Question 23

Discuss the advantages and limitations of the anion gap in the evaluation of acid-base disturbance

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College Answer

Definition AG -a derived variable for the evaluation of metabolic acidosis to 
determine the presence of unmeasured anions.

AG = [(Na + K)-(Cl + HC03)], normal reference range: 8-12 meq/ L

Utility: A raised AG is seen with elevated lactate, ketoacidosis, salicylates, alcohol 
poisonings, and pyroglutamate

Advantages of the anion gap: 
a) A simple measure to quantify and evaluate acid-base disturbance 
b) Can be· easily done at the bedside

1) Reduced unmeasured anions such as hypoalbuminemia (frequently seen in critical 
illness) will reduce the AG and may mask an elevated AG 
2) UnmeasUred cations such as elevated Li and hyperglobulinemia will reduce AG. 
3) Hypercalcemia and hypermagnesemia will also reduce the AG. 
4) Calculation of AG involves measurement of electrolytes and therefore depends on 
the accuracy of the measurement process.

To overcome the effects of the hypoalbuminemia on the AG, the corrected AG can be 
used which is AG + (0.25 * (40-albumin) expressed in G/L


The article by Kraut and Nicolaos is an excellent longform answer to this question.

The question itself is not even a "critically evaluate" type of question. It asks simply for the advantages and limitations.

Thus, there they are.

Advantages of the anion gap

  • Easy to calculate: (Na+ + K+) - (Cl- + HCO3-)
  • Offers a simple stratification of acid-base disorders into HAGMA and NAGMA

Limitations of the anion gap

  • Subject to laboratory error in the measurement of any of the constituents
  • Spurious sodium results can alter the anion gap (eg. in "pseudohyponatremia")
  • Spurious chloride results can alter the anion gap (eg. bromide and iodide can be mistaken for chloride in the laboratory)
  • Unmeasured or uncounted cation excess can alter the anion gap (eg. lithium, calcium, magnesium)
  • Strongly cationic drugs can decrease the anion gap, or even make it negative (eg. polymyxin B)
  • Modified by hypoalbuminaemia, and needs to be corrected (there is a 1mmol/L decrease in the "normal" anion gap for every 4g/L of albumin deficit below 40g/L)
  • Modified by hyperprotinaemia, eg. in some sort of myeloma-like illness (an excess of charged proteins changes the anion gap; it is impossible to say in which direction, as the proteins may be anionic or cationic)

A discussion of the anion gap is available locally in two forms: as a quick revision summary and as a massive rambling digression.


EMMETT, MICHAEL, and ROBERT G. NARINS. "Clinical use of the anion gap."Medicine 56.1 (1977): 38-54.


Figge, James, et al. "Anion gap and hypoalbuminemia." Critical care medicine26.11 (1998): 1807-1810.


Salem, Mahmoud M., and Salim K. Mujais. "Gaps in the anion gap." Archives of internal medicine 152.8 (1992): 1625-1629.


Kraut, Jeffrey A., and Nicolaos E. Madias. "Serum anion gap: its uses and limitations in clinical medicine." Clinical Journal of the American Society of Nephrology 2.1 (2007): 162-174.