66-year-old woman with tachypnea and bicarbonate of 13 mEq/L
A 66-year-old woman is evaluated on hospital day 5 for new lethargy and mild tachypnea. She was admitted following a mechanical fall at home that caused a non-displaced pubic ramus fracture. She lives alone and has had poor oral intake with a 6-kg weight loss over the preceding six months. Medications include omeprazole, subcutaneous heparin, and scheduled oral acetaminophen (650 mg every 6 hours). Blood pressure is 118/74 mm Hg, heart rate is 86/min, and respiratory rate is 22/min. Physical examination shows clear lungs and a soft, non-tender abdomen without surgical scars. Laboratory studies show: Sodium: 138 mEq/L Potassium: 3.9 mEq/L Chloride: 99 mEq/L Bicarbonate: 13 mEq/L Blood urea nitrogen: 19 mg/dL Creatinine: 1.0 mg/dL Glucose: 96 mg/dL Serum osmolality: 292 mOsm/kg (calculated: 288 mOsm/kg) Arterial blood gas (ambient air): pH: 7.27 PaCO2: 28 mm Hg PaO2: 94 mm Hg Additional laboratory studies: L-lactate: 1.1 mmol/L Beta-hydroxybutyrate: 0.1 mmol/L Serum salicylate: undetectable Serum acetaminophen: 16 mcg/mL (therapeutic range: 10–30 mcg/mL) Which of the following is the most likely diagnosis?
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C
Explanation
Clinical Pearl:
Pyroglutamic acidosis (5-oxoprolinuria) causes an unexplained high anion gap metabolic acidosis in malnourished or critically ill patients receiving therapeutic doses of acetaminophen due to glutathione depletion. Diagnosis is confirmed by demonstrating elevated 5-oxoproline in the urine or serum once other common causes of an elevated anion gap are excluded.
Explanation:
The patient has a high anion gap metabolic acidosis (anion gap of 26 mEq/L) with appropriate respiratory compensation that is attributable to pyroglutamic acidosis, also known as 5-oxoprolinuria. Therapeutic dosing of acetaminophen in patients with underlying glutathione depletion (such as malnutrition, chronic illness, sepsis, or advanced liver disease) disrupts the gamma-glutamyl cycle, relieving feedback inhibition on gamma-glutamylcysteine synthetase and shunting intermediates into 5-oxoproline. D-lactic acidosis is an alternative cause of high anion gap acidosis with normal L-lactate, but it occurs almost exclusively in individuals with short bowel syndrome or jejunoileal bypass who ingest unabsorbed carbohydrates that are fermented by colonic bacteria. Diabetic ketoacidosis is excluded by a normal blood glucose concentration and a normal serum beta-hydroxybutyrate level. Ethylene glycol intoxication produces a severe high anion gap acidosis but is accompanied by a substantially elevated serum osmolar gap (typically greater than 10 to 15 mOsm/kg), whereas this patient exhibits an osmolar gap of only 4 mOsm/kg. Salicylate intoxication leads to an elevated anion gap often paired with a primary respiratory alkalosis, but here the salicylate concentration is completely undetectable and the PaCO2 reflects predictable compensation rather than independent hyperventilation.
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