What causes an increase in lactate (lactic acid) in an Arterial Blood Gas (ABG)?

Causes of Elevated Lactate in Arterial Blood Gas

Elevated lactate in ABG most commonly results from tissue hypoperfusion and inadequate oxygen delivery to tissues, causing a shift to anaerobic metabolism, though it can also occur from accelerated aerobic glycolysis driven by beta-adrenergic stimulation independent of tissue hypoxia. 1, 2

Primary Pathophysiologic Mechanisms

Tissue Hypoperfusion and Shock States

• Hemorrhagic shock and major trauma represent the most critical causes, where lactate serves as both a diagnostic parameter and prognostic marker of oxygen debt and tissue hypoperfusion severity. 1
• Sepsis and septic shock cause lactic acidosis through both impaired tissue perfusion and inflammatory mediators affecting cellular metabolism. 2
• Cardiogenic shock, hypovolemic shock, and distributive shock all lead to inadequate tissue perfusion and subsequent lactate accumulation. 2
• The amount of lactate produced by anaerobic glycolysis serves as an indirect marker of oxygen debt and the severity of hemorrhagic shock. 1

Aerobic Glycolysis Without Hypoxia

• Beta-adrenergic stimulation (particularly from epinephrine) can elevate lactate through beta-2-adrenergic receptor activation in skeletal muscle, stimulating glycogenolysis and glycolysis independent of tissue perfusion status. 2, 3
• This mechanism explains why hyperlactatemia often neither correlates with traditional perfusion indicators nor diminishes with increased oxygen delivery. 3
• Aerobic glycolysis in skeletal muscle is linked to ATP provision for the Na+-K+ pump, with activity stimulated by epinephrine, potentially causing hyperlactatemia even in well-oxygenated tissues. 3

Specific Clinical Causes

Vascular Emergencies

• Acute mesenteric ischemia from arterial embolism causes sudden lactate elevation, typically presenting as intense abdominal pain with minimal physical findings in patients with atrial fibrillation or other embolic sources. 2
• Lactate >2 mmol/L with abdominal pain carries a 4.1-fold increased risk of irreversible intestinal ischemia (HR: 4.1,95% CI: 1.4-11.5). 2
• More than 88% of patients with mesenteric ischemia present with metabolic acidosis and elevated lactate. 2

Medication-Induced Causes

• Metformin causes lactic acidosis in patients with impaired clearance (renal failure with eGFR <30 mL/min/1.73 m²), impaired lactate clearance (liver failure), or conditions causing anaerobic metabolism (sepsis, hypoxia). 2
• Vasopressors and inotropic agents can elevate lactate through beta-adrenergic mechanisms during resuscitation efforts. 2

Metabolic and Systemic Causes

• Liver disease impairs lactate clearance, as released lactate must exceed the liver's metabolic capacity through the Cori cycle before systemic levels increase. 2
• Diabetic ketoacidosis can cause elevated lactate levels. 2
• Thiamine deficiency results in elevated lactate. 2

Prognostic Significance

• Initial lactate levels are higher in non-survivors after major trauma, with prolonged elevation >24 hours associated with post-traumatic organ failure development. 1
• Survival correlates directly with lactate clearance time: 100% survival when lactate normalizes within 24 hours, 77.8% if within 48 hours, and only 13.6% if elevated beyond 48 hours. 1, 2
• Serial lactate measurements provide early objective evaluation of patient response to therapy and represent a reliable prognostic index for circulatory shock. 1

Important Clinical Caveats

• Lactate elevation during exercise testing represents a normal physiologic response at the anaerobic threshold, where blood lactate increases as exercise intensity exceeds aerobic capacity. 1
• Alcohol consumption can independently increase blood lactate levels, making base deficit potentially a better predictor of prognosis than lactate in alcohol-associated trauma. 1
• Lactic acidosis in cardiac surgical patients manifests systemic inflammation and excess pro-inflammatory cytokine production, with increased lactate reliably associated with hemodynamic parameters, inotrope dosage, and cardiopulmonary bypass duration. 4
• Cerebral glucose depletion after severe brain injury can increase cerebral lactate as an alternative fuel source, even without brain hypoxia, suggesting lactate acts as supplemental brain fuel when glucose availability is limited. 5

Diagnostic Approach

• Base deficit values from ABG provide complementary but independent information about global tissue acidosis due to impaired perfusion, and these parameters don't strictly correlate with lactate levels. 1, 2
• Bicarbonate decreases almost reciprocally with lactate increase, making standard bicarbonate an acceptable alternative for determining metabolic status when lactate cannot be measured. 1
• Both lactate and base deficit should be independently assessed for comprehensive shock evaluation in trauma patients. 1