**4. Venous edema and Lymphedema**

CVD is the most common cause of edema with age 50 and over [68]. The venous edema is a very common clinical manifestation of CVD, particularly in C3 to C6 classes [68–72]. The chronic venous edema may blunt the metabolic and immunological capacity of tissues, thus contributing to the risk of venous ulcer [72]. Venous edema occurs when there is an imbalance between vascular filtration and reabsorption and lymphatic reabsorption [19]. About 90% of capillary filtration (proteins, plasma, and other components) is reabsorbed back to the blood, and the remaining 10% is reabsorbed by the lymphatic circulation [20, 73]. In CVD, blood filtration is increased due to the higher intravascular hydrostatic pressure and raised endothelial permeability due to inflammation [19, 73]. In these conditions, venous edema may occur [19, 20]. This is a pitting edema that gets worse through the day and improves during sleeping because of the lying position and leg elevation. Usually, this edema is accompanied by venous symptoms and signs [19, 20]. Clinically, venous edema is perceived as an increase in fluid volume of the skin and subcutaneous tissue, characteristically diminished by pressure [13]. Venous edema usually occurs around the ankle region, but may extend to the leg and foot [13].

The principal physiological function of the lymphatic circulation is to guarantee homeostasis between the vascular and interstitial fluid compartments [74] and this requires that the lymphatic system compensates the excessive blood filtration at the blood capillary level [19]. Any failure in this process will result in accumulation of a protein rich fluid in the interstitial space, which is associated with an inflammatory reaction, fibrosis, overgrowth of adipose and connective tissue, and other symptoms that characterize the lymphedema [74]. There is some evidence of lymphatic failure in venous disease. For example, studies with lymphoscintigraphy, reveal that in post thrombotic syndrome the subfascial lymphatic drainage is reduced that may explain edema and lipodermatoesclerosis seen in this situations. Also, patients with ulcer have reduced lymphatic drainage, suggesting that lymphedema is a contributing factor to ulceration [19]. Approximately 20- 30% of individuals with CDV have mix edema (with venous and lymphatic component), because of fluid overload or recurrent cellulitis [70].

Based on the cause, the lymphedema may be classified as primary (congenital or hereditary) and secondary (acquire) forms [74]. Over one third of patients with CVD will have secondary lymphatic dysfunction but when edema is present in these patients, there is the tendency to misdiagnosis it as primary lymphedema [20].

When edema is at the dorsum of the foot, it is associated to squaring of the toes, thick skin, and is of non-pitting edema type [33]. In these cases, it is assumed that a lymphatic compromise exists [33]. The lymphatic circulation may compensate for the excessive filtration, but lymph vessels also suffer damaged with time (microlymphoangiopathy), because of chronic inflammation and accompanying subcutaneous and skin lesions [20, 66]. Therefore, venous edema becomes compound with signs of lymphedema, with non-pitting edema and with hyperkeratosis, papillomatosis, most in retro and post malleolar regions an in the lateral border of the foot [19]. Clinically, this secondary lymphedema may decrease with limb elevation initially, but with time patients will refer aggravation of swelling in the morning and after the night sleep because an increased osmotic pressure in the interstitial space caused by protein blood extravasation [19].
