Question:

A 55-year-old man comes to the hospital due to progressive fatigue and weakness. Medical history includes type 2 diabetes mellitus and obesity. Laboratory results are as follows:

Serum chemistry
Sodium	138 mEq/L
Chloride	110 mEq/L
Bicarbonate	18 mEq/L

Which of the following is the most likely diagnosis?

Diabetic ketoacidosis

Lactic acidosis

Obesity hypoventilation

Primary hyperaldosteronism

Renal tubular acidosis

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Metabolic acidosis
Type	Normal anion gap	Elevated anion gap
Mechanism	Loss of bicarbonate	Accumulation of unmeasured acidic compounds
Common causes	Severe diarrhea Renal tubular acidosis Excessive saline infusion	Lactic acidosis Diabetic ketoacidosis Renal failure (uremia) Methanol, ethylene glycol Salicylate toxicity

This patient has low serum bicarbonate (HCO₃⁻) (<24 mEq/L), consistent with metabolic acidosis. The anion gap is normal at 10 mEq/L; therefore, the most likely diagnosis is renal tubular acidosis, a common cause of nonanion gap metabolic acidosis (NAGMA).

NAGMA results from loss of HCO₃⁻ (usually from the kidneys or gastrointestinal tract), leading to a relative increase in H⁺. In renal tubular acidosis, there is either impaired proximal tubular HCO₃⁻ reabsorption (type 2) or impaired distal tubular H⁺ secretion (types 1 and 4) leading to net HCO₃⁻ loss. Severe diarrhea, involving loss of HCO₃⁻ in the stool, is another common cause of NAGMA.

NAGMA is also referred to as hyperchloremic acidosis because the decrease in serum HCO₃⁻ is compensated for by an increase in serum Cl⁻ to maintain electronegative balance.

(Choices A and B) Anion gap metabolic acidosis results from the addition of unmeasured acidic compounds to the blood. The compounds donate H⁺ to bind up serum HCO₃⁻, reducing buffering capacity and causing metabolic acidosis. The remaining anionic component increases the anion gap. Common etiologies of anion gap metabolic acidosis include increased production of ketones (eg, acetoacetate, beta-hydroxybutyrate), which occurs with diabetic ketoacidosis, and increased production of lactic acid, which occurs with reduced organ and tissue perfusion (eg, sepsis).

(Choice C) Hypoventilation causes retention of CO₂ and respiratory acidosis. A compensatory metabolic alkalosis with increased serum HCO₃⁻ (>24 mEq/L) is expected.

(Choice D) Primary hyperaldosteronism causes excessive loss of H⁺ from the renal tubular collecting duct, leading to metabolic alkalosis with increased serum HCO₃⁻.

Educational objective:
Nonanion gap metabolic acidosis (NAGMA) results from the loss of bicarbonate (HCO₃⁻) (usually from the kidneys or gastrointestinal tract), leading to a relative increase in H⁺. Common causes include renal tubular acidosis and severe diarrhea. NAGMA is also referred to as hyperchloremic acidosis because the decrease in serum HCO₃⁻ is compensated for by an increase in serum chloride to maintain electronegative balance.