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Anion-gap interpretation: the old and the new

Nature Clinical Practice Nephrology volume 2, pages 4–5 (2006)Cite this article

All solutions of dissolved salts contain equal numbers of dissociated positive and negative charges. This simple principle was used by the Boston physiologist James L Gamble as a means of analyzing clinical electrolyte and acid–base disorders. Gamble popularized the method of comparing positive and negative charge concentrations in plasma and other fluids by displaying the ions graphically in the form of two stacked bars ('Gamblegrams')—a stack of cations adjacent to a stack of anions.1

In order to maintain electrical equality following any anion-concentration decrease, either the decrease must be accompanied by an identical reduction in the cation concentration, or the concentration of another anion must increase to fill the 'void'. Gamblegram analyses have proven to be most helpful for elucidating the pathophysiology of complex electrolyte and acid–base disorders and aiding the recognition of certain occult clinical disorders. Nevertheless, routine measurement of all the ions in a plasma sample is cumbersome, complicated, expensive and generally unnecessary. A more practical approach takes advantage of the fact that most plasma ions normally exist at relatively low concentrations and their pathological concentration excursions are quantitatively small. The three ions with the highest plasma concentrations and the largest concentration variances are sodium (Na), chloride (Cl) and bicarbonate (HCO3). The plasma concentration of Na normally exceeds the sum of Cl and HCO3, and such comparisons therefore yield what is called an 'anion gap': Na – (Cl + HCO3).2,3

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References

  1. Gamble JL (1947) Chemical anatomy, physiology and pathology of extracellular fluid; a lecture syllabus, edn 5. Cambridge: Harvard University Press

    Google Scholar 

  2. Emmett M and Narins RG (1977) Clinical use of the anion gap. Medicine (Baltimore) 56: 38–54

    Article  CAS  Google Scholar 

  3. Oh MS and Carroll HJ (1977) The anion gap. N Engl J Med 297: 814–817

    Article  CAS  Google Scholar 

  4. Winter SD et al. (1990) The fall of the serum anion gap. Arch Intern Med 150: 311–313

    Article  CAS  Google Scholar 

  5. Narins RG and Emmett M (1980) Simple and mixed acid–base disorders: a practical approach. Medicine (Baltimore) 59: 161–187

    Article  CAS  Google Scholar 

  6. Oster JR et al. (1988) Use of the anion gap in clinical medicine. South Med J 81: 229–237

    Article  CAS  Google Scholar 

  7. Carlisle EJ et al. (1991) Glue-sniffing and distal renal tubular acidosis: sticking to the facts. J Am Soc Nephrol 1: 1019–1027

    CAS  PubMed  Google Scholar 

  8. Figge J et al. (1998) Anion gap and hypoalbuminemia. Crit Care Med 26: 1807–1810

    Article  CAS  Google Scholar 

  9. Corey HE (2003) Stewart and beyond: new models of acid–base balance. Kidney Int 64: 777–787

    Article  CAS  Google Scholar 

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  1. Chairman of the Department of Internal Medicine at Baylor University Medical Center, and Clinical Professor of Medicine at the University of Texas Southwestern, Dallas, TX, USA

    Michael Emmett

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  1. Michael Emmett
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Correspondence to Michael Emmett.

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Emmett, M. Anion-gap interpretation: the old and the new. Nat Rev Nephrol 2, 4–5 (2006). https://doi.org/10.1038/ncpneph0073

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