Foundations · Year 1 · from Foundations
Case 2: Type 2 Lactic Acidosis (Metformin Toxicity)
Clinical Image
Source: Radiopaedia - Lactic acidosis - CC BY-NC-SA 3.0
Case Presentation
A 68-year-old woman with type 2 diabetes and chronic kidney disease (baseline creatinine 2.1 mg/dL) presents with altered mental status, nausea, vomiting, and abdominal pain for 2 days. She recently had a CT scan with IV contrast for abdominal pain evaluation. Her medications include metformin 1000 mg twice daily. On examination, she is confused with Kussmaul respirations (deep, rapid breathing). Laboratory studies reveal pH 7.12, pCO2 15 mmHg, HCO3 5 mEq/L, anion gap 28 mEq/L, lactate 14 mmol/L (normal <2), creatinine 4.8 mg/dL (acute kidney injury), and metformin level markedly elevated. She has metformin-associated lactic acidosis (MALA) precipitated by acute kidney injury from contrast nephropathy. Metformin inhibits hepatic gluconeogenesis and complex I of the mitochondrial electron transport chain; when it accumulates due to reduced renal clearance, it shifts metabolism toward anaerobic glycolysis, causing lactate accumulation. She is treated with IV bicarbonate and emergent hemodialysis to remove metformin. She recovers over several days.
Key Learning Points
- Lactic acidosis occurs when pyruvate is shunted to lactate production; this happens when the TCA cycle and oxidative phosphorylation are impaired and NAD+ must be regenerated anaerobically
- Metformin inhibits complex I of the electron transport chain and hepatic gluconeogenesis; it normally has a wide safety margin but accumulates dangerously with renal impairment
- Metformin should be held before and after IV contrast administration in patients with impaired kidney function to prevent metformin-associated lactic acidosis