Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1968 May;47(5):1181–1192. doi: 10.1172/JCI105807

Correction of metabolic alkalosis by the kidney after isometric expansion of extracellular fluid

Jordan J Cohen 1
PMCID: PMC297270  PMID: 5645861

Abstract

Metabolic alkalosis was induced in dogs by administering ethacrynic acid and sustained by feeding a chloride-deficient diet. At the height of the alkalosis extracellular fluid was expanded “isometrically,” i.e., with an infusion that duplicated plasma sodium, chloride, and bicarbonate concentrations. Correction of metabolic alkalosis promptly followed such expansion and was attributed to the selective retention by the kidneys of chloride from the administered solution. Since plasma chloride concentration was not increased as an immediate consequence of the infusion, it is concluded that the change in renal tubular function that led to the selective retention of chloride must have been mediated by factors independent of filtrate chloride concentration.

A decrease in circulating mineralocorticoid level, as a consequence of volume expansion, does not seem to account for this change in tubular function since identical studies in dogs receiving excessive amounts of 11-deoxycorticosterone acetate during the day of infusion yielded similar findings. Moreover, no other consequence of volume expansion appears to be sufficient to cause this change in tubular function in the absence of metabolic alkalosis; when the alkalosis was corrected with hydrochloric acid before infusion, isometric expansion of extracellular volume did not induce selective chloride retention.

We suggest that isometric expansion during metabolic alkalosis causes a decrease in proximal sodium reabsorption that relinquishes filtrate to a more distal site in the nephron and that this site may retain chloride preferentially when hypochloremia or chloride deficiency is present.

Full text

PDF
1181

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ATKINS E. L., SCHWARTZ W. B. Factors governing correction of the alkalosis associated with potassium deficiency; the critical role of chloride in the recovery process. J Clin Invest. 1962 Feb;41:218–229. doi: 10.1172/JCI104473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BANK N., SCHWARTZ W. B. The influence of anion penetrating ability on urinary acidification and the excretion of titratable acid. J Clin Invest. 1960 Oct;39:1516–1525. doi: 10.1172/JCI104171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. COTLOVE E., NISHI H. H. Automatic titration with direct read-out of chloride concentration. Clin Chem. 1961 Jun;7:285–291. [PubMed] [Google Scholar]
  4. DE GRAEFF J., STRUYVENBERG A., LAMEIJER L. D. THE ROLE OF CHLORIDE IN HYPOKALEMIC ALKALOSIS. BALANCE STUDIES IN MAN. Am J Med. 1964 Nov;37:778–788. doi: 10.1016/0002-9343(64)90026-9. [DOI] [PubMed] [Google Scholar]
  5. DE WARDENER H. E., MILLS I. H., CLAPHAM W. F., HAYTER C. J. Studies on the efferent mechanism of the sodium diuresis which follows the administration of intravenous saline in the dog. Clin Sci. 1961 Oct;21:249–258. [PubMed] [Google Scholar]
  6. DIRKS J. H., CIRKSENA W. J., BERLINER R. W. THE EFFECTS OF SALINE INFUSION ON SODIUM REABSORPTION BY THE PROXIMAL TUBULE OF THE DOG. J Clin Invest. 1965 Jul;44:1160–1170. doi: 10.1172/JCI105223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GULYASSY P. F., VAN YPERSELE DE STRIHOU C., SCHWARTZ W. B. On the mechanism of nitrate-induced alkalosis. The possible role of selective chloride depletion in acid-base regulation. J Clin Invest. 1962 Oct;41:1850–1862. doi: 10.1172/JCI104642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KASSIRER J. P., BERKMAN P. M., LAWRENZ D. R., SCHWARTZ W. B. THE CRITICAL ROLE OF CHLORIDE IN THE CORRECTION OF HYPOKALEMIC ALKALOSIS IN MAN. Am J Med. 1965 Feb;38:172–189. doi: 10.1016/0002-9343(65)90172-5. [DOI] [PubMed] [Google Scholar]
  9. Kassirer J. P., Schwartz W. B. Correction of metabolic alkalosis in man without repair of potassium deficiency. A re-evaluation of the role of potassium. Am J Med. 1966 Jan;40(1):19–26. doi: 10.1016/0002-9343(66)90183-5. [DOI] [PubMed] [Google Scholar]
  10. Kassirer J. P., Schwartz W. B. The response of normal man to selective depletion of hydrochloric acid. Factors in the genesis of persistent gastric alkalosis. Am J Med. 1966 Jan;40(1):10–18. doi: 10.1016/0002-9343(66)90182-3. [DOI] [PubMed] [Google Scholar]
  11. LEVINSKY N. G., LALONE R. C. THE MECHANISM OF SODIUM DURESIS AFTER SALINE INFUSION IN THE DOG. J Clin Invest. 1963 Aug;42:1261–1276. doi: 10.1172/JCI104811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LOGSDON E. E. A method for the determination of ammonia in biological materials on the autoanalyzer. Ann N Y Acad Sci. 1960 Jul 22;87:801–807. doi: 10.1111/j.1749-6632.1960.tb23237.x. [DOI] [PubMed] [Google Scholar]
  13. MILLS I. H., DE WARDENER H. E., HAYTER C. J., CLAPHAM W. F. Studies on the afferent mechanism of the sodium chloride diuresis which follows intravenous saline in the dog. Clin Sci. 1961 Oct;21:259–264. [PubMed] [Google Scholar]
  14. NEEDLE M. A., KALOYANIDES G. J., SCHWARTZ W. B. THE EFFECTS OF SELECTIVE DEPLETION OF HYDROCHLORIC ACID ON ACID-BASE AND ELECTROLYTE EQUILIBRIUM. J Clin Invest. 1964 Sep;43:1836–1846. doi: 10.1172/JCI105057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SCHWARTZ W. B., HAYS R. M., POLAK A., HAYNIE G. D. Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. II. Recovery, with special reference to the influence of chloride intake. J Clin Invest. 1961 Jul;40:1238–1249. doi: 10.1172/JCI104354. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES