Peripheral Vascular Disease

By | 2013-07-19

Peripheral vascular disease denotes disorders of peripheral vessels including arteries, arterioles, veins, venules, and lymphatics (Box Peripheral Vascular Diseases). Vascular lesions may result from primary vascular pathology or occur secondary to conditions originating in unrelated tissues or organ systems (Box Causes of Peripheral Lymphatic Disorders). Resultant conditions may remain asymptomatic with little or no effect on morbidity and mortality, or they may progress to become life threatening. The development of newer imaging techniques, including improvements in diagnostic ultrasound, has provided accessible methods to clinically characterize these disorders. Vascular abnormalities have been classified according to the type of vessel affected and functional significance of associated lesions (see Boxes Peripheral Vascular Diseases and Causes of Peripheral Lymphatic Disorders).

Peripheral Vascular Diseases

Diseases of Arteries and Arterioles

  • Occlusive diseases
  • Arterial embolism
  • Arterial thrombosis
  • Angiitis, vasculitis
  • Vasospasm, traumatic, toxic
  • Diabetic arteriopathy
  • Nonocclusive diseases
  • Arteriovenous (A-V) fistula
  • Arterial aneurysm
  • Arterial calcification
  • Arteriosclerosis, hyalinosis, amyloidosis
  • Atherosclerosis
  • Vasculitis

Diseases of Veins

  • Phlebectasia
  • Varicosis
  • Phlebitis and thrombophlebitis
  • Venous thrombosis
  • Venous malformations

Diseases of Lymphatics

  • Lymphangitis
  • Lymphedema
  • Lymphangiectasia
  • Lymphatic hypoplasia, aplasia, hyperplasia
  • Lymphangioma, lymphocysts
  • Lymphangiosarcoma

Tumors of Peripheral Blood Vessels

  • Angioma, hemangioma, hemangiosarcoma

Causes of Peripheral Lymphatic Disorders

Lymphangitis, Lymphedema, Lymphadenitis, Lymphadenopathy

  • Infection
  • Neoplasia
  • Reactive hyperplasia
  • Granuloma

Lymphedema

  • Primary developmental abnormality of lymphatics
  • Hypoplasia
  • Aplasia
  • Lymphangiectasia
  • Hyperplasia
  • Secondary acquired abnormalities of lymphatics
  • Surgical excision of lymphatics or lymph nodes
  • Posttraumatic lymphangiopathy
  • Neoplastic invasion
  • Extrinsic compression of lymph vessels or tissue
  • Acute obstructive lymphadenitis
  • Chronic sclerosing lymphadenitis/lymphangitis
  • Lymphatic atrophy with interstitial fibrosis
  • Radiation therapy

Lymphocysts

  • Cystic hygroma, lymphoceles, pseudocyst

Lymphangiomas

Techniques Used To Evaluate Peripheral Vascular Disease

Angiography

Angiography is the gold standard for evaluating peripheral vascular disease owing to its superior ability to characterize and visualize normal and abnormal vascular anatomy.

Diagnostic outcome requires careful attention to three important elements: (1) selection of radiopaque contrast agent, (2) technique for vascular delivery of contrast material, and (3) high-quality radiographic imaging.

Factors to be considered when selecting a contrast agent include patient safety, image quality, and cost. The features of safety and efficacy are somewhat related to the ionic composition of these materials. High osmolar ionic compounds include the diatrizoate and iothalamate salts (Conray, Mallinekrodt) (Renografin, Amersham Health). Low osmolar ionic compounds include iohexol (Omnipaque, Amersham Health), iopamidol (IsoVue), and ioversol (Optiray, Mallinekrodt). Low osmolar non-ionic compounds include ioxaglate (Hexabrix, Mallinekrodt). Lower osmolar agents, both ionic and nonionic, are generally tolerated best by patients, particularly those sensitive to an increase in intravascular volume or having advanced cardiac disease (high osmolar compounds can generate a greater osmotic load). Nonionic agents also have reduced risk of contrast-related anaphylactoid reactions such as urticaria, flushing, coughing, dyspnea, peripheral edema, and a sudden drop in blood pressure. Contrast related nephrotoxicity is independent of the contrast agent used but can be reduced by maintaining appropriate patient hydration and minimizing the dose of contrast agent used during the imaging study. Low osmolar agents are generally more expensive than high osmolar agents.

Arterial angiography, often performed using carotid or femoral arterial access, can be performed to evaluate normal or abnormal arterial vascular anatomy preoperatively; to assess vessels for occlusive disease including thromboembolism (TE); and to detect or characterize inherited or acquired lesions including peripheral aneurysms, vascular tumors, traumatic injury, and shunts. The specific catheterization technique to be used is guided by consideration of the anatomic location of interest, anticipated lesion, status of patient health, available equipment, and operator experience. After percutaneous or surgical arterial cutdown, a catheter is directed under fluoro-scopic guidance to the desired location and contrast agent is injected by hand or by the use of a mechanical injecting device. Images are acquired using mechanical rapid film changers or digitally. The advantages of digital angiography include rapid rate of acquisition, postprocessing capabilities, and reduced exposure to radiation. Digital subtraction angiography may be used to cancel out portions of an image and thereby improve visualization of structures of interest.

Venous angiography is generally less challenging than arterial angiography, owing to easier access and lower pressures of the venous system. A small intravenous line is placed in a superficial vein distal to the site of the vascular lesion and contrast material is injected. Images are obtained similarly to arteriography. This technique is often selected to detect venous clots (appearing as vascular filling defects) or stenosis. The presence of prolific collateral vasculature can indicate chronic obstruction. Contrast venography of the cranial and caudal vena cava can be performed to assess caval patency that may be associated by a variety of neoplastic, compressive, or thrombotic disorders.

l.ymphangiography helps to permit local assessment of the lymphatic system. The technique of indirect lymphangiography relies on the contrast 3gent, which is infused into tissue, to be selectively absorbed and transported through lymphatic channels. Direct lymphangiography is more challenging (unless lymphangiectases have formed) but provides superior results when successfully performed. Selective lymphatic cannulation requires aseptic cutdown over the lymphatic region of interest. (The identification of lymphangiectases may be facilitated by subcutaneous injection of vital dyes (e.g. 3% Evans blue dye or 11 % patent blue violet] into the toe web. By selective resorption of these dyes, the main lymphatic channels proximal to the metacarpus or metatarsus become grossly outlined.) The lymphatic vessel is then cannulated with a 27- or 30-gauge needle or a special lymphatic cannula. An iodine-containing soluble contrast medium such as sodium and meglumine diatrizoate (Renografin, Hypaque) is injected slowly into the vessel. Because water-soluble contrast media rapidly diffuse through lymphatic walls into surrounding tissues, the radiographic detail is blurred unless radiographs are taken shortly after dye injection. Alternatively, oily iodine-containing contrast agents (Lipiodol) are used, reducing leakage of contrast from the lymphatic vessels. The oily contrast agents are sequestered within the lymphatics and lymph nodes along the draining pathways. Patency of the lymphatic channels can be appreciated in addition to the size of regional lymph nodes. Metastatic disease to the lymph nodes (or granulomas) appears as filling defects within the contrast-filled node, l.ymphangiography can also be used to identify the location of lymphatic leakage.

Diagnostic Ultrasound

Ultrasound imaging provides a direct, noninvasive technique for assessing anatomic abnormalities, vascular patency, and function. ? Ultrasound can aid in the diagnosis of peripheral arterial occlusion, central and peripheral arteriovenous (A-V) fistulas, venous thrombosis, aneurysms, traumatic vascular disease, and compression of vascular structures from local disease processes.

Duplex ultrasonography incorporates gray-scale two-dimensional imaging, with pulsed wave (PW) and color flow Doppler techniques. Thrombi, foreign bodies, compression, and abnormal vascular anatomy can be identified with two-dimensional imaging. Color Doppler superimposed on the two-dimensional image can further help define anatomy and identify turbulence associated with vascular malformation and stenotic lesions. Normal arterial flow is laminar with the highest velocity recorded centrally, and the respective color Doppler image has a homogenous appearance. Arterial stenosis increases blood flow velocity across the narrowed lumen with corresponding change in color Doppler signal at and distal to the stenosis. pulsed wave Doppler velocity measurements are made along the length of the artery in question and at areas or interest indicated from color flow Doppler interrogation. pulsed wave Doppler imaging may help assess the degree (severity) of vascular narrowing by estimating the gradient across the stenosis by the modified Bernoulli equation: gradient (mm Hg) = (maximal velocity) x 4. Moreover, arterial blood flow results in characteristic Doppler waveforms (a rapid forward flow component during systole, transient reversal of flow during early diastole, and a prolonged slow forward flow during late diastole). With mild to moderate vascular stenosis, characteristic changes in the pulsed wave Doppler waveform include acceleration of peak systolic velocities and loss of diastolic flow reversal distal to the stenosis. Of course, with complete stenosis, blood flow is interrupted.

Magnetic Resonance Imaging

Magnetic resonance angiography (MRA) is a safe, noninvasive imaging technique that may be useful to evaluate the peripheral arterial system. In human medicine, both contrast and noncontrast MRA methods have been applied for planning interventional procedures (e.g. stent placements) in patients with peripheral vascular disease. Unlike other vascular imaging techniques, noncontrast MRA displays blood flow and not the blood vessel itself Limitations of noncontrast MRA include time of acquisition, variation of blood flow characteristics (e.g. diastolic flow reversal) in diseased vessels, and retrograde filling of arteries during complete occlusion resulting in artifacts and reduction of net forward flow on the image. Contrast-enhanced angiography using a non-nephrotoxic contrast material eliminates many of the previously mentioned limitations. Advantages of contrast-enhanced MRA include shorter acquisition times, high spatial resolution, and high signal-to-noise ratios.

Mechanisms Of Thrombosis

Hemostasis is a complex process that involves blood vessels, platelets, coagulation proteins, naturally occurring anticoagulants, and platelet inhibitors. Thrombosis results when one or more components of the hemostatic cascade are perturbed, tipping the balance between coagulation and fibrinolysis in favor of coagulation. Physiologic alterations leading to the formation of thrombi have frequently been classified into three main categories: (1) alterations in blood flow, (2) damage to vascular endothelium, and (3) changes in coagulation proteins and platelets, resulting in hypercoagulability.

Normal flow of blood through blood vessels is laminar, with the rapidly flowing red blood cells (RBCs) in the center of the vessel. Platelets and white blood cells (WBCs) are suspended in the blood near the vessel wall. Normal laminar flow can be disrupted by changes in the diameter of the vascular lumen and blood velocity, resulting in simultaneous regions of blood stasis and turbulence (e.g. atherosclerosis). When blood stasis occurs, increased contact occurs between platelets, coagulation factors, and the endothelium, thus promoting coagulation. Turbulent flow also causes a denuding endothelial injury that eliminates the anticoagulant function of the endothelium and promotes thrombus formation.

Because under normal conditions the endothelium plays an important role for anticoagulation, factors that cause endothelial injury or dysfunction promote thrombosis. For example, the presence of atherosclerotic plaques is a well-known risk factor for thrombosis in humans and hypothyroid dogs. In addition, elevated levels of homocytseine (a sulfur-containing amino acid produced by the metabolism of methionine) act as a thrombogenic agent by promoting vascular smooth muscle cell proliferation and inhibition of endothelial cell growth. Hyperhomocysteinemia is a risk factor for thromboembolic disease in humans and possibly, cats.

Disorders that result in an imbalance of the hemostatic system toward the development of thrombosis are termed hypercoagulable, a physiologic alteration linked to the development of thrombosis. Either increased activity of platelets and coagulation factors or decreased activity of naturally occurring anticoagulants such as antithrombin HI can result in hypercoagulability.

When a thrombus becomes dislodged from the site of formation, it moves to a distal site (i.e. embolizes). Clinical consequences are generally related to local or systemic effects associated with resultant end-organ ischemia. Arterial thromboembolism can result in many organ systems. Venous thrombi may dislodge, resulting in pulmonary TE, or can result in local disruption of blood flow and venous stasis.

Arterial Thromboembolism

Vascular thrombosis is most readily identified when arteries are affected, and the clinical consequences are generally acute and severe. The aortic trifurcation is one of the most common locations for arterial thromboembolism in cats and dogs. Atherosclerosis leads to the majority of human thromboembolic disease and is most commonly localized to the carotid, coronary, or cerebral arteries. The differences in cholesterol metabolism in dogs and cats may partially explain the low frequency of atherosclerotic-related arterial thromboembolism in veterinary patients compared with humans. Most thrombi are formed in the left heart and embolize distally. Thrombi formed in the arterial system where the blood flow rate is high consist primarily of platelets and have been termed white thrombi.

Venous Thromboembolism

Thrombi formed in the venous circulation under low blood flow conditions are composed of fibrin and erythrocytes and have been termed red thrombi. Venous thrombosis frequently causes fewer clinical abnormalities than arterial thrombosis and consequently is frequently undetected. Deep venous thrombosis, a major risk factor for pulmonary thromboembolism in over 90% of cases in humans, is not known to be a risk factor for pulmonary thromboembolism in animals. Pulmonary thromboembolism occurs in several disease states associated with hypercoagulability. These include nephrotic syndrome, hyperadrenocorticism, immune-mediated hemolytic anemia (IMHA), thrombocytosis, cardiac disease, sepsis, disseminated intravascular coagulation (DIC), heartworm disease, and neoplasia Antithrombin III deficiency may be involved in thrombogenesis as part of a number of these diseases. For example, destruction of RBCs in IMHA releases thrombogenic substances. Antithrombin III inactivates thrombin and other clotting factors, and even a mild reduction in antithrombin III can result in thrombosis or TE. A deficiency of antithrombin III can be secondary to decreased synthesis (e.g. congenital), increased consumption (e.g. DIC), loss of antithrombin from the intravascular compartment (e.g. nephrotic syndrome), and increased protein catabolism (e.g. Cushing’s disease). Protein C and protein S are vitamin-K dependent protein factors and major inhibitors of the procoagulant system. Deficiencies of both of these proteins have been associated with clinical thrombotic disorders in humans. A single case report of protein C deficiency has been reported in a thoroughbred colt. The presence of multiple concurrent disorders in patients with thromboembolism is common. For example, 47% of cats with necropsy confirmed pulmonary thromboembolism had multiple concurrent predisposing disorders.

Clinical Disorders Frequently Associated With Thromboembolic Disease

Therapy Of Thromboembolic Disease

Vascular Diseases

Atherosclerosis

Lymphancioma, Lymphangiosarcoma

Lymphangiomas are benign tumors of lymphatic capillaries and are thought to develop when primitive lymphatic sacs fail to establish venous communication. Lymphangiomas can be classified into three categories based on their histologic appearance: (1) capillary lymphangiomas comprised of a network of capillary-sized lymphatic channels, (2) cavernous lymphangiomas composed of dilated lymphatics that infiltrate the surrounding tissue, and (3) cystic hygromas (unilocular or multilocular, cystic masses lined by a single layer of endothelium supported by a connective tissue stroma and containing a straw-colored, proteinaceous [1.3 to 4.5 gm/dL] fluid). The lesions present as large, fluctuant masses in the subcutaneous, fascial, mediastinal, and retroperitoneal spaces. Lymphangiomas have also been diagnosed on the extremities, metacarpal pads, nasopharynx, axilla, inguinal and mammary region, retroperitoneal space, and skin of dogs. Clinical signs are related to the size, location, and extent of the lymphangioma. They can exert pressure on surrounding structures and may interfere with muscle function, breathing (compression of the trachea), urination, or intestinal function. Lymph may ooze to the skin surface through single or multiple fistulous tracts. Differential diagnoses include other space-occupying masses such as abscesses, enlarged lymph nodes, neoplasms, and congenital cysts of nonlymphogenic origin. The prognosis can be good after appropriate surgical excision, marsupialization, or radiation therapy. Risk of recurrence is high due to inherent inability to identify distinct boundaries.

Lymphangiosarcoma originates from lymphatic endothelial cells.MS It is a rare malignant tumor in dogs and cats, although it is frequently reported secondary to chronic lymphedema in humans. A breed or sex predisposition has not been detected, but medium to large breeds may be at highest risk, and both young and older animals are affected. Metastasis occurs commonly in dogs and cats, although an isolated case without metastasis has been reported. Clinical signs include pitting edema of the extremities, inguinal region, axilla, and head and neck. In a report of 12 cats with lymphangiosarcoma, nine presented with fast-growing, noncircumscribed subcutaneous masses and the others with a thoracic or abdominal mass. In all cats affected the tumor was invasive, and complete surgical resection was not possible. Associated chylous effusions (pleural, abdominal, subcutaneous) have been reported. Pulmonary lymphangiosarcoma was diagnosed in one dog with a chylous effusion. Diagnosis is confirmed by obtaining a biopsy specimen. Histologically, tumors of lymphatic endothelial origin are characterized by a neoplastic proliferation of endothelial cells. Immunocytochemical stains have been used to confirm the diagnosis in dogs. The identification of the factor VIH-related antigen and vimentin indicates the cells are of endothelial origin. The intensity and distribution of the stain has been used to attempt to differentiate lymphangiosarcomas from hemangiosarcomas but is often inaccurate. Newer specific markers to identify lymphatic endothelial cells have been identified in humans and remain to be validated in the canine patient. The prognosis with lymphangiosarcoma is poor, with a high rate of local recurrence and metastasis.