A patient has an elevated anion gap of 19 with a normal serum bicarbonate; what does this suggest and what should be the initial work‑up and management?

Elevated Anion Gap with Normal Bicarbonate: Diagnostic Approach

An elevated anion gap of 19 with normal serum bicarbonate most likely represents either a mixed acid-base disorder (high anion gap metabolic acidosis with concurrent metabolic alkalosis) or a laboratory artifact, and you should immediately obtain an arterial blood gas to determine the true acid-base status. 1

Understanding the Discordance

• This presentation is physiologically unusual because a true high anion gap metabolic acidosis should always be accompanied by a reduced serum bicarbonate—the anion gap rises because unmeasured anions accumulate and consume bicarbonate. 2

• The most common explanation is a mixed disorder: the patient has both a high anion gap acidosis (which lowers bicarbonate) and a concurrent metabolic alkalosis (which raises bicarbonate), resulting in a "normal" bicarbonate on the chemistry panel. 3

• Laboratory interference must be ruled out first: severe hypertriglyceridemia or paraproteinemia can cause pseudo-hypobicarbonatemia on enzymatic assays, creating a falsely elevated anion gap when the calculated bicarbonate from blood gas is actually normal. 4

Immediate Diagnostic Steps

First-Line Testing

• Obtain arterial blood gases immediately to measure the true pH and calculated bicarbonate—this will definitively distinguish between a real metabolic acidosis (pH <7.35, low HCO₃⁻) versus a laboratory artifact (normal pH, normal calculated HCO₃⁻). 1, 4

• Inspect the serum for lipemia: if the sample appears milky or turbulent, order a lipid panel to assess for severe hypertriglyceridemia (often >1,000 mg/dL), which can falsely lower measured bicarbonate on chemistry analyzers. 4

• Calculate the osmolar gap if toxic ingestion is a consideration, particularly methanol or ethylene glycol, which can present with elevated anion gaps before bicarbonate falls significantly in early poisoning. 1, 2

Expanded Laboratory Workup

• If ABG confirms true metabolic acidosis (low pH, low bicarbonate on blood gas despite "normal" chemistry bicarbonate), proceed with the standard high anion gap workup: 1

  • Plasma glucose and serum/urine ketones (diabetic ketoacidosis, including euglycemic DKA from SGLT2 inhibitors)
  • Serum lactate (lactic acidosis from sepsis, shock, tissue hypoxia)
  • Blood urea nitrogen and creatinine (uremic acidosis)
  • Toxicology screen and serum osmolality (toxic alcohols, salicylates)
  • Urinalysis for calcium oxalate crystals (ethylene glycol)

• If ABG shows normal pH and normal calculated bicarbonate, the elevated anion gap is spurious and requires investigation of the laboratory interference: 4

  • Serum triglycerides
  • Serum protein electrophoresis (paraproteinemia)
  • Repeat electrolytes on a non-lipemic sample if possible

Mixed Acid-Base Disorder Assessment

• When true metabolic acidosis coexists with metabolic alkalosis, look for clinical clues: 3
  • Vomiting or nasogastric suction (generates metabolic alkalosis)
  • Diuretic use (contraction alkalosis)
  • Concurrent ketoacidosis or lactic acidosis (generates high anion gap acidosis)
  • The "delta-delta" calculation (Δ anion gap / Δ bicarbonate) can help identify mixed disorders, though discrepancies must be interpreted cautiously as the 1:1 relationship is not always reliable. 3

Critical Thresholds for Urgent Intervention

• If anion gap >27 mmol/L (using Na⁺ + K⁺ − Cl⁻ − HCO₃⁻) with suspected ethylene glycol poisoning, immediately initiate hemodialysis regardless of bicarbonate level, as mortality exceeds 20% at this threshold. 1, 5

• If anion gap 23–27 mmol/L with suspected toxic alcohol ingestion, strongly consider hemodialysis and administer fomepizole to block toxic metabolite formation. 1

• If diabetic ketoacidosis is confirmed (glucose typically >250 mg/dL, though SGLT2 inhibitors can cause euglycemic DKA), begin aggressive isotonic saline resuscitation at 15–20 mL/kg/hour for the first hour, followed by insulin therapy. 1, 6

Common Pitfalls to Avoid

• Do not assume the anion gap is clinically significant without confirming true acidosis on ABG—a normal bicarbonate makes isolated high anion gap acidosis extremely unlikely. 4

• Do not overlook hypoalbuminemia, which lowers the baseline anion gap; a "normal" anion gap of 12 in a patient with albumin of 2.0 g/dL may actually represent a hidden high anion gap acidosis. 7

• Do not rely solely on chemistry panel bicarbonate in lipemic samples—enzymatic assays are notoriously unreliable in severe hypertriglyceridemia, and blood gas calculated bicarbonate is the gold standard. 4

• Remember that acute kidney injury or ketoacidosis can overestimate certain toxic metabolites (e.g., glycolate in ethylene glycol poisoning), potentially inflating the anion gap beyond what the toxin alone would cause. 1, 5