Chronic Venous Insufficiency and Venous Ulcers: Pathophysiology



Progression of a clinical Class 2 venous disease to higher classes is an unpredictable but unfortunate event in the natural history of chronic venous disorders (CVD). It is not an essential event in all patients with CVD. Only a subset of patients go through this process. The triggering factors responsible for this transformation are not well understood. It is a slow degenerative process taking months and years. But when it does happen, the venous reflux which initially commenced in the superficial system extends to involve the deep veins and the perforators. Other symptoms such as edema (C3), venous eczema/lipodermatosclerosis (C4), and ulcers (C5–6) also become prominent. The term, primary chronic venous insufficiency (CVI) or simply CVI, is used to denote this condition. It includes the clinical classes from C3 to C6. Venous hypertension with microcirculatory impairment is the root cause for the clinical manifestations. The intensity of the morbidity associated with CVI was comparable with those seen in congestive cardiac failure and chronic lung disease [1].


Varicose Vein Calf Muscle Venous Hypertension Venous Ulcer Superficial Vein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Carradice D, Mazari FAK, Samuel N, Allgar V, Hattfield J, ChetterI C. Modelling the effect of venous disease on quality of life. Br J Surg. 2011;98:1089–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Eklof B, Rutherford RR, Bergan JJ, Carpentier PH, Gloviczki P, Kistner RL, Meisssner MH, Moneta GL, Myers K, Padberg FT, Perrin C, Ruckley V, Coleridge- Smith P, Wakefield TW. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg. 2004;40:1248–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Kistner RL, Eklof B. Classification and etiology of chronic venous disease. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 37–46.Google Scholar
  4. 4.
    Robertson L, Lee AJ, Gallagher K, Carmichael SJ, Evans CJ, Mc Kinstry BH, Fraser SCA, Allan PL, Welder D, Ruckley C, Fowkes FG. Risk factors for chronic ulceration in patients with varicose veins, a case control study. J Vasc Surg. 2009;49:1490–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Scott TE, LaMorte WW, Gorin DR, Menzoian JO. Risk factors for chronic venous insufficiency: a dual-case control study. J Vasc Surg. 1995;22:622–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Muller- Buhl U, Leutgeb R, Engeser P, Archankeng EN, Szecsenyi J, Laux G. Varicose veins are a risk factor for deep vein thrombosis in general practice patients. Vasa. 2012;41(5):360–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Raju S. Surgical repair of deep vein valve incompetence. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 472–82.Google Scholar
  8. 8.
    Evans CJ, Fowkes FGR, Ruckley CV, Lee AAJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53:149–53.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Zamboni P, Toganazzo S, Izzo M, Pancaldi F, Scapoli GL, Liboni A, Gemmati D. Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration. J Vasc Surg. 2005;42:309–14.PubMedCrossRefGoogle Scholar
  10. 10.
    Tognazzo S, Gemmati D, Palazzo A, Catozzi L, Carandina S, Legnaro A, Giovanna Tacconi G, Scapoli GL, Zamboni P. Prognostic role of factor XIII gene variants in non healing venous leg ulcers. J Vasc Surg. 2006;44(4):815–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Bergan JJ, Pascarella L, Schmid-Sconbein GW. Pathogenesis of primary chronic venous disease: insights from animal models of venous hypertension. J Vasc Surg. 2008;47:183–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Dodd H, Cockett FB. The pathology and surgery of the veins of the lower limbs. 2nd ed. Edinburgh/London: Churchill Livingston; 1976. p. 246–66.Google Scholar
  13. 13.
    Strandness Jr DE, Thiele BL. Selected topics in venous disorders. New York: Futura Publishing Company; 1981. p. 17.Google Scholar
  14. 14.
    Pegum JM, Fegan WG. Physiology of venous return from the foot. Cardiovasc Res. 1967;1:249–54.CrossRefGoogle Scholar
  15. 15.
    Burnand KG, Wadoodi A. The physiology and hemodynamics of chronic venous insufficiency of the lower limb. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 47–55.Google Scholar
  16. 16.
    Sethia KK, Darke SG. Long saphenous incompetence as a cause of venous ulceration. Br J Surg. 1984;71:754–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Hoare MC, Nicolaides AN, Miles ER, Shull K, Jury RP, Needham TN, Dudley HAF. Role of primary varicose veins in venous ulceration. Surgery. 1982;92:450–3.PubMedGoogle Scholar
  18. 18.
    Negus D, Friedgood A. The effective management of venous ulceration. Br J Surg. 1983;70:623–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Burnand KG, O’ Donnel TF, Thomas ML, Browse NL. Relative importance of incompetent communicating veins in the production of varicose veins and venous ulcers. Surgery. 1977;82:9–14.PubMedGoogle Scholar
  20. 20.
    Recek C. Impact of the calf perforating vein on the venous haemodynamics in primary varicose veins. J Cardio Vasc Surg (Torino). 2006;47(6):629–35.Google Scholar
  21. 21.
    Zukowski AJ, Nicolaides AN, Szendro G, Irvine A, Lewis R, Malouf GM, Hobbs JT, Dudley HA. Haemodynamic significance of incompetent perforating veins. Br J Surg. 1991;78(5):625–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, Gloviczki ML, Lohr JM, Mc Lafferty RB, Meissner MH, Murad MH, Padberg FT, Pappas PJ, Passman MA, Raffeto JD, Vasquez MA, Wakefield TW. The care of patient with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53(5 suppl):2s–48.PubMedCrossRefGoogle Scholar
  23. 23.
    Kistner RL. Primary venous valve incompetency of the leg. Am J Surg. 1980;140:218–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Raju S. Venous insufficiency of the lower limbs and stasis ulceration changing concepts and management. Ann Surg. 1983;197:688–97.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Lim KH, Hill G, Tarr G, van Rij A. Deep venous reflux: definition and associated clinical and physiological significance. J. Vasc Surg: Venous and Lymphatic Disorders. 2013;1(4):325–32.Google Scholar
  26. 26.
    Lim CS, Davies AH. Pathogenesis of primary varicose veins. Br J Surg. 2009;11:1231–42.CrossRefGoogle Scholar
  27. 27.
    Vincent JR, Jones GT, Hill GB, van Rij AM. Failure of microvenous valves in small superficial veins is key to the skin changes of venous insufficiency. J Vasc Surg. 2011;54:62s–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Neglen P. Endovascular reconstruction for chronic iliofemoral vein obstruction. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 491–502.Google Scholar
  29. 29.
    Yang D, Yvonne K, VandongenY K, Stacey MC. Changes in calf muscle in chronic venous disease. Cardiovasc Surg. 1999;7–4:451–6.CrossRefGoogle Scholar
  30. 30.
    Qiao T, Liu C, Ran F. The impact of gastrocnemius muscle cell changes in chronic venous insufficiency. Eur J Vasc Endovasc Surg. 2005;30:430–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Yamaki T, Nozaki M, Sakurai H, Soejima K, Kono T, Hamahata A. Advanced chronic venous insufficiency is associated with increased calf muscle deoxygenation. Eur J Vasc Endovasc Surg. 2010;39(6):787–94.PubMedCrossRefGoogle Scholar
  32. 32.
    Padberg FT, Johnston MV, Sisto SA. Structured exercise improves calf muscle pump function in chronic venous insufficiency. J Vasc Surg. 2004;39(1):79–87.PubMedCrossRefGoogle Scholar
  33. 33.
    Bermudez K, Knudson MM, Morabito D, Kessel O. Fasciotomy, chronic venous insufficiency and the calf muscle pump. Arch Surg. 1998;133(12):1356–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Singh N, Sidaway AN, Bottoni CR, Antedomenico E, Gawley TS, Harada D, Gillepsie DL, Uyehara CF, Cordts PR. Physiological changes in venous haemodynamics associated with elective fasciotomy. Ann Vasc Surg. 2006;20(3):301–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Davies JA, Bull RH, Farrelly IJ, Wakelin MJ. A home based exercise programme improves ankle range of motion in long term venous ulcer patients. Phlebology. 2007;2:86–9.CrossRefGoogle Scholar
  36. 36.
    Barwel JR, Taylor M, Deacon J, Davies C, Whyman MR, Poskitt KR. Ankle motility is a risk factor for healing of chronic venous leg ulcers. Phlebology. 2001;16:38–40.CrossRefGoogle Scholar
  37. 37.
    Back TL, Padberg FT, Araki CT, Thompson PN, Hobson RW. Limited range of motion is a significant factor in venous ulceration. J Vasc Surg. 1995;22:519–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Kugler C, Strunk M, Rudofsky G. Venous pressure dynamics of the healthy human leg: role of muscle activity, joint mobility and anthropometric factors. J Vasc Surg. 2001;38:20–9.Google Scholar
  39. 39.
    Eliska O, Eliskova M. Morphology of lymphatics in human venous crural ulcers with lipodermatosclerosis. Lymphology. 2001;34(3):111–23.PubMedGoogle Scholar
  40. 40.
    Perrin M, Ramelet AA. Pharmacological treatment of primary chronic venous disease; rationale, results and unanswered questions. Eur J Vasc Endovasc Surg. 2011;41:117–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Bergan JJ, Scmid- Schonben G, Coleridge Smith P, Niccolaides A, Boisseau M, Eklof B. Chronic venous disease. N Engl J Med. 2006;355:488–98.PubMedCrossRefGoogle Scholar
  42. 42.
    Lim CS, Shalhoub J, Gohel MS, Shepherd AC, Davies AH. Matrix metalloproteinases in vascular diseases – a potential therapeutic target? Curr Vasc Pharmacol. 2010;8:75–85.PubMedCrossRefGoogle Scholar
  43. 43.
    Pappas P, Lal BK, Padberg Jr FT, Zickler RW, Duran WN. Pathogenesis of varicose veins and cellular pathophysiology of chronic venous insufficiency. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 56–69.Google Scholar
  44. 44.
    Steins A, Hahn M, Jünger M. Venous ulcers and microcirculation. Clin Hemorheol Microcirc. 2001;24(3):147–53.PubMedGoogle Scholar
  45. 45.
    Jünger M, Steins A, Hahn M, Hafner HM. Microcirculatory dysfunction in chronic venous insufficiency. Microcirculation. 2000;7(S1):S 3–12.CrossRefGoogle Scholar
  46. 46.
    Shami SK, Shields DA, Scurr JH, Coleridge- Smith PD. Leg ulceration in venous disease. Postgrad Med J. 1992;68:779–85.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration; a new hypothesis. BMJ. 1988;296:1726–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Pappas PJ, De Fouw DO, Venezio LM, Gorti R, Padberg FT, Silva Jr MB, Goldberg MC, Duran WN, Hobson RW. Morphometric assessment of dermal microcirculation in patients with chronic venous insufficiency. J Vasc Surg. 1997;26(5):784–95.PubMedCrossRefGoogle Scholar
  49. 49.
    Falanga V, Eaglestein WH. The trap hypothesis of venous ulceration. Lancet. 1993;341:1006–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Hasan A, Murata H, Flabella A, Ochoa S, Zhou L, Badiavas E, Falanga V. Dermal fibroblasts are unresponsive to the action of transforming growth factor – B1. J Dermatol Sci. 1997;16(1):59–66.PubMedCrossRefGoogle Scholar
  51. 51.
    Stanley AC, Park H, Phillips TJ, Russakoysky V, Menzoian JO. Reduced growth of dermal fibroblasts from chronic venous ulcers can be stimulated with growth factors. J Vasc Surg. 1997;26:994–1001.PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  1. 1.General SurgeryAmrita Institute of Medical Sciences, Amrita LaneKochiIndia

Personalised recommendations