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]

Overview

Metabolic acidosis is occured in different situations such as poisoning, ketoacidosis, renal, gastrointestinal, cardiac, endocrine, and systemic diseases. 

Metabolic Acidosis Differential Diagnosis

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

To review differential diagnosis of high anion gap metabolic acidosis, click here.

To review differential diagnosis of high osmolar gap metabolic acidosis, click here.

To review differential diagnosis of metabolic acidosis and lactic 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
+ − − − + − − + ↓ + ↓ ↓ ↓ ↓ Nl Nl Nl ↑ ↑ Nl + ↑ Nl ↑ Nl Nl or ↑ ↓ + + Clinical manifestation
  • Not applicable
Toluene toxicity[11] + − + − + − − + ↓ − ↓ ↓↓ ↓ Nl Nl Nl Nl Nl ↓ Nl − ↑ Nl or ↑ Nl ↑ ↑ ↓ − + Clinical manifestation
  • Most widely abused inhaled drugs
Salicylates overdose[12] + − − − + − + + ↓ + ↓ ↓ ↓↓ ↓ Nl Nl Nl to ↓ Nl ↓ Nl − ↑ ↑ ↑ ↑ ↑ ↓ − − Clinical and elevated serum salicylate level
Metformin[13] + − − − + − − + ↓ ± Agitated ↓ ↓ Nl Nl to ↑ ↓ ↓ Nl Nl Nl Nl ↑ ↑ ↑ Nl or ↑ Nl ↓ − − Clinical manifestation
Isoniazid[14] + − − − + − − + ↑ + Agitated ↓ ↓ Nl Nl ↓ Nl Nl Nl Nl Nl ↑ ↑ Nl Nl or ↑ Nl ↓ − − Clinical manifestation
Acetazolamide[15] − + − − − − − − ↓ + Nl ↓ ↓ Nl to ↓ Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl or ↑ Nl ↓ − − Clinical manifestation
  • Not applicable
Amphotericin B[16] − − + − + + − + ↓ + ↓ ↓ ↓ Nl to ↓ Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl ↑ ↑ ↓ − − Clinical manifestation
  • Not applicable
Carbon monoxide poisoning[17] + − + − ± − − + Nl − ↓↓ ↓ ↓ Nl to ↓ Nl Nl Nl Nl Nl Nl Nl ↑ ↑ Nl Nl Nl ↓ − − Clinical manifestation
  • Not applicable
Cyanide poisoning[18] + − − − + − − + ↓ ± ↓↓ ↓ ↓ ↓ 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[19] + − − + + + + + ↓ + ↓ ↓ ↓ 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[20] + − − − + − − + ↓ + ↓ ↓ ↓ Nl Nl Nl Nl to ↓ Nl ↓ ↓ ↑ Nl ↑ Nl Nl Nl Nl + − Clinical manifestation
Alcoholic ketoacidosis (Ethanol)[21] + − − − + ± − + ↓ ↑ + Agitated ↓ ↓ ↓ Nl to ↑ Nl to ↑ ↓ Nl ↑ Nl ↓ ↓ ↑↑ ↑ ↑ ↑↑ ↑ Nl ↓ + + Clinical manifestation + ketosis
Systemic Sepsis[22] + − − + + − + + ↓ ↑ + ↓ ↓ ↓ Nl to ↓ ↑ Nl Nl Nl ↑ ↓ Nl Nl to ↑ Nl Nl ↑ ↑ Nl − − Clinical manifestation and lab finding
  • Not applicable
Ischemia[23] + − − − + − + + ↓ + − ↓ ↓ ↑ Nl to ↓ Nl to ↑ Nl Nl Nl ↑ ↓ Nl Nl to ↑ Nl Nl Nl to ↑ Nl to ↑ Nl − − Clinical manifestation and lab finding
  • Not applicable
Lactic acidosis[24] + − − ± + − − + ↓ ↑ ± Agitated ↓ ↓ ↓ Nl to ↑ ↓ Nl Nl Nl Nl Nl ↑ ↑ ↑ Nl or ↑ Nl ↓ − − Clinical manifestation and lab finding
  • Not applicable
Renal Uremia[25] − − + + + − − + ↓ ↑ ± ↓ ↓ ↓ Nl to ↓ ↑ ↓ Nl Nl ↑ ↑ Nl Nl ↑ ↑ ↑ ↑ ↓ + − Clinical manifestation and lab finding
Renal failure[26] − − + − + − − + ↓ + ↓ ↓ ↓ Nl to ↓ ↑ ↓ Nl ↑ ↑ ↓ Nl Nl ↑ ↑ ↑ ↑ ↓ − − Renal function test
  • Not applicable
Renal tubular acidosis[27] Type I[28] − − + ± ± − − − ↓ ↑ − − ↓ ↓ Nl Nl Nl Nl ↑ ↓ ↓ Nl Nl Nl Nl ↑ ↑ ↑ + − Clinical manifestation and lab finding
Type II − + − ± ± − − − ↓ ↑ − − ↓ ↓ Nl Nl Nl Nl ↑ ↓ Nl Nl Nl Nl Nl Nl Nl Nl − − Clinical manifestation and lab finding
  • Not applicable
Type IV − − + ± ± ± − − ↓ − − ↓ ↓ Nl Nl Nl Nl ↑ ↑ Nl Nl Nl Nl Nl Nl Nl Nl + − Clinical manifestation and lab finding
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
Heart Heart failure[29] + + − − ± − + + ↓ ↑ + − ↓ ↓ ↑ ↓ Nl Nl Nl Nl ↓ ↓ Nl Nl Nl Nl Nl to ↑ Nl to ↑ Nl − − Clinical manifestation+ echocardiogram
Myocardial infarction[30] + − − − + − + + ↓ ↑ − ↓ ↓ ↓ ↑ Nl to ↓ Nl to ↑ Nl Nl Nl ↑ ↓ Nl ↑ Nl Nl Nl to ↑ Nl to ↑ Nl − − Clinical manifestation + ECG
  • Not applicable
GI Diarrhea[31] − + − ± + + − + ↓ + May be lethargic ↓ ↓ Nl Nl ↓ ↓ ↑ ↑ Nl Nl Nl Nl Nl ↑ Nl Nl − − Stool exam
  • Not applicable
Hyperalimentation[32] + + − − − + − − Nl − − ↓ ↓ Nl Nl ↓ Nl ↑ ↑ Nl Nl Nl Nl Nl Nl Nl Nl − − Clinical manifestation
  • Not applicable
Liver failure[33] − + − − + + − + ↓ + Confused ↓ ↓ Nl Nl ↓ ↓ ↑ ↑ ↓ ↓ Nl Nl Nl Nl Nl Nl Nl − − Liver biopsy
  • Not applicable
Endocrine Hyperparathyroidism[34] − + + − + − − − Nl + Confused ↓ ↓ Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl Nl to ↑ Nl Nl − − PTH level
  • Not applicable
Addison's disease[35] − + − − + + − − ↓ + Irritable ↓ ↓ Nl Nl Nl ↓ Nl ↑ ↓ Nl Nl Nl Nl Nl Nl Nl − − Hormone level
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. ↑ Ashurst JV, Nappe TM. Toxicity, Isopropanol. [Updated 2018 Mar 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493181/
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ Teppema, Luc J.; Balanos, George M.; Steinback, Craig D.; Brown, Allison D.; Foster, Glen E.; Duff, Henry J.; Leigh, Richard; Poulin, Marc J. (2007). "Effects of Acetazolamide on Ventilatory, Cerebrovascular, and Pulmonary Vascular Responses to Hypoxia". American Journal of Respiratory and Critical Care Medicine. 175 (3): 277–281. doi:10.1164/rccm.200608-1199OC. ISSN 1073-449X.
  16. ↑ Bates, D. W.; Su, L.; Yu, D. T.; Chertow, G. M.; Seger, D. L.; Gomes, D. R. J.; Dasbach, E. J.; Platt, R. (2001). "Mortality and Costs of Acute Renal Failure Associated with Amphotericin B Therapy". Clinical Infectious Diseases. 32 (5): 686–693. doi:10.1086/319211. ISSN 1058-4838.
  17. ↑ Piantadosi CA (June 1999). "Diagnosis and treatment of carbon monoxide poisoning". Respir Care Clin N Am. 5 (2): 183–202. PMID 10333448.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ Howard RD, Bokhari S. PMID 28613672. Vancouver style error: initials (help); Missing or empty |title= (help)
  22. ↑ Ganesh K, Sharma RN, Varghese J, Pillai MG (2016). "A profile of metabolic acidosis in patients with sepsis in an Intensive Care Unit setting". Int J Crit Illn Inj Sci. 6 (4): 178–181. doi:10.4103/2229-5151.195417. PMC 5225760. PMID 28149822.
  23. ↑ Kimmoun, Antoine; Novy, Emmanuel; Auchet, Thomas; Ducrocq, Nicolas; Levy, Bruno (2015). "Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside". Critical Care. 19 (1). doi:10.1186/s13054-015-0896-7. ISSN 1364-8535.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ Gil-Peña, Helena; Mejía, Natalia; Santos, Fernando (2014). "Renal Tubular Acidosis". The Journal of Pediatrics. 164 (4): 691–698.e1. doi:10.1016/j.jpeds.2013.10.085. ISSN 0022-3476.
  28. ↑ Hemstreet, Brian A (2004). "Antimicrobial-Associated Renal Tubular Acidosis". Annals of Pharmacotherapy. 38 (6): 1031–1038. doi:10.1345/aph.1D573. ISSN 1060-0280.
  29. ↑ Park, Jin Joo; Choi, Dong-Ju; Yoon, Chang-Hwan; Oh, Il-Young; Lee, Ju Hyun; Ahn, Soyeon; Yoo, Byung-Su; Kang, Seok-Min; Kim, Jae-Joong; Baek, Sang-Hong; Cho, Myeong-Chan; Jeon, Eun-Seok; Chae, Shung Chull; Ryu, Kyu-Hyung; Oh, Byung-Hee (2015). "The prognostic value of arterial blood gas analysis in high-risk acute heart failure patients: an analysis of the Korean Heart Failure (KorHF) registry". European Journal of Heart Failure. 17 (6): 601–611. doi:10.1002/ejhf.276. ISSN 1388-9842.
  30. ↑ Mann, Sarah; Bajulaiye, Akinyemi; Sturgeon, Kathleen; Sabri, Abdelkarim; Muthukumaran, Geetha; Libonati, Joseph R. (2014). "Effects of acute angiotensin II on ischemia reperfusion injury following myocardial infarction". Journal of the Renin-Angiotensin-Aldosterone System. 16 (1): 13–22. doi:10.1177/1470320314554963. ISSN 1470-3203.
  31. ↑ Guerrant, R. L.; Van Gilder, T.; Steiner, T. S.; Thielman, N. M.; Slutsker, L.; Tauxe, R. V.; Hennessy, T.; Griffin, P. M.; DuPont, H.; Bradley Sack, R.; Tarr, P.; Neill, M.; Nachamkin, I.; Reller, L. B.; Osterholm, M. T.; Bennish, M. L.; Pickering, L. K. (2001). "Practice Guidelines for the Management of Infectious Diarrhea". Clinical Infectious Diseases. 32 (3): 331–351. doi:10.1086/318514. ISSN 1058-4838.
  32. ↑ Erlingsson, Styrbjörn; Herard, Sebastian; Dahlqvist Leinhard, Olof; Lindström, Torbjörb; Länne, Toste; Borga, Magnus; Nystrom, Fredrik H. (2009). "Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women". Metabolism. 58 (7): 995–1001. doi:10.1016/j.metabol.2009.02.028. ISSN 0026-0495.
  33. ↑ Lange, Christian M.; Bojunga, Jörg; Hofmann, Wolf Peter; Wunder, Katrin; Mihm, Ulrike; Zeuzem, Stefan; Sarrazin, Christoph (2009). "Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function". Hepatology. 50 (6): 2001–2006. doi:10.1002/hep.23346. ISSN 0270-9139.
  34. ↑ Bilezikian, John P.; Potts, John T.; Fuleihan, Ghada El-Hajj; Kleerekoper, Michael; Neer, Robert; Peacock, Munro; Rastad, Jonas; Silverberg, Shonni J.; Udelsman, Robert; Wells, Samuel A. (2002). "Summary Statement from a Workshop on Asymptomatic Primary Hyperparathyroidism: A Perspective for the 21st Century". The Journal of Clinical Endocrinology & Metabolism. 87 (12): 5353–5361. doi:10.1210/jc.2002-021370. ISSN 0021-972X.
  35. ↑ Ten, Svetlana; New, Maria; Maclaren, Noel (2001). "Addison's Disease 2001". The Journal of Clinical Endocrinology & Metabolism. 86 (7): 2909–2922. doi:10.1210/jcem.86.7.7636. ISSN 0021-972X.
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