A. Epidemiology

1. Common diseases of lower limbs
2. Typically manifest by varicose veins and venous ulcers
3. Increasing prevalence with age
4. In 18-64 year olds (Scotland Study)
   1. Telangiectasisas / reticular veins in ~80% of men, 85% of women
   2. Vericose veins 40% of men, 16% of women
   3. Ankle edema 7% of men, 16% of women
   4. Active or healed venous le ulcers in ~1% of general population
5. Accounts for ~2% of health care budgets in developed countries

B. Symptoms

1. Aching, heaviness
2. Feeling of swelling
3. Cramps
4. Itching
5. Tingling
6. Restless legs
7. Reduced quality of life

C. Classification (Table 1, Ref [1])

1. C0: 0 no visiable or palpable signs of venous disease
2. C1: Telangiectasias, reticular veins, malleolar flare
   1. Telangiectasias are dilated intradermal venules <1mm diameter
   2. Reticular veins are dilated, nonpalpable, subdermal veins <3mm diameter
3. C2: Varicose Veins
   1. Dilated, palpable subcutaneous veins
   2. Usually >3mm diameter
4. C3: Edema without Skin Changes
5. C4: Skin Changes Due to Venous Disease
   1. C4a: pigmentation and/or venous eczema
   2. C4B: lipodermatosclerosis and/or atrophie blanche
6. C5: Skin changes with healed ulcerations
7. C6: Skin changes with active ulceration

D. Pathophysiology

1. Venous hypertension (HTN) is likely responsible for most or all manifestations
   1. Venous HTN is nearly always caused by reflux through incompetent valves
   2. Venous outflow obstruction (including thrombosis)
   3. Failure of calf-muscle pump due to obesity and/or leg immobility
2. Reflux may occur in superficial or deep veins or both
   1. Superficial reflux alone ~45%
   2. Deep vein reflux alone ~12%
   3. Superficial and deep reflux ~43%
3. Normal Venous Valve Function
   1. Competent venous valves ensure lower extremity venous blood flows back to heart
   2. The valves allow emptying the deep and superficial venous sytems and reduce pressure
   3. Small leg movements cause reductions in foot-vein pressures from ~90mm to 30-50mm
   4. Normal walking associated with foot-vein pressures ~10mm
   5. In legs with dysfunction valves, reductions in pressures do not occur with movement
4. Valvular Incompetence
   1. Primary (idiopathic) incompetence ~75%
   2. Congenital anomaly ~2%
   3. Secondary incompetence (trauma, deep vein thrombosis) ~20%
5. Pathogenesis of Valvular Incompetence
   1. After 24-48 hours of venous hypertension, monocytes/macrophages infiltrate veins
   2. Infiltration associated with areas of valve endothelium expression cell adhesion molecules
   3. Elevated pressures and non-laminar (turbulant and reversing) flow activate endothelium
   4. Activated endothelium on valves produces various factors that stimulate abnormal collagen synthesis, smooth muscle proliferation leading to valvular dysfunction
6. Normal and Abnormal Endothelium
   1. Normal endothelium produces antithrombotic factors which maintain homeostasis
   2. Antithrombotic factors: nitric oxide (NO), prostacyclin, thrombomoduliln, tissue plasminogen activator (TPA)
   3. Turbulant or reverse-flow stress (particularly with venous HTN) induce prothrombotic, cell adhesion, vasoconstrictive, mitogenic, permeability and fibrotic factors
   4. These factors come from endothelium as well as leukocytes
   5. Prothrombotic / vasoconstrictive factors include endothelin, angiotensin II
   6. Cell adhesion molecules include VCAM-1 and macrophage chemoattractant MCP-1
   7. Mitogenic factors include platelet derived growth factor (PDGF)
   8. Permeatility factors include vascular endoethelial growth factor (VEGF)
   9. Fibrotic factors include transforming growth factor ß (TGFß)
7. Skin Changes
   1. VEGF likely plays major role increasing microvascular permeability
   2. Plasma levels of VEGF increase during venous HTN
   3. VEGF also allows red blood cell (RBC) leakage into extravascular space
   4. This leads to deposition of ferritin and ferric iron which causes hyperpigmentation
   5. TGFß is a fibrotic cytokine, stimulating collagen synthesis by dermal fibroblasts

E. Varicose Veins

1. Etiology (see above)
   1. Superficial venous insufficiency
   2. Primary: localized only to superficial system (younger patients)
   3. Secondary: deep system and perforator dysfunction (majority of patients)
   4. Valvular insufficiency: "circus motion" of blood (especially under gravity)
2. Symptoms
   1. Pain / Cosmesis
   2. Hemorrhage
   3. Phlebitis
3. Treatment
   1. None
   2. Sclerotherapy: inflame vessel walls causing sclerosis
   3. Surgery [2]
   4. Ligation and stripping
   5. Generally well tolerated operations with 0.8% major complications (no mortality)

F. Overview of Treatments

1. Compression stockings - reduce venous pressures, improve blood return, reduce edema
2. Sclerotherapy for unsightly veins
3. Surgical repair

References

1. Bergan JJ, Schmid-Schonbein GW, Smith PD, et al. 2006. NEJM. 355(5):488
2. Critchley G, Handa A, Maw A, et al. 1997. Ann R Coll Surg Engl. 79(2):105