Most Common Cause of Lactic Acidosis in Younger Adults
In younger adults, the most common cause of lactic acidosis is tissue hypoxia from circulatory disorders, particularly sepsis and shock, which account for the majority of Type A lactic acidosis cases. 1
Primary Causes by Mechanism
Type A Lactic Acidosis (Tissue Hypoxia) - Most Common Overall
Circulatory disorders represent the dominant cause in younger adults:
- Sepsis and severe infections are the leading etiology, especially in patients with underlying conditions like diabetes mellitus 1
- Shock states (cardiogenic, hypovolemic, distributive) cause inadequate tissue perfusion and trigger anaerobic metabolism 1
- Cardiac failure with hypoperfusion leads to oxygen delivery-demand mismatch 1
These conditions force tissues to regenerate ATP without oxygen, producing lactate at rates that overwhelm clearance mechanisms by orders of magnitude 2
Type B Lactic Acidosis (Without Tissue Hypoxia) - Important Secondary Causes
While less common than Type A in younger adults, several Type B causes merit consideration:
Medication-induced lactic acidosis:
- Metformin is the most clinically significant drug cause, with an incidence of 2-9 per 100,000 patients/year, though this risk increases dramatically with renal impairment 1, 3
- Nucleoside reverse transcriptase inhibitors (NRTIs), particularly stavudine and didanosine in HIV treatment, cause mitochondrial toxicity with an incidence of approximately 1.3 cases per 1,000 person-years of NRTI exposure 4, 1
Other Type B causes:
- Liver disease impairs lactate clearance since the liver is the major site of lactate removal through gluconeogenesis 1
- Malignancies can cause lactate overproduction 2
- Thiamine deficiency affects pyruvate dehydrogenase function 1
Critical Diagnostic Considerations
Laboratory criteria for lactic acidosis:
- Arterial pH <7.3 with blood lactate >2 mmol/L (elevated), >5 mmol/L (abnormal), and >10 mmol/L (life-threatening) 1
- Increased anion gap >16 (calculated as Na - [Cl+CO2]) 1
Clinical presentation varies but commonly includes:
- Gastrointestinal symptoms (nausea, vomiting, abdominal pain) 4, 1
- Respiratory symptoms (tachypnea, dyspnea, Kussmaul respirations) 1, 5
- Neurological symptoms (weakness, confusion, altered consciousness) 1, 5
Age-Specific Context for Younger Adults
Why sepsis/shock predominates in younger adults:
Younger patients typically lack the chronic comorbidities (advanced renal disease, decompensated cirrhosis, severe heart failure) that predispose to Type B lactic acidosis 3. When lactic acidosis occurs in this population, it most commonly results from acute, severe illness causing tissue hypoxia rather than chronic metabolic derangements or medication accumulation.
Metformin-associated lactic acidosis is less common in younger adults because the primary risk factors—renal impairment (eGFR <45 mL/min/1.73 m²), advanced age (≥65 years), and hepatic dysfunction—are more prevalent in older populations 3. The FDA notes that elderly patients have greater likelihood of hepatic, renal, or cardiac impairment 3.
HIV-related NRTI toxicity represents an important consideration in younger adults with HIV infection, particularly those on older antiretroviral regimens, though incidence has decreased as newer agents have replaced stavudine and didanosine 1.
Common Clinical Pitfalls
Do not ignore subtle early symptoms such as nonspecific gastrointestinal complaints, dyspnea, or generalized weakness—these often precede severe acidosis and should prompt lactate measurement 1
Proper lactate measurement technique is essential: Use prechilled fluoride-oxalate tubes, transport immediately on ice, process within 4 hours, and collect without tourniquet or fist-clenching 4, 1
Persistent hyperlactatemia (≥2 mmol/L) without hypotension still indicates tissue hypoperfusion and requires aggressive evaluation for sepsis or occult shock, as it meets criteria for severe sepsis 1
In younger adults presenting with lactic acidosis, immediately assess for: