Acid-base and metabolic responses to anion infusion in the anesthetized dog

Abstract

This study evaluated the acid-base and metabolic effects of several organic anions which might have application in the correction of metabolic acidosis during hemodialysis. Anesthetized dogs were infused intravenously with the sodium salts of either chloride, bicarbonate, acetate, lactate, or pyruvate. Acetate perturbated metabolism more than any of the other organic anions infused. These perturbations included hypoxemia, reductions in serum potassium and phosphorus, a decrease in plasma, glucose, and increases in intermediary metabolites such as lactate, acetoacetate and beta-hydroxybutyrate. Transferance of our findings to hemodialysis suggests that acetate would compromise the ability of dialysis to reduce body burdens of potassium and phosphorus and provide proper base repletion. Pyruvate would appear superior to acetate as a base substitute by virtue of its lesser effects on oxygen consumption and electrolyte distribution and its capacity to produce glucose. However, the significant production of lactate with pyruvate infusion, coupled with diffusive losses of bicarbonate during dialysis and the possible instability of pyruvate in solution, would still hinder proper base repletion. Bicarbonate generation with lactate infusion was too slow to provide a practical alternative for base repletion in hemodialysis. Bicarbonate infusion caused minimal alterations in intermediary metabolism. This, in conjunction with obviating diffusive losses, suggests the use of bicarbonate would allow more appropriate base repletion during hemodialysis.

Hemodialysis-AssociatedHypoxemia

“…The intrave nous administration of sodium acetate in patients with end-stage renal disease is associated with hypoxemia [22]. Wathen et al [23] confirmed this observation in anesthetized dogs. Eiser et al [20] showed that acetate dialysis results in increased oxygen consumption and decreased C 0 2 production: Oh et al [17] confirmed that the reduction of respiratory quotient during acetate dial ysis is due only in minimal part to C 0 2 losses in the dia lyzer and that the most important component is a change in endogenous C 0 2 production and oxygen consump tion.…”

“…Furthermore, Sherlock et al [15] had shown an increased consumption of oxygen during dialysis which also results in changing the respiratory quotient and which cannot be related to dialyzer loss of carbon dioxide. Finally, as described below, a number of studies [17,18,22,23,25] have shown that acetate metabolism, per se, may result directly in a change in respiratory quotient which could largely explain the findings.…”

Pyruvate in the Correction of Intracellular Acidosis: A Metabolic Basis as a Novel Superior Buffer

“…Lac infusion was associated with a significantly slower rate of bicarbonate level rising in comparison with Pyr, indicating that the additional metabolic steps are required [50]. The oxidation of Lac-reduced [NADH 2 ]c may take place either in cytoplasm-coupled reactions associated with gluconeogenesis, or a mitochondrial route in the presence of oxygen.…”

“…This rate-limited step, which would display while the [NADH 2 ]c load is increased, may be another interpretation of the retardation of pHi recovery in addition to the elevated proton load, per se, from the Lac oxidation and the [NADH]c increment [10]. Although the ratio of [NAD + /NADH]c determines the balance between Pyr and Lac (equation 3), the reaction is in favor of the direction from Pyr to Lac as the lesser rise in blood Pyr concentration with Lac infusion than in blood Lac level with equal Pyr infusion [50]. Several recent findings evidently supported that Pyr would be superior to Lac in the treatment of clinic metabolic acidemia including lactic acidosis.…”

Validation of a Simple Method for Assessing Sodium Intake in Dialysis Patients

“…This is probably due to the fact that some doubts exist on whether the method is reliable in uremic patients under dialysis. In these patients the cellular sodium-exchange system is altered [17,18], the intracellular osmolality is affected by transcellular unbalances of urea [19] and of electrolytes such as potassium [20], the use of sodium bicarbonate as buffer in the dialysate might influence transcellular distribution of sodium [21], TBW determination could be incorrect. In spite of all these putative interfering factors it has been possible to prove with our study that sodium intake may be estimated with precision by the changes in plasma sodium concentration and body water volume.…”