Which of the following can cause a non‑anion‑gap metabolic acidosis in this patient: diarrhea, vomiting, hypovolemia, all of the above, or diarrhea and vomiting only?

Diarrhea is the Primary Cause of Non-Anion Gap Metabolic Acidosis

Diarrhea causes non-anion gap metabolic acidosis through direct gastrointestinal bicarbonate loss, making it the correct answer among the options provided. 1, 2

Understanding Non-Anion Gap Metabolic Acidosis Mechanisms

Non-anion gap (hyperchloremic) metabolic acidosis develops when bicarbonate is lost from the body or when chloride accumulates disproportionately. 1 The two primary mechanisms are:

• Gastrointestinal bicarbonate loss (diarrhea, fistulas, ureterosigmoidostomy) 1, 2
• Renal bicarbonate wasting or impaired acid excretion (renal tubular acidosis, hypoaldosteronism) 2, 3

The urinary anion gap serves as a critical diagnostic tool: a negative urinary anion gap (-20 ± 5.7 mmol/L) indicates gastrointestinal bicarbonate loss, while a positive gap suggests renal tubular acidosis. 2

Why Each Option Does or Does Not Cause Non-Anion Gap Acidosis

Diarrhea: YES – Direct Bicarbonate Loss

Diarrhea is the most common extrarenal cause of non-anion gap metabolic acidosis. 1, 3 The mechanism is straightforward:

• Intestinal secretions contain high bicarbonate concentrations (50-70 mEq/L) 3
• Massive fluid loss during diarrhea results in direct bicarbonate depletion 1
• The kidney responds by retaining chloride to maintain electroneutrality, creating hyperchloremic acidosis 1, 3
• The urinary anion gap becomes negative (-20 ± 5.7 mmol/L) as the kidney appropriately increases ammonium excretion to compensate 2

In children with severe diarrhea and dehydration, non-anion gap acidosis is the predominant acid-base disturbance and correlates with mortality risk. 4

Vomiting: NO – Causes Metabolic Alkalosis

Vomiting causes metabolic alkalosis, not acidosis, through gastric hydrochloric acid loss. 5 When gastric contents are lost:

• Hydrogen ions (H+) and chloride (Cl-) are removed from the body 5
• Bicarbonate accumulates in the bloodstream, raising pH above 7.45 5
• The result is hypochloremic metabolic alkalosis with volume contraction 5

The only scenario where vomiting might contribute to acidosis is in chronic pancreatitis with pancreatic fistula, where pancreatic bicarbonate-rich secretions are lost—but this represents fistula drainage, not typical vomiting. 6

Hypovolemia: NO – Indirect Effect Only

Hypovolemia alone does not cause non-anion gap metabolic acidosis; it causes high anion gap lactic acidosis when severe. 7, 8 The pathophysiology differs fundamentally:

• Severe hypovolemia impairs tissue perfusion, leading to anaerobic metabolism 7, 8
• Lactate accumulates as an unmeasured anion, creating high anion gap metabolic acidosis 8
• The anion gap rises above 12 mEq/L (typically 16-20 mEq/L or higher) 5, 8

Hypovolemia can indirectly worsen non-anion gap acidosis only when it occurs secondary to diarrhea—but the primary mechanism remains bicarbonate loss, not the volume depletion itself. 7, 1

Diagnostic Algorithm for Non-Anion Gap Acidosis

When confronted with metabolic acidosis (pH <7.35, HCO₃⁻ <22 mmol/L), follow this systematic approach: 3

1. Calculate the anion gap: Na⁺ - (Cl⁻ + HCO₃⁻)

   • Normal: 10-12 mEq/L 5
   • If >12 mEq/L: high anion gap acidosis (lactic acidosis, ketoacidosis, uremia, toxins) 5, 8
   • If ≤12 mEq/L: proceed to step 2 3

2. Assess clinical history for bicarbonate loss:

   • Diarrhea (acute or chronic) → gastrointestinal bicarbonate loss 1, 2, 3
   • Recent large-volume saline administration → iatrogenic hyperchloremic acidosis 1
   • Urinary diversion procedures → urinary bicarbonate reabsorption 3

3. Check serum potassium:

   • Hypokalemia (K⁺ <3.5 mEq/L): suggests diarrhea, proximal RTA, or distal RTA 3
   • Hyperkalemia (K⁺ >5.5 mEq/L): suggests type 4 RTA or hypoaldosteronism 3

4. Calculate urinary anion gap (if diagnosis unclear): Urine Na⁺ + K⁺ - Cl⁻

   • Negative (<-20 mEq/L): appropriate renal response → gastrointestinal bicarbonate loss (diarrhea) 2
   • Positive (>+20 mEq/L): impaired renal acidification → renal tubular acidosis 2, 3

Critical Clinical Pitfalls

Do not confuse the fluid resuscitation for diarrhea-induced hypovolemia with the cause of acidosis. The acidosis stems from bicarbonate loss in stool, not from the volume depletion. 1, 2 Aggressive isotonic saline resuscitation (15-20 mL/kg/h) treats the hypovolemia but can paradoxically worsen hyperchloremic acidosis through chloride loading. 1, 4

Use balanced crystalloids (Lactated Ringer's or Plasma-Lyte) rather than normal saline when resuscitating patients with diarrhea-induced acidosis to avoid iatrogenic worsening of the non-anion gap component. 4

Bicarbonate therapy is rarely indicated for diarrhea-induced non-anion gap acidosis unless pH falls below 7.0, which is exceedingly rare. 1 The primary treatment is rehydration and addressing the underlying cause of diarrhea. 1, 4

Answer Summary

The correct answer is "Diarrhea" alone. 1, 2, 3

• Diarrhea: YES – causes non-anion gap acidosis via direct bicarbonate loss 1, 2
• Vomiting: NO – causes metabolic alkalosis via gastric acid loss 5
• Hypovolemia: NO – causes high anion gap lactic acidosis when severe 7, 8