Can acute or chronic watery diarrhea cause a normal anion‑gap metabolic acidosis?

Does Diarrhea Cause Normal Anion Gap Acidosis?

Yes, acute or chronic watery diarrhea is a well-established cause of normal anion gap (hyperchloremic) metabolic acidosis due to gastrointestinal bicarbonate loss. 1, 2, 3

Mechanism of Diarrhea-Induced Acidosis

Diarrhea causes normal anion gap metabolic acidosis through direct loss of bicarbonate in stool, which is then replaced by chloride to maintain electroneutrality. 1, 2 This results in:

• Decreased serum bicarbonate (<22 mmol/L) with proportional increase in serum chloride 1
• Normal anion gap (10-12 mEq/L) because the lost bicarbonate is replaced by chloride, maintaining the balance of unmeasured anions 1, 4
• Acidemic pH (<7.35) when bicarbonate depletion is severe enough to overwhelm compensatory mechanisms 1

The kidneys respond appropriately by increasing urinary ammonium excretion to eliminate excess hydrogen ions, which distinguishes diarrhea from renal tubular acidosis. 3, 5

Clinical Evidence

In patients with acute diarrhea, metabolic acidosis develops with characteristic laboratory findings that confirm appropriate renal compensation: 5

• Plasma pH decreases from 7.42 to 7.39 5
• Serum bicarbonate falls from 25.8 to 23.7 mEq/L 5
• Urine pH drops significantly from 6.67 to 5.5, demonstrating effective urinary acidification 5
• Urinary ammonium excretion increases dramatically from 87 to 229 mg/g creatinine 5

The urinary anion gap becomes negative (-20 ± 5.7 mmol/L) in diarrhea patients, reflecting increased ammonium excretion, which is the key diagnostic feature distinguishing gastrointestinal bicarbonate loss from renal tubular acidosis. 3

Diagnostic Algorithm

When evaluating hyperchloremic metabolic acidosis, use this approach:

Step 1: Calculate the anion gap = Na⁺ - (HCO₃⁻ + Cl⁻), with normal being 10-12 mEq/L 1

Step 2: If anion gap is normal, calculate the urinary anion gap = (Urine Na⁺ + Urine K⁺) - Urine Cl⁻ 3

Step 3: Interpret the urinary anion gap: 3

• Negative urinary anion gap (-20 to -27 mmol/L) = gastrointestinal bicarbonate loss (diarrhea) with appropriate renal compensation
• Positive urinary anion gap (+23 to +39 mmol/L) = renal tubular acidosis with impaired urinary acidification

Step 4: Confirm clinical context: 2

• History of diarrhea, laxative use, or gastrointestinal disease supports GI bicarbonate loss
• Absence of diarrhea with Cl⁻/Na⁺ ratio >0.79 suggests RTA

Common Causes of Diarrhea-Related Acidosis

Acute watery diarrhea from any cause can produce normal anion gap acidosis: 6, 7

• Infectious gastroenteritis (viral, bacterial, parasitic) 6
• Laxative-induced diarrhea for bowel preparation 5
• Bile acid malabsorption (post-cholecystectomy, terminal ileum resection) 8, 7
• Inflammatory bowel disease (ulcerative colitis, Crohn's disease) 6, 7
• Celiac disease with malabsorption 6, 7
• Medication-induced diarrhea (magnesium products, metformin, NSAIDs) 6, 7

Management Principles

Treatment focuses on rehydration and addressing the underlying cause of diarrhea, not on directly correcting the acidosis with bicarbonate therapy. 6

For mild-to-moderate dehydration (3-9% fluid deficit): 6

• Oral rehydration with 50-90 mEq/L sodium-containing solution at 50 mL/kg over 2-4 hours 6
• The acidosis typically resolves spontaneously once fluid losses are replaced and diarrhea stops 1

For severe dehydration (≥10% fluid deficit) with signs of shock: 6

• Isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour to restore intravascular volume 6, 1
• Use balanced crystalloids (Lactated Ringer's or Plasma-Lyte) rather than continued normal saline to avoid iatrogenic hyperchloremic acidosis 1, 9

Bicarbonate therapy is NOT indicated for diarrhea-induced acidosis unless pH falls below 7.0, which is extremely rare. 1 The kidneys are functioning appropriately and will correct the acidosis once volume is restored and bicarbonate losses cease.

Critical Pitfall to Avoid

Do not administer large volumes of 0.9% normal saline for resuscitation, as this can worsen hyperchloremic acidosis by further increasing serum chloride and reducing the strong ion difference. 1, 9 Switch to balanced crystalloids after initial resuscitation to facilitate faster correction of acidosis. 1