title: Diabetic foot cellular hypoxia may be due to capillary shunting--a novel hypothesis.
abstract: Diabetic foot is traditionally attributed to a triad of neuropathy, ischemia and infection. Cellular hypoxia in diabetic foot can neither be attributed to an occlusive large artery disease (which are mostly patent) nor to the so called diabetic small vessel disease (where such occlusion was never proved). The physiological findings that accompany cellular hypoxia are confusing: elevated local blood flow and high oxygen saturation in both the tissue and its collecting veins. It is well known that some tissues (e.g. skin) are wired with two types of capillaries: True capillaries - also known as exchange capillaries, where nutrients and gases exchange takes place, and metarteriole thoroughfare channels - also known as shunting capillaries. We hypothesize that in the diabetic foot tissue blood flow is rerouted through the metarteriole thoroughfare channel, bypassing the exchange capillaries. Hence, nutrient and gas exchange is disabled and tissue cells became hypoxic regardless of the tissue blood flow. As a result of the shunt, arterial oxygen is not consumed and the oxygen saturation in the collecting veins remains high. The hereby hypothesis suggests that mal-perfusion rather than hypo-perfusion is the underlying cause of cellular hypoxia in diabetic foot. This hypothesis complies with the findings of patent arteries proximal to the affected site, normal to elevated tissue blood flow and high oxygen saturation in the affected tissue and its collecting veins.
authors.affiliation: School of Medicine, Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Itay E
authors.initials: IE
authors.lastname: Gabbay
authors.affiliation: Clalit Health Services, Dan-Petach Tikva District, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Gabbay
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: ugabai@post.tau.ac.il.
authors.forename: Uri
authors.initials: U
authors.lastname: Gabbay
mesh_terms: D002196:Capillaries / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D017719:Diabetic Foot / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology