Standard, Appropriate, and Advanced Care and Medical-Legal Considerations: Part Two -- Venous Ulcerations

William J. Ennis, DO, MBA, FACOS, Patricio Meneses, PhD

Disclosures

Wounds. 2003;15(4) 

In This Article

Pathophysiology

Despite the fact that 66 percent of the circulating blood is located on the venous side of the circulation at any one time, there is a paucity of definitive information concerning the pathophysiology of venous disease. Most of the focus has been placed on the diagnosis and treatment of arterial disorders. Reasons for this discrepancy include lack of vascular surgeon interest, lack of funding opportunities, fewer available venous diagnostic studies, lack of general awareness of atherosclerosis and heart disease in the general population, and the mistaken concept that there is a lack of life- or limb-threatening sequelae of venous diseases. Another limitation has been the difficulty in developing an adequate animal model to study venous disorders.[27]

A brief description of the calf pump is necessary to understand venous physiology.[28] The pump, or deep compartment, is located below the knee in the leg. The deep veins of the lower leg all empty into the outflow tract (popliteal vein). The superficial compartment includes the long and short saphenous veins and a network of subcutaneous venules and veins that empty into the deep system. An analogy to cardiac pump physiology can be drawn. During systole, blood is ejected from the superficial compartment to the deep and then on through the outflow tract via the calf pump. Causes of calf pump failure include muscle weakness, overall chamber size reduction (i.e., analogous to decreased end-diastolic filling), valvular incompetency (either superficial, deep, communicating, or any combination therein), or outflow obstruction. Normally, the resting venous pressure in the foot and leg decreases during calf contraction (ambulation or muscle contraction/compression). With any of the above-mentioned disorders, the venous pressure remains elevated throughout the gait cycle leading to chronic venous hypertension and its associated sequelae. By definition, a venous ulcer cannot exist in the presence of normally functioning calf pump. The difficulty lies in deciding which disorder is most responsible for the pump dysfunction. The inter-relationship between venous insufficiency and calf pump function was nicely researched by Araki, et al., in 1994.[29] Recently, exercise therapy directed at the calf pump has been proposed as a mechanism to increase healing and prevent venous ulcer recurrence.[30]

Most of the published work on pump dysfunction focuses on the impact of varicose veins and valvular incompetency. The first appreciation of the association between varicose veins and venous ulcers is attributed to Hippocrates in the Greek text De Ulceribus.[31] In 1867, John Gay stated, "The ulceration is not a direct consequence of the varicosity but of other conditions of the venous system with which varicosity is not infrequently a complication."[31] Lower-limb symptoms have correlated poorly with the presence of varicosities. However, there has been a shift in thinking towards a positive correlation between primary varicose veins and ulceration.[32,33]

Homans first noted the important role of incompetent valves in the communicating veins of the calf as a cause of venous ulcerations.[34] The problem is in determining which system of incompetent valves (deep, superficial, communicating) is either the most critical or the sole cause of calf pump dysfunction. Many patients have coexisting incompetence in all three locations, further compounding the problem. The most recent evidence supports the linear correlation of the number, size, and incompetence of calf communicating veins with the deteriorating clinical grade of the venous insufficiency.[35] Others have shown a distribution of incompetence among the three systems.[36,37,38] Further complicating the issue has been the poor correlation between the prior anatomic site of a deep venous clot and the anatomical site of the subsequent valvular damage.[39] Other researchers have focused on the hemodynamic effects of outflow obstruction when studying venous disease.[40]

Recently, much attention has been focused on the local, cellular, and biochemical impact of calf pump dysfunction and sustained elevated venous pressures. The resultant tissue damage, ulceration, and lipodermatosclerosis may be a product of both venous pressure and time. The significance of high pressures for short duration versus low pressures for longer time frames needs to be elucidated. Clearly, an analogy can be drawn here to the pathogenesis of callus formation and diabetic foot ulceration. Much of the recent research on venous ulcer treatment options has been founded on the cellular physiology.

Homans is credited with the suggestion that "stasis" of venous return was responsible for the problem of venous ulcers as a result of stagnant anoxia.[34] The term stasis is actually a misnomer. The concept has been disproved in the literature, but the term is still frequently used.[41] It has actually been shown that venous blood has a normal or increased oxygen level and the flow characteristics failed to demonstrate stasis.[42] The increased pressures previously described in chronic venous insufficiency have been shown to propagate all the way back to the nutritive capillaries.[43] Current investigations analyze the microcirculation in venous ulcers and the periulcer tissue with conflicting results.[44,45,46,47] Recently, this type of analysis has demonstrated a prognostic index used for venous ulcer healing.[48] Another theory has focused on the role of arteriovenous shunting as the etiology for increased microvascular flow and subsequent venous disease.[49,50]

The original theories of venous ulceration centered around the concept of the "fibrin cuff," proposed by Browse and Burnand in 1982.[51] Elevated venous pressures lead to biochemical disturbances when the analysis is taken out to the cellular level. Transcutaneous oxygen (TcpO2) measurements at the ulcer margin showed significantly lower values than control; however, there was marked heterogeneity in two clinical trials.[52,53] Falanga, et al., confirmed the presence of fibrin cuffs but disputed their contribution to ulcer formation.[54] The extent to which edema contributes to venous ulcer formation is now being assessed by such techniques as high frequency ultrasound.[55] Fluid dynamics clearly play a role in the evolution of venous ulcerations; however, the exact mechanisms are still being analyzed.[56,57] Additional theories have focused on the "trapping" of growth factors and white blood cells (WBCs).[58,59,60,61,62] Free radical formation secondary to perfusion-reperfusion effects and even gut-derived oxidative stress reactions have been implicated at the cellular level.[63,64] Systemic fibrinolysis abnormalities and hypercoaguable conditions can add to the complexity of venous disease.[65,66,67,68,69] A recent model proposes "senescent" cells, which are living but not biologically active or responsive to cytokine stimulation, as additional mechanisms at play in the pathogenesis of venous ulcerations.[70] It should be apparent from this brief review of the pathophysiology of venous disease that debate still continues as to the exact mechanism that leads to the ulceration. As mentioned, the lack of adequate animal models further compounds the problem and blocks scientific inquiry. The cause is likely a balance between calf pump abnormalities and the microcirculatory cellular response to elevated venous pressures.

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