Normal Anion Gap Acidosis is Associated with Severe Diarrhea
Severe diarrhea (option D) is the condition most closely associated with normal anion gap acidosis. Normal anion gap acidosis occurs when the reduction in bicarbonate is balanced by a reciprocal increase in chloride concentration, maintaining a normal anion gap 1.
Understanding Anion Gap Acidosis
The anion gap is calculated as: Na⁺ - (Cl⁻ + HCO₃⁻)
- Normal anion gap: 8-12 mEq/L (varies by laboratory)
- Elevated anion gap: >12 mEq/L
Types of Metabolic Acidosis:
High Anion Gap Metabolic Acidosis:
- Caused by accumulation of unmeasured anions
- Options A, B, and C all cause high anion gap acidosis
Normal Anion Gap Metabolic Acidosis:
- Also called hyperchloremic metabolic acidosis
- Characterized by reciprocal increase in chloride as bicarbonate decreases
- Option D (severe diarrhea) is the classic cause
Why Severe Diarrhea Causes Normal Anion Gap Acidosis
Diarrhea leads to significant loss of bicarbonate-rich intestinal fluids. This bicarbonate loss is compensated by increased chloride reabsorption in the kidneys, resulting in:
- Decreased serum bicarbonate
- Increased serum chloride
- Maintained normal anion gap
Evidence from research confirms this relationship. In patients with diarrhea, the urinary anion gap is typically negative (approximately -20 ± 5.7 mmol per liter), indicating gastrointestinal bicarbonate loss 2.
Why Options A, B, and C Cause High Anion Gap Acidosis
A. Ketoacidosis
- Results from accumulation of ketone bodies (acetoacetate and β-hydroxybutyrate)
- These unmeasured anions increase the anion gap
- Diagnostic criteria for DKA include an anion gap >10-12 mEq/L 3
B. Lactic Acidosis
- Caused by accumulation of lactate, an unmeasured anion
- Significantly increases the anion gap
- Often seen in shock, sepsis, and certain drug toxicities 3
C. Salicylate Poisoning
- Leads to accumulation of salicylate and organic acids
- These unmeasured anions increase the anion gap
- Salicylates are specifically listed as a cause of high anion gap acidosis 1
Differential Diagnosis of Normal Anion Gap Acidosis
Other causes of normal anion gap acidosis include:
- Renal tubular acidosis (RTA)
- Carbonic anhydrase inhibitors
- Ammonium chloride ingestion
- Hyperalimentation with amino acid hydrochloride salts
- Urinary diversions
However, severe diarrhea remains the most common cause of normal anion gap acidosis encountered in clinical practice 4.
Clinical Pearls
- In patients with unexplained hyperchloremic (normal anion gap) metabolic acidosis, always inquire about diarrhea, even if not initially reported
- The urinary anion gap can help differentiate between gastrointestinal causes (negative gap) and renal causes (positive gap) of normal anion gap acidosis 2
- When evaluating acid-base disorders, calculate the anion gap and correct for albumin for more accurate assessment 5
- Remember that mixed acid-base disorders can complicate the clinical picture