From the Research
The etiology of a small anion gap includes hypoalbuminemia, paraproteinemias, lithium toxicity, bromide intoxication, and multiple myeloma, with hypoalbuminemia being the most common cause, as it significantly contributes to the normal anion gap through its negative charges 1. The calculation of the anion gap is crucial in determining the underlying cause of metabolic acidosis, as it helps to divide the metabolic acidoses into two categories: high anion gap metabolic acidosis and hyperchloremic metabolic acidosis, thereby delimiting the potential etiologies of the disorder 1. Some of the key causes of a small anion gap include:
- Hypoalbuminemia, which decreases the anion gap by approximately 2.5 mEq/L for every 1 g/dL decrease in albumin
- Paraproteinemias, including multiple myeloma, which introduce positively charged proteins that neutralize unmeasured anions
- Lithium toxicity, which can occur with levels above 1.5 mEq/L and contributes to the total positive charge
- Bromide intoxication, which can falsely lower chloride measurements on some analyzers
- Severe hypermagnesemia, hypercalcemia, and hyperkalemia, which can contribute to a small anion gap by increasing measured cations It is essential to consider laboratory error when an unexpectedly small anion gap is found, and identifying the underlying cause is crucial for proper management, as the small anion gap itself is not treated but rather the condition causing it 2. In clinical practice, calculating the serum anion gap allows determination of coexisting acid-base processes in a patient, and comparing the Δ anion Gap/ΔHCO3- can help to narrow down the differential diagnosis 2.