Clinical Significance of an Anion Gap of 1
An anion gap of 1 mmol/L is abnormally low and warrants immediate investigation for laboratory error, hypoalbuminemia, paraproteinemia (particularly IgG multiple myeloma), or severe dilutional states, as this value falls well below the modern reference range of 3-11 mmol/L. 1, 2
Immediate Diagnostic Considerations
Laboratory Error Assessment
- Verify the electrolyte measurements immediately, as an anion gap of 1 is extremely rare and may represent analytical error or specimen handling issues 1, 2
- Recalculate using the formula: Na+ + K+ - Cl- - HCO3- to confirm the value 3
- An anion gap <2 mmol/L should prompt quality control checks of electrolyte measurements 1
Primary Differential Diagnosis for Low Anion Gap
Paraproteinemia (Multiple Myeloma)
- IgG multiple myeloma is a critical diagnosis to exclude, as documented cases have presented with anion gaps as low as 2 mmol/L 1
- Order serum protein electrophoresis, immunofixation, and quantitative immunoglobulins urgently 1
- The cationic paraproteins increase unmeasured cations, thereby lowering the calculated anion gap 2
Hypoalbuminemia
- Severe hypoalbuminemia can significantly lower the anion gap, as albumin is a major unmeasured anion 4, 2
- Check serum albumin level immediately 2
- Each 1 g/dL decrease in albumin lowers the anion gap by approximately 2.5 mmol/L 5
Other Causes to Consider
- Lithium or barium intoxication (increase unmeasured cations) 4, 2
- Severe dilutional states or laboratory interference 2
- Bromide intoxication (falsely elevates chloride measurement) 2
Critical Clinical Implications
Masking of High Anion Gap Acidosis
- A baseline low anion gap can mask concurrent high anion gap metabolic acidosis, potentially delaying recognition of life-threatening conditions like lactic acidosis, ketoacidosis, or toxic ingestions 2
- If the patient appears clinically acidotic despite the low calculated anion gap, consider that a pathologic acidosis may be present but obscured 2
- Check arterial blood gas to assess actual acid-base status 3
Modern Reference Ranges
- The reference range for anion gap has shifted from the historical 8-16 mmol/L to 3-11 mmol/L (or 5-12 mmol/L) due to ion-selective electrode methodology 1, 2
- An anion gap <3 mmol/L is definitively abnormal and requires investigation 2
- Your patient's value of 1 mmol/L is 2 standard deviations below the lower limit 1
Common Pitfalls to Avoid
- Do not dismiss a low anion gap as clinically insignificant—it may be the only clue to occult malignancy or serious intoxication 2
- Do not assume normal acid-base status based solely on the low anion gap; obtain arterial blood gases if clinical suspicion exists 2
- Do not delay workup for multiple myeloma in patients with unexplained low anion gap, as this can be a presenting sign 1
- Be aware that the low anion gap itself does not indicate the direction of acid-base disturbance, only that unmeasured cations are elevated or unmeasured anions are decreased 2, 5