What is the role of serum anion gap in the workup of metabolic alkalosis?

Updated: Dec 10, 2020
  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Calculation of the serum anion gap may help to differentiate between primary metabolic alkalosis and metabolic compensation for respiratory acidosis. The anion gap is frequently elevated to a modest degree in metabolic alkalosis because of the increase in the negative charge of albumin and the enhanced production of lactate.

Normal values for the anion gap vary in different laboratories and between individual patients, however, so it is important to know the range of normal for the particular clinical laboratory and the prevailing baseline value for a particular patient. [11] In any event, the only definitive way to diagnose metabolic alkalosis is with a simultaneous blood gases analysis that shows elevation of both pH and PaCO2 and increased calculated bicarbonate.

Serum bicarbonate concentration can be calculated from a blood gas sample using the Henderson-Hasselbalch equation, as follows:

pH = 6.10 + log (HCO3- ÷ 0.03 × PaCO2)

Alternatively, HCO3- = 24 × PaCO2 ÷ [H+]

Because pH and PaCO2 are directly measured, bicarbonate can be calculated.

Another means of assessing serum bicarbonate concentration is with the total carbon dioxide content in serum, which is routinely measured with serum electrolytes obtained from venous blood. In this method, a strong acid is added to serum, which interacts with bicarbonate in the serum sample, forming carbonic acid. Carbonic acid dissociates to carbon dioxide and water; then, carbon dioxide is measured.

Note that the carbon dioxide measured includes bicarbonate and dissolved carbon dioxide. The contribution of dissolved carbon dioxide is quite small (0.03 × PaCO2) and is usually ignored, although it accounts for a difference of 1-3 mEq/L between the measured total carbon dioxide content in venous blood and the calculated bicarbonate in arterial blood. Thus, at a PaCO2 of 40, a total carbon dioxide content of 25 means a true bicarbonate concentration of 23.8 (ie, 25 - 0.03 × 40).

The Henderson-Hasselbalch equation may fail to account for acid-base findings in critically ill patients. An alternative method of acid-base analysis, known as the quantitative, or strong ion, approach, [12] determines pH on the basis of the following 3 independent variables (see Metabolic Acidosis):

  • Strong ion difference (SID): Ions almost completely dissociated at physiologic pH (the cations Na+, K+, Ca+, and Mg+, and the anions Cl- and lactate)

  • Total weak acid concentration: Ions that can be dissociated or associated at physiologic pH (albumin and phosphate)

  • pCO2 (mm Hg)

In a study that compared the conventional Henderson-Hasselbalch equation with the strong ion approach, carried out in 100 patients with trauma who were admitted to a surgical intensive care unit, the investigators concluded that the strong ion approach provides a more accurate means of diagnosing acid-base disorders, including metabolic alkalosis and tertiary disorders. [13]

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