Use of anion gap in the evaluation of a patient with metabolic acidosis

Am J Kidney Dis. 2014 Oct;64(4):653-7. doi: 10.1053/j.ajkd.2014.05.022. Epub 2014 Aug 15.


High anion gap (AG) metabolic acidosis, a common laboratory abnormality encountered in clinical practice, frequently is due to accumulation of organic acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney function. The cause of high AG metabolic acidosis often is established easily using historical and simple laboratory data. Despite this, several challenges in the diagnosis and management of high AG metabolic acidosis remain, including quantifying the increase in AG, understanding the relationship between changes in AG and serum bicarbonate level, and identifying the cause of high AG metabolic acidosis when common causes are ruled out. The present case was selected to highlight the importance of the correction of AG for serum albumin level, the use of actual baseline AG rather than mean normal AG, the relationship between changes in serum bicarbonate level and AG, and a systematic diagnostic approach to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis).

Keywords: 5-Oxoproline acidosis; acetaminophen; cysteine; glutamate–cysteine ligase; glutathione; high anion gap metabolic acidosis; pyroglutamic acidosis.

Publication types

  • Case Reports

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetylcysteine / administration & dosage*
  • Acid-Base Equilibrium*
  • Acidosis* / chemically induced
  • Acidosis* / complications
  • Acidosis* / physiopathology
  • Acidosis* / therapy
  • Aged, 80 and over
  • Bicarbonates / blood
  • Confusion / etiology
  • Drug Substitution
  • Female
  • Free Radical Scavengers / administration & dosage
  • Humans
  • Pyrrolidonecarboxylic Acid / metabolism*
  • Serum Albumin / analysis*
  • Treatment Outcome


  • Bicarbonates
  • Free Radical Scavengers
  • Serum Albumin
  • Acetaminophen
  • Pyrrolidonecarboxylic Acid
  • Acetylcysteine