People can have a low anion gap for a number of reasons. This value, which compares the concentration of positively charged ions in the blood to negatively charged ions in the blood, can become abnormal by a number of metabolic derangements. Having low levels of albumin, a negatively charged protein, can cause a decreased anion gap. High concentrations of positively charged proteins can also cause this change. Lab error, lithium intoxication, and bromide ingestion can all also cause a low anion gap.
In order to understand the significance of a low anion gap, it helps to understand what the anion gap is, how it is measured, and what it means. The anion gap is calculated after measuring the concentrations of different electrolytes in the serum. Typically, it is calculated by subtracting negatively charged substances, including chloride and bicarbonate, from positively charged substances, including sodium. A normal value is typically around 12. Having a low anion gap is fairly rare, and in some studies has been shown to be present in less than 1 percent of hospitalized patients.
Patients who have decreased levels of albumin — a protein made by the liver that circulates in the blood — can have a low anion gap. Albumin has a negative charge, and when the concentrations of this protein decrease in the blood, the body compensates by keeping more negatively charged ions including chloride in the blood. Higher levels of chloride and bicarbonate lead to a decreased anion gap. Patients with liver disease, malnutrition, and kidney disease commonly have decreased levels of albumin in their blood.
Conditions that result in the excess production of positively-charged protein can also cause a decreased anion gap. Multiple myeloma, for example, is a malignancy in which patients produce large amounts of proteins that are typically used as antibodies. As these proteins have a positive charge, the body compensates by excreting positively charged ions such as sodium. Therefore, the anion gap is decreased.
Some intoxications in which patients take in negatively charged ions can also cause a low anion gap. An overdose of lithium, which is a medication commonly used to treat bipolar disorder, increases the amount of negative ions in the serum, decreasing the anion gap. Taking excess bromide can cause a similar effect.
Another cause of a low anion gap is laboratory error. If the values provided for serum concentrations of sodium, chloride, and bicarbonate are incorrect, then the anion gap could be calculated as low when in reality it is normal. Doctors or other health care professionals should use their clinical judgment when interpreting laboratory values, and be sure to question values that don’t make sense. The best way to determine if there is a laboratory error is to recheck the serum electrolyte concentrations.