Version July 2025
INTRODUCTION —
Chronic venous disorders are a common medical problem that can result in significant morbidity and mortality. The clinical presentation spans a spectrum from asymptomatic but cosmetically troublesome small ectatic veins (spider veins and reticular veins), to varicosities and edema, to severe skin changes including fibrosing panniculitis, dermatitis, and ulceration.
The terms "chronic venous disorders" and "chronic venous disease" encompass the spectrum of signs and symptoms using the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification (table 1) (ie, CEAP classifications 1 through 6), whereas chronic venous insufficiency refers to advanced venous disease (ie, CEAP 4 through 6). (See "Clinical manifestations of lower extremity chronic venous disorders" and "Classification of lower extremity chronic venous disorders".)
The final common pathway that leads to more severe clinical signs and symptoms is the development of venous hypertension. Venous hypertension results from structural problems such as obstruction to venous flow (eg, thrombus), dysfunction of venous valves, and/or functional problems that increase venous pressure (eg, heart failure, obesity) or failure of the "venous pump" (eg, weak musculature, reduced foot/ankle movements). In these situations, venous pressures are elevated, producing vein dilation, local tissue inflammation fibrosis, and sometimes, ulceration.
Venous anatomy and physiology, and the pathophysiology of venous hypertension with its clinical consequences are reviewed. Other aspects of chronic venous insufficiency are discussed separately. (See "Overview of lower extremity chronic venous disease".)
VENOUS ANATOMY —
The lower extremity venous system is composed of the following three types of veins (table 2) (see "Classification of lower extremity chronic venous disorders", section on 'Anatomy (The "A" component of CEAP)'):
●Superficial veins – The superficial veins are a network of subcutaneous veins that are superficial to the deep muscular fascia. The great saphenous and small saphenous veins are called "axial veins," as they course up and down the leg (figure 1 and figure 2). The "accessory veins" course parallel to the axial veins. "Circumflex veins" run oblique to saphenous canal, and "communicating veins" connect veins in the same compartments. "Tributary veins" are any veins that connect to the axial veins. The rest are considered "simple branch veins."
●Deep veins – The deep veins are located deep to the muscle fascia (figure 3). Deep veins are either within the muscle (ie, intramuscular, such as the gastrocnemius and soleus) or between the muscles (ie, intermuscular); the latter are more important in the development of chronic venous insufficiency [1]. The intermuscular veins, which accompany the lower extremity arteries, include the anterior tibial, posterior tibial, peroneal (fibular), popliteal, and femoral veins. The lower leg intermuscular veins are exposed to high subfascial pressures during calf muscle contraction.
●Perforator veins – The perforator veins communicate between the deep and superficial venous systems though the fascia. Some sources may refer to thigh perforators veins as Hunter veins, perforators above and below the knee as Dodd and Boyd veins, and calf perforators as Cockett veins. We prefer to use the anatomic description [2].
DETERMINANTS OF VENOUS FLOW —
The venous system is a large-volume, low-pressure, low-velocity, and low-resistance system. For the venous blood to return to the heart, it must overcome hydrostatic pressure induced by gravity and the column of blood from the right atrium to the foot.
The venous valves and "venous pump" are the two major determinants of this venous flow.
Venous valves are typically bicuspid. Venous valves direct flow from distal to proximal and from the superficial system to the deep system preventing retrograde flow. An exception to this flow is in the foot, where flow is directed from the deep system to the superficial system via perforators [3]. Venous valves increase in number in direct relation to the hydrostatic pressure; in the distal deep veins, for example, they may occur every 2 centimeters [1].
The venous pump refers to the pumping effect of calf and intrinsic foot muscles on venous flow. These muscle contractions produce pressure to assist venous return in the lower extremities against gravity by increasing subfascial pressure above intramuscular vein hydrostatic pressure. The pressure differential augments blood flow from the superficial system into the deep venous system, draining the skin and subcutaneous tissues.
The effectiveness of the pump is dependent upon the presence of adequate muscle contraction and competent venous valves [4]. Competent valves serve two main functions: they prevent the transmission of sudden rises in venous pressure in the superficial veins and capillaries during muscular contraction, and, at the end of muscle contraction, the valves prevent retrograde flow back. Venous pressures vary greatly depending on positioning and can be 15 mmHg when in the decubitus position, 55 to 75 mmHg while sitting, 75 to 90 mmHg while standing, and 40 to 55 mmHg when walking [5].
GENESIS AND CONSEQUENCES OF CHRONIC VENOUS HYPERTENSION —
Venous hypertension results from structural problems such as obstruction to venous flow (eg, thrombus), dysfunction of venous valves or the "venous pump," and/or functional problems that increase venous pressure. Examples of functional causes include obesity, heart failure, and obstructive sleep apnea, as these can elevate central venous pressures. Weak calf muscles, reduced feet and ankle movement, and dependent edema can contribute to the failure of the "venous pump."
In the presence of these, venous pressures are elevated, and ambulatory venous pressures can stay elevated at 60 to 90 mmHg. This level of venous pressure constitutes venous hypertension producing vein dilation which is capable of initiating associated anatomic, physiologic, and histologic changes discussed below (table 3) [6-9]. (See 'Anatomic changes' below and 'Physiologic changes' below and 'Histologic changes' below.)
A genetic predisposition has always been suspected given its high heritability, but no single culprit gene has been identified [10-12]. Many studies have identified candidate genes, gene expression, and gene-related proteins responsible for matrix metalloproteinases, vascular endothelial growth factors, and vascular development. Other genes responsible for abnormal iron metabolism (hemochromatosis C282Y gene mutation) and the development of collagen have also been implicated in the development of chronic venous insufficiency and ulceration [13,14]. Efforts using genome-wide association studies are underway to identify common gene variants associated with varicose veins [12,13,15]. However, the current understanding is that this not a single gene, but rather a multifactorial disease with epigenetic influences.
Anatomic changes — Valvular incompetence is synonymous with venous reflux, in which the vein valves fail to close, causing venous blood to flow in a retrograde direction. This is the most common anatomic abnormality associated with venous hypertension. The resulting increase in transmitted venous pressure causes venous dilation. As the deep and superficial veins become distended with excess volume, anatomic distortion of the vessel wall produces further valvular incompetence. The process becomes a vicious cycle.
Venous obstruction also leads to venous fibrosis, resulting in valvular damage, which increases venous pressures. Changes in the vein wall result in persistent venous hypertension regardless of whether veins are recanalized. When accompanied by clinical symptoms, this defines "post-thrombotic syndrome." Valvular incompetence can also be associated with fewer valves per unit length, which contributes to higher venous pressures [16].
The actual volume of refluxed blood in patients with venous insufficiency may be relatively small. However, when the superficial veins are already maximally distended, only a small increase in volume produces a large increases in pressure [17-19]. It is the transmission of this excess pressure that leads to inflammatory changes within the vessel wall and soft tissue deterioration that is responsible for most of the skin changes characteristic of advanced venous disease. (See "Clinical manifestations of lower extremity chronic venous disorders".)
Physiologic changes — Standing is normally associated with reflex constriction of the precapillary arterioles; by diminishing the transmission of arterial pressure to the capillary bed, this response protects the capillary bed from surges in venous hydrostatic pressure when assuming an upright posture. Patients with venous hypertension may lose this reflex; as a result, large increases in venous pressure are transmitted directly to the superficial capillary system [20-22].
The role of endothelial dysfunction and associated inflammation have been explored as key components of pathogenesis. Shear stress is inversely related to venous pressure. Thus, venous hypertension is associated with a reduction in shear stress. Low shear forces and mechanical stress activate endothelial cells which in turn promotes the release of inflammatory cells into the vein wall and valves promoting local inflammation. Endothelial cells are capable of detecting reductions in shear stress and changes in the microenvironment and respond by releasing nitric oxide, prostacyclin and anti-inflammatory substances [23,24]. However, unchecked local inflammation can lead to endothelial cell dysfunction with reduced production of vasoactive mediators and anti-inflammatory properties [23,24]. This cascade of events ultimately leads to venous wall and valvular damage with abnormal venous wall remodeling characterized by venous dilation and insufficiency [25-27].
Histologic changes — Sustained venous hypertension is associated with characteristic histologic and ultrastructural changes that underlie the cutaneous manifestations of chronic venous disorders.
Venous hypertension is associated with changes in the venous wall, including variation in wall thickness, increases in type 1 collagen, decreases in type III collagen, degradation of extracellular matrix, and reductions in the number of smooth muscle cells [28-30]. These changes weaken the vessel wall and may lead to abnormal venous dilation, including tortuous (eg, telangiectasias, varicose veins) and nontortuous segments [31]. The chronic release of inflammatory mediators is a fundamental cause for the trophic skin changes associated with venous insufficiency.
●Leukocytes accumulate and adhere to the endothelium of small vessels and become activated [32,33]. This microvascular leukocyte-trapping hypothesis is supported by histologic findings of increased numbers of macrophages, T lymphocytes, and mast cells in the tissue of patients with chronic venous hypertension [34,35].
●Increased expression of matrix metalloproteinases and other proteinases by the vessel cells breaks down the vascular extracellular matrix and leads to abnormal vascular permeability and edema.
●The presence of proteolytic enzymes in the subcutaneous tissues leads to the formation of cutaneous ulcers, which can be slow to heal [36].
●Migration of erythrocytes from the vascular space into tissue, and their subsequent degradation, result in the characteristic brown hyperpigmentation in the gaiter area. The release of ferritin and ferric oxide from the erythrocytes may result in oxidative stress and additional metalloproteinase activation, promoting tissue damage, ulcer formation, and delayed ulcer healing [37].
Patients with significant venous insufficiency can develop a severe fibrosing panniculitis of the subcutaneous tissue; the clinical representation of the panniculitis is known as lipodermatosclerosis. (See "Clinical manifestations of lower extremity chronic venous disorders".)
Lipodermatosclerosis presents as an area of indurated inflammatory tissue that binds the skin down to the subcutaneous tissue (picture 1A-C). Lipodermatosclerosis is associated with abnormal, elongated, "glomerular-like" capillaries with increased vascular permeability [38]. Dermal fibrosis may be the result of TGF-β1 fibrogenic cytokine release from activated leukocytes that have migrated out of the abnormally permeable vessels into the tissues. TGT-β1 cytokine increases the production of collagen and subcutaneous fibrosis [35]. Capillaries are virtually absent in areas of fibrotic scars, leading to a condition known as atrophie blanche (picture 2) or livedoid vasculopathy (picture 3) [39]. The lack of blood flow may explain the proclivity for these areas to develop ulcers. (See "Livedoid vasculopathy".)
As with valvular incompetence, worsening lipodermatosclerosis may become part of a vicious cycle. As the fibrosis increases, it may become so extensive and constrictive as to girdle and strangle the lower leg, further impeding lymphatic and venous flow.
SUMMARY AND RECOMMENDATIONS
●Chronic venous disorders – Chronic venous disorders are common medical problems that can negatively impact quality of life. The final common pathway that leads to more severe clinical signs and symptoms is the development of venous hypertension, often including the deep venous system. (See 'Introduction' above.)
●Physiology – Venous valves direct flow from distal to proximal and from the superficial veins to the deep veins. Blood is directed proximally within the deep venous system by muscular contraction (ie, the "venous pump"). The effectiveness of this pumping action depends on the presence of competent vein valves to prevent retrograde flow. (See 'Genesis and consequences of chronic venous hypertension' above.)
●Venous hypertension – Valvular incompetence and venous obstruction are structural causes of venous hypertension, whereas functional causes for venous hypertension include obesity, heart failure, obstructive sleep apnea, dependent edema, and failure of the "venous pump." Anatomic distortion of the vessel wall from excessive venous pressure exacerbates valvular incompetence. (See 'Anatomic changes' above and 'Determinants of venous flow' above.)
●Histologic changes – Sustained venous hypertension is associated with histologic and structural changes that lead to increased vascular permeability (edema) and the chronic release of inflammatory mediators that are the fundamental cause of cutaneous hyperpigmentation, trophic skin changes, and ulceration. (See 'Physiologic changes' above and 'Histologic changes' above.)
ACKNOWLEDGMENT —
The editorial staff at UpToDate acknowledges Patrick C Alguire, MD, FACP, who contributed to an earlier version of this topic review.
