**4. Pathophysiology**

Clinical manifestations of CVI occur primarily due to ambulatory venous hypertension in the upright position or during ambulation. These result in clinical sign of edema, subcutaneous fibrosis, pigmentation, chronic pain and ulceration. The severity of chronic venous disease is closely related to the magnitude of venous hypertension. Patients with ambulatory venous pressures less than 40 mmHg have had a lower incidence of venous ulceration compared to patients with ambulatory venous hypertension greater than 80 mmHg [16].

The indications of ambulatory venous pressure are complex. Determinants of ambulatory venous pressure include venous reflux and obstruction as well as calf muscle pump function [17]. Studies have shown that calf muscle pump dysfunction occurs early in the development of CVI and it does not worsen with skin changes and ulceration [18].

In the normal case, the lower extremity muscle pumps and valves limit the accumulation of blood in the lower extremity veins. Failure of the lower extremity muscle pump is associated with peripheral venous insufficiency due to outflow obstruction, musculofascial weakness, loss of joint motion or valvular impairment. However, an effective peripheral pump becomes a compensator for some degrees of reflux and obstruction and prevents symptoms of CVI [13].

When the system operates normally, the ambulatory venous pressure in the superficial system is maintained between 20 and 30 mmHg. The superficial venous pressure may increase up to 60–90 mmHg in cases of venous occlusion, venous valve insufficiency or inappropriate muscle contraction. As mentioned above, this level causes venous hypertension. Thus, it shows that anatomic, physiologic and histological changes associated with chronic venous insufficiency begin. Chronic venous hypertension leads to some histological changes in the capillary bed, which is known as venous hypertensive microangiopathy. These changes include the folding and expansion of the capillary bed and increased endothelial surface [19].

Valvular failure is associated with a rapid recovery time after muscle contraction. If deep venous valves are insufficient, blood simply oscillates within the deep veins and there is no reduction in pressure. Chronic venous hypertension or persistent pressure results in pathological effects in the deep subcutaneous tissues such as edema, pigmentation, fibrosis and ulceration [13].
