What are the causes of lactic acidosis?

Causes of Lactic Acidosis

Lactic acidosis is primarily classified into two major types: Type A (hypoxic) caused by tissue hypoperfusion and Type B (non-hypoxic) caused by underlying metabolic disorders or medications. 1

Type A Lactic Acidosis (Hypoxic/Tissue Hypoperfusion)

Type A lactic acidosis occurs when the body must regenerate ATP without adequate oxygen, resulting in anaerobic metabolism and lactate overproduction. Common causes include:

• Shock states:

  • Septic shock
  • Cardiogenic shock
  • Hypovolemic shock
  • Hemorrhagic shock

• Respiratory failure/hypoxemia:

  • Severe pneumonia
  • Acute respiratory distress syndrome
  • Severe asthma/COPD exacerbation

• Severe anemia

• Carbon monoxide poisoning

• Cyanide poisoning (impairs cellular oxygen utilization) 2

• Mesenteric ischemia (intestinal hypoperfusion) 1

Type B Lactic Acidosis (Non-Hypoxic)

Type B lactic acidosis occurs without evidence of tissue hypoxia and is further subdivided:

Type B1: Associated with underlying diseases

• Liver disease/failure (impaired lactate clearance)
• Kidney failure (reduced lactate elimination)
• Malignancies (especially hematologic)
• Diabetes mellitus (particularly with ketoacidosis)
• Short bowel syndrome (D-lactic acidosis) 1
• Sepsis (even without hypoperfusion)

Type B2: Medication/toxin-induced

• Metformin: Can cause lactic acidosis, especially in patients with:

  • Renal impairment (eGFR <30 mL/min/1.73m²)
  • Liver dysfunction
  • Heart failure
  • Excessive alcohol intake
  • Hypoxic states 3

• Other medications:

  • Nucleoside reverse transcriptase inhibitors (NRTIs), especially stavudine and didanosine 4
  • Propofol (propofol infusion syndrome)
  • Linezolid
  • Isoniazid
  • Salicylates

• Toxins:

  • Ethanol
  • Methanol
  • Ethylene glycol
  • Propylene glycol

Type B3: Inborn errors of metabolism

• Pyruvate dehydrogenase deficiency
• Mitochondrial myopathies
• Glucose-6-phosphatase deficiency
• Fructose-1,6-diphosphatase deficiency

Clinical Presentation and Diagnosis

Lactic acidosis typically presents with:

• Nonspecific symptoms: malaise, myalgias, abdominal pain, respiratory distress, somnolence
• In severe cases: hypotension, resistant bradyarrhythmias 3
• Laboratory findings:
  • Elevated blood lactate (>2 mmol/L is elevated, >5 mmol/L indicates severe lactic acidosis)
  • Increased anion gap (Na - [Cl+CO2] >16)
  • Decreased serum bicarbonate
  • Decreased arterial pH (<7.35) 4, 1

Risk Factors for Developing Lactic Acidosis

• Advanced age (>65 years)
• Renal impairment
• Liver dysfunction
• Cardiac failure
• Respiratory failure
• Sepsis
• Obesity (for metformin-associated lactic acidosis)
• Female gender (higher risk with NRTIs) 4
• Pregnancy/postpartum period (with certain antiretrovirals) 4

Management Considerations

The cornerstone of management is treating the underlying cause:

• For Type A: Restore tissue perfusion and oxygenation
• For Type B: Remove offending medications, treat underlying conditions
• For metformin-associated lactic acidosis: Immediate discontinuation of metformin and prompt hemodialysis 3
• Serial lactate measurements (every 4-6 hours) to assess clearance and treatment efficacy 1

Important Clinical Pitfalls

• Lactate levels must be measured correctly: prechilled fluoride-oxalate tubes, transported on ice, processed within 4 hours, collected without tourniquet or fist-clenching 4
• Normal lactate levels don't exclude early tissue hypoperfusion
• Metformin should be temporarily discontinued during acute illness, before iodinated contrast procedures, or surgery 3
• Patients with liver dysfunction may require more aggressive intervention due to impaired lactate metabolism 1

Remember that lactic acidosis is often multifactorial, with both increased production and decreased clearance contributing to the clinical picture. Prompt recognition and treatment of the underlying causes remain the cornerstone of management 2, 5.