About the pathophysiology of venous leg ulceration

Abstract

In the March 2001 issue of the Journal, there was an excellent CME article about chronic venous insufficiency (CVI) and venous leg ulceration.1Valencia IC Falabella A Kirsner RS Eaglstein WH. Chronic venous insufficiency and venous leg ulceration.J Am Acad Dermatol. 2001; 44: 401-421Abstract Full Text Full Text PDF PubMed Scopus (405) Google Scholar Three hypotheses regarding the pathophysiology of venous leg ulcer were presented: (1) a hypothesis about pericapillary fibrin cuffs and fibrinolytic abnormalities, (2) a hypothesis about trapping of growth factors, and (3) a hypothesis about trapping of white cells. I would like to stress the importance of disturbances in the microcirculatory hemodynamics in the pathogenesis of venous leg ulceration. Very old studies from the early 20th century have shown that the oxygen content of venous blood obtained from legs with CVI is elevated when compared with the venous blood obtained from the cubital vein or from the vein of the opposite lower extremity.2Blalock A. Oxygen content of blood in patients with varicose veins.Arch Surg. 1929; 19: 898-905Crossref Google Scholar, 3Fontaine R. The John Homans Memorial Lecture Remarks concerning venous thrombosis and its sequelae.Surgery. 1957; 41: 6-25PubMed Google Scholar On angiography, premature venous filling has been observed in legs with CVI when compared with healthy legs.4Haimovici H Steinman C Caplan LH. Role of arteriovenous anastomoses in vascular disease of the lower extremity.Ann Surg. 1966; 164: 990-1002Crossref PubMed Scopus (41) Google Scholar, 5Schalin L. Arteriovenous communication to varicose veins in the lower extremities studied by dynamic angiography.Acta Chir Scand. 1980; 146: 397-406PubMed Google Scholar Blood flow has been found to be increased in the skin of legs with CVI as well.6Partsch H. Hyperaemic hypoxia in venous ulceration.Br J Dermatol. 1984; 110: 249-250Crossref PubMed Scopus (39) Google Scholar However, the density of capillaries of the skin in legs with CVI has been found to be reduced compared with that of healthy legs,7Luetolf O Bull RH Bates DO Mortimer PS. Capillary underperfusion in chronic venous insufficiency: a cause for leg ulceration.Br J Dermatol. 1993; 128: 249-254Crossref PubMed Scopus (37) Google Scholar which can reflect hypoperfusion of the nutritive capillaries. All of these findings could be explained by arteriovenous (AV) shunting of blood in legs with CVI. When AV shunting is prolonged and severe enough, it may steal blood from the nutritive capillaries in the skin, and, by causing ischemia in the skin, also contributes to ulcer formation. The possibility of AV shunting has been challenged on the basis of old radioisotope perfusion studies, which had been done without correlation with angiography.8Lofferer O Mostbeck A Partsch H. Arteriovenose Kurzschlusse der Exremitäten. Nuklearmedizinishe Untersuchungen mit besonderer Berucksichtigung des posttrombotischen Unterschenkelgeschwurs.Zentralbl Phlebol. 1969; 8: 2-22PubMed Google Scholar Recently, with the use of angiography and Duplex scanning, it has been confirmed that the peripheral resistance is lowered in arteries of legs with venous ulcers9Malanin K Haapanen A Havu V. Lowered peripheral resistance in arteries of legs with venous ulcer.Acta Derm Venereol (Stockh). 1994; 74: 110-112PubMed Google Scholar and that the more severe the CVI, the lower is the peripheral resistance.10Malanin K Haapanen A Kolari PJ Helander I Havu VK. The peripheral resistance in arteries of legs is inversely proportional to the severity on chronic venous insufficiency.Acta Derm Venereol (Stockh). 1997; 77: 22-25PubMed Google Scholar Furthermore, with the use of laser Doppler and continuous wave Doppler ultrasound scanning, a single intermittent pneumatic compression treatment has been found to increase the peripheral resistance in arteries as well as laser Doppler flux of the skin in legs with venous ulceration more than in healthy legs.11Malanin K Kolari PJ Havu VK. The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers.Acta Derm Venereol (Stockh). 1999; 79: 156-160Crossref PubMed Scopus (13) Google Scholar These findings suggest that elimination of edema causes redistribution of skin blood flow in the legs with venous ulceration, favoring the superficial capillary perfusion in skin. This could explain why compression treatment promotes healing on venous leg ulcers. The AV shunting can be considered to be a physiologic response to elevated venous pressure without the need for any specific anatomic shunt vessels.11Malanin K Kolari PJ Havu VK. The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers.Acta Derm Venereol (Stockh). 1999; 79: 156-160Crossref PubMed Scopus (13) Google Scholar It is regrettable that despite so much indirect evidence for the existence of AV shunting in skin of legs with CVI, it is not currently accepted as a possible concomitant pathogenetic factor in the formation of venous ulcer. This is reflected in the paucity of studies in this field during recent years, despite the possibilities offered by modern technology to gain more information about the microcirculatory hemodynamics in skin of legs with CVI.