Types of Lactic Acidosis
Lactic acidosis is classified into two major types based on pathophysiology: Type A results from tissue hypoxia and hypoperfusion, while Type B occurs without hypoxia due to metabolic disturbances, drug toxicity, or malignancy. 1, 2
Type A Lactic Acidosis (Hypoxic/Hypoperfusion)
Type A lactic acidosis occurs when tissues cannot receive adequate oxygen, forcing anaerobic metabolism and excessive lactate production. 3, 4
Common causes include:
- Circulatory shock states (septic, cardiogenic, hypovolemic) with inadequate tissue perfusion 5, 3
- Cardiac failure and myocardial infarction causing decreased oxygen delivery 5, 3
- Severe infections particularly in patients with underlying conditions like diabetes 3
- Respiratory failure with impaired oxygen transfer 4
- Hemoglobin disorders affecting oxygen-carrying capacity 4
Clinical presentation typically includes:
- Hypotension requiring vasopressor support 5
- Signs of end-organ hypoperfusion 2
- Lactate levels typically ≥4 mmol/L in septic shock 5
- Metabolic acidosis with pH <7.35 and elevated anion gap (>16) 1, 3
Type B Lactic Acidosis (Non-Hypoxic)
Type B lactic acidosis occurs without tissue hypoxia, resulting from metabolic disturbances, drug toxicity, or impaired lactate clearance. 1, 2, 6
Type B is further subdivided into:
Type B1: Associated with underlying diseases
- Malignancy-related (particularly B-cell lymphoma) due to the Warburg effect where cancer cells preferentially use anaerobic metabolism even with adequate oxygen 2, 7
- Liver disease impairing lactate clearance and gluconeogenesis 3, 4
- Renal failure reducing lactate removal capacity 4
- Thiamine deficiency causing pyruvate dehydrogenase dysfunction, particularly in malignancy or malnutrition 3, 8
Type B2: Drug and toxin-induced
Metformin-associated lactic acidosis characterized by lactate >5 mmol/L, anion gap acidosis, increased lactate:pyruvate ratio, and metformin levels >5 mcg/mL 9
Nucleoside reverse transcriptase inhibitors (NRTIs) particularly stavudine and didanosine, causing mitochondrial toxicity 1, 3
Beta-agonists (albuterol) can cause type B lactic acidosis through increased metabolic activity 6
Type B3: Inborn errors of metabolism
- Organic acidemias including methylmalonic acidemia, propionic acidemia, and maple syrup urine disease 1
- Disorders of energy metabolism and fatty acid oxidation defects 1
D-Lactic Acidosis (Special Subtype)
D-lactic acidosis occurs in patients with short bowel syndrome and preserved colon, where bacterial overgrowth produces D-lactate that standard laboratory assays may not detect. 3
Mixed Type A and Type B
Both types can coexist, particularly in critically ill patients with malignancy who develop septic shock or in patients with underlying metabolic disorders who experience hypoperfusion. 7 This makes management particularly challenging and requires addressing both tissue perfusion and the underlying metabolic disturbance. 7
Critical Diagnostic Thresholds
- Lactate 2-5 mmol/L: Elevated, warrants investigation for cause 5, 3
- Lactate >5 mmol/L: Abnormal, requires urgent evaluation 5, 3
- Lactate >10 mmol/L: Life-threatening, indicates severe tissue hypoperfusion regardless of cause 5
Common Pitfall
The most critical error is assuming all lactic acidosis is Type A (hypoxic). When aggressive resuscitation fails to correct lactic acidosis despite restored hemodynamics, clinicians must actively search for Type B causes including medications (metformin, NRTIs), malignancy, thiamine deficiency, or D-lactate production. 3, 2, 7, 8 Early symptoms of drug-induced lactic acidosis are often nonspecific (nausea, weakness, myalgias) and can be mistakenly attributed to the underlying disease rather than medication toxicity. 3, 9