Disturbance of Inorganic Phosphate Metabolism in Diabetes Mellitus: Its Relevance to the Pathogenesis of Diabetic Retinopathy
Figure 2
Flow chart of decreased oxygen availability/demand ratio in the diabetic retina. Hyperglycemia (lower right corner) leads to the formation of with increased binding of oxygen compared with hemoglobin A. This, combined with hypophosphatemia, leads to affinity hypoxia with decreased oxygen delivery to the venous part of the microvasculature, resulting in loss of tone in venous capillaries and venules. The resultant sluggish flow and decreased shear rate, erythrocyte aggregation, and blood viscosity (caused by increased plasma fibrinogen and alpha2-globulin) lead to venous microcirculatory stasis and stagnant hypoxia. Because retina has a high oxygen demand, tissue hypoxia leads to secretion of vascular endothelium growth factor (VEGF), erythropoietin (EPO), and possibly other growth factors. Capillary closure and ischemic hypoxia lead to further secretion of VEGF and other growth factors (see text).
