Western (Cohen-Woods) Classification of Lactic Acidosis
Lactic acidosis is classified into Type A (tissue hypoxia/hypoperfusion) and Type B (non-hypoxic causes), with Type B further subdivided into B1 (underlying diseases), B2 (drugs/toxins), and B3 (inborn errors of metabolism). 1, 2, 3
Type A Lactic Acidosis: Tissue Hypoxia/Hypoperfusion
Type A occurs when oxygen delivery fails to meet tissue metabolic demands, forcing cells into anaerobic metabolism with pyruvate conversion to lactate to regenerate NAD+. 4
Clinical conditions causing Type A:
- Circulatory shock states (cardiogenic, hypovolemic, distributive) with inadequate tissue perfusion 4
- Cardiac failure with low cardiac output and tissue hypoperfusion 5, 4
- Acute mesenteric ischemia from intestinal hypoperfusion 5
- Respiratory failure resulting in severe hypoxemia 5, 4
- Severe anemia limiting oxygen-carrying capacity 4
- Sepsis and severe infections causing tissue hypoperfusion despite adequate oxygen delivery 4
Laboratory findings:
- Blood lactate >5 mmol/L (abnormal), >10 mmol/L (life-threatening) 4, 6
- Arterial pH <7.35 4, 7
- Increased anion gap (Na - [Cl+HCO3-] >16) 4
- Increased lactate:pyruvate ratio 6
Type B Lactic Acidosis: Non-Hypoxic Causes
Type B occurs without tissue hypoxia, involving impaired lactate clearance or metabolic disturbances. 1, 2, 3
Type B1: Underlying Diseases
Hepatic dysfunction:
- Liver disease impairing lactate oxidation and gluconeogenesis 1
- Decreased hepatic uptake of lactate 6
Renal impairment:
- Kidneys contribute to lactate removal; dysfunction increases accumulation risk 1
- Metformin accumulation in renal impairment (eGFR <45 mL/min/1.73 m²) significantly increases lactic acidosis risk 6
Malignancy-associated:
- Cancer cells undergo metabolic reprogramming (Warburg effect) with enhanced glycolysis and lactate production despite adequate oxygen 2, 8
- Particularly seen with hematologic malignancies (B-cell lymphoma) and neuroendocrine tumors 2, 8
Type B2: Drugs and Toxins
Metformin:
- Decreases liver uptake of lactate, increasing blood levels 6
- Risk factors: eGFR <30 mL/min/1.73 m² (contraindicated), age ≥65 years, hepatic/cardiac impairment 6
- Metformin plasma levels generally >5 mcg/mL in lactic acidosis cases 6
Nucleoside reverse transcriptase inhibitors (NRTIs):
- Inhibit DNA polymerase γ, causing mitochondrial dysfunction 5, 4
- Stavudine and didanosine combination particularly high-risk, especially in pregnant/postpartum women 5
- Risk factors: female sex, obesity, prolonged NRTI use 5
Other toxins:
- Cyanide poisoning causing cellular oxygen utilization failure 1
Type B3: Inborn Errors of Metabolism
Thiamine deficiency:
D-lactic acidosis (special subtype):
- Occurs exclusively in patients with short bowel syndrome and preserved colon 5, 4
- Colonic bacteria degrade fermentable carbohydrates to D-lactate, which is absorbed but poorly metabolized 5
- Presents with metabolic acidosis, large anion gap, and elevated D-lactate in blood/urine 5
Clinical Presentation Across Types
Gastrointestinal symptoms:
Respiratory manifestations:
- Tachypnea and dyspnea as compensatory hyperventilation attempts to eliminate CO2 5, 4, 9
- Respiratory failure may follow if work of breathing becomes unsustainable, requiring mechanical ventilation 5, 9
Neurological symptoms:
Critical Diagnostic Pitfalls
Mixed presentations are common:
- Type A and Type B can coexist, particularly in critically ill patients with malignancy and septic shock 2, 8
- Persistently elevated lactate despite adequate resuscitation should prompt evaluation for Type B causes 2, 8
Laboratory considerations:
- Lactate levels 2-5 mmol/L are elevated and require symptom correlation 5
- Proper sample handling essential: prechilled fluoride-oxalate tubes, immediate ice transport, processing within 4 hours, no tourniquet use 5
- Hypoalbuminemia may mask the anion gap 3
- Concomitant alkalosis may raise pH despite lactic acidosis 3