Classification and diagnostic approach to metabolic alkalosis

Generally speaking, metabolic alkalosis is a neglected and poorly understood beast. Perhaps there is an impression that it is somehow less dangerous and thus less interesting than metabolic acidosis. The acid-base enthusiast must become familiar with this process.

Exogenous strong cation excess

Sodium bicarbonate or citrate administration

β-lactam associated metabolic alkalosis

Exotic buffer substances, eg THAM

Milk-alkali syndrome and hypercalcemia in general

Primary derangement of homeostatic mechanisms

Failure of bicarbonate excretion in end-stage renal failure


Enteric chloride depletion

Dietary chloride restriction

Gastric loss of chloride ions

Chloride loss due to villous adenoma

Renal chloride depletion

Diuretic-induced metabolic alkalosis

Post-hypercapneic state

Bartter's syndrome and Gitelman's syndrome

Pseudo-Bartter's syndrome of cystic fibrosis



Mineralocorticoid excess

Renin-secreting adenoma

Renal artery stenosis and malignant hypertension

Primary hyperaldosteronism

Licorice overindulgeance

Corticosteroids and fludrocortisone

Cushing syndrome

Causes of congential hyperadrenalism

Liddle syndrome

Again, I reproduce a table to list the various causes of metabolic alkalosis according to the findings of one's clinical examination history and biochemistry.

Causes of Metabolic Alkalosis; Organised by Diagnostic Features
Classification Causes and pathophysiology Literature reference

The diagnostic pathway can therefore be reduced into a flowchart:

The approach to metabolic alkalosis

Background history

  • History of congential adrenal hypoplasia
  • History of cystic fibrosis
  • History of CCF (suggesting chronic exposure to diuretics)
  • History of uncontrolled hypertension (malignant hypertension or renal artery stenosis)

Recent history

  • Recent antacic consumption
  • Recent use of calcium supplements
  • β-lactam antibiotic use
  • Massive abuse of licorice
  • History of diarrhoea (villous adenoma) or vomiting (chloride loss)
  • History of recent hypercapneic respiratory failure


  • Clinically, findings consistent with severe hypertension (eg. retinal changes)
  • Renal artery stenosis bruit
  • Peripheral oedema (suggesting chronic exposure to diuretics)


  • Serum potassium
  • Serum magnesium
  • Urinary chloride
  • Serum renin levels
  • Serum aldosterone levels


Medarov, Boris I. "Milk-alkali syndrome." Mayo Clinic Proceedings. Vol. 84. No. 3. Elsevier, 2009.

Waked, Alain, Abdallah Geara, and Badiaa El-Imad. "Hypercalcemia, metabolic alkalosis and renal failure secondary to calcium bicarbonate intake for osteoporosis prevention-‘modern’milk alkali syndrome: a case report." Cases journal 2 (2009).

Zietse, Robert, Roeland Zoutendijk, and E. J. Hoorn. "Fluid, electrolyte and acid–base disorders associated with antibiotic therapy." Nature Reviews Nephrology 5.4 (2009): 193-202.

Zaki, Syed Ahmed, and Vijay Lad. "Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis." Indian journal of pharmacology 43.5 (2011): 609.

Kennedy, J. D., et al. "Pseudo-Bartter's syndrome in cystic fibrosis." Archives of disease in childhood 65.7 (1990): 786-787.

Mersin, S. S., et al. "Urinary chloride excretion distinguishes between renal and extrarenal metabolic alkalosis." European journal of pediatrics 154.12 (1995): 979-982.

Eiam-Ong, Somchai, Neil A. Kurtzman, and Sandra Sabatini. "Effect of furosemide-induced hypokalemic metabolic alkalosis on renal transport enzymes." Kidney Int 43 (1993): 1015-1020.

Luke, Robert G., and John H. Galla. "It is chloride depletion alkalosis, not contraction alkalosis." Journal of the American Society of Nephrology 23.2 (2012): 204-207.

Fujita, Kazushige. "(2) Clinical Study on Elevation of pH (Alkalemia) in Chronic Respiratory Failure, Especially Associated with Chronic Hypercapnia."Japanese Journal of Medicine 15.2 (1976): 154-155.

Cogan, Martin G. "Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat." Journal of Clinical Investigation 74.6 (1984): 1942.

Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." studies 28 (2006): 29.

Eiam-ong, S. O. M. C. H. A. I., et al. "Effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes." American Journal of Physiology 267 (1994): F390-F390.

STARR, ALBERT, STERLING MUELLER, and JOHN R. McKITTRICK. "Villous adenoma of the colon associated with severe hypopotassemia." AMA archives of surgery 73.6 (1956): 995-998.

Favero, Marta, et al. "Bartter’s and Gitelman’s diseases." Best Practice & Research Clinical Rheumatology 25.5 (2011): 637-648.

Rastergar, A., and M. Soleimani. "Hypokalaemia and hyperkalaemia."Postgraduate medical journal 77.914 (2001): 759-764.

Amlal, Hassane, Khalid Habo, and Manoocher Soleimani. "Potassium deprivation upregulates expression of renal basolateral Na+-HCO3− cotransporter (NBC-1)." American Journal of Physiology-Renal Physiology279.3 (2000): F532-F543.

Al-Ghamdi, Saeed MG, Eugene C. Cameron, and Roger AL Sutton. "Magnesium deficiency: pathophysiologic and clinical overview." American Journal of Kidney Diseases 24.5 (1994): 737-752.

Wolfe, Sidney M., and Maurice Victor. "The relationship of hypomagnesemia and alkalosis to alcohol withdrawal symptoms." Annals of the New York Academy of Sciences 162.2 (1969): 973-984.

Bunchman, Timothy E., and Alan R. Sinaiko. "Renovascular hypertension presenting with hypokalemic metabolic alkalosis." Pediatric Nephrology 4.2 (1990): 169-170.

Baruch, Dominique, et al. "Diagnosis and treatment of renin-secreting tumors. Report of three cases." Hypertension 6.5 (1984): 760-766.

Laragh, John H., et al. "Aldosterone secretion and primary and malignant hypertension." Journal of Clinical Investigation 39.7 (1960): 1091.

Christy, Nicholas P., and John H. Laragh. "Pathogenesis of hypokalemic alkalosis in Cushing's syndrome." New England Journal of Medicine 265.22 (1961): 1083-1088.

Schambelan, M., P. E. Slaton Jr, and E. G. Biglieri. "Mineralocorticoid production in hyperadrenocorticism: Role in pathogenesis of hypokalemic alkalosis." The American journal of medicine 51.3 (1971): 299-303.

GLYNN, RUSSELL D., et al. "Effects of glucocorticoid steroids on renal and systemic acid-base metabolism." (1980).

Palmer MD, Biff F., and Robert J. Alpern MD. "Liddle’s syndrome." The American journal of medicine 104.3 (1998): 301-309.

Lin, Shih-Hua, et al. "An unusual cause of hypokalemic paralysis: chronic licorice ingestion." The American journal of the medical sciences 325.3 (2003): 153-156.

Epstein, M. T., et al. "Liquorice toxicity and the renin-angiotensin-aldosterone axis in man." British medical journal 1.6055 (1977): 209.

Kassirer, Jerome P., et al. "On the pathogenesis of metabolic alkalosis in hyperaldosteronism." The American journal of medicine 49.3 (1970): 306-315.

Speiser, Phyllis W., and Perrin C. White. "Congenital adrenal hyperplasia." New England Journal of Medicine 349.8 (2003): 776-788.

LIfton, Richard P., et al. "A chimaeric llβ-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension." (1992): 262-265.