Anion Gap Approach

The first and most widely used tool for investigating metabolic acidosis is the anion gap (AG), developed by Emmit and Narins in 1975.^[28] This is based on the law of electrical neutrality and is entirely consistent with the work of Stewart and Fencl. The system is based on data that were not easily available or known at the time of publication: the contribution to electrical neutrality ascribed to weak acids (phosphate and albumin) and UMAs. The sum of the difference in charge of the common extracellular ions reveals an unaccounted for a gap of -10 to -12 mEq/L, because the AG is equal to Na⁺ + K⁺ − (Cl⁻ + HCO₃ ⁻ ) ( Fig. 41-4 ). If the patient develops a metabolic acidosis, and the gap "widens" to, for example, -16 mEq/L, the acidosis is caused by UMAs (lactate or ketones). If the gap does not widen, the anions are being measured, and the acidosis has been caused by hyperchloremia (bicarbonate cannot independently influence acid-base status). Although this is a useful tool, it is weakened by the assumption of what is or is not a normal gap.^[29] Most critically ill patients are hypoalbuminemic, and many are also hypophosphatemic. ^[30] Consequently, the gap may be normal in the presence of UMAs. This has been extensively studied by Fencl and Figge,^[19] who provided a variant known as the corrected anion gap:

Anion gap corrected (for albumin) = calculated anion gap + 2.5 × (normal albumin [in g/dL] − observed albumin [in g/dL])

Figure 41-4 The anion gap represents the difference in charge between measured cations and measured anions. The missing negative charge is made up of weak acids (A^- ), such as albumin and phosphate, and strong unmeasured anions (UMAs), such as lactate.

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