Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs.

Abstract

Metabolic acidosis due to organic acids infusion fails to elicit hyperkalemia. Although plasma potassium levels may rise, the increase is smaller than in mineral acid acidosis. The mechanisms responsible for the different effects of organic acid acidosis and mineral acid acidosis remain undefined, although dissimilar hormonal responses by the pancreas may explain the phenomena. To test this hypothesis, beta-hydroxybutyric acid (7 meq/kg) or hydrochloric acid (3 meq/kg) was infused over 30 min into conscious dogs (n = 12) with chronically implanted catheters in the portal, hepatic, and systemic circulation, and flow probes were placed around the portal vein and hepatic artery. Acid infusion studies in two groups of anesthetized dogs were also done to assess the urinary excretion of potassium (n = 14), and to evaluate the effects of acute suppression of renal electrolyte excretion on plasma potassium and on the release/uptake of potassium in peripheral tissues of the hindleg (n = 17). Ketoacid infusion caused hypokalemia and a significant increase in portal vein plasma insulin, from the basal level of 27±4 uU/ml to a maximum of 84±22 ,U, ml at 10 min, without changes in glucagon levels. By contrast, mineral acid acidosis of similar severity resulted in hyperkalemia and did not increase portal insulin levels but enhanced portal glucagon concentration from control values of 132±25 pg/ml to 251±39 pg/ml at 40 min. A significant decrease in plasma glucose levels due to suppression of hepatic release was observed during ketoacid infusion, while no changes were observed with mineral acid infusion. Plasma flows in the portal vein and hepatic artery remained unchanged from control values in both acid infusion studies. Differences in renal potassium excretion were ruled out as determinants of the disparate kalemic responses to organic acid infusion compared with HCO acidosis. Evaluation of the arteriovenous potassium difference across the hindleg during ketoacid infusion demonstrates that peripheral uptake of potassium is unlikely to be responsible for the observed hypokalemia. Although the tissue responsible for the different kalemic responses could not be defined with certainty, the data are compatible with an hepatic role in response to alterations in the portal vein insulin and/or glucagon levels in both acid infusion studies. We propose that cellular uptake of potassium is enhanced by hyperinsulinemia Correspondence and reprint requests should be addressed to Dr.

Risk Factors for the Development of Hypokalemia in Neonatal Diarrheic Calves

“…It was found that the presence of d ‐lactataemia in acidemic calves resulted in significantly lower odds for hyperkalemia but significantly higher odds for the presence of hypokalemia 8. This is in line with the results of experimental studies which reported that a hyperkalemic state can be induced by infusions with inorganic acids such as HCl or ammonium chloride but not if organic acids such as lactic acid, acetic acid or ß‐hydroxybutyrate are infused 24, 25, 26. This disparate effect on K + homeostasis was related to intracellular moving of organic anions which is believed to result in a higher degree of intracellular acidosis and Na + loading and consequently a higher Na + /K + ‐ATPase activity resulting in a net cellular uptake of potassium ions 27.…”

Effects of pH on Potassium

“…32 Moreover, differential effects of organic versus hyperchloremic acidosis on insulin and glucagon secretion may contribute to the differing effects of these forms of acidosis on plasma K ϩ as discussed earlier. 33 Although skeletal muscle is the predominant source of intracellular K ϩ content, there is evidence that the effect of organic acid-induced insulin secretion on plasma K ϩ is mediated at least in part by hepatic K ϩ uptake. 33 The interactions of acid-base disturbances with other hormonal systems are at present incompletely defined.…”

“…33 Although skeletal muscle is the predominant source of intracellular K ϩ content, there is evidence that the effect of organic acid-induced insulin secretion on plasma K ϩ is mediated at least in part by hepatic K ϩ uptake. 33 The interactions of acid-base disturbances with other hormonal systems are at present incompletely defined.…”

PCO2 and [K+]p in Metabolic Acidosis

“…The authors report that acute NH 4 Cl-induced metabolic acidosis resulted in increased plasma insulin and decreased glucagon levels. Their data are reminiscent of those observed with acute organic acid-induced acidosis (ketoacid infusion) in conscious dogs (which elicited a hypokalemic response) but not those with mineral acidinduced acidosis (which yielded transient hyperkalemia) (10). Thus it would appear that the intravenous administration of 350 ml/h of 5% glucose during the course of acid infusion to the normal volunteers, and not the mineral-acid load itself, was responsible for the reported increase in plasma insulin and decrease in plasma glucagon levels.…”

“…These derangements in glucoregulation were independent of the activity of the sympathetic nervous system (8). Similar studies were carried out in conscious dogs infused with HCl to discount a confounding effect of pentobarbital anesthesia (10). Acute HCl-induced acidemia caused small and transient but significant increases in plasma glucose levels in hepatic-vein blood but not in arterial blood.…”