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The affinity of hemoglobin for oxygen may increase significantly in subjects who are hypophosphatemic and alkalotic. We studied the organic phosphate content and oxygen binding by hemoglobin of red cells in subjects undergoing hemodialysis, during which time a decrease in plasma inorganic phosphate and an increase in blood pH may occur. Red cell 2,3-DPG was not correlated with plasma inorganic phosphorus, whereas red cell ATP was highly correlated with plasma inorganic phosphorus when analyses were made on predialysis samples. Predialysis red cell inorganic phosphorus was highly correlated with plasma inorganic phosphorus, supporting the concept that intraerythrocytic inorganic phosphorus is maintained by a gradient from plasma to cell. Plasma inorganic phosphorus decreased by 45% during the period of hemodialysis, whereas red cell inorganic phosphorus did not change. Red cell 2,3-DPG, ATP, and oxygen binding by hemoglobin at standard conditions of temperature, pH, and pCO2 were not altered after 6 hr of hemodialysis. Plasma pH and base excess increased during dialysis. The increase in base excess, an estimate of the non-pH-dependent effect of CO2 on oxygen binding by hemoglobin, counterbalanced a portion of the effect of elevated pH on hemoglobin— oxygen affinity under in vivo conditions. Hence, only a slight increase in oxygen binding by hemoglobin occurred. Moreover, late dialysis symptoms were not associated with the degree of alkalosis or with the extent of change in hemoglobin’s affinity for oxygen. Red cell 2,3-DPG content was lower and hemoglobin’s affinity for oxygen was higher in subjects with chronic renal disease than in nonazotemic subjects with similar hemoglobin deficits. Moreover, increased red cell ATP in chronic renal disease patients did not influence oxygen binding by hemoglobin.

Radiographic contrast materials added to blood reduce the red cell membrane potential by balancing the internal impenetrable anions, hemoglobin and organic phosphates. In so doing, a redistribution of protons occurs such that plasma is acidified. The time course of acidification of plasma is measured in seconds, with a nadir of pH occurring 12 to 15 seconds after addition of Hypaque (1.5 to 3.0 ml10 ml blood) and a half-time of acidification requiring about 6 seconds. The acidification process is slowed in part by an initial alkalosis due to Hypaque. The. acidification of blood is more rapid after addition of Renografin (1.5 to 3.0 ml10 ml blood) than after addition of Hypaque since the former solution is slightly acidic. The time course of plasma acidification indicates that a maximal reduction in blood pH may not occur in the capillaries of a regional circulation following injection of contrast materials into its afferent vessel, since the transit time of the contrast material may be less than the time required for maximal acidification of plasma.

Construction of oxygen-hemoglobin dissociation curves based on extracellular pH and using blood tonometered with 5 CO2, is misleading under certain experimental conditions. These include the presence in blood of poorly penetrating non-ionic molecules like sucrose or poorly penetrating anionic compounds like radiographic contrast materials. False conclusions regarding the position of the oxygen-hemoglobin dissociation curve can result because of the disturbance of the normal pH gradient between plasma and red cell induced by such chemicals.

The affinity of hemoglobin for oxygen may increase significantly in subjects who are hypophosphatemic and alkalotic. We studied the organic phosphate content and oxygen binding by hemoglobin of red cells in subjects undergoing hemodialysis, during which time d decrease in plasma inorganic phosphate and an increase in blood pH may occur. Red cell 2,3-DPG was not correlated with plasma inorganic phosphorus, whereas red cell ATP was highly correlated with plasma inorganic phosphorus when analyses were made on predialysis samples. Predialysis red cell inorganic phosphorus was highly correlated with plasma inorganic phosphorus, supporting the concept that intraerythrocytic inorganic phosphorus is maintained by a gradient from plasma to cell. Plasma inorganic phosphorus decreased by 45% during the period of hemodialysis, whereas red cell inorganic phosphorus did not change. Red cell 2,3-DPG, ATP, and oxygen binding by hemoglobin at standard conditions of temperature, pH, and pCO2were not altered after 6 hr of hemodialysis. Plasma pH and base excess increased during dialysis. The increase in base excess, an estimate of the non-pH-dependent effect of CO2on oxygen binding by hemoglobin, counterbalanced a portion of the effect of elevated pH on hemoglobin-oxygen affinity under in vivo conditions. Hence, only a slight increase in oxygen binding by hemoglobin occurred. Moreover, late dialysis symptoms were not associated with the degree of alkalosis or with the extent of change in hemoglobin’s affinity for oxygen. Red cell 2,3-DPG content was lower and hemoglobin’s affinity for oxygen was higher in subjects with chronic renal disease than in nonazotemic subjects with similar hemoglobin deficits. Moreover, increased red cell ATP in chronic renal disease patients did not influence oxygen binding by hemoglobin.

The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h speciments of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h-1 and 856 ng 24 h-1 respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine axcretion.