What are the types of lactic acidosis?

Types of Lactic Acidosis

Lactic acidosis is primarily classified into two major types: Type A, caused by tissue hypoxia/hypoperfusion, and Type B, which occurs in the absence of tissue hypoxia due to metabolic disturbances.

Type A Lactic Acidosis

Type A lactic acidosis results from tissue hypoxia and/or hypoperfusion, making it the most common form encountered clinically 1. This type occurs when oxygen delivery to tissues is inadequate, forcing cells to shift to anaerobic metabolism.

Common causes of Type A lactic acidosis:

• Circulatory failure: Shock states (septic, cardiogenic, hypovolemic)
• Respiratory failure: Severe hypoxemia
• Severe anemia: Reduced oxygen-carrying capacity
• Carbon monoxide poisoning: Impaired oxygen transport

In acute mesenteric ischemia, elevated serum lactate levels >2 mmol/L are associated with irreversible intestinal ischemia (hazard ratio: 4.1) 2. The presence of lactic acidosis combined with abdominal pain, even when the patient doesn't appear critically ill, should prompt consideration of early CT angiography.

Type B Lactic Acidosis

Type B lactic acidosis occurs without evidence of tissue hypoxia or hypoperfusion and is further subdivided into three categories 3:

Type B1: Associated with underlying diseases

• Malignancies: Particularly hematologic malignancies like lymphoma and leukemia due to the Warburg effect 1, 4
• Liver disease: Impaired lactate clearance
• Renal failure: Reduced lactate elimination
• Diabetes mellitus: Altered metabolism
• Inborn errors of metabolism: Such as fatty acid oxidation defects (FAOD) 2

Type B2: Medication/toxin-induced

• Metformin: Can cause lactic acidosis, especially in patients with renal impairment, characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis, and increased lactate:pyruvate ratio 5
• Nucleoside reverse transcriptase inhibitors (NRTIs): Associated with lactic acidosis due to mitochondrial toxicity, particularly with prolonged use (>6 months) 2
• Beta-agonists: Both short-acting and long-acting beta-agonists can cause lactic acidosis through increased glycolysis and stimulation of Na+/K+-ATPase 6, 7
• Alcohols: Ethanol potentiates metformin's effect on lactate metabolism 5
• Cyanide: Blocks cellular respiration

Type B3: Associated with inborn errors of metabolism

• Organic acidemias: Group of disorders with increased excretion of organic acids in urine 2
• Primary hyperoxaluria Type 1 (PH1): Autosomal recessive disorder of glyoxylate metabolism 2
• Glycogen storage diseases: Can lead to lactic acidosis, especially during metabolic stress 2
• Fatty acid oxidation defects (FAOD): Inherited metabolic diseases that can present with hypoketotic hypoglycemia and acute metabolic acidosis 2

Clinical Presentation and Diagnosis

Lactic acidosis typically presents with:

• Increased anion gap metabolic acidosis
• Elevated serum lactate (>5 mmol/L indicates abnormal levels, >10 mmol/L indicates serious, potentially life-threatening condition) 2
• Clinical symptoms may include tachypnea, dyspnea, abdominal pain, nausea, vomiting, and altered mental status

For NRTI-associated lactic acidosis, early symptoms may include:

• Nonspecific gastrointestinal symptoms (abdominal distention, nausea, vomiting, diarrhea)
• Generalized weakness
• Ascending neuromuscular weakness
• Myalgias, paresthesias
• Weight loss
• Hepatomegaly 2

Management Considerations

Management depends on the type and underlying cause:

Type A:

• Primary approach: Treat the underlying cause of tissue hypoxia/hypoperfusion
• Supportive measures: Fluid resuscitation, vasopressors if needed, oxygen therapy
• Hemodialysis: May be considered in severe cases, particularly drug-induced

Type B:

• Drug-induced: Discontinue the offending agent
• For metformin-associated lactic acidosis: Prompt hemodialysis is recommended to correct acidosis and remove accumulated metformin 5
• For NRTI-induced lactic acidosis: Discontinue antiretroviral treatment; consider bicarbonate infusions and hemodialysis in severe cases 2
• For FAOD: Management involves dietary recommendations regarding fat and carbohydrate content and controlling the length of fasting periods; intravenous glucose infusion of at least 10 mg/kg/min to maintain serum glucose above 100 mg/dL during a crisis 2

Important Clinical Considerations

1. Pregnancy risk: Pregnant women on NRTIs (particularly stavudine and didanosine) have increased risk of lactic acidosis, especially in the third trimester 2

2. Monitoring: For patients on medications with risk of lactic acidosis (like metformin or NRTIs), regular monitoring of electrolytes and liver function is recommended 2, 5

3. Proper lactate measurement: Requires standardized sample handling with prechilled fluoride-oxalate tubes transported immediately on ice and processed within 4 hours; blood should be collected without tourniquet use or fist-clenching 2

4. Risk factors for metformin-associated lactic acidosis: Renal impairment, age ≥65 years, radiologic studies with contrast, surgery, hypoxic states, and excessive alcohol intake 5