Non anion gap acidosis

Background

• Non-anion gap metabolic acidosis (NAGMA) = metabolic acidosis with a normal anion gap (typically 8-12)
• Caused by loss of bicarbonate (GI or renal) or addition of chloride (hyperchloremic acidosis)
• Mnemonic: HARDUPS — Hyperalimentation, Acetazolamide, RTA, Diarrhea, Ureteral diversion, Pancreatic fistula, Saline infusion
• Distinguish from anion gap metabolic acidosis (AGMA) which has a different differential

Clinical Features

• Symptoms of underlying cause (diarrhea, polyuria)
• Kussmaul breathing (compensatory hyperventilation)
• May be asymptomatic if mild

Differential Diagnosis

• Hyperkalemia
  • Resolving DKA
  • Early uremic acidosis
  • Early obstructive uropathy
  • RTA Type IV
  • Hypoaldosteronism
  • K-sparing diuretics
• Hypokalemia
  • RTA Type I
  • RTA Type II
  • Acetazolamide
  • Acute diarrhea
    • (May be assoc with gap if hypoperfusion -> lactic acidosis)
• CKD
• Intestinal, pancreatic, biliary fistula
• Hyperchloremic IVF infusions
• Hyperalimentation

GI Bicarbonate Loss

• Diarrhea (most common cause)
• Pancreatic fistula or drainage
• Ureteral diversion (ileal conduit, ureterosigmoidostomy)
• Cholestyramine

Renal Bicarbonate Loss / Impaired Acid Excretion

• Renal tubular acidosis (RTA)
  • Type 1 (distal): impaired H+ secretion, urine pH >5.5, hypokalemia
  • Type 2 (proximal): impaired HCO3 reabsorption, urine pH <5.5 after bicarb depleted
  • Type 4 (hypoaldosteronism): hyperkalemia, urine pH <5.5
• Early renal failure
• Carbonic anhydrase inhibitors (acetazolamide, topiramate)

Iatrogenic

• Excessive normal saline infusion (dilutional/hyperchloremic)
• Hyperalimentation (TPN)

Evaluation

• BMP: calculate anion gap (Na - Cl - HCO3), check potassium
• Urine anion gap (Na + K - Cl) helps distinguish GI from renal cause:
  • Negative urine AG = GI loss (kidneys appropriately excreting NH4+)
  • Positive urine AG = renal cause (RTA — kidneys cannot excrete acid)
• Urine pH: >5.5 suggests Type 1 RTA
• Serum potassium: low (Type 1, 2 RTA, diarrhea), high (Type 4 RTA)
• Urine electrolytes

Management

• Treat underlying cause (e.g., volume replacement for diarrhea)
• Sodium bicarbonate for severe acidosis (pH <7.1) or symptomatic
• Correct potassium abnormalities
• Stop offending medications (acetazolamide, excessive NS)
• Type 4 RTA: treat hyperkalemia, consider fludrocortisone

Disposition

• Admit if severe acidosis, hemodynamically unstable, or significant electrolyte derangement
• Discharge if mild, correctable cause identified, and electrolytes stable

See Also

• Metabolic acidosis
• Anion gap metabolic acidosis
• Hyperkalemia
• Acid-Base Disorders