What are the causes of elevated lactic acid levels?

Causes of Elevated Lactic Acid

Primary Mechanisms

Elevated lactic acid occurs through two fundamental mechanisms: increased production (typically from tissue hypoxia) or decreased clearance (from impaired hepatic/renal metabolism). 1, 2

Type A: Tissue Hypoxia and Hypoperfusion

• Shock states (cardiogenic, hypovolemic, obstructive) cause inadequate tissue oxygen delivery, forcing anaerobic metabolism and lactate accumulation 1, 3
• Cardiac failure reduces cardiac output and systemic perfusion, triggering lactate production 1
• Myocardial infarction creates regional hypoperfusion with systemic inflammatory response 1
• Mesenteric ischemia (arterial embolism, arterial thrombosis, venous thrombosis, non-occlusive) produces marked lactate elevation; levels >2 mmol/L with abdominal pain carry a 4.1-fold increased risk of irreversible intestinal ischemia 4, 1
• Compartment syndrome restricts blood flow to affected tissues 1

Type B: Non-Hypoxic Causes

Impaired Lactate Clearance

• Liver disease severely impairs lactate metabolism since the liver handles up to 70% of lactate clearance 1, 3
• Renal impairment reduces lactate removal capacity and increases risk of drug-induced lactic acidosis 5

Metabolic Disorders

• Diabetic ketoacidosis frequently presents with elevated lactate alongside ketoacidosis 1
• Thiamine deficiency impairs pyruvate metabolism, causing lactate accumulation 1, 6
• Glycogen storage disease type I causes persistently elevated blood lactate due to blocked gluconeogenesis; lactate rises rapidly when blood glucose drops below 70 mg/dL 4

Medication-Induced

• Metformin is the most clinically significant drug cause; risk increases dramatically with eGFR <45 mL/min/1.73 m², characterized by lactate >5 mmol/L and metformin levels >5 mcg/mL 5, 1
• High-dose vasopressors can cause non-occlusive mesenteric ischemia leading to lactic acidosis 1
• Antiretroviral medications may cause mild elevations (2-3 mmol/L) 1

Other Causes

• Malignancy (particularly hematological) increases lactate production 3, 7
• Seizures cause transient lactate elevation from intense muscle activity 8
• Vigorous exercise produces lactate when oxygen delivery cannot meet demand; this occurs physiologically at peak exercise in healthy individuals 4, 1
• Childbirth causes physiologic stress-related lactate elevation 1

Clinical Interpretation

Normal and Abnormal Ranges

• Normal lactate: <2 mmol/L 1
• Mild elevation: 2-5 mmol/L warrants close monitoring; often represents dehydration, medication effects, or recent exertion 4, 1
• Moderate elevation: 5-10 mmol/L indicates serious pathology requiring urgent investigation 1
• Severe elevation: >10 mmol/L represents life-threatening conditions 1

Context-Dependent Significance

• Lactate 2-3 mmol/L without symptoms may represent false positives from exercise, medication effects (metformin, antiretrovirals), or mild dehydration 4, 1
• Lactate >2 mmol/L with abdominal pain should prompt immediate consideration of mesenteric ischemia even if the patient appears stable; D-dimer is often elevated concurrently 4, 1
• Lactate elevation during exercise testing (RER >1.0) reflects CO₂ production from bicarbonate buffering of lactic acid, marking the anaerobic threshold at approximately 50-60% of predicted VO₂max 4

Critical Pitfalls to Avoid

• Do not automatically attribute elevated lactate to sepsis—non-infectious causes are common and require different management 1
• Do not dismiss lactate 2-3 mmol/L with concerning symptoms—this level can indicate early mesenteric ischemia or other serious pathology when accompanied by abdominal pain 4, 1
• Do not overlook medication history—metformin-associated lactic acidosis requires immediate drug discontinuation and often hemodialysis (metformin is dialyzable with clearance up to 170 mL/min) 5
• Do not delay imaging in suspected mesenteric ischemia—lactic acidosis with abdominal pain warrants immediate CT angiography even when the patient appears clinically well 4

Diagnostic Approach

When encountering elevated lactate, systematically evaluate:

1. Perfusion status: Check blood pressure, cardiac output, signs of shock 1, 3
2. Oxygenation: Assess for hypoxemia, anemia, carbon monoxide exposure 4, 1
3. Medication review: Specifically metformin (check renal function), vasopressors, antiretrovirals 1, 5
4. Organ function: Liver disease, renal impairment 1, 3
5. Metabolic causes: Diabetic ketoacidosis, thiamine deficiency 1
6. Ischemia: Mesenteric (especially with abdominal pain), compartment syndrome 4, 1
7. Recent activity: Exercise, seizures, childbirth 4, 1