Anion Gap Panel
Anion Gap is a measure of the balance between positively and negatively charged electrolytes in the blood. An abnormal anion gap may indicate acid-base imbalances, kidney disease, or other health problems.
iollo markers that associate with Anion Gap Panel
Acetylcarnitine
Acetylcarnitine is formed from acetyl-CoA, which if accumulated (e.g. due to PDH deficiency) can be hydrolyzed to acetate anions and increase the anion gap.
References
References
Morgan Nordstrom, L. O’Brien, Michael Hooper, Mark Flemmer, Paul Ellis Marik. “An unusual case of severe high anion gap metabolic acidosis”. BMC Research Notes (2011). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421581/
Daniel Batlle, Jamie Chin-Theodorou, Bryan M Tucker. “Laboratory diagnostic approaches in metabolic disorders”. American Journal of Kidney Diseases (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331366/
Aconitic acid
Aconitic acid is converted to isocitrate in the citric acid cycle. Elevated aconitic acid levels may slightly increase organic anions and the anion gap.
References
References
Francis G Bowling, Director of Biochemical Diseases, Mater Children’s Hospital. “Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis”. Critical Care (2006). https://ccforum.biomedcentral.com/articles/10.1186/cc4954
Aspartic Acid
Like glutamic acid, aspartic acid is metabolized to organic anions (e.g. oxaloacetate) that can increase the anion gap if elevated.
References
References
J. A. Smith, A. R. Johnson, C. E. Williams, D. P. Evans. Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria. Journal of Proteomics (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232244/
Glutamic Acid
Glutamic acid can be converted to alpha-ketoglutarate, an organic anion that contributes to the anion gap when levels are increased.
References
References
Kovesdy, C. P., et al.. Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis - NCBI. Clinical Journal of the American Society of Nephrology (2023). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785829/
Medscape. Anion Gap: Reference Range, Interpretation, Collection and Panels. Medscape (2019). https://emedicine.medscape.com/article/2087291-overview
Sathasivam, S., et al.. An Unsuspected Case of Euglycemic Diabetic Ketoacidosis With Twists. Case Reports in Endocrinology (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091341/
Hydroxyglutaric acid
Hydroxyglutaric acids are organic acid intermediates. Significant accumulation of these organic anions could increase the anion gap.
References
References
Duran, M., Abdenur, J. E., Farias, A. C., & Martins, E. V.. L-2-hydroxyglutaric aciduria – review of literature and case series. Journal of Inherited Metabolic Disease (1980). https://link.springer.com/article/10.1007%2FBF00487339
Lactic acid
Lactic acid is a key contributor to the anion gap. Elevated lactic acid levels from anaerobic metabolism or impaired clearance can increase the anion gap.
References
References
Ronco, J. J., Sibbald, W. J., Bellomo, R., & Ronco, C.. Anion Gap as a Screening Tool for Elevated Lactate in Patients with an Unknown Sepsis Status. Critical Care Medicine (2008). https://www.sciencedirect.com/science/article/abs/pii/S0736467908002436
Gunnerson, K. J., Saul, M., Kellum, J. A., & Palevsky, P.. Relationship Between the Anion Gap and Serum Lactate in Hypovolemic Shock. Critical Care Medicine (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069407/
Koyfman, A., & Long, B.. High Anion Gap Metabolic Acidosis - StatPearls - NCBI Bookshelf. NCBI Bookshelf (2022). https://www.ncbi.nlm.nih.gov/books/NBK448090/
Kumar, A., & Clark, P.. Anion Gap: Reference Range, Interpretation, Collection and Panels. Medscape (2019). https://emedicine.medscape.com/article/2087291-overview
Kellum, J. A.. Evaluating a low anion gap: A practical approach. CCJM (2020). https://www.ccjm.org/content/90/10/619
Succinic acid
Succinic acid is an intermediate in the citric acid cycle. Accumulation of succinate anions can modestly contribute to an increased anion gap.
References
References
Kurtz, I., & Kraut, J. A.. Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis. Postgraduate Medical Journal (2005). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297631/
Fenves, A. Z., & Lehnert, H.. L-lactic acidosis: pathophysiology, classification, and causes. Best Practice & Research Clinical Endocrinology & Metabolism (2019). https://www.sciencedirect.com/science/article/pii/S0085253819308981
Kurtz, I., & Kraut, J. A.. Krebs cycle anions in metabolic acidosis. Critical Care (2005). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297638/
Lam, J. T. Y., et al.. A transepithelial pathway delivers succinate to pro-inflammatory macrophages. Cell Reports (2021). https://www.cell.com/cell-reports/fulltext/S2211-1247%2821%2900952-9
Bailey, D. G.. Acidosis and Anion Gap. IntechOpen (2022). https://www.intechopen.com/chapters/71488