Could Gut-Liver Function Derangements Cause Chronic Venous Insufficiency?

Abstract

Upregulation of adhesion molecules and neutrophil infiltration of venous valve cusps may be risk factors for chronic venous insufficiency. But studies that focus on the target organ (vein) fail to consider the influence of systemic inflammation on WBC behavior in the microcirculation. This study probes the gut-liver axis as a potential source of gut-derived oxidative stress and free radical production leading to white blood cell activation in chronic venous insufficiency.

Venous hemodynamics (ambulatory venous pressure, air plethysmography, duplex) and gut-derived oxidative stress markers were studied in nine patients with chronic venous insufficiency (group I) and nine age and sex-matched control subjects with no venous disease (group II). Group I had healed venous ulcers (class 5, CEAP) but near-normal ambulatory venous pressure, to eliminate high ambulatory venous pressure as a chronic venous insufficiency risk factor. Markers of gut-derived oxidative stress included: stool analysis; intestinal permeability; hepatic detoxification challenges with caffeine, salicylate, and acetaminophen; and urine lipid peroxides.

Ambulatory venous pressure did not significantly differ (group I, 42.5 ±5.3 mm Hg; group II, 35.5 ±5.5 mm Hg; p = NS). Candida overgrowth in stool distinguished group I from group II (7/9 pts vs 1/9 pts, respectively; p=0.015). Increased intestinal permeability (lactulose/mannitol ratio) was prevalent in both groups (group I 0.07 ±0.02, group II 0.17 ±0.08, p=NS; normal range, 0.01-0.03). Both groups showed similar incidence of elevated urine lipid peroxides (5/9 pts vs 6/9 pts, respectively; p = NS), yet group I exhibited underfunction of both sulfation (group I 16.8 ±2.9%, group II 43.3 ±11%, p<0.03; normal acetaminophen recovery 16-36%) and glucuronidation (group I 30.4 ±4.1%, group II 64.1 ±14.4%, p<0.04; normal acetaminophen recovery 27%-56%) relative to oxidative stress, perhaps an indicator of diminished antioxidant capacity in patients with chronic venous insufficiency.

Gut dysbiosis (as indicated by stool yeast) and hepatic detoxification challenge pathway exhaustion may lead to subclinical, systemic inflammation and peripheral white blood cell adhesion in chronic venous insufficiency. Further exploration of the relationship between oxidative stress and venous disease is needed.

Get full access to this article

View all access options for this article.

References

1. Cheatle TR , Scott HJ : History of venous ulceration. In: Microcirculation in Venous Disease. 2nd ed. Coleridge Smith PD (ed). Austin: Landes Bioscience, 1998, pp 1-13.

2. Magnotti LJ , Upperman JS , Xu D , et al: Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock. Ann Surg 228:518-527, 1998.

3. Baker SM : Detoxification and Healing: The Key to Optimal Health. 1st ed. New Canaan: Keats Publishing, 1997.

4. Porter JM , Moneta GL , International Consensus Committee on Venous Disease: Reporting standards in venous disease: An update. J Vasc Surg 21:635-645, 1995.

5. Trowbridge JP , Walker M : The Yeast Syndrome. 1st ed. New York: Bantam Books, 1986.

6. Kaminski MV , Cordts PR : Gut-derived oxidative stress: A pathological factor in leg ulcers with and without chronic venous insufficiency. Wounds Compen Clin Res Pract 10:33-37, 1998.

7. Shields D , Sahary M : White cell activation. In: Microcirculation in Venous Disease. 2nd ed. Coleridge Smith PD (ed). Austin: Landes Bioscience, 1998, pp 141-170.

8. Sahary M , Shields DA , Porter JB , et al: Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease. J Vasc Surg 25:265-273. 1997.