What is lactic acidosis?

What is Lactic Acidosis

Lactic acidosis is a metabolic acidosis characterized by elevated blood lactate levels (>5 mmol/L) combined with arterial pH <7.35, resulting from an imbalance between lactate production and clearance. 1, 2

Pathophysiology and Mechanisms

Lactic acidosis occurs when lactate accumulates faster than the body can clear it, with production and clearance mechanisms typically differing by an order of magnitude. 2, 3 The condition develops through two primary pathophysiological mechanisms:

Type A Lactic Acidosis

• Caused by tissue hypoxia and inadequate oxygen delivery, resulting in anaerobic metabolism where the body must regenerate ATP without oxygen 1, 4, 3
• Common causes include circulatory shock, pulmonary failure, severe anemia, carbon monoxide poisoning, and cyanide toxicity 3, 5
• Associated with septic shock, where hypoperfusion leads to end-organ dysfunction and escalating lactate despite aggressive resuscitation 5

Type B Lactic Acidosis

• Occurs without tissue hypoxia, with maintained tissue oxygenation but metabolic disturbances affecting lactate metabolism 4, 3
• Results from underutilization of lactate through impaired oxidation or conversion to glucose 3
• Causes include liver disease, inhibition of gluconeogenesis, thiamine deficiency affecting pyruvate dehydrogenase, and uncoupling of oxidative phosphorylation 3
• Drug-induced lactic acidosis, particularly from nucleoside reverse transcriptase inhibitors (NRTIs), occurs through mitochondrial toxicity by inhibiting DNA polymerase γ, the enzyme responsible for mitochondrial DNA synthesis 1
• Malignancy-associated lactic acidosis occurs through the Warburg effect, where cancer cells preferentially use glycolysis even with adequate oxygen 5

Clinical Presentation

Early Symptoms

The initial clinical signs are variable and nonspecific, making early recognition challenging 1:

• Nonspecific gastrointestinal symptoms: nausea, vomiting, abdominal pain, abdominal distention, diarrhea, anorexia 1
• Systemic symptoms: generalized weakness, fatigue, myalgias, paresthesias, weight loss 1
• Respiratory symptoms: dyspnea, tachypnea (compensatory hyperventilation) 1

Severe Manifestations

Progressive mitochondrial toxicity can produce severe lactic acidosis manifested clinically by tachypnea and dyspnea, potentially progressing to respiratory failure requiring mechanical ventilation. 1

Laboratory Findings

Lactate Levels

When interpreting serum lactate, levels of 2–5 mmol/L are considered elevated and need to be correlated with symptoms. Levels >5 mmol/L are abnormal, and levels >10 mmol/L indicate serious and possibly life-threatening situations. 1

For clinical management: 1

• Lactate 2–5 mmol/L: Close monitoring advised
• Lactate <2 mmol/L: No intervention necessary
• Lactate >5 mmol/L with pH <7.35: Diagnostic of lactic acidosis 1, 4

Associated Laboratory Abnormalities

Beyond hyperlactatemia, laboratory evaluation typically reveals 1:

• Increased anion gap (Na − [Cl+CO2] >16), though hypoalbuminemia may mask this 4
• Elevated aminotransferases (hepatic enzymes)
• Elevated creatine phosphokinase, lactic dehydrogenase, lipase, and amylase 1
• Metabolic acidosis with low bicarbonate 1

Critical Sampling Considerations

Because substantial technical problems are associated with lactate testing, measurement requires standardized sample handling 1:

• Use prechilled fluoride-oxalate tubes
• Transport immediately on ice to laboratory
• Process within 4 hours after collection
• Collect blood without tourniquet, without fist-clenching, and without stasis 1

Imaging Findings

Echotomography and computed tomography scans might indicate an enlarged fatty liver, and histologic examination may reveal microvesicular steatosis, particularly in NRTI-induced cases 1

High-Risk Populations and Settings

NRTI-Associated Lactic Acidosis

Risk factors include obesity, female sex, and prolonged use of NRTIs, though cases occur with unknown risk factors 1. The syndrome is associated with a high mortality rate 1.

Pregnancy represents a particularly high-risk state: severe lactic acidosis with or without pancreatitis, including fatal cases, were reported during later stages of pregnancy or postpartum in women receiving stavudine and didanosine combinations 1. The incidence may be increased because pregnancy itself can mimic early symptoms of lactic acidosis 1.

Critical Care Settings

Lactic acidosis is the most common cause of metabolic acidosis in the critical care setting and has been associated with a large increase in mortality 2. In septic shock, elevated lactate >2 mmol/L defines the condition and substantially increases mortality 1.

Prognostic Significance

Lactate level is often used as a prognostic indicator and may be predictive of favorable outcome if it normalizes within 48 hours 4. In established acute mesenteric ischemia, elevated serum lactate >2 mmol/L was associated with irreversible intestinal ischemia (Hazard Ratio: 4.1,95% CI: 1.4–11.5) 1.

However, the routine measurement of serum lactate should not determine therapeutic interventions in isolation—clinical context is essential 4.

Important Clinical Caveats

• Lactic acidosis can occur with normal pH when concomitant alkalosis is present 4
• The presence of lactic acidosis due to dehydration and decreased oral intake must be differentiated from irreversible bowel injury, as lactate elevation alone is not reliable without other clinical evidence 1
• Ethanol intoxication does not cause clinically significant lactate elevation—elevated lactate should not be attributed to ethanol alone and warrants evaluation for alternative causes 6
• In acute mesenteric ischemia, lactic acidosis combined with abdominal pain when the patient may not otherwise appear clinically ill should lead to consideration for early CT angiography 1