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pyroglutamic acidosis
Etiology:
- chronic acetaminophen ingestion
- can occur with 4000 mg/day [3]
Epidemiology:
- female (80%)
Pathology:
- pyroglutamic acid accumulates in critically ill patients in association with
a) acetaminophen metabolism
b) oxidative stress
c) sepsis
d) 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
Related
pyroglutamic acid; pyroglutamate; pidolic acid; pidolate
General
metabolic acidosis
References
- Medical Knowledge Self Assessment Program (MKSAP) 15, 17, 18.
American College of Physicians, Philadelphia 2009, 2015, 2018.
- Geriatric Review Syllabus, 11th edition (GRS11)
Harper GM, Lyons WL, Potter JF (eds)
American Geriatrics Society, 2022
- Hunter RW, Lawson C, Galitsiou E et al.
Pyroglutamic acidosis in association with therapeutic paracetamol use.
Clin Med. 2016;16(6):524-529
PMID: 27927815 PMCID: PMC6297337 Free PMC article