Anatomy

Standardized nomenclature of lower extremity venous anatomy was published by Caggiati and colleagues in 2002,⁷ and this terminology should be adopted to provide uniform description and treatment of CVI. The venous system can be considered as three interconnected groups: (1) superficial veins, which lie above the fascia and drain both the skin and subcutaneous tissue; (2) deep veins, which lie below the fascia and drain the leg musculature; and (3) perforating veins (PVs), which penetrate the fascia and connect the deep and superficial systems. These veins have bicuspid valves that are found at the termination of major tributaries, with increasing numbers found more distally in the venous tree.⁸ The superficial veins are usually involved with CVI and include the great and small saphenous veins. The great saphenous vein connects to the femoral vein at the saphenofemoral junction; a valve lies at this junction in 94% to 100% of individuals, and this is the most common site for clinically significant reflux.⁹ The great saphenous vein has approximately six valves and branches into an anterior branch and posterior arch below the knee. The small saphenous vein runs along the calf, has 7 to 10 valves. Although the anatomy has much variation, it usually connects to the deep system at the popliteal vein via the saphenopopliteal junction.⁹

There are more than 150 PVs in the lower extremity; however, only four groups are clinically significant, and they may be found within the foot, medial and lateral leg, and thigh.¹⁰ These perforators directly empty into the deep venous system or indirectly via venous sinuses of the lower leg. The thigh and calf perforators contain one to three valves and provide a pathway for blood to flow from the superficial to deep venous system. In contrast, perforating veins in the foot direct blood from the deep to superficial systems.¹⁰ The medial lower leg perforators include the paratibial (or Sherman and Boyd) and posterior tibial (or Cockett) PV. Paratibial PV direct blood from the posterior arch and great saphenous vein to the posterior tibial veins, whereas posterior tibial PV connect the posterior accessory great saphenous vein with the posterior tibial veins. The medial thigh PV includes the inguinal and femoral canal (Dodd) perforators, and these connect the great saphenous vein with the superficial femoral vein at the groin or proximal to the knee, respectively.⁷

The deep veins run with their similarly named arterial counterparts and are subfascial structures. The number of valves increases distally, with one valve at the external iliac-common femoral junction, one valve at the saphenofemoral junction, three valves in the proximal superficial femoral vein, two valves in the distal superficial femoral and popliteal veins, and numerous valves in the anterior and posterior tibial veins as well as the peroneal veins.^8,10 Venous sinuses are present in the deep compartments of the lower extremity, with both gastrocnemius and soleal sinuses. Although these muscular venous sinuses are valveless, they empty into adjacent valved veins and are the principle collecting system within the calf.⁸

Pathophysiology

The physiology of venous return is useful in understanding the signs, symptoms, and treatments available for venous disease. Resting venous pressure is a function of capillary inflow, valve function, outflow obstruction, and muscle pump action. Approximately 90% of blood return occurs through the deep venous system through muscular contraction of the foot, calf, and thigh.¹¹ Under normal conditions, postcapillary venous pressure ranges between 12 and 18 mm Hg. However, in the dependent lower extremity, hydrostatic pressures can range from 30 to 100 mm Hg.¹² Contraction of the calf can generate pressures as high as 250 mm Hg, with a resultant ejection fraction of 65%.¹³ Clinically it has been demonstrated that after walking 7 to 12 steps, lower-extremity venous pressure is reduced from 100 mm Hg to a mean of 22 mm Hg.¹⁴ With intermittent muscle pump action (in the presence of competent valves), the deep veins empty, and the resting venous pressure is reduced. During muscular relaxation, venous pressure slowly rises secondary to capillary inflow as well as emptying from the superficial venous system via perforators. Thus, the valves serve to compartmentalize the hydrostatic column of blood and prevent reflux.¹⁵

Valvular dysfunction reduces venous emptying and contributes to venous hypertension through pathologic retrograde flow. In addition, in the presence of incompetent perforator valves, increased pressure may be transmitted back to the superficial venous system.¹² Venous hypertension can also lead to dilation of the venous segment below the malfunctioning valve, resulting in subsequent failure of the valve at this level. This simple pathology explains why patients with CVI consistently report that their symptoms are minimized in the morning, before getting out of bed. In the supine position, the effect of gravity is essentially eliminated from the venous system, thus minimizing pressure gradients across the valves. Large varicosities, essentially branches of refluxing veins that have been chronically under high pressure, may all but disappear with leg elevation.

The underlying etiology of venous disorders may be congenital, primary, or secondary. Primary venous disorders pertain to pathology without a precipitating event and involve structural and biochemical changes of the venous wall, whereas secondary disorders occur after an event, such as an acute deep venous thrombosis (DVT). According to the North American subfascial endoscopic perforator surgery (SEPS) registry, CVI results from primary venous disease in 70% of the population and from a postthrombotic state in 30%.¹⁶ The pathogenesis of primary valve dysfunction is not entirely clear; however, connective tissue defects involving both the cellular and extracellular matrix have been identified. Multiple investigators have documented smooth muscle cell proliferation and infiltration, increased numbers of fibroblasts, and atrophied vasa vasora.^17–19 The composition of varicose veins has been found to have reduced total elastin content,²⁰ variations in both the content and types of collagen, and alterations in the activity of matrix metalloproteinases as well as their tissue inhibitors.^18,21,22 These changes in venous composition are thought to compromise the structural integrity of the vein wall, resulting in venous dilatation and the development of valvular incompetence, with reflux as a consequence.²³

With secondary venous disorders, a deep venous thrombus can trigger an inflammatory response, which creates vein wall injury. The direct apposition of thrombus against the vein wall has been shown to activate leukocytes, upregulate activity of matrix metalloproteinases, and promote fibrosis.²⁴ In addition, recanalization of the vein is often incomplete with only 55% of patients demonstrating complete resolution of DVT within 6 to 9 months.²⁵ The resulting hemodynamic abnormality is thus one of both reflux and obstruction.²⁶

The interaction of venous anatomy and physiology has yet to completely explain the clinical manifestations of CVI. Venous ulceration is not clearly colocalized with perforating veins, and single lesions may be associated with multiple levels of valvular incompetence within the superficial, deep, or perforating systems.²⁷ Despite these minor discrepancies, chronic venous hypertension typically has physical signs concordant with the severity of the underlying disease. Prolonged venous hypertension creates a hydrostatic profile that favors edema formation because of the transudation and exudation of macromolecules and fluid.²⁸ Hyperpigmentation can result from hemosiderin deposits within dermal macrophages after extravasated red blood cells are broken down.²⁹ Early signs of advanced disease are corona phlebectatica: numerous, fine intradermal veins overlying the medial or lateral aspects of the foot found in a fan-shaped pattern.¹ With more severe venous disease, fibrosis of the skin and subcutaneous tissue, known as lipodermatosclerosis, results secondary to localized, chronic inflammation.¹ Atrophie blanche is a localized, atrophic, white area of skin surrounded by dilated capillaries or hyperpigmentation, and is also a sign of severe CVI.¹ Venous ulceration is the most advanced form of venous disease and manifests as a full-thickness defect in the skin, with greater than 75% of lesions localized to the medial aspect of the ankle, about the distribution of the posterior arch.²⁷

Classification

Given the panoply of signs and symptoms, the classification and treatment of CVI suffered from tremendous heterogeneity. A consensus statement regarding chronic venous disorders was released at the American Venous Forum in 1994, which proposed a standardized categorization of chronic venous disorders based on both the clinical classification and severity of disease.¹¹ The CEAP system was later updated in 2004 with seven categories of clinical manifestations (C), four etiologic categories (E), four categories of anatomic distribution (A), and four basic pathophysiologic categories (P)¹ (Table 51-1). The subgroups that describe the clinical manifestations include: class 0, no visible or palpable signs of venous disease (i.e., symptoms only); class 1, telangiectasias or reticular veins; class 2, varicose veins; class 3, edema; class 4, skin changes due to venous disease; class 5, skin changes with healed ulceration; and class 6, skin changes with active ulceration. The etiologic classification includes congenital, primary, secondary (post-thrombotic), or without any venous cause. Anatomic classification includes superficial, perforator, or deep veins, as well as no identifiable venous location. Finally, the basic pathophysiologic classification describes reflux, obstruction, both reflux and obstruction, or no venous pathophysiology identifiable.

TABLE 51-1 Classification of Chronic Venous Insufficiency

In the CEAP revision, the following example is offered. A patient has painful swelling of the leg, varicose veins, lipodermatosclerosis, and active ulceration. Duplex scanning shows great saphenous vein reflux above and below the knee, incompetent calf perforator veins, and axial reflux in the femoral and popliteal veins. There are no signs of postthrombotic obstruction. Classification according to basic CEAP: C6s, Ep, Aspd, Pr.¹ Of note, physician-derived CEAP scores have been demonstrated to predict both symptom severity and patient-reported quality of life.³⁰

Diagnosis

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) released practice guidelines for the care of patients with CVI.³¹ The workup for CVI starts with a complete history and physical examination. There is a fair amount of variation in the presenting symptoms for the condition, but there are common elements in the history that are of great use in securing the diagnosis. Symptoms include pain, sensations of heaviness, swelling, aching, restless legs, cramps, itching, tingling, throbbing, and tired legs.² One of the hallmarks of CVI is symptom progression throughout the day, particularly when the patient has been standing for prolonged periods of time. This is true for subjective complaints such as heaviness and fatigue, as well as more objective signs like swelling and engorged varicosities. Many patients, after determining this for themselves, will have learned to elevate their legs or have even started wearing compression stockings. Symptoms that occur during and after exercise, and improve with rest and leg elevation, may be indicative of venous claudication.³² The history may also establish whether the etiology is primary, secondary, or congenital. The presence of prior DVT, history of a hypercoagulable state or any other factors that predispose patients to thrombosis (e.g., oral contraceptives, pregnancies, smoking), and family history of CVI or thrombotic disorders should be elicited.

The physical examination is useful not only for arriving at the diagnosis of CVI, but also for determining the pattern of disease. Patients should be examined standing, with attention paid to the presence of varicosities, palpable cords, tenderness, thrills, bruits, or pulsatility. The presence of telangiectasia, leg swelling, induration, hyperpigmentation, corona phlebectatica, lipodermatosclerosis, atrophie blanche, or ulceration must be carefully noted.³¹ CVI can certainly coexist with peripheral arterial disease; therefore the pedal pulses must be checked and documented. The saphenous veins themselves should be sought, and if they can be seen or felt, their size and depth should be noted. For patients with numerous varicosities, a diagram can be drawn or a digital photograph taken. Swelling is best documented by taking measurements of the leg below the knee and at the ankle. The time of day of the measurements should be recorded as well, for there can be considerable variation as was previously described. Finally, one must record the presence of any varicosities that have eroded, or appear to be on the verge of eroding, through the skin. When this occurs, the bleeding can be impressive, and patients should be instructed on how to dress their leg if this occurs.

The anatomic pattern should be established, with an attempt to determine whether signs are localized to the superficial, deep, or perforator systems; this can be accomplished with duplex ultrasonography.³¹ This modality is more accurate than continuous-wave Doppler ultrasound, as B-mode imaging can help to identify anatomic points of obstruction or turbulence and to determine directionality of flow.¹² The SVS/AVF clinical practice guidelines describe four components of the examination: visibility, compressibility, venous flow, and augmentation.³¹ In addition, confirmation of valvular incompetence should be performed in the upright position using one of the following methods. A Valsalva maneuver will increase intraabdominal pressure, and should be performed in conjunction with duplex assessment of the common femoral vein or the saphenofemoral junction. Alternatively, manual or cuff compression and release of the limb distal to the point of examination can be performed to evaluate the more distal veins.³¹ Many noninvasive vascular laboratories have a protocol for CVI, and the clinician should always specify why the venous examination is being ordered. The study should include all the elements of a DVT study as well as examination of the great and small saphenous veins. Notation should be made whether reflux occurs spontaneously, and it is useful to document the presence of reflux with the patient in a standing position. The recommended cutoff value for reflux is 1 second in the femoral and popliteal veins, whereas it is 500 ms for the great saphenous, small saphenous, tibial, deep femoral, and perforating veins.³¹ However, many health insurers require greater times; therefore the actual time should be carefully recorded in the study. The sizes of the saphenous veins are needed as well, and these structures should be measured at the level of the saphenofemoral junction, the mid thigh and just below the knee (for great saphenous vein [GSV]), and at the popliteal space and ankle (for small saphenous vein [SSV]). These size measurements should also be performed with the patient in a standing position. Larger varicosities should be examined as well, and reflux should be reported if present. As with the saphenous veins, the sizes of the branches need to be recorded in the study. Finally, perforator veins need to be noted in the study. Those with an outward flow of duration greater than 500 ms or a diameter greater than 3.5 mm, which are associated with a healed or open venous ulcer, are considered pathologic, but these perforators should be noted even in the absence of localized disease.³¹

The basic CEAP system, described earlier, should be used to determine the class, etiology, anatomy, and pathophysiologic classification of CVI.¹ An adjunct evaluative instrument, the revised Venous Clinical Severity Score (VCSS) released by Vasquez and colleagues, should also be incorporated to document the severity of CVI.³³ It generates a score based on (1) patient-reported intensity of pain or other discomfort, (2) severity of varicose veins, (3) severity of lower extremity edema, (4) degree of skin pigmentation, (5) extent of inflammation, (6) distribution of induration, (7) number of active ulcers, and (8) duration of active ulceration.³³ In conjunction, these instruments will provide unambiguous classification and a means of serial assessment for patients with CVI.