Normal anion gap acidosis

Differential diagnosis

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
• 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.
• 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
• 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.

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.

References

References

1. Kharsa, Antoine. (2025). "Anion Gap and Non-Anion Gap Metabolic Acidosis". StatPearls Publishing.
2. "Metabolic Acidosis: Acid-Base Regulation and Disorders: Merck Manual Professional".
3. (August 1974). "Magnitude of metabolic acidosis in primary hyperparathyroidism". Arch. Intern. Med..