What are the possible causes of a high‑anion‑gap metabolic acidosis due to lactic acidosis with concomitant hyperglycaemia in an otherwise healthy 19‑year‑old?

Causes of Lactic Acidosis with Hyperglycemia in a Young Adult

In a 19-year-old with high anion gap metabolic acidosis from lactic acidosis plus hyperglycemia, diabetic ketoacidosis (DKA) is the most likely diagnosis, but you must also actively exclude toxic ingestions, medication-induced lactic acidosis (particularly metformin or NRTIs), and sepsis/tissue hypoperfusion. 1, 2, 3

Primary Diagnostic Considerations

Diabetic Ketoacidosis (Most Likely)

• DKA presents with plasma glucose >250 mg/dL, arterial pH <7.3, bicarbonate <15 mEq/L, and anion gap >10-12 mEq/L, with the magnitude of anion gap elevation correlating directly with severity 1, 2, 3
• The classical presentation includes polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, and Kussmaul respirations, though the entire symptomatic picture can evolve acutely in <24 hours 1
• Check serum and urine ketones immediately—positive ketones distinguish DKA from other causes of high anion gap acidosis 1, 2
• DKA can be the initial presentation of previously undiagnosed diabetes in young adults, with no prior warning symptoms 1

Lactic Acidosis (Primary or Concurrent)

• Measure blood lactate level immediately to quantify the contribution of lactic acidosis versus ketoacidosis 1
• Lactic acidosis from tissue hypoperfusion (sepsis, hypovolemia, hypoxia) is a leading cause of high anion gap acidosis and can coexist with or mimic DKA 3, 4
• Metformin use must be specifically sought in the history—metformin-associated lactic acidosis presents with severe acidosis and hyperglycemia in the setting of renal impairment or acute illness 1
• If the patient is on antiretroviral therapy, NRTI-induced lactic acidosis should be considered, particularly with stavudine or didanosine, presenting with nonspecific GI symptoms, abdominal distention, and elevated anion gap 1

Toxic Ingestions (Must Exclude)

• Obtain a comprehensive toxicology screen including salicylates, methanol, ethylene glycol, and acetaminophen levels 1, 3
• Calculate the osmolar gap using 2×[Na+] + (glucose/18)—an elevated osmolar gap suggests methanol or ethylene glycol poisoning 1, 3
• Ethylene glycol poisoning with anion gap >27 mEq/L indicates severe toxicity requiring immediate hemodialysis 2, 3
• Look for calcium oxalate crystals in urine (ethylene glycol) or characteristic breath odor (paraldehyde) 1
• Chronic therapeutic-dose acetaminophen can cause 5-oxoproline (pyroglutamic) acidosis, especially with malnutrition or chronic illness—this resolves with acetaminophen cessation and IV fluids 5, 6, 4

Essential Immediate Workup

Laboratory Evaluation

• Arterial blood gas, serum electrolytes (Na+, K+, Cl-, HCO3-), calculate anion gap: Na+ - (Cl- + HCO3-) 2, 3
• Serum and urine ketones (nitroprusside method), blood lactate level 1, 2, 3
• Plasma glucose, BUN, creatinine, effective serum osmolality 1, 3
• Toxicology screen (salicylates, methanol, ethylene glycol, acetaminophen) 1, 3
• Liver enzymes, lipase, amylase—NRTI-induced lactic acidosis may show elevated transaminases without marked enzyme elevation initially 1

Clinical Assessment

• Search for precipitating factors: infection (may be normothermic or hypothermic), medication history (metformin, NRTIs, chronic acetaminophen), recent illness, drug/alcohol ingestion 1
• Mental status ranges from alert to coma—profound alteration suggests severe acidosis or hyperosmolarity 1
• Physical exam: assess hydration status, respiratory pattern (Kussmaul), signs of infection, abdominal tenderness 1

Critical Pitfalls to Avoid

• Do not attribute high anion gap acidosis solely to lactic acidosis without actively excluding DKA and toxic ingestions, especially in a young patient with no clear sepsis 3
• Do not stop insulin once glucose normalizes in DKA—continue insulin at 0.05-0.1 U/kg/h with dextrose-containing fluids until bicarbonate ≥18 mEq/L and pH >7.3 to prevent rebound ketoacidosis 2, 3
• Hypothermia in the setting of suspected infection is a poor prognostic sign despite the presence of infection 1
• Monitor for treatment complications: hypoglycemia, hypokalemia, and hyperchloremic acidosis from excessive saline administration 2
• In NRTI-associated lactic acidosis, clinical prodromes include unexplained GI symptoms, dyspnea, weakness, and hepatomegaly—lactate testing requires immediate processing in prechilled fluoride-oxalate tubes on ice 1