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Updated: Dec 10, 2025

Measurement and Analysis of Extracellular Acid Production to Determine Glycolytic Rate
Published on: December 12, 2015
Anion-gap metabolic acidemia: case-based analyses
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jseifter@bwh.harvard.edu.
Abstract:
Not all metabolic acidosis is associated with an elevated chloride replacing the low bicarbonate concentration. When other acids, usually non-Cl organic acids are introduced into the blood an "Anion Gap" metabolic acidosis exists. The serum anion gap is calculated as [Na+] - ([Cl-] + [HCO3-]) = Unmeasured anions - Unmeasured cations. The normal gap is mostly due to negatively charged albumin: (Normal range: 8-12 meq/l) as the unmeasured anions, since albumin is usually reported in grams per liter (not meq/l). For diagnostic purposes, calculating the serum anion gap allows determination of coexisting acid-base processes in a patient. Assuming a 1:1 fall in bicarbonate compared with rise in anion gap in a usual gap acidosis, one can compare the Δ anion Gap/ΔHCO3-: Δ gap = observed anion gap - normal anion gap and the Δ HCO3- = normal HCO3- - observed HCO3-. A ratio of 1 suggests a simple anion gap acidosis; if <1 a superimposed non-gap acidosis is lowering HCO3- and if >1 a superimposed metabolic alkalosis is raising HCO3-. Comparing the anion gap and osmolar gap can narrow the differential diagnosis to include toxic alcohol ingestions with acidic metabolites such as ethylene glycol and methanol. Not all metabolic acidosis is associated with an elevated chloride replacing the low bicarbonate concentration. When other acids, usually non-Cl organic acids are introduced into the blood an "Anion Gap" metabolic acidosis exists. This review will consider the generation of anion-gap acidoses through case discussions.
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