the temperature is often decreased. Veins peripheral to the fistula are usually distended and varicose. Large and long-standing arteriovenous fistulae produce high cardiac output and widened pulse pressure. Digital pressure on the artery leading to the fistula or the fistula itself may decrease the tachycardia (Branham’s sign).

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 by intravenous bolus, followed by a maintenance infusion of 18 units/kg/hr). Heparin quickly reduces thrombin generation and fibrin formation, minimizing 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 not candidates because clot lysis generally takes 6 to 72 hours. Patients with limb-threatening ischemia cannot tolerate several more hours of ischemia without tissue or limb loss. Fibrinolytic therapy is generally reserved for patients with in situ thrombosis and non–limb-threatening ischemia.

Intra-arterial fibrinolytic agents induce clot lysis in the 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 another episode of thrombosis. After successful fibrinolytic therapy, most patients require secondary bypass grafting or percutaneous transluminal 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 more organized and less likely to achieve successful lysis.

Fogarty Catheter Thrombectomy: The Fogarty catheter is most frequently used for iliac, femoral, and popliteal embolectomy, often with only local anesthesia.¹³ Aortic saddle embolus is removed by sequentially passing the Fogarty catheter through bilateral common femoral arteriotomies.

Newly formed in situ thrombosis can 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.

Peripheral Percutaneous Transluminal Angioplasty: The initial success and long-term patency achieved with angioplasty depend on the location of the lesion and the extent of atheromatous disease. Proximal larger arteries (e.g., iliac, femoropopliteal) have the best initial and long-term results. Discrete stenotic lesions (<5 cm) have better long-term patency rates than vessels that are diffusely involved or have multiple involved segments. Balloon angioplasty is the accepted treatment for isolated stenotic lesions in the renal, iliac, and superficial femoral vessels.

Transluminal angioplasty with intravascular stent is used in more distal vessels, including the popliteal and tibial circulation, in cases of more diffuse lesions, and for patients who are prohibitive surgical risks, although its value remains to be determined.¹⁴

Recanalization devices include the percutaneous atherectomy catheter, percutaneous angioscope, hot-tip laser, excimer laser, and high-speed rotating wire and drill.

Grafting: Vascular grafting is associated with a variety of complications that can be diagnosed in the emergency department. Autogenous vein grafts (usually a reversed greater saphenous vein) provide excellent long-term patency for small arteries. Vein grafts respond to arterial pressure with gradual intimal proliferation and medial fibrosis. They may develop atherosclerosis, which can lead to graft stenosis and thrombosis. False aneurysms can form along the suture line.

Polytetrafluoroethylene (Teflon) prosthetic grafts are widely used in medium and large arteries that are impossible to bridge with smaller vein grafts. Prosthetic grafts have a higher rate of thrombosis than venous grafts. Distal emboli may result from poor fixation of luminal fibrin. If the prosthetic graft has not been adequately covered by viable tissue, it can erode into adjacent structures and hollow viscera. Prosthetic graft infection is a devastating complication requiring removal of the entire graft.

Vascular grafts can be used to bypass arterial occlusions and reconstruct a diseased arterial bifurcation, or can be interposed between sections of resected artery. The two most common complications of both prosthetic and vein grafts are thrombosis and development of a false aneurysm at one or more suture lines. Bypass grafting is most often used as palliative treatment for symptoms of atherosclerotic occlusive disease. Patients with localized unilateral stenosis (<3-5 cm in length) may have a comparable rate of success with percutaneous transluminal angioplasty with or without stent placement.¹⁵

Patients with calf claudication from superficial femoral or popliteal occlusive disease can slow progression if they stop smoking and maintain an active exercise regimen. Patients who have progression of disease, significant rest pain, or tissue loss require surgical revascularization.

Sympathectomy: Lumbar sympathectomy is no longer used for treatment of ischemia from arterial occlusion. The benefit of sympathectomy in patients with symptomatic Raynaud’s phenomenon is unclear, but it remains a potential intervention to assist healing of superficial ischemic ulcers and relieve rest pain in patients with Buerger’s disease.¹⁶

Clinical Features and Differential Diagnosis: Acute arterial occlusion from embolism, thrombosis, or trauma is ruled out primarily by history. Atheromatous emboli from proximal ulcerated plaques or aneurysms can cause small scattered ischemic lesions in the toes, feet, or legs, causing blue toe syndrome (Fig. 87-2). The peripheral pulses are present in blue toe syndrome. Exercise-induced claudication must be distinguished from the nocturnal muscle cramps that frequently occur during rest in elderly patients. Aortoiliac occlusive disease must be differentiated from osteoarthritis of the hip, which tends to be more variable from day to day, is not relieved completely with rest, and is not reliably reproduced by the same amount of exercise. Pseudoclaudication from the cauda equina syndrome is caused by narrowing of the lumbar canal from spondylosis, disease of the intervertebral disks, or spinal cord tumor. The symptoms mimic intermittent claudication but are less closely related to exercise and rest than true claudication.