Causes of metabolic alkalosis
- Michael Emmett, MD
Michael Emmett, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Chief of Internal Medicine
- Baylor University Medical Center
- Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
Harold Szerlip, MD, FACP, FCCP, FASN, FNKF
- Director, Nephrology Division, Baylor University Medical Center, Dallas
- Program Director, Nephrology Training Program, Baylor University Medical Center
- Clinical Professor of Medicine, Texas A&M College of Medicine
- Adjunct Professor of Medicine, Texas College of Osteopathic Medicine
Metabolic alkalosis, a disorder that elevates the serum bicarbonate, can result from several mechanisms: intracellular shift of hydrogen ions; gastrointestinal loss of hydrogen ions; excessive renal hydrogen ion loss; administration and retention of bicarbonate ions; or volume contraction around a constant amount of extracellular bicarbonate (contraction alkalosis) (table 1) [1-4].
Hydrogen ions are derived from the dissociation of water into hydrogen and hydroxyl ions; therefore, when hydrogen ions are removed from the extracellular fluid, the remaining hydroxyl ion combines with carbon dioxide to form bicarbonate. Gastrointestinal and renal hydrogen loss is usually accompanied by the loss of chloride and potassium, resulting in hypochloremia and hypokalemia.
Patients with preserved renal function will most often rapidly excrete excess bicarbonate in the urine. Thus, metabolic alkalosis can only persist if the ability to excrete excess bicarbonate in the urine is impaired due to one of the following causes: hypovolemia; reduced effective arterial blood volume (due, for example, to heart failure or cirrhosis); chloride depletion; hypokalemia; reduced glomerular filtration rate; hyperaldosteronism; or combinations of these factors [3,5,6].
The causes of metabolic alkalosis will be reviewed here. The pathogenesis, evaluation, and treatment of this disorder are discussed separately. (See "Pathogenesis of metabolic alkalosis" and "Clinical manifestations and evaluation of metabolic alkalosis" and "Treatment of metabolic alkalosis".)
INTRACELLULAR SHIFT OF HYDROGEN
Metabolic alkalosis can be generated by a shift of hydrogen ions into the cells. This most often occurs in patients with potassium deficits and hypokalemia. This may be an important pathophysiologic mechanism in patients with metabolic alkalosis due to vomiting or nasogastric suction . (See "Potassium balance in acid-base disorders".)
- Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.559.
- Palmer BF, Alpern RJ. Metabolic alkalosis. J Am Soc Nephrol 1997; 8:1462.
- Galla JH. Metabolic alkalosis. J Am Soc Nephrol 2000; 11:369.
- Khanna A, Kurtzman NA. Metabolic alkalosis. J Nephrol 2006; 19 Suppl 9:S86.
- Seldin DW, Rector FC Jr. Symposium on acid-base homeostasis. The generation and maintenance of metabolic alkalosis. Kidney Int 1972; 1:306.
- Luke RG, Galla JH. It is chloride depletion alkalosis, not contraction alkalosis. J Am Soc Nephrol 2012; 23:204.
- Halperin ML, Scheich A. Should we continue to recommend that a deficit of KCl be treated with NaCl? A fresh look at chloride-depletion metabolic alkalosis. Nephron 1994; 67:263.
- 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.
- Kassirer JP, Schwartz WB. The response of normal man to selective depletion of hydrochloric acid. Factors in the genesis of persistent gastric alkalosis. Am J Med 1966; 40:10.
- Perez GO, Oster JR, Rogers A. Acid-base disturbances in gastrointestinal disease. Dig Dis Sci 1987; 32:1033.
- Giovannini I, Greco F, Chiarla C, et al. Exceptional nonfatal metabolic alkalosis (blood base excess +48 mEq/l). Intensive Care Med 2005; 31:166.
- Mitchell JE, Seim HC, Colon E, Pomeroy C. Medical complications and medical management of bulimia. Ann Intern Med 1987; 107:71.
- Stemmer CL, Oster JR, Vaamonde CA, et al. Effect of routine doses of antacid on renal acidification. Lancet 1986; 2:3.
- Madias NE, Levey AS. Metabolic alkalosis due to absorption of "nonabsorbable" antacids. Am J Med 1983; 74:155.
- Gennari FJ, Weise WJ. Acid-base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol 2008; 3:1861.
- 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.
- Harrington JT, Hulter HN, Cohen JJ, Madias NE. Mineralocorticoid-stimulated renal acidification: the critical role of dietary sodium. Kidney Int 1986; 30:43.
- Hropot M, Fowler N, Karlmark B, Giebisch G. Tubular action of diuretics: distal effects on electrolyte transport and acidification. Kidney Int 1985; 28:477.
- CANNON PJ, HEINEMANN HO, ALBERT MS, et al. "CONTRACTION" ALKALOSIS AFTER DIURESIS OF EDEMATOUS PATIENTS WITH ETHACRYNIC ACID. Ann Intern Med 1965; 62:979.
- Garella S, Chang BS, Kahn SI. Dilution acidosis and contraction alkalosis: review of a concept. Kidney Int 1975; 8:279.
- Wall SM, Lazo-Fernandez Y. The role of pendrin in renal physiology. Annu Rev Physiol 2015; 77:363.
- POLAK A, HAYNIE GD, HAYS RM, SCHWARTZ WB. Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. I. Adaptation. J Clin Invest 1961; 40:1223.
- SCHWARTZ WB, HAYS RM, POLAK A, HAYNIE GD. 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; 40:1238.
- ROTHERAM EB Jr, SAFAR P, ROBIN E. CNS DISORDER DURING MECHANICAL VENTILATION IN CHRONIC PULMONARY DISEASE. JAMA 1964; 189:993.
- Hulter HN, Sebastian A, Toto RD, et al. Renal and systemic acid-base effects of the chronic administration of hypercalcemia-producing agents: calcitriol, PTH, and intravenous calcium. Kidney Int 1982; 21:445.
- Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982; 97:242.
- Abreo K, Adlakha A, Kilpatrick S, et al. The milk-alkali syndrome. A reversible form of acute renal failure. Arch Intern Med 1993; 153:1005.
- Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol 2010; 21:1440.
- VAN GOIDSENHOVEN GM, GRAY OV, PRICE AV, SANDERSON PH. The effect of prolonged administration of large doses of sodium bicarbonate in man. Clin Sci 1954; 13:383.
- Máttar JA, Weil MH, Shubin H, Stein L. Cardiac arrest in the critically ill. II. Hyperosmolal states following cardiac arrest. Am J Med 1974; 56:162.
- Levin T. What this patient didn't need: a dose of salts. Hosp Pract (Off Ed) 1983; 18:95.
- Kelleher SP, Schulman G. Severe metabolic alkalosis complicating regional citrate hemodialysis. Am J Kidney Dis 1987; 9:235.
- Pearl RG, Rosenthal MH. Metabolic alkalosis due to plasmapheresis. Am J Med 1985; 79:391.
- Gupta M, Wadhwa NK, Bukovsky R. Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate. Am J Kidney Dis 2004; 43:67.
- Diskin CJ, Stokes TJ, Dansby LM, et al. Recurrent metabolic alkalosis and elevated troponins after crack cocaine use in a hemodialysis patient. Clin Exp Nephrol 2006; 10:156.
- Bishop D, Claudius B. Effects of induced metabolic alkalosis on prolonged intermittent-sprint performance. Med Sci Sports Exerc 2005; 37:759.
- Street D, Nielsen JJ, Bangsbo J, Juel C. Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium. J Physiol 2005; 566:481.
- Miller PD, Berns AS. Acute metabolic alkalosis perpetuating hypercarbia. A role for acetazolamide in chronic obstructive pulmonary disease. JAMA 1977; 238:2400.
- Kennedy JD, Dinwiddie R, Daman-Willems C, et al. Pseudo-Bartter's syndrome in cystic fibrosis. Arch Dis Child 1990; 65:786.
- Sweetser LJ, Douglas JA, Riha RL, Bell SC. Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis. Respirology 2005; 10:254.
- Augusto JF, Sayegh J, Malinge MC, et al. Severe episodes of extra cellular dehydration: an atypical adult presentation of cystic fibrosis. Clin Nephrol 2008; 69:302.
- INTRACELLULAR SHIFT OF HYDROGEN
- GASTROINTESTINAL HYDROGEN LOSS
- Loss of gastric secretions
- EXCESSIVE RENAL HYDROGEN LOSS
- Primary mineralocorticoid excess
- Loop or thiazide diuretics
- Bartter and Gitelman syndromes
- Pendred syndrome
- Posthypercapnic alkalosis
- Hypercalcemia and the milk (or calcium)-alkali syndrome
- ALKALI ADMINISTRATION
- CONTRACTION ALKALOSIS