Table 1.

Causes of a low or negative serum anion gap

CauseComments
Low serum anion gap
    laboratory errorMost frequent cause of low anion gap
    underestimation of serum sodiumMost frequent with severe hypernatremia or hypertriglyceridemia
    overestimation of serum chlorideRare with ion selective electrodes
    overestimation of serum bicarbonateSpurious elevation in serum HCO3 if cells not separated from sera
    hypoalbuminemiaSecond most common cause of low serum anion gap
    monoclonal IgG gammopathyLevel of anion gap correlates with serum concentration of paraprotein
    polyclonal gammopathyMight be more common cause of low anion gap than monoclonal gammopathy
    bromide intoxicationAnion gap depends on serum bromide concentration
    lithium intoxicationLow anion gap with lithium >4 mEq/L
    hypercalcemiaInconsistent finding more likely with hypercalcemia associated with primary hyperparathyroidism
    hypermagnesemiaTheoretical cause but not documented in literature
    polymyxin BAnion gap depends on serum level; occurs with preparation with chloride
    iodide intoxicationRare cause
Negative serum anion gap
    laboratory errorMay be most common cause
    bromide intoxicationSecond most common cause; values as low as −60 mEq/L reported
    multiple myelomaRare cause, more likely to have low anion gap
    iodide intoxicationRare cause of negative anion gap