Specifically, the anion gap evaluates the difference between measured and unmeasured electrical particles (ions or electrolytes) in the fluid portion of the blood. According to the principle of electrical neutrality, the number of positive ions (cations) and negative ions (anions) should be equal. However, not all ions are routinely measured. The calculated AG result represents the unmeasured ions and primarily consists of anions, hence the name “anion gap.” The most commonly used formula is:

Anion Gap (AG) = Sodium - (Chloride + Carbon Dioxide)

However, there are other AG formulas, so reference ranges are not interchangeable. Each laboratory formula will have an established normal range that should be referenced.

The anion gap is non-specific. It is increased when the number of unmeasured anions increases, indicating a state of anion-gap metabolic acidosis, but it does not tell the doctor what is causing the imbalance. The metabolic acidosis must be treated to restore the acid/base balance, but the underlying condition must also be identified and treated. Causes can include uncontrolled diabetes, starvation, kidney damage, and ingestion of potentially toxic substances such as antifreeze, excessive amounts of aspirin, or methanol. A low anion gap can also occur; this is most commonly seen when albumin (an anion as well as a protein) is low, while immunoglobulins (cations as well as proteins) are increased.