Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pathogenesis of metabolic alkalosis

Michael Emmett, MD
Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
Section Editor
Richard H Sterns, MD
Deputy Editor
John P Forman, MD, MSc


Metabolic alkalosis is a relatively common disorder that is most often generated by diuretic therapy or the loss of gastric secretions due to vomiting (which may be surreptitious) or nasogastric suction. Metabolic alkalosis may also result from severe hypokalemia, alkali ingestion when renal function is markedly diminished, primary aldosteronism, or disorders that mimic primary aldosteronism.

The pathogenesis of metabolic alkalosis will be reviewed here. The causes, evaluation, and treatment of this disorder are discussed separately. (See "Causes of metabolic alkalosis" and "Clinical manifestations and evaluation of metabolic alkalosis" and "Treatment of metabolic alkalosis".)


The development of metabolic alkalosis and its subsequent maintenance generally have distinct and separate explanations [1-3]:

An elevation in the plasma bicarbonate concentration can develop due to excessive hydrogen ion loss in the urine or gastrointestinal tract, hydrogen ion movement into the cells, the administration of bicarbonate salts (or other alkalinizing salts such as sodium acetate or lactate), or volume contraction around a relatively constant amount of extracellular bicarbonate (called a contraction alkalosis). (See "Causes of metabolic alkalosis".)

An elevated bicarbonate concentration is maintained by conditions that reduce bicarbonate filtration, enhance bicarbonate reabsorption, or impair bicarbonate secretion, and thereby prevent rapid excretion of the excess bicarbonate in the urine. Rapid bicarbonate excretion would otherwise correct the alkalosis [1,4].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Mar 28, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.551.
  2. Galla JH. Metabolic alkalosis. J Am Soc Nephrol 2000; 11:369.
  3. Laski ME, Sabatini S. Metabolic alkalosis, bedside and bench. Semin Nephrol 2006; 26:404.
  4. Sabatini S, Kurtzman NA. The maintenance of metabolic alkalosis: factors which decrease bicarbonate excretion. Kidney Int 1984; 25:357.
  5. Hamm LL, Nakhoul N, Hering-Smith KS. Acid-Base Homeostasis. Clin J Am Soc Nephrol 2015; 10:2232.
  6. Galla JH, Bonduris DN, Luke RG. Effects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosis. J Clin Invest 1987; 80:41.
  7. Wesson DE. Augmented bicarbonate reabsorption by both the proximal and distal nephron maintains chloride-deplete metabolic alkalosis in rats. J Clin Invest 1989; 84:1460.
  8. Galla JH, Gifford JD, Luke RG, Rome L. Adaptations to chloride-depletion alkalosis. Am J Physiol 1991; 261:R771.
  9. Wagner CA, Giebisch G, Lang F, Geibel JP. Angiotensin II stimulates vesicular H+-ATPase in rat proximal tubular cells. Proc Natl Acad Sci U S A 1998; 95:9665.
  10. Turban S, Beutler KT, Morris RG, et al. Long-term regulation of proximal tubule acid-base transporter abundance by angiotensin II. Kidney Int 2006; 70:660.
  11. Cano A, Miller RT, Alpern RJ, Preisig PA. Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells. Am J Physiol 1994; 266:C1603.
  12. Khadouri C, Marsy S, Barlet-Bas C, Doucet A. Short-term effect of aldosterone on NEM-sensitive ATPase in rat collecting tubule. Am J Physiol 1989; 257:F177.
  13. Harrington JT, Hulter HN, Cohen JJ, Madias NE. Mineralocorticoid-stimulated renal acidification: the critical role of dietary sodium. Kidney Int 1986; 30:43.
  14. Schuster VL. Cortical collecting duct bicarbonate secretion. Kidney Int Suppl 1991; 33:S47.
  15. Levine DZ, Iacovitti M, Harrison V. Bicarbonate secretion in vivo by rat distal tubules during alkalosis induced by dietary chloride restriction and alkali loading. J Clin Invest 1991; 87:1513.
  16. Galla JH, Rome L, Luke RG. Bicarbonate transport in collecting duct segments during chloride-depletion alkalosis. Kidney Int 1995; 48:52.
  17. Cogan MG, Carneiro AV, Tatsuno J, et al. Normal diet NaCl variation can affect the renal set-point for plasma pH-(HCO3-) maintenance. J Am Soc Nephrol 1990; 1:193.
  18. Luke RG, Galla JH. It is chloride depletion alkalosis, not contraction alkalosis. J Am Soc Nephrol 2012; 23:204.
  19. Norris SH, Kurtzman NA. Does chloride play an independent role in the pathogenesis of metabolic alkalosis? Semin Nephrol 1988; 8:101.
  20. Rodan AR, Cheng CJ, Huang CL. Recent advances in distal tubular potassium handling. Am J Physiol Renal Physiol 2011; 300:F821.
  21. Adam WR, Koretsky AP, Weiner MW. 31P-NMR in vivo measurement of renal intracellular pH: effects of acidosis and K+ depletion in rats. Am J Physiol 1986; 251:F904.
  22. Capasso G, Jaeger P, Giebisch G, et al. Renal bicarbonate reabsorption in the rat. II. Distal tubule load dependence and effect of hypokalemia. J Clin Invest 1987; 80:409.
  23. Wingo CS, Smolka AJ. Function and structure of H-K-ATPase in the kidney. Am J Physiol 1995; 269:F1.
  24. Cheval L, Barlet-Bas C, Khadouri C, et al. K(+)-ATPase-mediated Rb+ transport in rat collecting tubule: modulation during K+ deprivation. Am J Physiol 1991; 260:F800.
  25. Eiam-Ong S, Kurtzman NA, Sabatini S. Regulation of collecting tubule adenosine triphosphatases by aldosterone and potassium. J Clin Invest 1993; 91:2385.
  26. Hulter HN, Sigala JF, Sebastian A. K+ deprivation potentiates the renal alkalosis-producing effect of mineralocorticoid. Am J Physiol 1978; 235:F298.
  27. Garella S, Chazan JA, Cohen JJ. Saline-resistant metabolic alkalosis or "chloride-wasting nephropathy". Report of four patients with severe potassium depletion. Ann Intern Med 1970; 73:31.