Causes of metabolic alkalosis

CICM fellowship SAQs about this topic are generally of two varieties. Most recent SAQs are short, worth little in terms of marks, and satisfied by the candidate merely identifying the disorder as a metabolic alkalosis, or possibly throwing around a few differentials. Most older SAQs trend to the thoughtfully physician-like answer, asking the candidate to articulate their approach to diagnosis of metabolic alkalosis.

The SAQs have so far consisted of the following:

Owing to the highly successful renal bicarbonate excretion mechanism, metabolic alkalosis cannot continue without some sort of maintenance process.

This table is an abridged version.

For completeness, the initiating and maintenance processes can be expanded upon, and presented in a table where the relevant aetiologies are grouped according to purely academic criteria, i.e. according to which major anion or cation is being affected.

Causes of Metabolic Alkalosis; Organised by Inorganic Ion

If one were inclined towards brutally pragmatic functional classification methods, one might try to separate the causes of metabolic alkalosis into groups according to the results of biochemical investigations and clinical features. Such an attempt would result in a complicated table, which would look something like this:

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


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.

Ferrara, A., et al. "[Physiopathological and clinical data on post-hypercapnic metabolic alkalosis. A case of severe hypercapnia treated with drugs and in an" iron lung"]." Minerva medica 70.1 (1979): 67-73.

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

Pahari, D. K., et al. "Diagnosis and management of metabolic alkalosis."JOURNAL-INDIAN MEDICAL ASSOCIATION 104.11 (2006): 630.

Palmer, Biff F., and Robert J. Alpern. "Metabolic alkalosis." Journal of the American Society of Nephrology 8.9 (1997): 1462-1469.

Gennari, F. John. "Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport." American Journal of Kidney Diseases 58.4 (2011): 626-636.

Ferrara, A., et al. "[Physiopathological and clinical data on post-hypercapnic metabolic alkalosis. A case of severe hypercapnia treated with drugs and in an" iron lung"]." Minerva medica 70.1 (1979): 67-73.

Banga, Amit, and G. C. Khilnani. "Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay." COPD: Journal of Chronic Obstructive Pulmonary Disease 6.6 (2009): 437-440.

Webster, Nigel R., and Vivek Kulkarni. "Metabolic Alkalosis in the Critically III." Critical reviews in clinical laboratory sciences 36.5 (1999): 497-510.