Microcirculatory Aspects of Venous Ulceration

Abstract

BACKGROUND. Articles were identified from a literature search based on Index Medicus from 1983 onwards with additional, as yet, unpublished data obtained directly from ongoing research at The Middlesex Hospital Vascular Laborato y. Original scientific articles were selected if they addressed the mechanisms causing venous ulceration in relation to the events in the microcirculation. OBJECTIVE. To review the mechanisms proposed recently to explain the pathogenesis of venous Ulceration. RESULTS. Recent data suggest that there is a systemic inflammato y response associated with the presence of venous disease in the lower limb, as indicated by measuring plasma neutrophil elastase and lactoferrin. In volunteers without venous disease white cell activation may be produced by experimental venous hypertension lasting 30 minutes, produced by applying a venous tourniquet to the lower limb or by standing without moving for 30 minutes. CONCLUSION. Inflammato y mechanisms play a significant role in the pathogenesis of venous disease but the exact mechanisms producing venous ulceration remain to be elucidated. J Dermatol Surg Oncol 1994;20:474-480.'enous valvular incompetence is present in up to 10% of the population of Western countries, and 0.2% have venous ulceration as a con~equence.'-~ It is generally agreed that sustained venous hypertension is an essential prerequisite to the development of ulcers, but the precise pathophysiological mechanism remains o b s c~r e .~,~ Various theories of the etiology of venous ulceration have been put forward, of which the two currently most popular are the fibrin cuff theory of Browse and Burnand6 and the white cell trapping theory of Coleridge Smith et al.' Research has failed to show that fibrin cuffs present a dffusion barrier to the passage of oxygen "and other nutrients,"8 and cutaneous oxygen tension is actually higher in patients with venous d i~e a s e .~The white cell trapping hypothesis suggests that increased venous pressure causes a reduction in capillary blood flow, resulting in trapping of the white blood cells in the leg. These cells may plug the capillaries, resulting in areas of localized ischemia, and become activated, releasing toxic oxygen metabolites (free radicals), proteolytic enzymes, and chemotactic substances. White cell margination has been shown to occur in the postcapillary venules when blood flow is reduced,I0 and increased numbers of white cells have been demonstrated in the skin of patients with lipodermatosclerosis (LDS)." We have recently obtained di-

Chronic Venous Insufficiency and Venous Ulceration

“…10,33 Sustained hypertension at the capillary level is associated with many morphologic changes including elongation and dilation of the capillary bed, increased surface area of the endothelium, increased type IV collagen in the basement membrane, and the formation of a pericapillary fibrin cuff. 12,[34][35][36][37] These abnormal capillaries are more permeable to large molecules, including fibrinogen, 38 and it has been hypothesized that leaked fibrinogen is converted to fibrin in the pericapillary space. 37,38 Other studies have shown that the fibrinolytic activity of blood and tissues is deficient in patients with lipodermatosclerosis, resulting in a decreased clearance of fibrin.…”

Application of various power densities of ultrasound in the treatment of leg ulcers

“…3,4 As a result, blood flow velocity in the microcirculation decreases, which in turn favours the adhesion of leukocytes to the capillary walls (the leukocyte trap theory). [5][6][7] The trapped leukocytes damage the capillaries (they cause increased permeation of leukocytes through the vein walls to the surrounding tissue 6 ) and lead to local hypoxia. In a hypoxic environment the leukocytes are stimulated and release various substances: cytokines (mainly alpha-tumor necrosis factor, interleukins), leukotrienes and proteolitic enzymes (elastase, collagenase).…”

Chronic Venous Insufficiency and Venous Ulceration

“…10,33 Sustained hypertension at the capillary level is associated with many morphologic changes including elongation and dilation of the capillary bed, increased surface area of the endothelium, increased type IV collagen in the basement membrane, and the formation of a pericapillary fibrin cuff. 12,[34][35][36][37] These abnormal capillaries are more permeable to large molecules, including fibrinogen, 38 and it has been hypothesized that leaked fibrinogen is converted to fibrin in the pericapillary space. 37,38 Other studies have shown that the fibrinolytic activity of blood and tissues is deficient in patients with lipodermatosclerosis, resulting in a decreased clearance of fibrin.…”