**3.2. Pathophysiology**

and excluding other causes of leg ulcerations. The main purpose of venous ulcer management includes healing of the ulcer and prevention of recurrence. This chapter highlights the epidemiology, pathophysiology, clinical presentation, diagnostic testing, differential diagno‐

Venous leg ulcers (VLUs) are the most common lower extremity ulceration and responsible for 70% of all leg ulcers, with overall prevalence ranging from 0.06 to 2% [1–4]. It occurs frequently between the ages of 60 and 80 years; however, most people have their first ulcer before the age of 60 years [5, 6]. VLUs have slight female predominance, with a female‐to‐male

Venous ulcers have a significant socioeconomic impact with reduced work productivity and quality of life. Long‐term treatments are needed and recurrence is widely common, ranging from 54 to 78% of treated subjects [9]. The overall cost of VLU treatments was 1–2% of the healthcare budgets of European countries [10]. In the United States, approximately 2.5 billion

Advancing age, sex, race, phlebitis, family history, obesity, occupation involving prolonged standing, and number of pregnancies are risk factors that have been described with chronic

The venous system of the lower extremities includes the superficial veins, perforator veins, and the deep veins according to their relationship to the muscular fascia. The superficial veins comprises the reticular veins, the large (larger) and small (smaller) saphenous veins, and their tributaries. The great saphenous vein originates from where the dorsal vein of the first digit merges with the dorsal venous arch of the foot. After passing in front of the medial malleolus, it ascends the medial side of the leg. It joins the femoral vein just below the inguinal ligament. The small saphenous vein arises from the dorsal venous arch of the foot and ascends poster‐ olaterally from behind the lateral malleolus. Usually, it drains into the popliteal vein near the popliteal fossa. The reticular veins, a network of veins parallel to the skin surface, communicate with either saphenous tributaries or the deep veins through perforators. The perforator veins connect the superficial and deep vein systems. The deep venous system is categorized as either intramuscular or intermuscular. Intermuscular veins are three paired tibial veins including, the posterior tibial vein, the anterior tibial vein, and the peroneal vein. These veins join to form the popliteal vein in the popliteal area. At the level of the adductor canal, the popliteal vein is renamed the superficial femoral vein. This vessel joins the deep femoral vein in the femoral

sis, and treatment of venous ulcers.

280 Wound Healing - New insights into Ancient Challenges

ratio ranging from 1.5:1 to 10:1 [7, 8].

dollars was expended for the treatment of VLUs per year [11].

**3.1. Normal venous anatomy and physiology**

venous insufficiency and, subsequently, with venous ulcers [12, 13].

**2. Epidemiology**

**3. Pathogenesis**

In patients with venous disease or failure, venous pressure in deep system falls less than normal during ambulation and rises in orthostatic position, and this is termed venous hypertension. In conclusion, venous hypertension in the deep veins may be transmitted to the superficial veins [4, 16]. There is no general consensus about the transition from venous hypertension to venous ulceration. Several hypotheses have been proposed.

## *(a) Precapillary fibrin cuffs and fibrinolytic abnormalities hypotheses:*

According to this theory of Browse and Burnand [17], venous hypertension leads to distention of capillary walls and leakage of macromolecules such as fibrinogen into the dermis and subcutaneous tissues of the calf. The leaked fibrinogen polymerizes to form precapillary fibrin cuffs in the extravascular space. These precapillary cuffs were assumed to act as a physical barrier, which impede the diffusion of oxygen and nutrients, resulting in ischemia, cell death, and ulceration [17–19]. In addition, local and systemic fibrinolytic/coagulation abnormalities such as prolonged euglobulin lysis time, elevated plasma fibrinogen levels, increased levels of protein C, fibrin‐related antigens, D‐dimer, D‐monomer, fibrin monomer, and reduction in factor XIII activity may present in patients with venous disease [20–22]. However, it is unclear whether these abnormalities are primary or secondary to venous disease.

### *(b) Leukocyte trapping hypothesis:*

As a result of venous hypertension, there is a decreased pressure in capillary bed perfusion and capillary flux. This gives rise to erythrocyte aggregation and leukocyte plugging in the capillaries, leading to local ischemia. Moreover, these leukocytes release cytokines, tumor necrosis factor α (TNF‐α), proteolytic enzymes, and free radicals which can cause increased vascular permeability resulting in the leakage of fibrinogen into the pericapillary tissues and the decreased fibrinolytic activity [23–25].

### *(c) The growth factor trap hypothesis:*

Falanga and Eaglstein [26] recommended that macromolecules such as fibrinogen and α2macroglobulin, which leak into the dermis as a result of venous hypertension, bind to or trap growth factors, which then become unavailable for the maintenance of tissue integrity and repair process. The precapillary fibrin cuff of the venous ulcer contains growth factors such as transforming growth factor β (TGF‐β). Trapping of growth factors can impair activation of the cells that are needed for healing process [27].
