Related Subjects:
|Metabolic acidosis
|Aspirin or Salicylates toxicity
|Ethylene glycol toxicity
|Renal Tubular Acidosis
|Pyroglutamic acidosis
|Lactic acidosis
Pyroglutamic acidosis is an example of an endogenous acidosis caused by elevated pyroglutamic acid. It is often seen in patients who are already glutathione-depleted.
📖 About
- Acidosis due to glutathione depletion.
🧬 Aetiology
- Pyroglutamic acid is produced from gamma-glutamyl cysteine by the enzyme gamma-glutamyl cyclotransferase.
- When glutathione levels are low ➝ activity of gamma-glutamyl cyclotransferase increases ➝ accumulation of pyroglutamic acid.
- Glutathione is depleted by paracetamol, sepsis, chronic liver disease, and malnutrition.
🖼️ Diagram
⚡ Causes
- Genetic Disorders: Glutathione synthetase deficiency, 5-oxoprolinase deficiency → disrupt gamma-glutamyl cycle.
- Medication-Induced: Prolonged paracetamol, high-dose antibiotics (flucloxacillin, netilmicin) → alter glutathione metabolism.
- Critical Illness: Sepsis, CKD, malnutrition → oxidative stress + impaired detoxification.
- Dietary Factors: Low glycine/cysteine intake, high glutamic acid intake → imbalance in amino acids needed for glutathione synthesis.
- Metabolic Conditions: Diabetes, chronic alcoholism → increase glutathione demand, leading to depletion.
⚠️ Risk Factors
- Paracetamol ingestion
- Severe sepsis
- Renal failure
- Chronic alcoholism or chronic liver disease
- Malnutrition or unusual diets
- Inherited enzyme deficiencies
- Drugs: flucloxacillin, vigabatrin, netilmicin
- Female gender (higher susceptibility due to enzyme activity differences)
- Diminished 5-oxoproline clearance
🩺 Clinical Features
- Acidotic Kussmaul respirations
- May present with sepsis
- History of paracetamol ingestion
🔎 Investigations
- Blood Gas: High anion gap metabolic acidosis.
- U&E + Anion Gap: Elevated gap due to pyroglutamic acid accumulation.
- Urine Organic Acids: GC-MS confirms elevated pyroglutamic acid.
- Plasma 5-Oxoproline: Elevated, diagnostic.
- Toxicology: Check for paracetamol or other drug-induced causes.
- Liver Function Tests: Assess for underlying liver dysfunction.
💊 Management
- Discontinue causative agents: Stop paracetamol/other glutathione-depleting drugs.
- Replete glutathione: N-acetylcysteine (NAC) IV/PO.
- Correct acidosis: Sodium bicarbonate infusion if severe acidosis.
- Supportive care: Adequate hydration, monitor U&E.
- Treat underlying triggers: e.g., infection, sepsis, malnutrition.
- Monitoring: Regularly check pH, anion gap, and 5-oxoproline until stabilised.
📚 References
