New Advances in the Understanding of the Pathophysiology of Chronic Venous Insufficiency

Abstract

Chronic venous insufficiency (CVI) is inseparably linked to elevated venous pressure and is accompanied by vascular, dermal, and subcutaneous tissue damage and restructuring. Abundant evidence exists both in humans and in experimental models to suggest that the tissue damage may be initiated by generation of an inflammatory reaction. Inflammatory indicators include elevation of endothelial permeability; attachment of circulating leukocytes to the endothelium; infiltration of monocytes, lymphocytes, and mast cells into the connective tissue; and development of fibrotic tissue infiltrates and several molecular markers, such as growth factor or membrane adhesion molecule generation. Indicators of an inflammatory reaction are already detectable at early stages of CVI and may be involved in the development of primary venous valve dysfunction. One of the important questions is to identify trigger mechanisms for the inflammatory reaction in CVI. Current evidence suggests that, among several possible mechanisms (hypoxia, humoral stimulation), a shift in fluid shear stress from normal physiological levels and endothelial distension under the influence of elevated venous pressure may serve as trigger mechanisms for inflammation.

The inflammatory reaction during chronic venous disease of lower limbs.

“…Several studies confirm the "white cell trapping" hypothesis and massive leukocytes activation in the microcirculation followed by their migration to subcutaneous tissue [51]. This phenomenon is responsible for production and releasing of cytotoxic substances which lead to skin ulceration and also valve cups and the venous wall destruction [52][53][54][55].…”

Hypertension

“…11 Elevation of systemic capillary pressure above this range has several potentially deleterious effects, including the following: (1) interstial edema, which can have dramatic effects on the brain as exemplified in hypertensive encephalopathy 12 ; (2) disruption of capillary wall structure, with extravasation of plasma proteins and blood cells 13 ; and (3) activation of the microvascular endothelium, which may trigger or amplify an inflammatory cascade, 14 of importance, for example, in the pathogenesis of venous ulcers. 15 Pleiotropic changes in the functional behavior of arterioles have been noted in both clinical and experimental hypertension, including hyperresponsiveness to vasoconstrictor stimuli, 16,17 leading to their constriction or even complete closure, 16,18,19 endothelial dysfunction, 20,21 and reduced bioactivity of endothelium-derived NO. 22 It is being increasingly recognized that endothelial dysfunction in hypertension depends in part on the scavenging of NO by reactive oxygen species, the latter produced in high quantities because of the abnormal activation of membrane-bound reduced nicotinamide dinucleotide phosphate oxidase, mediated in particular by the stimulation of type 1 receptors to angiotensin II.…”

The correction of endothelium functional state disturbances in patients with post-thrombotic syndrome of the lower extremities

“…Патофизиологические механизмы, изложенные в работах [16,17], помогают понять процессы, происходящие при хронической венозной не-достаточности: повышенное венозное давление способствует повреждению эндотелия сосудов, адгезии лейкоцитов, повреждению клапанного аппарата, нарушению микроциркуляции. Нару-шение функционального состояния эндотелия при нарушении венозного оттока приводит к про-дукции медиаторов воспаления, изменению про-ницаемости стенок сосудов для плазмы, крупных молекул, эритроцитов и фибриногена, что ухуд-шает обмен между циркулирующей кровью и тканями.…”