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. 1985 Mar;75(3):798–808. doi: 10.1172/JCI111775

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

H J Adrogué, Z Chap, T Ishida, J B Field
PMCID: PMC423607  PMID: 3884666

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 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 microU/ml to a maximum of 84 +/- 22 microU/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 HCl 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 in ketoacid infusion, and release of potassium results from increased glucagon levels in HCl acidosis. Whether the changes in plasma potassium that other types od organic acid acidosis produce are accounted for by a similar hormonal mechanism remains to be determined.

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Selected References

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  1. ANDRES R., BALTZAN M. A., CADER G., ZIERLER K. L. Effect of insulin on carbohydrate metabolism and on potassium in the forearm of man. J Clin Invest. 1962 Jan;41:108–115. doi: 10.1172/JCI104452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adrogué H. J., Madias N. E. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 1981 Sep;71(3):456–467. doi: 10.1016/0002-9343(81)90182-0. [DOI] [PubMed] [Google Scholar]
  3. Adrogué H. J., Stinebaugh B. J., Gougoux A., Lemieux G., Vinay P., Tam S. C., Goldstein M. B., Halperin M. L. Decreased distal acidification in acute hypercapnia in the dog. Am J Physiol. 1983 Jan;244(1):F19–F27. doi: 10.1152/ajprenal.1983.244.1.F19. [DOI] [PubMed] [Google Scholar]
  4. BRADLEY A. F., SEVERINGHAUS J. W., STUPFEL M. Accuracy of blood pH and PCO2 determinations. J Appl Physiol. 1956 Sep;9(2):189–196. doi: 10.1152/jappl.1956.9.2.189. [DOI] [PubMed] [Google Scholar]
  5. BRADLEY A. F., SEVERINGHAUS J. W., STUPFEL M. Variations of serum carbonic acid pK with pH and temperature. J Appl Physiol. 1956 Sep;9(2):197–200. doi: 10.1152/jappl.1956.9.2.197. [DOI] [PubMed] [Google Scholar]
  6. Bia M. J., DeFronzo R. A. Extrarenal potassium homeostasis. Am J Physiol. 1981 Apr;240(4):F257–F268. doi: 10.1152/ajprenal.1981.240.4.F257. [DOI] [PubMed] [Google Scholar]
  7. Cox M., Sterns R. H., Singer I. The defense against hyperkalemia: the roles of insulin and aldosterone. N Engl J Med. 1978 Sep 7;299(10):525–532. doi: 10.1056/NEJM197809072991007. [DOI] [PubMed] [Google Scholar]
  8. DeFronzo R. A., Felig P., Ferrannini E., Wahren J. Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am J Physiol. 1980 May;238(5):E421–E427. doi: 10.1152/ajpendo.1980.238.5.E421. [DOI] [PubMed] [Google Scholar]
  9. DeFronzo R. A., Sherwin R. S., Dillingham M., Hendler R., Tamborlane W. V., Felig P. Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. Studies with somatostatin in normal dogs and in normal and diabetic human beings. J Clin Invest. 1978 Feb;61(2):472–479. doi: 10.1172/JCI108958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Epstein F. H., Rosa R. M. Adrenergic control of serum potassium. N Engl J Med. 1983 Dec 8;309(23):1450–1451. doi: 10.1056/NEJM198312083092308. [DOI] [PubMed] [Google Scholar]
  11. GIEBISCH G., BERGER L., PITTS R. F. The extrarenal response to acute acid-base disturbances of respiratory origin. J Clin Invest. 1955 Feb;34(2):231–245. doi: 10.1172/JCI103076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartley C. J., Cole J. S. An ultrasonic pulsed Doppler system for measuring blood flow in small vessels. J Appl Physiol. 1974 Oct;37(4):626–629. doi: 10.1152/jappl.1974.37.4.626. [DOI] [PubMed] [Google Scholar]
  13. Hartley C. J., Hanley H. G., Lewis R. M., Cole J. S. Synchronized pulsed Doppler blood flow and ultrasonic dimension measurement in conscious dogs. Ultrasound Med Biol. 1978;4(2):99–110. doi: 10.1016/0301-5629(78)90035-2. [DOI] [PubMed] [Google Scholar]
  14. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  15. Ishida T., Lewis R. M., Hartley C. J., Entman M. L., Field J. B. Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs. Endocrinology. 1983 Mar;112(3):1098–1109. doi: 10.1210/endo-112-3-1098. [DOI] [PubMed] [Google Scholar]
  16. MADISON L. L., MEBANE D., UNGER R. H., LOCHNER A. THE HYPOGLYCEMIC ACTION OF KETONES. II. EVIDENCE FOR A STIMULATORY FEEDBACK OF KETONES ON THE PANCREATIC BETA CELLS. J Clin Invest. 1964 Mar;43:408–415. doi: 10.1172/JCI104925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. MORTIMORE G. E. Effect of insulin on potassium transfer in isolated rat liver. Am J Physiol. 1961 Jun;200:1315–1319. doi: 10.1152/ajplegacy.1961.200.6.1315. [DOI] [PubMed] [Google Scholar]
  18. Massara F., Martelli S., Cagliero E., Camanni F., Molinatti G. M. Influence of glucagon on plasma levels of potassium in man. Diabetologia. 1980 Nov;19(5):414–417. doi: 10.1007/BF00281818. [DOI] [PubMed] [Google Scholar]
  19. Miles J. M., Haymond M. W., Gerich J. E. Suppression of glucose production and stimulation of insulin secretion by physiological concentrations of ketone bodies in man. J Clin Endocrinol Metab. 1981 Jan;52(1):34–37. doi: 10.1210/jcem-52-1-34. [DOI] [PubMed] [Google Scholar]
  20. Oster J. R., Perez G. O., Vaamonde C. A. Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis. Am J Physiol. 1978 Oct;235(4):F345–F351. doi: 10.1152/ajprenal.1978.235.4.F345. [DOI] [PubMed] [Google Scholar]
  21. Perez G. O., Oster J. R., Katz F. H., Vaamonde C. A. The effect of acute metabolic acidosis on plasma cortisol, renin activity and aldosterone. Horm Res. 1979;11(1):12–21. doi: 10.1159/000179033. [DOI] [PubMed] [Google Scholar]
  22. Perez G. O., Oster J. R., Vaamonde C. A. Serum potassium concentration in acidemic states. Nephron. 1981;27(4-5):233–243. doi: 10.1159/000182061. [DOI] [PubMed] [Google Scholar]
  23. Polonsky K., Jaspan J., Pugh W., Dhorajiwala J., Abraham M., Blix P., Moossa A. R. Insulin and glucagon breakthrough of somatostatin suppression: importance of portal vein hormone measurements. Diabetes. 1981 Aug;30(8):664–669. doi: 10.2337/diab.30.8.664. [DOI] [PubMed] [Google Scholar]
  24. ROGERS T. A., WACHENFELD A. E. Effect of physiologic acids on electrolytes in rat diaphragm. Am J Physiol. 1958 Jun;193(3):623–626. doi: 10.1152/ajplegacy.1958.193.3.623. [DOI] [PubMed] [Google Scholar]
  25. Rebolledo O. R., Hernandez R. E., Zanetta A. C., Gagliardino J. J. Insulin secretion during acid-base alterations. Am J Physiol. 1978 Apr;234(4):E426–E429. doi: 10.1152/ajpendo.1978.234.4.E426. [DOI] [PubMed] [Google Scholar]
  26. SIMMONS D. H., AVEDON M. Acid-base alterations and plasma potassium concentration. Am J Physiol. 1959 Aug;197:319–326. doi: 10.1152/ajplegacy.1959.197.2.319. [DOI] [PubMed] [Google Scholar]
  27. SWAN R. C., AXELROD D. R., SEIP M., PITTS R. F. Distribution of sodium bicarbonate infused into nephrectomized dogs. J Clin Invest. 1955 Dec;34(12):1795–1801. doi: 10.1172/JCI103234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. SWAN R. C., PITTS R. F. Neutralization of infused acid by nephrectomized dogs. J Clin Invest. 1955 Feb;34(2):205–212. doi: 10.1172/JCI103073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sterns R. H., Cox M., Feig P. U., Singer I. Internal potassium balance and the control of the plasma potassium concentration. Medicine (Baltimore) 1981 Sep;60(5):339–354. doi: 10.1097/00005792-198109000-00002. [DOI] [PubMed] [Google Scholar]
  30. TOBIN R. B. Varying role of extracellular electrolytes in metabolic acidosis and alkalosis. Am J Physiol. 1958 Dec;195(3):685–692. doi: 10.1152/ajplegacy.1958.195.3.685. [DOI] [PubMed] [Google Scholar]

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