eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Metabolic Alkalosis: Differential Diagnoses & Workup

Author: Sameer Yaseen, MD, Staff Nephrologist, Department of Internal Medicine, Division of Nephrology, Mercy Hospital of Des Moines
Coauthor(s): Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Contributor Information and Disclosures

Updated: Aug 18, 2009

Differential Diagnoses

Respiratory Acidosis

Workup

Laboratory Studies

  • Diagnosis is made by obtaining serum electrolytes and an arterial blood gas.
    • If the etiology of metabolic alkalosis is not clear from the clinical history and physical examination, including drug use and the presence of hypertension, then a urine chloride ion concentration can be obtained. Metabolic alkalosis secondary to volume depletion is usually associated with a low urine chloride ion concentration (<20 mEq/L).
    • Measurement of urine sodium ion concentration is used in many conditions to determine volume status, especially in patients with oliguria. However, volume depletion in metabolic alkalosis may not lead to low urine sodium. In the first few days of vomiting, the loss of acidic gastric secretions leads to an increase in serum bicarbonate concentration. The kidneys try to excrete the excess bicarbonate as the sodium or potassium salt. Therefore, despite volume depletion, the urine sodium level may be inappropriately high.
  • Plasma renin activity and aldosterone level
    • Plasma renin activity and aldosterone level may help to find the etiology of metabolic alkalosis, especially in patients with hypertension, hypokalemic metabolic alkalosis, and renal potassium wasting without diuretic use.
    • Low renin activity and high plasma aldosterone levels are found in primary hyperaldosteronism, including glucocorticoid-remediable hyperaldosteronism.
    • Low plasma renin activity and low aldosterone levels are found in Cushing syndrome, exogenous steroid use, CAH, 11B-HSD deficiency, DOC-secreting tumors, and Liddle syndrome.
    • Both plasma renin activity and aldosterone levels are high in renal artery stenosis, diuretic use, renin-secreting tumors, and in the hypotensive Bartter and Gitelman syndromes.
  • Primary hyperaldosteronism: Measure aldosterone levels in a 24-hour urine collection after salt loading to diagnose primary hyperaldosteronism.
  • Cushing syndrome: Evaluate plasma cortisol at midnight during sleep, 24-hour urine free cortisol, or dexamethasone suppression test in Cushing syndrome.
  • Measuring urine cortisol metabolites in the syndrome of AME: In this syndrome and other causes of 11B-HSD deficiency, the proportion of cortisol to cortisone metabolites is increased (ie, ratio of tetrahydrocortisol and 5-alpha-tetrahydrocortisol to tetrahydrocortisone).
  • High plasma and urine levels of DOC and 11-deoxycortisol in 11-hydroxylase deficiency: In 17-hydroxylase deficiency, DOC is elevated while 11-deoxycortisol is low. Another important difference between the 2 conditions is the impaired adrenal androgen synthesis in the latter and enhanced synthesis in the former. Therefore, measuring plasma or urine adrenal androgens (eg, dehydroepiandrosterone [DHEA], testosterone) may help to differentiate between the 2 conditions.
  • Diuretic use: Obtain a urine diuretics screen to exclude surreptitious diuretic use in patients having unexplained hypokalemic metabolic alkalosis.

Imaging Studies

  • Perform adrenal imaging studies (eg, CT scan, MRI) to find the etiology of primary hyperaldosteronism, Cushing syndrome, and DOC excess.
  • Renal Doppler ultrasound, captopril renogram, MRI, and renal angiography are helpful in diagnosing renovascular hypertension (ie, significant renal artery stenosis).

Other Tests

  • Gene analysis is helpful to diagnose inherited causes of hypokalemic alkalosis. Examples are Liddle syndrome, glucocorticoid-remediable hypertension, Bartter syndrome, Gitelman syndrome, syndrome of AME, and CAH.

More on Metabolic Alkalosis

Overview: Metabolic Alkalosis
Differential Diagnoses & Workup: Metabolic Alkalosis
Treatment & Medication: Metabolic Alkalosis
Follow-up: Metabolic Alkalosis
Multimedia: Metabolic Alkalosis
References
Further Reading
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References

  1. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. Jan 2007;2(1):162-74. [Medline]. [Full Text].

  2. Stewart PA. How to understand acid-base: a quantitative acid-base primer for biology and medicine. [AcidBase.org]. Available at http://www.acidbase.org/index.php?show=sb. Accessed Aug 10, 2009.

  3. Kaplan LJ, Cheung NH, Maerz L, et al. A physicochemical approach to acid-base balance in critically ill trauma patients minimizes errors and reduces inappropriate plasma volume expansion. J Trauma. Apr 2009;66(4):1045-51. [Medline].

  4. Gennari FJ, Weise WJ. Acid-base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol. Nov 2008;3(6):1861-8. [Medline].

  5. Weise WJ, Serrano FA, Fought J, Gennari FJ. Acute electrolyte and acid-base disorders in patients with ileostomies: a case series. Am J Kidney Dis. Sep 2008;52(3):494-500. [Medline].

  6. Medarov BI. Milk-alkali syndrome. Mayo Clin Proc. Mar 2009;84(3):261-7. [Medline].

  7. Banieghbal B. Rapid correction of metabolic alkalosis in hypertrophic pyloric stenosis with intravenous cimetidine: preliminary results. Pediatr Surg Int. Mar 2009;25(3):269-71. [Medline].

  8. Adrogue HJ, Madias NE. Management of life-threatening acid-base disorders. Second of two parts. N Engl J Med. Jan 8 1998;338(2):107-11. [Medline].

  9. Anderson LE, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. Southern Medical Journal. 1987;80:729- 33. [Medline].

  10. Babior BM. Villous adenoma of the colon. Study of a patient with severe fluid and electrolyte disturbances. American Journal of Medicine. 1966;41:615- 21. [Medline].

  11. Cruz DN, Perazella MA. Hypertension and hypokalemia: unusual syndromes. Conn Med. Feb 1997;61(2):67-75. [Medline].

  12. DuBose TD Jr. Metabolic alkalosis. In: Brenner and Rector's The Kidney. 6th ed. Philadelphia: WB Saunders; 2000:971-997.

  13. Galla JH. Metabolic Alkalosis. Journal of the American Society of Nephrology. 2000;11:369- 75. [Medline].

  14. Geller DS, Farhi A, Pinkerton N. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. Jul 7 2000;289(5476):119-23. [Medline].

  15. Hixson R, Christmas D. Use of omeprazole in life-threatening metabolic alkalosis. Intensive Care Med. Oct 1999;25(10):1201. [Medline].

  16. Hodgkin JE, Soeprono FF, Chan DM. Incidence of metabolic alkalemia in hospitalized patients. Critical Care Medicine. 1980;8:725- 8. [Medline].

  17. Kaplan NM. Primary aldosteronism. In: Clinical Hypertension. 7th ed. Philadelphia: Williams & Wilkins; 1998:365-79.

  18. Kaplan NM. Hypertension induced by cortisol or deoxycorticosterone. In: Clinical Hypertension. 7th ed. Philadelphia: Williams & Wilkins; 1998:383-392.

  19. Kelleher SP, Schulman G. Severe metabolic alkalosis complicating regional citrate hemodialysis. Am J Kidney Dis. Mar 1987;9(3):235-6. [Medline].

  20. Koeppen BM, Stanton BA. Regulation of acid-base balance. In: Vander AJ, ed. Renal Physiology. 2nd ed. New York: McGraw-Hill; 1997:135-55.

  21. Kunau RT, et al. Acid-base balance. In: MKSAP: Nephrology and Hypertension Book. 1998. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 252-69.

  22. Leblanc M, Farah A. Severe metabolic alkalosis corrected by hemodialysis. Clin Nephrol. Jul 1997;48(1):65. [Medline].

  23. Mauri S, Pedroli G, Rudeberg A. Acute metabolic alkalosis in cystic fibrosis: prospective study and review of the literature. Miner Electrolyte Metab. 1997;23(1):33-7. [Medline].

  24. Mazur JE, Devlin JW, Peters MJ. Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial. Crit Care Med. Jul 1999;27(7):1257-61. [Medline].

  25. McAuliffe JJ, Lind LJ, Leith DE. Hypoproteinemic alkalosis. Am J Med. Jul 1986;81(1):86-90. [Medline].

  26. Online Mendelian Inheritance in Man (OMIM). McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). OMIM. 2000. [Full Text].

  27. Palmer BF, Alpern RJ. Metabolic alkalosis. J Am Soc Nephrol. Sep 1997;8(9):1462-9. [Medline].

  28. Rose BD. Metabolic alkalosis. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York: McGraw-Hill; 1994:515-35.

  29. Rose BD. Acid-base physiology and regulation of acid-base balance. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York: McGraw-Hill; 1994:274-339.

  30. Rose BD. Metabolic alkalosis. UpToDate. Available at www.uptodate.com.

  31. Scheinman SJ, Guay-Woodford LM, Thakker RV. Genetic disorders of renal electrolyte transport. N Engl J Med. Apr 15 1999;340(15):1177-87. [Medline].

  32. Seldin DW, Rector FC. Symposium on acid-base homeostasis. The generation and maintenance of metabolic alkalosis. Kidney Int. May 1972;1(5):306-21. [Medline].

  33. Stewart PM. Cortisol as a mineralocorticoid in human disease. J Steroid Biochem Mol Biol. Apr-Jun 1999;69(1-6):403-8. [Medline].

  34. Stewart PM, Walker BR, Holder G. 11 beta-Hydroxysteroid dehydrogenase activity in Cushing''s syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab. Dec 1995;80(12):3617-20. [Medline].

  35. Toto RD, Alpern RJ. Metabolic acid-base disorders. In: Kokko JP, Tannen RL, eds. Fluids and Electrolytes. 3rd ed. Philadelphia: WB Saunders; 1996:201-56.

  36. Zucchelli P, Santoro A. Correction of acid-base balance by dialysis. Kidney Int Suppl. Jun 1993;41:S179-83. [Medline].

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Further Reading

Related eMedicine topics:
Alkalosis, Metabolic
Bartter Syndrome [Nephrology]
Bartter Syndrome [Pediatrics: General Medicine]
Hyperchloremic Acidosis
Hypertrophic Pyloric Stenosis
Hypertrophic Pyloric Stenosis, Surgical Treatment
Metabolic Acidosis [Emergency Medicine]
Metabolic Acidosis [Nephrology]
Respiratory Alkalosis

Clinical guidelines:
Evidence based clinical practice guideline hypertrophic pyloric stenosis. Cincinnati Children's Hospital Medical Center - Hospital/Medical Center.  2001 Aug 8 (revised 2007 Nov 4).  17 pages.  NGC:006224

Clinical trials:
Acetazolamide for Respiratory Failure in Combination With Metabolic Alkalosis
Treatment of Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis

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Keywords

metabolic alkalosis, alkalosis, metabolic acidosis, anion gap, respiratory alkalosis, respiratory metabolic alkalosis, bicarbonate, metabolic anion gap, contraction alkalosis, chloride-resistant alkalosis, chloride-responsive alkalosis

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Contributor Information and Disclosures

Author

Sameer Yaseen, MD, Staff Nephrologist, Department of Internal Medicine, Division of Nephrology, Mercy Hospital of Des Moines
Sameer Yaseen, MD is a member of the following medical societies: American Society of Nephrology and Renal Physicians Association
Disclosure: Nothing to disclose.

Coauthor(s)

Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians
Disclosure: Genzyme Grant/research funds Other

Medical Editor

Anil Kumar Mandal, MD, Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida School of Medicine
Anil Kumar Mandal, MD is a member of the following medical societies: American College of Clinical Pharmacology, American College of Physicians, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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