Effect of Plasma Inorganic Phosphate on Tissue Oxygenation during Recovery from Diabetic Ketoacidosis

Abstract

As early as in 1939 Guest and Rapoport emphasized that a striking decrease occurs in the content of 2,3-diphosphoglycerate (2,3-DPG) of the red blood cells of diabetics in ketoacidosis (1). The physiological implication of this finding has only recently emerged based on an appreciation of the allosteric behaviour of hemoglobin during oxygenation and of the unique effect of 2,3-DPG on the affinity of hemoglobin for oxygen (2,3). An increase in the concentration of 2,3-DPG in the red blood cells will produce a shift to the right in the oxyhemoglobin dissociation curve (ODC), thus facilitating oxygen release at the tissue level. A decrease in the 2,3-DPG content will increase the affinity of hemoglobin to oxygen, cause a shift of the ODC to the left, thus making less oxygen available. 2,3-DPG is formed as an intermediary product of glycolysis in the red cells and this fraction is decreased in acidosis due to the inhibitory effect of increased hydrogen ion and dehydration on glycolysis. In diabetic ketoacidosis there is also a significant depletion of the phosphorus stores in the body as shown by the immediate response of plasma and urinary phosphorus to insulin. With insulin treatment there occurs a precipitous fall in both plasma and urinary phosphorus level, and the plasma phosphate level may remain subnormal for as long as a week. Since inorganic phosphate (Pi) is known to act as a cofactor in the glycolysis of the red cells by stimulating both the phospho-fructokinase and the glyceraldehyde-3-phosphate-dehydrogenase (4,5,6) and thereby the formation of 2,3-DPG, the concentration of Pi may be a determining factor for the rate of resynthesis of red cell 2,3-DPG and the normalization of the affinity of hemoglobin for oxygen. In evaluating this possibility we have studied the interrelationship between the concentration of plasma inorganic phosphate, red cell 2,3-DPG, and the position of the oxyhemoglobin dissociation curve in patients in and during recovery from severe diabetic ketoacidosis.