Causes of Lactic Acidosis
Lactic acidosis is primarily caused by tissue hypoxia resulting from decreased oxygen delivery, low cardiac output states, or conditions like sepsis where oxygen consumption is impaired despite adequate oxygen delivery. 1
Types of Lactic Acidosis
Lactic acidosis can be classified into two main types:
Type A (Hypoxic) Lactic Acidosis
- Decreased oxygen delivery conditions:
- Hypoxemia
- Low cardiac output states
- Severe anemia
- Carbon monoxide poisoning
- Clinical scenarios:
- Shock (cardiogenic, hypovolemic, septic)
- Cardiac arrest
- Severe respiratory failure
- Severe anemia
- Trauma with significant blood loss
Type B (Non-hypoxic) Lactic Acidosis
- Occurs despite adequate tissue oxygenation due to:
- Medication-induced:
- Metabolic disorders:
- Diabetic ketoacidosis
- Liver failure (impaired lactate clearance)
- Renal failure
- Thiamine deficiency
- Other causes:
- Malignancies
- Alcoholism
- Seizures
- Excessive exercise
- D-lactic acidosis (short bowel syndrome)
Pathophysiological Mechanisms
Increased Production of Lactic Acid
- During tissue hypoxia, cells shift to anaerobic metabolism
- Pyruvate is converted to lactate to regenerate NAD+ for continued glycolysis
- Epinephrine (in sepsis and stress states) stimulates aerobic glycolysis, increasing lactate production even with adequate oxygen
- Peak exercise in healthy individuals can cause transient metabolic acidosis 1
Decreased Clearance of Lactic Acid
- Liver disease impairs lactate metabolism (liver clears ~70% of lactate)
- Renal impairment (kidneys clear ~30% of lactate)
- Inhibition of gluconeogenesis
- Pyruvate dehydrogenase deficiency (e.g., thiamine deficiency)
Special Clinical Scenarios
Metformin-Associated Lactic Acidosis
- Occurs primarily in patients with significant renal impairment
- Risk increases with:
- eGFR <30 mL/min/1.73m² (contraindicated) 2
- Excessive alcohol intake
- Hepatic impairment
- Hypoxic states (heart failure, respiratory failure)
- Dehydration
- Sepsis
- Contrast administration
HIV Medication-Related Lactic Acidosis
- Nucleoside reverse transcriptase inhibitors (NRTIs) can cause lactic acidosis
- Mechanism: inhibition of mitochondrial DNA polymerase γ
- Higher risk with stavudine and didanosine 1
- Risk factors: obesity, female gender, pregnancy, prolonged NRTI use 1
- Symptoms: nausea, vomiting, abdominal pain, dyspnea, weakness 1
Non-Occlusive Mesenteric Ischemia (NOMI)
- Can cause lactic acidosis due to intestinal hypoperfusion
- Risk factors: cardiac failure, low flow states, vasopressors, multi-organ dysfunction 1
- Elevated lactate with abdominal pain should prompt consideration of mesenteric ischemia 1
Clinical Presentation
- Early symptoms may be nonspecific:
- Nausea
- Vomiting
- Abdominal pain
- Dyspnea
- Generalized weakness
- Laboratory findings:
- Arterial pH <7.35
- Elevated serum lactate (>2 mmol/L)
- Increased anion gap
- Elevated liver enzymes (may be present)
Common Pitfalls in Diagnosis
- Delayed recognition: Symptoms may be vague and nonspecific
- Failure to identify the underlying cause: Multiple factors often contribute
- Sampling errors: Lactate measurement requires proper handling (prechilled fluoride-oxalate tubes, transported on ice, processed within 4 hours)
- Misinterpretation of lactate levels: Levels >5 mmol/L are abnormal, >10 mmol/L indicate serious, potentially life-threatening conditions 1
Key Points to Remember
- Lactic acidosis is characterized by blood pH <7.35 and elevated blood lactate levels (>5 mmol/L) 3
- The presence of lactic acidosis with abdominal pain when the patient may not otherwise appear clinically ill should prompt consideration of mesenteric ischemia 1
- In patients with HIV on NRTIs who develop unexplained symptoms (nausea, vomiting, abdominal pain), consider lactic acidosis 1
- Alcohol potentiates metformin's effect on lactate metabolism, increasing risk of lactic acidosis 2