Metabolic alkalosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Overview

Metabolic alkalosis might be consequence of several conditions such as exogenous HCO3− loads, medications and poisoning, gastrointestinal, renal, endocrine, and systemic diseases.

Metabolic Alkalosis

Differential diagnosis of metabolic alkalosis is as follow:

Category Disease Mechanism Clinical Paraclinical Gold standard diagnosis Other findings
Symptoms Signs Lab data
ABG Chemistry Enzyme Renal function
Hydrogen loss Accumulation of base Chloride depletion Mineralocorticoid excess Fever Dyspnea Edema Toxic/ill BP Dehydration HCO3− paCO2 O2 Cl− K+ Na+ Ca+ Mg+ Renin Bun Cr Urine Cl−
Exogenous HCO3− loads Acute alkali administration[1] − + − − − + − + ↓ − ↑ ↑ ↓ ↓ ↓ ↓ ↑ Nl Nl ↑ ↑ Nl Clinical manifestations
Milk−alkali syndrome[2] − + − + − + − + ↓ + ↑ ↑ ↓ ↓ ↓ ↓ ↑ ↓ ↑ ↑ ↑ Nl Clinical manifestationsk + exclusion of other causes of hypercalcemia
Transfusion[3] − + − − ± ± − + ↓ − ↑ ↑ ↓ ↓ ↓/↑ ↓ ↓ ↑ ↑ Nl to ↑ Nl to ↑ Nl History of administration of large quantities of blood products that contain sodium citrate
Drugs/Medication Chloruretic diuretics[4] + − + + − − − − ↓ + ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl to ↑ ↑ History of diuretic use
Penicillin[5] + − − − − − − − Nl − ↑ ↑ Nl ↓ ↓ ↑ Nl ↓ ↑ Nl Nl Nl History of penicillin use
  • Not applicable
Licorice[6][7] + − − + − − − + Nl to ↑ − ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl to ↑ Nl Clinical manifestations
Laxative abuse[8] + − + − − − ± + ↓ + ↑ ↑ Nl ↓ ↓ ↑ Nl ↑ ↑ Nl to ↑ Nl ↓ High level of suspicion
Antacids[9][10]
  • Aluminum hydroxide
  • Sodium polystyrene sulfonate  
 + + − − − − − − Nl − ↑ ↑ Nl ↓ ↓ ↑ Nl ↑ Nl Nl to ↑ Nl to ↑ Nl Clinical manifestations
  • Not applicable
Category Disease Hydrogen loss Accumulation of base Chloride depletion Mineralocorticoid excess Fever Dyspnea Edema Toxic/ill BP Dehydration HCO3− paCO2 O2 Cl− K+ Na+ Ca+ Mg+ Renin Bun Cr Urine Cl− Gold standard diagnosis Other findings
Gastrointestinal origin Vomiting[11] + − + − ± − − + ↓ + ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl ↓ Clinical manifestations
  • Not applicable
Nasogastric tube suction[12] + − + − − − − + ↓ + ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl ↓ Clinical manifestations
Zollinger−Ellison syndrome[13] + − + − − − − + ↓ + ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl ↓ Serum gastrin concentration + secretin stimulation test 
Bulimia nervosa[14] + − + − − − ± + ↓ + ↑ ↑ Nl ↓ ↓ ↓ Nl ↓ ↑ Nl to ↑ Nl ↓ High level of suspicion
Congenital chloridorrhea[15] + − + − − − ± + ↓ + ↑ ↑ Nl ↓ ↓ ↓ ↓ ↓ ↑ Nl to ↑ Nl to ↑ Nl to ↑ Clinical manifestations+ lab findings
Pyloric stenosis[16] + − + − − − − + ↓ + ↑ ↑ Nl ↓ ↓ ↓ ↑ Nl Nl ↑ Nl to ↑ Nl ↓ Physical exam + imaging
  • Palpation of the “olive”
Villous adenoma[17] + − + − − − − + ↓ + ↑ ↑ Nl ↓ ↓ ↓ ↓ ↓ ↑ Nl to ↑ Nl ↑ Colonoscopy
Gastrocystoplasty[18] − − + − − − + − ↓ − ↑ ↑ Nl ↓ Nl Nl Nl Nl Nl Nl to ↑ Nl to ↑ Nl History of operation
Category Disease Hydrogen loss Accumulation of base Chloride depletion Mineralocorticoid excess Fever Dyspnea Edema Toxic/ill BP Dehydration HCO3− paCO2 O2 Cl− K+ Na+ Ca+ Mg+ Renin Bun Cr Urine Cl− Gold standard diagnosis Other findings
Renal origin Posthypercapnic state[19] − − + + − ± − − Nl − ↑ ↑↑ ↓ ↓ ↓ ↑ Nl Nl ↑ Nl Nl Nl Lab findings
Hypomagnesemia[20] + − − − − − − − Nl − ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl Nl Nl Lab findings
  • Not applicable
Hypokalemia[21] + − − − − − − − Nl − ↑ ↑ Nl ↓ ↓ ↑ Nl Nl ↑ Nl Nl Nl Lab findings
  • Not applicable
Bartter's syndrome[22] + − − + − − − − Nl + ↑ ↑ Nl ↓ ↓↓ ↓ ↓ Nl ↑ Nl to ↑ Nl to ↑ Nl Genetic testing
Gitelman’s syndrome[23][24] + − − + − − − − ↓ + ↑ ↑ Nl ↓ ↓↓ ↓ Nl ↓ ↑ Nl Nl Nl Genetic testing
Renal artery stenosis[25] + − + − − + + + ↑ + ↑ ↑ ↓ ↓ ↑ ↓ ↑ Nl ↑ ↑ ↑ Nl Clinical manifestations+ imaging
Liddle syndrome[26] + − − + − − − − ↑ + ↑ ↑ Nl ↓ ↓↓ ↓ Nl ↓ ↑ Nl Nl Nl Genetic testing
  • Not applicable
Renal tumors[27] + − + − − + + + ↑ + ↑ ↑ ↓ ↓ ↑ ↓ ↑ Nl ↑ ↑ ↑ Nl Biopsy
  • Not applicable
Endocrine Cushing's syndrome[28] + − + − − − + − ↑ + ↑ ↑ Nl ↓ ↑ ↓ ↑ Nl ↓ ↑ ↑ Nl 24−hour urinary cortisol excretion + low−dose dexamethasone suppression test
Hyperaldosteronism Primary[29] + − + − − − + − ↑ + ↑ ↑ Nl ↓ Nl to ↓ ↓ ↑ Nl ↓ ↑ ↑ Nl Lab findings
Secondary[30] + − + − − + + + ↑ + ↑ ↑ Nl ↓ ↓ ↑ Nl ↓ ↑ ↑ ↑ Nl Lab findings
Congenital adrenal hyperplasia 11β−Hydroxylase deficiency[31] − − − + − − + − ↑ + ↑ ↑ Nl ↓ ↓ ↓ ↑ Nl ↓ Nl Nl Nl Genetic testing
17α−Hydroxylase deficiency[32] − − − + − − + − ↑ + ↑ ↑ Nl ↓ ↓ ↓ ↑ Nl ↓ Nl Nl Nl Genetic testing
Systemic Cystic fibrosis[33] + − + − − + − + ↓ + ↑ ↑ Nl ↓ ↓ Nl Nl Nl ↑ Nl to ↑ Nl ↑ Genetic testing
Category Disease Hydrogen loss Accumulation of base Chloride depletion Mineralocorticoid excess Fever Dyspnea Edema Toxic/ill BP Dehydration HCO3− paCO2 O2 Cl− K+ Na+ Ca+ Mg+ Renin Bun Cr Urine Cl− Gold standard diagnosis Other findings

References

  1. ↑ Máttar, João A.; Weil, Max Harry; Shubin, Herbert; Stein, Leon (1974). "Cardiac arrest in the critically III". The American Journal of Medicine. 56 (2): 162–168. doi:10.1016/0002-9343(74)90593-2. ISSN 0002-9343.
  2. ↑ Abreo, Kenneth (1993). "The Milk-Alkali Syndrome". Archives of Internal Medicine. 153 (8): 1005. doi:10.1001/archinte.1993.00410080065011. ISSN 0003-9926.
  3. ↑ Gupta M, Wadhwa NK, Bukovsky R (January 2004). "Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate". Am. J. Kidney Dis. 43 (1): 67–73. PMID 14712429.
  4. ↑ Luke, R. G.; Galla, J. H. (2012). "It Is Chloride Depletion Alkalosis, Not Contraction Alkalosis". Journal of the American Society of Nephrology. 23 (2): 204–207. doi:10.1681/ASN.2011070720. ISSN 1046-6673.
  5. ↑ Zaki, SyedAhmed; Lad, Vijay (2011). "Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis". Indian Journal of Pharmacology. 43 (5): 609. doi:10.4103/0253-7613.84986. ISSN 0253-7613.
  6. ↑ Meltem, Akkas Camkurt; Figen, Coskun; Nalan, Metin Aksu; Mahir, Kunt; Sebnem, Bozkurt; Mehlika, Isildak; Kasim, Kilic Ahmet; Miyase, Bayraktar (2009). "A hypokalemic muscular weakness after licorice ingestion: a case report". Cases Journal. 2 (1): 8053. doi:10.4076/1757-1626-2-8053. ISSN 1757-1626.
  7. ↑ Lin, Shih-Hua; Yang, Sung-Sen; Chau, Tom; Halperin, Mitchell L. (2003). "An Unusual Cause of Hypokalemic Paralysis: Chronic Licorice Ingestion". The American Journal of the Medical Sciences. 325 (3): 153–156. doi:10.1097/00000441-200303000-00008. ISSN 0002-9629.
  8. ↑ Roerig, James L.; Steffen, Kristine J.; Mitchell, James E.; Zunker, Christie (2010). "Laxative Abuse". Drugs. 70 (12): 1487–1503. doi:10.2165/11898640-000000000-00000. ISSN 0012-6667.
  9. ↑ Sahani, Mandeep M.; Brennan, John F.; Nwakanma, Chukwuemeka; Chow, May T.; Ing, Todd S.; Leehey, David J. (2001). "Metabolic Alkalosis in a Hemodialysis Patient After Ingestion of a Large Amount of an Antacid Medication". Artificial Organs. 25 (4): 313–315. doi:10.1046/j.1525-1594.2001.06714.x. ISSN 0160-564X.
  10. ↑ Vanpee, Dominique; Delgrange, Etienne; Gillet, Jean-Bernard; Donckier, Julian (2000). "Ingestion of antacid tablets (Rennie®) and acute confusion". The Journal of Emergency Medicine. 19 (2): 169–171. doi:10.1016/S0736-4679(00)00206-7. ISSN 0736-4679.
  11. ↑ Gan, Tong J.; Meyer, Tricia; Apfel, Christian C.; Chung, Frances; Davis, Peter J.; Eubanks, Steve; Kovac, Anthony; Philip, Beverly K.; Sessler, Daniel I.; Temo, James; Tram??r, Martin R.; Watcha, Mehernoor (2003). "Consensus Guidelines for Managing Postoperative Nausea and Vomiting". Anesthesia & Analgesia: 62–71. doi:10.1213/01.ANE.0000068580.00245.95. ISSN 0003-2999.
  12. ↑ Gilbertson, Heather Ruth; Rogers, Elizabeth Jessie; Ukoumunne, Obioha Chukwunyere (2011). "Determination of a Practical pH Cutoff Level for Reliable Confirmation of Nasogastric Tube Placement". Journal of Parenteral and Enteral Nutrition. 35 (4): 540–544. doi:10.1177/0148607110383285. ISSN 0148-6071.
  13. ↑ Hung, Patrick D.; Schubert, Mitchell L.; Mihas, Anastasios A. (2003). "Zollinger-Ellison syndrome". Current Treatment Options in Gastroenterology. 6 (2): 163–170. doi:10.1007/s11938-003-0017-6. ISSN 1092-8472.
  14. ↑ Shapiro, Jennifer R.; Berkman, Nancy D.; Brownley, Kimberly A.; Sedway, Jan A.; Lohr, Kathleen N.; Bulik, Cynthia M. (2007). "Bulimia nervosa treatment: A systematic review of randomized controlled trials". International Journal of Eating Disorders. 40 (4): 321–336. doi:10.1002/eat.20372. ISSN 0276-3478.
  15. ↑ Wedenoja, S.; Hã–Glund, P.; Holmberg, C. (2010). "Review article: the clinical management of congenital chloride diarrhoea". Alimentary Pharmacology & Therapeutics. 31 (4): 477–485. doi:10.1111/j.1365-2036.2009.04197.x. ISSN 0269-2813. C1 control character in |last2= at position 3 (help)
  16. ↑ Bakal, Unal; Sarac, Mehmet; Aydin, Mustafa; Tartar, Tugay; Kazez, Ahmet (2016). "Recent changes in the features of hypertrophic pyloric stenosis". Pediatrics International. 58 (5): 369–371. doi:10.1111/ped.12860. ISSN 1328-8067.
  17. ↑ Gennari, F. J.; Weise, W. J. (2008). "Acid-Base Disturbances in Gastrointestinal Disease". Clinical Journal of the American Society of Nephrology. 3 (6): 1861–1868. doi:10.2215/CJN.02450508. ISSN 1555-9041.
  18. ↑ Kurzrock, Eric A.; Baskin, Laurence S.; Kogan, Barry A. (1998). "GASTROCYSTOPLASTY: LONG-TERM FOLLOWUP". The Journal of Urology. 160 (6): 2182–2186. doi:10.1016/S0022-5347(01)62289-4. ISSN 0022-5347.
  19. ↑ Banga, Amit; Khilnani, G. C. (2009). "Post-hypercapnic Alkalosis is Associated with Ventilator Dependence and Increased ICU stay". COPD: Journal of Chronic Obstructive Pulmonary Disease. 6 (6): 437–440. doi:10.3109/15412550903341448. ISSN 1541-2555.
  20. ↑ Elisaf M, Milionis H, Siamopoulos KC (1997). "Hypomagnesemic hypokalemia and hypocalcemia: clinical and laboratory characteristics". Miner Electrolyte Metab. 23 (2): 105–12. PMID 9252977.
  21. ↑ Galla JH (February 2000). "Metabolic alkalosis". J. Am. Soc. Nephrol. 11 (2): 369–75. PMID 10665945.
  22. ↑ Simon, David B.; Karet, Fiona E.; Hamdan, Jahed M.; Pietro, Antonio Di; Sanjad, Sami A.; Lifton, Richard P. (1996). "Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na–K–2CI cotransporter NKCC2". Nature Genetics. 13 (2): 183–188. doi:10.1038/ng0696-183. ISSN 1061-4036.
  23. ↑ Fremont, Oliver T.; Chan, James C. M. (2012). "Understanding Bartter syndrome and Gitelman syndrome". World Journal of Pediatrics. 8 (1): 25–30. doi:10.1007/s12519-012-0333-9. ISSN 1708-8569.
  24. ↑ Colussi G, Macaluso M, Brunati C, Minetti L (1994). "Calcium metabolism and calciotropic hormone levels in Gitelman's syndrome". Miner Electrolyte Metab. 20 (5): 294–301. PMID 7700218.
  25. ↑ Safian, Robert D.; Textor, Stephen C. (2001). "Renal-Artery Stenosis". New England Journal of Medicine. 344 (6): 431–442. doi:10.1056/NEJM200102083440607. ISSN 0028-4793.
  26. ↑ Salih, Mahdi; Gautschi, Ivan; van Bemmelen, Miguel X.; Di Benedetto, Michael; Brooks, Alice S.; Lugtenberg, Dorien; Schild, Laurent; Hoorn, Ewout J. (2017). "A Missense Mutation in the Extracellular Domain ofαENaC Causes Liddle Syndrome". Journal of the American Society of Nephrology. 28 (11): 3291–3299. doi:10.1681/ASN.2016111163. ISSN 1046-6673.
  27. ↑ Lasseigne, Brittany N.; Brooks, James D. (2018). "The Role of DNA Methylation in Renal Cell Carcinoma". Molecular Diagnosis & Therapy. doi:10.1007/s40291-018-0337-9. ISSN 1177-1062.
  28. ↑ Araujo Castro, Marta; Marazuela Azpiroz, Mónica (2018). "Two types of ectopic Cushing syndrome or a continuum? Review". Pituitary. doi:10.1007/s11102-018-0894-2. ISSN 1386-341X.
  29. ↑ Martell-Claros, Nieves; Abad-Cardiel, María; Alvarez-Alvarez, Beatriz; García-Donaire, José A.; Pérez, Cristina Fernández (2015). "Primary aldosteronism and its various clinical scenarios". Journal of Hypertension. 33 (6): 1226–1232. doi:10.1097/HJH.0000000000000546. ISSN 0263-6352.
  30. ↑ Monticone S, Losano I, Tetti M, Buffolo F, Veglio F, Mulatero P (May 2018). "Diagnostic approach to low renin hypertension". Clin. Endocrinol. (Oxf). doi:10.1111/cen.13741. PMID 29758100.
  31. ↑ Baş F, Toksoy G, Ergun-Longmire B, Uyguner ZO, Abalı ZY, Poyrazoğlu Ş, Karaman V, Avcı Ş, Altunoğlu U, Bundak R, Karaman B, Başaran S, Darendeliler F (April 2018). "Prevalence, clinical characteristics and long-term outcomes of classical 11 β-hydroxylase deficiency (11BOHD) in Turkish population and novel mutations in CYP11B1 gene". J. Steroid Biochem. Mol. Biol. doi:10.1016/j.jsbmb.2018.04.001. PMID 29626607.
  32. ↑ Goldsmith, Oliver; Solomon, David H.; Horton, Richard (1967). "Hypogonadism and Mineralocorticoid Excess". New England Journal of Medicine. 277 (13): 673–677. doi:10.1056/NEJM196709282771302. ISSN 0028-4793.
  33. ↑ Bates CM, Baum M, Quigley R (February 1997). "Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent". J. Am. Soc. Nephrol. 8 (2): 352–5. PMID 9048354.
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