How to Spot a Falsely Normal Anion Gap

• Laboratory error
• Hypoalbuminemia
• Increased unmeasured cations
• Monoclonal and polyclonal gammopathy; and,
• Salicylate poisoning

The solution

After calculating the anion gap and finding it to be normal, look at the serum bicarbonate again. If it is low, then you must be dealing with either a metabolic acidosis or respiratory alkalosis. If the history and physical examination do not clearly point to the cause of hypobicarbonatemia (like diarrhea, early acute renal failure, tachypnea), then assume that you are dealing with an occult organic acid load, until proven otherwise.

You can help prove otherwise by checking the following:

• Repeat serum electrolytes (to rule out laboratory error)
• Attempt to measure serum organic acid load more or less directly (lactic acid, urine for ketones)
• Check serum albumin level (low albumin will artificially lower the anion gap)
• Check serum cations such as calcium, magnesium, potassium, and lithium (high serum cation will artificially lower the anion gap)
• Check serum and urine protein electrophoresis and immunofixation, and with serum free light chain assay
• Check serum salicylate level

And finally,

“[O]nce laboratory error and hypoalbuminemia have been excluded [as a cause of low serum anion gap], a search for accumulation of IgG should be initiated. In patients with disturbed mentation or unexplained clinical findings, the possibility of lithium ingestion, bromism, or iodide intoxication should be considered. When the serum anion gap is negative in the absence of laboratory error … bromide intoxication, iodide intoxication, and [multiple] myeloma should be excluded.”

Jeffrey A. Kraut, Serum Anion Gap: Its Uses and Limitations in Clinical Medicine. Clinical Journal of the American Society of Nephrology, January 2007, vol. 2  no. 1  162-174 (free here)