High anion gap metabolic acidosis 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]

High Anion Gap Metabolic Acidosis Differential Diagnosis

Differential diagnosis of high anion gap metabolic acidosis is as follow:[1][2][3][4]

To review differential diagnosis of metabolic acidosis, click here.

Category Disease Mechanism Clinical Paraclinical Gold standard diagnosis Other findings
Symptoms Signs Lab data
ABG CBC Chemistry Renal U/A
↑ acid
production 		Loss of
bicarbonate 		↓ renal acid
excretion 		Fever N/V Diarrhea Dyspnea Toxic/ill BP Dehydration Level of consciousness HCO3− paCO2 O2 WBC Hb BS Cl− K+ Na+ Ketones Lactic acid Serum AG[5] Osmolar gap[6] Bun Cr Urine pH Urine AG Urine ketone
Toxin/Medication[7] Alcohol poisoning[8][9] + − − − + − − + ↓ ↑ + ↓ ↓ ↓ ↓ Nl Nl ↑ ↑ ↑ Nl + ↑ ↑ ↑ Nl or ↑ Nl or ↑ ↓ + + Clinical manifestation
Toluene toxicity[10] + − + − + − − + ↓ − ↓ ↓↓ ↓ Nl Nl Nl Nl Nl ↓ Nl − ↑ Nl or ↑ Nl ↑ ↑ ↓ − + Clinical manifestation
  • Most widely abused inhaled drugs
Salicylates overdose[11] + − − − + − + + ↓ + ↓ ↓ ↓↓ ↓ Nl Nl Nl to ↓ Nl ↓ Nl − ↑ ↑ ↑ ↑ ↑ ↓ − − Clinical and elevated serum salicylate level
Metformin[12] + − − − + − − + ↓ ± Agitated ↓ ↓ Nl Nl to ↑ ↓ ↓ Nl Nl Nl Nl ↑ ↑ ↑ Nl or ↑ Nl ↓ − − Clinical manifestation
Isoniazid[13] + − − − + − − + ↑ + Agitated ↓ ↓ Nl Nl ↓ Nl Nl Nl Nl Nl ↑ ↑ Nl Nl or ↑ Nl ↓ − − Clinical manifestation
Carbon monoxide poisoning[14] + − + − ± − − + Nl − ↓↓ ↓ ↓ Nl to ↓ Nl Nl Nl Nl Nl Nl Nl ↑ ↑ Nl Nl Nl ↓ − − Clinical manifestation
  • Not applicable
Cyanide poisoning[15] + − − − + − − + ↓ ± ↓↓ ↓ ↓ ↓ Nl to ↑ ↓ Nl Nl Nl Nl Nl ↑ ↑ Nl Nl or ↑ Nl ↓ − − Blood cyanide concentration
  • Not applicable
Category Disease ↑ acid
production 		Loss of
bicarbonate 		↓ renal acid
excretion 		Fever N/V Diarrhea Dyspnea Toxic/ill BP Dehydration Level of consciousness HCO3− paCO2 O2 WBC Hb BS Cl− K+ Na+ Ketones Lactic acid Serum AG Osmolar gap Bun Cr Urine pH Urine AG Urine ketone Gold standard diagnosis Other findings
Ketoacidosis Diabetic ketoacidosis[16] + − − + + + + + ↓ + ↓ ↓ ↓ Nl to ↓ ↑ Nl to ↑ ↑↑ Nl ↑ ↓ ↑ ↑ ↑ ↑ Nl to ↑ Nl ↓ + + Clinical + hyperglycemia + ketosis
  • Labs might show elevated K+ even in K+ depletion due to extravasation of intracellular K+ in exchanged with extracellular H+
Starvation[17] + − − − + − − + ↓ + ↓ ↓ ↓ Nl Nl Nl Nl to ↓ Nl ↓ ↓ ↑ Nl ↑ Nl Nl Nl Nl + − Clinical manifestation
Alcoholic ketoacidosis (Ethanol)[18] + − − − + ± − + ↓ ↑ + Agitated ↓ ↓ ↓ Nl to ↑ Nl to ↑ ↓ Nl ↑ Nl ↓ ↓ ↑↑ ↑ ↑ ↑↑ ↑ Nl ↓ + + Clinical manifestation + ketosis
Systemic Lactic acidosis[19] + − − ± + − − + ↓ ↑ ± Agitated ↓ ↓ ↓ Nl to ↑ ↓ Nl Nl Nl Nl Nl ↑ ↑ ↑ Nl or ↑ Nl ↓ − − Clinical manifestation and lab finding
  • Not applicable
Renal Uremia[20] − − + + + − − + ↓ ↑ ± ↓ ↓ ↓ Nl to ↓ ↑ ↓ Nl Nl ↑ ↑ Nl Nl ↑ ↑ ↑ ↑ ↓ + − Clinical manifestation and lab finding
Renal failure[21] − − + − + − − + ↓ + ↓ ↓ ↓ Nl to ↓ ↑ ↓ Nl ↑ ↑ ↓ Nl Nl ↑ ↑ ↑ ↑ ↓ − − Renal function test
  • Not applicable
Category Disease ↑ acid
production 		Loss of
bicarbonate 		↓ renal acid
excretion 		Fever N/V Diarrhea Dyspnea Toxic/ill BP Dehydration Level of consciousness HCO3− paCO2 O2 WBC Hb BS Cl− K+ Na+ Ketones Lactic acid Serum AG Osmolar gap Bun Cr Urine pH Urine AG Urine ketone Gold standard diagnosis Other findings

References

  1. ↑ Lim S (2007). "Metabolic acidosis". Acta Med Indones. 39 (3): 145–50. PMID 17936961.
  2. ↑ Morris, C. G.; Low, J. (2008). "Metabolic acidosis in the critically ill: Part 1. Classification and pathophysiology". Anaesthesia. 63 (3): 294–301. doi:10.1111/j.1365-2044.2007.05370.x. ISSN 0003-2409.
  3. ↑ Morris CG, Low J (April 2008). "Metabolic acidosis in the critically ill: part 2. Causes and treatment". Anaesthesia. 63 (4): 396–411. doi:10.1111/j.1365-2044.2007.05371.x. PMID 18336491.
  4. ↑ Casaletto, Jennifer J. (2005). "Differential Diagnosis of Metabolic Acidosis". Emergency Medicine Clinics of North America. 23 (3): 771–787. doi:10.1016/j.emc.2005.03.007. ISSN 0733-8627.
  5. ↑ Brubaker RH, Meseeha M. High Anion Gap Metabolic Acidosis. [Updated 2017 Oct 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448090/
  6. ↑ Kraut JA, Xing SX (September 2011). "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis". Am. J. Kidney Dis. 58 (3): 480–4. doi:10.1053/j.ajkd.2011.05.018. PMID 21794966.
  7. ↑ Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W. (2015). "Drug-Induced Metabolic Acidosis". F1000Research. doi:10.12688/f1000research.7006.1. ISSN 2046-1402.
  8. ↑ Zehtabchi S, Sinert R, Baron BJ, Paladino L, Yadav K (2005). "Does ethanol explain the acidosis commonly seen in ethanol-intoxicated patients?". Clin Toxicol (Phila). 43 (3): 161–6. PMID 15902789.
  9. ↑ Roberts, Darren M.; Yates, Christopher; Megarbane, Bruno; Winchester, James F.; Maclaren, Robert; Gosselin, Sophie; Nolin, Thomas D.; Lavergne, Valéry; Hoffman, Robert S.; Ghannoum, Marc (2015). "Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning". Critical Care Medicine. 43 (2): 461–472. doi:10.1097/CCM.0000000000000708. ISSN 0090-3493.
  10. ↑ Camara-Lemarroy, Carlos Rodrigo; Rodríguez-Gutiérrez, René; Monreal-Robles, Roberto; González-González, José Gerardo (2015). "Acute toluene intoxication–clinical presentation, management and prognosis: a prospective observational study". BMC Emergency Medicine. 15 (1). doi:10.1186/s12873-015-0039-0. ISSN 1471-227X.
  11. ↑ Wright, Dallas; Sop, Jessica (2015). "Normal anion gap salicylate poisoning". The American Journal of Emergency Medicine. 33 (11): 1714.e3–1714.e4. doi:10.1016/j.ajem.2015.03.042. ISSN 0735-6757.
  12. ↑ Galiero, Francesca; Consani, Giovanni; Biancofiore, Gianni; Ruschi, Stefano; Forfori, Francesco (2018). "Metformin intoxication: Vasopressin's key role in the management of severe lactic acidosis". The American Journal of Emergency Medicine. 36 (2): 341.e5–341.e6. doi:10.1016/j.ajem.2017.10.057. ISSN 0735-6757.
  13. ↑ Watkins RC, Hambrick EL, Benjamin G, Chavda SN (January 1990). "Isoniazid toxicity presenting as seizures and metabolic acidosis". J Natl Med Assoc. 82 (1): 57, 62, 64. PMC 2625939. PMID 2304098.
  14. ↑ Piantadosi CA (June 1999). "Diagnosis and treatment of carbon monoxide poisoning". Respir Care Clin N Am. 5 (2): 183–202. PMID 10333448.
  15. ↑ Baud FJ, Borron SW, Mégarbane B, Trout H, Lapostolle F, Vicaut E, Debray M, Bismuth C (September 2002). "Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning". Crit. Care Med. 30 (9): 2044–50. doi:10.1097/01.CCM.0000026325.65944.7D. PMID 12352039.
  16. ↑ Wolfsdorf, Joseph I; Allgrove, Jeremy; Craig, Maria E; Edge, Julie; Glaser, Nicole; Jain, Vandana; Lee, Warren WR; Mungai, Lucy NW; Rosenbloom, Arlan L; Sperling, Mark A; Hanas, Ragnar (2014). "Diabetic ketoacidosis and hyperglycemic hyperosmolar state". Pediatric Diabetes. 15 (S20): 154–179. doi:10.1111/pedi.12165. ISSN 1399-543X.
  17. ↑ Mostert M, Bonavia A (October 2016). "Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period". Am J Case Rep. 17: 755–758. PMC 5070574. PMID 27752032.
  18. ↑ Howard RD, Bokhari S. PMID 28613672. Vancouver style error: initials (help); Missing or empty |title= (help)
  19. ↑ Kraut, Jeffrey A.; Ingelfinger, Julie R.; Madias, Nicolaos E. (2014). "Lactic Acidosis". New England Journal of Medicine. 371 (24): 2309–2319. doi:10.1056/NEJMra1309483. ISSN 0028-4793.
  20. ↑ Brown, Denver; Melamed, Michal L. (2018). "New Frontiers in Treating Uremic Metabolic Acidosis". Clinical Journal of the American Society of Nephrology. 13 (1): 4–5. doi:10.2215/CJN.11771017. ISSN 1555-9041.
  21. ↑ Kraut, Jeffrey A.; Madias, Nicolaos E. (2016). "Metabolic Acidosis of CKD: An Update". American Journal of Kidney Diseases. 67 (2): 307–317. doi:10.1053/j.ajkd.2015.08.028. ISSN 0272-6386.
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