Metabolic Alkalosis

Chloride-Resistant Alkaloses
When potassium depletion is associated with a mild-to-moderate metabolic alkalosis, oral KCl 40 to 60 mEq four or five times per day usually will suffice for correction. If, however, a cardiac arrhythmia or generalized weakness is present, intravenous KCl may be given at rates as high as 40 mEq/h in concentrations not to exceed 60 mEq/L. These very high rates should be used only when life-threatening situations are encountered. The patient should be monitored by electrocardiogram and frequent determinations of plasma potassium concentration because muscle uptake of potassium may initially be diminished by downregulation of muscle Na,K-ATPase. Glucose should be omitted initially from the solution used to administer potassium because stimulated insulin secretion may cause plasma potassium concentration to decrease even further. However, once potassium repletion has begun, the presence of glucose in the infusion will facilitate cellular potassium repletion. Because nephropathy due to potassium depletion may impair free water excretion, plasma sodium should be monitored, particularly if hypotonic fluids are administered.

When mineralocorticoid excess is the proximate cause, therapy is directed at either removal of the source or its blockade. Potassium-sparing diuretics, specifically spironolactone with hyperaldosteronism, will effectively reverse the adverse effects of mineralocorticoid excess on sodium, potassium, and bicarbonate excretion. Restriction of sodium and the addition of potassium to the diet will also ameliorate the alkalosis and the hypertension. Correction of the potassium deficit reverses the alkalinizing effects, but elimination of aldosterone excess is essential to permanent correction. In glucocorticoid-suppressible hyperaldosteronism, dexamethasone (0.25 mg mornings and 0.75 mg evenings) is the agent of choice to suppress ACTH secretion.

Many primary disorders of mineralocorticoid excess are definitively treated by tumor ablation. ACTH-secreting pituitary tumors may be removed by trans-sphenoidal resection or irradiation. With adrenal tumors, adrenalectomy, either unilateral or bilateral as appropriate, may be curative. In the ectopic ACTH syndrome, the ideal treatment of the secreting tumor can rarely be accomplished. In this instance and in metastatic adrenal tumors, metyrapone, which inhibits the final step in cortisol synthesis, or aminoglutethimide, which inhibits the initial step in steroid biosynthesis, will blunt the myriad manifestations of hypercortisolism. In those disorders in which curative surgery cannot be carried out, mitotane (o,p-DDD), which produces selective destruction of the zona fasiculata and reticularis and leaves aldosterone production intact, or cisplatin has also been used to control effectively many of the manifestations of the disease. However, to the extent that severe fluid and electrolyte disturbances are due solely to aldosterone production, mitotane may not suffice when hypokalemic alkalosis is present; metyrapone or aminoglutethimide would be better choices. Detailed discussion of the use of these drugs is beyond the scope of this review.

In BS and GS syndromes, the principal goal of therapy is to minimize urinary potassium loss. In BS, converting enzyme inhibitors, which reduce angiotensin II production and decrease aldosterone secretion, have been shown to be effective and should be tried first [42] . Because renal prostaglandin production is increased in BS and may contribute to sodium, chloride, and potassium wasting, prostaglandin synthase inhibitors may ameliorate, but usually will not completely correct, the hypokalemic alkalosis. Magnesium depletion, which may also increase urinary potassium wasting, should be corrected. However, the degree to which magnesium repletion corrects alkalosis is uncertain, and magnesium salts often produce an unacceptable degree of gastrointestinal irritation that may compound the patient’s problems.

In GS, potassium-sparing diuretics, such as amiloride 5 or 10 mg daily, triamterene 100 mg twice a day, or spironolactone 25 to 50 mg four times a day, will blunt the urinary losses but dietary potassium supplementation may also be needed. When causative, licorice intake or carbenoxolone should be stopped. In Liddle syndrome, amiloride is a reasonable first choice.

In the milk-alkali syndrome, cessation of alkali ingestion and the calcium sources (often milk and calcium carbonate), and chloride and volume repletion for the commonly associated vomiting, usually will lead to the prompt resolution of these abnormalities.

Journal of the American Society of Nephrology, Volume 11 Number 2 February 2000
Copyright 2000 American Society of Nephrology

John H. Galla
Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Copyright ? 2000 by the American Society of Nephrology


1. Hodgkin JE, Soeprono FF, Chan DM: Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med 8: 725-732, 1980 abstract

2. Anderson LE, Henrich WL: Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J 80: 729-733, 1987 abstract

3. Tannen RL: Effect of potassium on renal acidification and acid-base homeostasis. Semin Nephrol 7: 263-273, 1987 abstract

4. Javaheri S, Kazemi H: Metabolic alkalosis and hypoventilation in humans. Am Rev Respir Dis 136: 1101-1016, 1987 citation

5. Singer RB, Clark JK, Barker ES, Crosley AP Jr, Elkington JR: The acute effects in man of rapid intravenous infusion of hypertonic sodium bicarbonate solution. I. Changes in acid-base balance and distribution of excess buffer base. Medicine 34: 51-95, 1955

6. Seldin DW, Rector FC Jr: The generation and maintenance of metabolic alkalosis. Kidney Int 1: 306-321, 1972 citation

7. Johnson LR: Physiology of the Gastrointestinal Tract, New York, Raven, 1987

8. Plawker MW, Rabinowitz SS, Etwaru DJ, Glassberg KI: Hypergastrinemia, dysuria-hematuria and metabolic alkalosis: Complications associated with gastrocystoplasty. J Urol 154: 546-549, 1995 abstract

9. Babior BM: Villous adenoma of the colon. Am J Med 41: 615-621, 1966 citation

10. Hogland P, Haila S, Socha J, Tomaszewski L, Saarilho-Kere U, Karjalainen-Lindsberg M-L, Airola, K, Holmberg C, de la Chapelle A, Kere J: Mutations of the down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nat Genet 14: 316-317, 1996 abstract

11. Holmberg C, Perheentupa J, Launiala K, Hallman N: Congenital chloride diarrhea: Clinical analysis of 21 Finnish patients. Arch Dis Child 52: 255-267, 1977 abstract

12. Ellison DH: The physiologic basis of diuretic synergism: Its role in treating diuretic resistance. Ann Intern Med 114: 886-894, 1991 abstract

13. Hropot M, Fowler N, Karlmark B, Giebisch G: Tubular action of

diuretics: Distal effects on electrolyte transport and acidification. Kidney Int 28: 477-489, 1985 abstract

14. Chan YL, Biagi B, Giebisch G: Control mechanism of bicarbonate transport across the rat proximal convoluted tubule. Am J Physiol 242: F532-F543, 1982 abstract

15. Rosen RA, Julian BA, Dubovsky EV, Galla JH, Luke RG: On the mechanism by which chloride corrects metabolic alkalosis in man. Am J Med 84: 449-458, 1988 abstract

16. Verlander JW, Madsen KM, Tisher CC: Effect of acute respiratory acidosis on two populations of intercalated cells in the rat cortical collecting duct. Am J Physiol 253: F1142-F1156, 1987 abstract

17. Levitin H, Branscome W, Epstein FH: The pathogenesis of hypochloremia in respiratory acidosis. J Clin Invest 37: 1667-1675, 1958

18. Pedroli G, Liechti-Gallati S, Birrer P, Kraemer R, Foletti-Jaggi C, Bianchetti MG: Chronic metabolic alkalosis: Not uncommon in young children with severe cystic fibrosis. Am J Nephrol 15: 245-250, 1995 abstract

19. Kassirer JP, Schwartz WB: Correction of metabolic alkalosis in man without repair of potassium deficiency. Am J Med 40: 19-26, 1966 citation

20. Schwartz WB, van Ypersele de Strihou C, Kassirer JP: Role of anions in metabolic alkalosis and potassium deficiency. N Engl J Med 279: 630-639, 1968 citation

21. Cohen JJ: Correction of metabolic alkalosis by the kidney after isometric expansion of extracellular fluid. J Clin Invest 47: 1181-1192, 1968 citation

22. Galla JH, Gifford JD, Luke RG, Rome L: Adaptations to chloride-depletion alkalosis. Am J Physiol 261: R771-R781, 1991 abstract

23. 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. J Clin Invest 80: 41-50, 1987 abstract

24. Galla JH, Bonduris DN, Sanders PW, Luke RG: Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. J Clin Invest 74: 2002-2008, 1984 abstract

25. Gifford JD, Sharkins K, Work J, Luke RG, Galla JH: Total CO2 transport in rat cortical collecting duct in chloride-depletion alkalosis. Am J Physiol 258: F848-F853, 1990 abstract

26. Verlander JW, Madsen KM, Galla JH, Luke RG, Tisher CC: Response of intercalated cells to chloride depletion metabolic alkalosis. Am J Physiol 262: F309-F319, 1991

27. Jones JW, Sebastian A, Hulter HN, Schambelan M, Sutton JM, Biglieri EG: Systemic and renal acid-base effects of chronic dietary potassium depletion in humans. Kidney Int 21: 402-410, 1982 citation

28. Cannon PJ, Ames RP, Laragh JH: Relation between potassium balance and aldosterone secretion in normal subjects and in patients with hypertensive and renal tubular disease. J Clin Invest 45: 865-879, 1966 citation

29. Nakamura S, Amlal H, Galla JH, Soleimani M: NH4 + secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+ -K+ -ATPase. Kidney Int 56: 2160-2167, 1999 abstract

30. Hernandez RE, Schambelan M, Cogan MG, Colman J, Morris RC Jr, Sebastian A: Dietary NaCl determines severity of potassium depletion-induced metabolic alkalosis. Kidney Int 31: 1356-1367, 1987 abstract

31. Kassirer JP, London AM, Goldman DM, Schwartz WB: On the pathogenesis of metabolic alkalosis in hyperaldosteronism. Am J Med 49: 306-315, 1970 citation

32. Lifton RP, Dhuly RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM: A chimaeric 11B-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 355: 262-265, 1992 abstract

33. Young WF Jr, Hogan MJ: Renin-independent hypermineralocorticoidism. Trends Endocrinol Metab 5: 97-106, 1994

34. Warnock DG: Liddle syndrome: An autosomal dominant from of human hypertension. Kidney Int 53: 18-24, 1998 citation

35. Sabatini S: The cellular basis of metabolic alkalosis. Kidney Int 49: 906-917, 1996 citation

36. Luke RG, Levitin H: Impaired renal conservation of chloride and the acid-base changes associated with potassium depletion in the rat. Clin Sci 32: 511-517, 1967 citation

37. Amlal H, Wang Z, Soleimani M: Potassium depletion downregulates chloride-absorbing transporters in rat kidney. J Clin Invest 101: 1045-1054, 1998 abstract

38. Kurtz I: Molecular pathogenesis of Bartter’s and Gitelman’s syndromes. Kidney Int 54: 1396-1410, 1998 citation

39. Cummings JH, Sladen GE, James OFW, Sarner M, Misiewicz JJ: Laxative-induced diarrhoea: A continuing clinical problem. Br Med J 1: 537-541, 1974 citation

40. Adrogue HJ, Madias NE: Management of life-threatening acid-base disorders. N Engl J Med 338: 107-111, 1998 citation

41. Aichbichler BW, Zerr CH, Santa Ana CA, Porter JL, Fordtran JS: Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea. N Engl J Med 336: 106-109, 1997 citation

42. Hene RJ, Koomans HA, Dorhout Mees EJ, van de Stolpe A, Verhoef GEG, Boer P: Correction of hypokalemia in Bartter’s syndrome by enalapril. Am J Kidney Dis 9: 200-205, 1987 abstract

Print This Post Print This Post

Pages: 1 2 3