Which substances are examples of unmeasured anions that can accumulate in anion-gap metabolic acidosis?

• A. Ammonia and phosphate
• B. Chloride and bicarbonate
• C. Lactate and ketoacids
• D. Potassium and magnesium

Answer: (C)

Anion-gap metabolic acidosis shows up when unmeasured anions build up in the blood, increasing the negative charges not accounted for in the standard electrolyte panel (sodium minus chloride minus bicarbonate). Lactate and ketoacids are classic examples of these unmeasured anions. When tissues become hypoxic or processes like diabetic ketoacidosis or alcoholic/starvation states drive excess production of ketoacids, these acids accumulate as negatively charged species that aren’t included in the measured ions, so the measured gap widens.

Ammonia is not an anion, and while phosphate is an unmeasured anion, the common, clinically emphasized culprits driving a high anion gap are lactate and ketoacids. Chloride and bicarbonate are the measured ions in the gap calculation, not unmeasured anions, and potassium and magnesium are cations, not anions.