What are the causes of a low anion gap?

People can have a low anion gap for various reasons. This value, which compares the concentration of positively charged ions in the blood to negatively charged ions in the blood, can become abnormal due to various metabolic disorders. 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. Laboratory error, lithium poisoning, and bromide ingestion can also cause a low anion gap.

To understand the importance of a low anion gap, it helps to understand what 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 quite rare, and has been shown in some studies to be present in less than 1 percent of hospitalized patients.

Patients who have low levels of albumin, a protein produced by the liver that circulates in the blood, may have a low anion gap. Albumin has a negative charge, and when concentrations of this protein drop 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 decrease in the anion gap. Patients with liver disease, malnutrition, and kidney disease commonly have decreased levels of albumin in their blood.

Conditions that result in excess production of positively charged protein can also cause a decrease in the anion gap. Multiple myeloma, for example, is a malignancy in which patients produce large amounts of proteins that are usually used as antibodies. Since these proteins have a positive charge, the body compensates by excreting positively charged ions such as sodium. Therefore, the anion gap decreases.

Some poisonings in which patients ingest 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, lowering the anion gap. Taking too much bromide can cause a similar effect.

Another cause of a low anion gap is laboratory error. If the values ​​provided for serum sodium, chloride, and bicarbonate concentrations are incorrect, then the anion gap could be calculated as low when it is actually normal. Physicians or other health professionals should use their clinical judgment when interpreting laboratory values ​​and be sure to question values ​​that do not make sense. The best way to determine if there is a laboratory error is to recheck serum electrolyte concentrations.

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