pyroglutamic acidosis

Etiology

• chronic acetaminophen ingestion
  • can occur with 4000 mg/day

Epidemiology

• female (80%)

Pathology

• pyroglutamic acid accumulates in critically ill patients in association with
  • acetaminophen metabolism
  • oxidative stress
  • sepsis
  • depleted glutathione levels
• 5-oxoproline accumulates due to disruption of the gamma-glutamyl transpeptidase (GGT) cycle
  • GGT cycle facilitates amino acid absorption from the gut & proximal tubule & is used by the liver for chemical detoxification
  • glutathione depletion from sepsis & acetaminophen use lead to increased 5-oxoproline production
• most common occurs with
  • poor nutrition
  • liver disease
  • kidney disease
• penicillin inhibits 5-oxoprolinase thus oxoproline breakdown
• occurs in vegetarians

Clinical manifestations

• mental status changes ranging from confusion to coma

Laboratory

• basic metabolic panel
  • anion gap metabolic acidosis
  • serum bicarbonate low, example 9 meq/L
• no osmolal gap
• serum lactate of 1.2 mmol/L (normal 0.5-2.2 mmol/L)
• 5-oxoproline in urine

Differential diagnosis

• propofol infusion (lactic acidosis)
• lorazepam infusion (contains propylene glycol, thus osmolal gap)
• sepsis (lactic acidosis)

Management

• discontinue acetaminophen
• consider N-acetylcysteine to regenerate depleted glutathione

More general terms

• metabolic acidosis

Additional terms

• pyroglutamic acid; pyroglutamate; pidolic acid; pidolate