Normal Anion Gap Acidosis Associations
Normal anion gap acidosis is most commonly associated with severe diarrhea (d). 1
Understanding Normal Anion Gap Acidosis
Normal anion gap metabolic acidosis (NAGMA) occurs when the reduction in bicarbonate is balanced by a reciprocal increase in chloride concentration, maintaining the anion gap within normal limits. This is distinct from high anion gap metabolic acidosis (HAGMA), which results from accumulation of unmeasured anions.
Key Causes of Normal Anion Gap Acidosis:
Gastrointestinal bicarbonate loss:
Renal tubular acidosis (RTA):
- Type 1 (distal) RTA
- Type 2 (proximal) RTA
- Type 4 RTA (associated with hyperkalemia) 1
Medication-induced:
- Carbonic anhydrase inhibitors
- Hydrochloride salts of amino acids
- Amphotericin B
- Spironolactone
- Non-steroidal anti-inflammatory drugs 2
Diagnostic Approach
The urinary anion gap (UAG) is a critical diagnostic tool for differentiating causes of normal anion gap acidosis:
- Negative UAG: Suggests gastrointestinal bicarbonate loss (e.g., diarrhea) 3
- Positive UAG: Suggests renal tubular acidosis 3
UAG calculation: (Na⁺ + K⁺) - Cl⁻ 4
Ruling Out Other Options
- Ketoacidosis (a): Causes high anion gap acidosis due to accumulation of ketone bodies 5
- Lactic acidosis (b): Results in high anion gap acidosis from lactate accumulation 5
- Salicylate poisoning (c): Typically causes high anion gap metabolic acidosis 5, 6
- Uremic acidosis (e): Presents as high anion gap acidosis due to retention of unmeasured anions 5
Clinical Pearls
- Consider RTA in patients with a high chloride level when the Cl⁻/Na⁺ ratio exceeds 0.79 (in the absence of diarrhea) 1
- In patients with hyperkalemia, evaluate for Type 4 RTA, especially in diabetic patients with relatively preserved renal function 1
- D-lactic acidosis, which can occur in patients with short bowel syndrome and preserved colon, causes high anion gap acidosis (not normal anion gap) 7
In summary, severe diarrhea is the most common cause of normal anion gap acidosis, while the other options listed (ketoacidosis, lactic acidosis, salicylate poisoning, and uremic acidosis) all cause high anion gap metabolic acidosis.