The differential diagnosis of normal anion gap acidosis is relatively short (when compared to the differential diagnosis of acidosis):

• Hyperalimentation (e.g. from TPN containing ammonium chloride)
• Chloride administration, often from normal saline
• Acetazolamide and other carbonic anhydrase inhibitors
• Renal tubular acidosis^[1]
• Diarrhea: due to a loss of bicarbonate. This is compensated by an increase in chloride concentration, thus leading to a normal anion gap, or hyperchloremic, metabolic acidosis. The pathophysiology of increased chloride concentration is the following: fluid secreted into the gut lumen contains higher amounts of Na⁺ than Cl⁻; large losses of these fluids, particularly if volume is replaced with fluids containing equal amounts of Na⁺ and Cl⁻, results in a decrease in the plasma Na⁺ concentration relative to the Cl⁻concentration. This scenario can be avoided if formulations such as lactated Ringer’s solution are used instead of normal saline to replace GI losses.^[2]
• Ureteroenteric fistula – an abnormal connection (fistula) between a ureter and the gastrointestinal tract
• Pancreaticoduodenal fistula – an abnormal connection between the pancreas and duodenum
• Spironolactone
• High ostomy output^[1]
• Hyperparathyroidism – can cause hyperchloremia and increase renal bicarbonate loss, which may result in a normal anion gap metabolic acidosis. Patients with hyperparathyroidism may have a lower than normal pH, slightly decreased PaCO2 due to respiratory compensation, a decreased bicarbonate level, and a normal anion gap.^[3]

As opposed to high anion gap acidosis (which involves increased organic acid production), normal anion gap acidosis involves either increased production/administration of chloride (hyperchloremic acidosis) or increased excretion of bicarbonate.

• High anion gap metabolic acidosis