Background: The purpose of this review is to provide a differential diagnosis for a low anion gap.
Methods: We describe the anatomy of the anion gap. Also, we follow-up with a review of the English-language literature describing the causes of a low anion gap. During the past 15 years, the introduction and widespread clinical use of ion-selective electrode methodology for measuring serum electrolyte values has caused a major fall in the normal range of the anion gap from 12 mEq/L +/- 4 mEq/L to 6 mEq/L +/- 3 mEq/L; therefore, a new definition for a low anion gap is in order.
Results: Based on current clinical data, an anion gap value of < 3 mEq/L should be considered low. A low anion gap is a useful diagnostic tool, but its clinical significance is often unrecognized. Also, it may be a handy clinical clue for the diagnosis of life-threatening intoxications or occult neoplasms, such as multiple myeloma. The baseline low anion gap may mask the identification of a high gap metabolic acidosis in certain patients.
Conclusions: Interpretation of a low anion gap can provide valuable clinical information.