What are the causes of a high anion‑gap metabolic acidosis with hypertension in a stable 19‑year‑old male?

High Anion Gap Metabolic Acidosis with Hypertension in a Stable 19-Year-Old Male

In a stable 19-year-old male presenting with high anion gap metabolic acidosis and hypertension, the most likely causes are toxic ingestions (particularly methanol, ethylene glycol, or salicylates), diabetic ketoacidosis, or acute severe ethanol intoxication—with toxic alcohols being the primary concern given the unusual combination of hypertension in this age group.

Immediate Diagnostic Workup

Order the following tests immediately to identify the cause:

• Arterial blood gas to determine pH and PaCO₂, confirming metabolic acidosis (pH <7.35, bicarbonate <22 mmol/L) 1
• Calculate the anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), with normal being 8-12 mEq/L and high anion gap >12 mEq/L 1
• Serum osmolal gap calculation to detect low molecular weight toxins like methanol and ethylene glycol 1
• Blood lactate measurement to diagnose lactic acidosis 1
• Plasma glucose and serum/urine ketones to evaluate for diabetic ketoacidosis (glucose >250 mg/dL, pH <7.3, bicarbonate <15 mEq/L, positive ketones) 1, 2
• Serum salicylate levels if salicylate poisoning is suspected 1
• Complete metabolic panel including BUN, creatinine, and electrolytes to assess for renal failure 1, 2
• Toxicology screen to identify specific toxic alcohols or other ingestions 3

Differential Diagnosis Algorithm

Primary Causes to Consider in This Clinical Context:

1. Toxic Alcohol Ingestions (Most Concerning Given Hypertension)

• Methanol poisoning produces both an anion gap and osmolar gap due to being a low-molecular weight organic compound 1
• Ethylene glycol poisoning causes anion gap acidosis through its metabolite glycolate; an anion gap >27 mmol/L strongly indicates need for extracorporeal treatment 1
• Salicylate poisoning characteristically produces high anion-gap metabolic acidosis and can cause hypertension; consider extracorporeal removal if pH ≤7.20 1
• An osmolal gap >20 mOsm/kg typically indicates toxic alcohol ingestion 4, 3

2. Severe Acute Ethanol Intoxication

• Acute isolated ethanol intoxication can rarely cause marked increase in osmolal gap (>90 mOsm/kg) with high anion gap metabolic acidosis 3
• Calculate osmolal concentration of ethanol: serum ethanol level (mg/dL) divided by 3.7 3

3. Diabetic Ketoacidosis

• Results from insulin deficiency with elevated counterregulatory hormones 1
• Diagnostic criteria: blood glucose >250 mg/dL, arterial pH <7.3, bicarbonate <15 mEq/L, positive ketones 1, 2
• Less likely to present with hypertension unless severely volume depleted

4. Lactic Acidosis

• Results from tissue hypoxia due to decreased oxygen delivery or impaired oxygen utilization 1
• Can occur from shock states, severe hypoxemia, carbon monoxide poisoning, or mitochondrial dysfunction 1
• Blood lactate measurement is essential for diagnosis 1

5. Renal Failure

• Leads to accumulation of organic acids and impaired acid excretion 1
• Typically presents with elevated BUN, creatinine, and hyperkalemia 1
• Less likely in a previously healthy 19-year-old unless acute kidney injury

6. Rare Causes

• 5-oxoproline (pyroglutamic acid) acidosis can occur with chronic acetaminophen use and malnutrition 5, 6
• Laboratory analysis of organic acids can help identify inborn errors of metabolism 1

Critical Management Decisions

If Toxic Alcohol Ingestion is Suspected:

• Initiate extracorporeal treatment (hemodialysis) immediately if anion gap >27 mmol/L or consider if 23-27 mmol/L 1
• Do not delay treatment waiting for confirmatory levels if clinical suspicion is high 1
• Monitor serum salicylate levels during treatment if salicylate poisoning 1

If Diabetic Ketoacidosis is Confirmed:

• Fluid resuscitation with isotonic saline at 15-20 mL/kg/h during the first hour 1, 2
• Continuous IV regular insulin at 0.1 units/kg/h after confirming serum potassium >3.3 mEq/L 1, 2
• Bicarbonate therapy is NOT indicated unless pH falls below 6.9-7.0 1, 2
• Monitor venous pH and anion gap every 2-4 hours 1, 2

If Lactic Acidosis is Identified:

• Focus on restoring tissue perfusion with fluid resuscitation and vasopressors if needed 1
• Sodium bicarbonate should not be used to treat metabolic acidosis from tissue hypoperfusion 1

Key Clinical Pitfalls to Avoid

• Do not rely solely on osmolal gap to rule out toxic alcohol ingestion—the gap may be normal if metabolism is complete or if baseline gap was elevated 1, 4
• The anion gap may overestimate glycolate concentration in ethylene glycol poisoning when acute kidney injury or ketoacidosis is present 1
• Hypoalbuminemia can underestimate the true anion gap and toxicity 1
• Do not administer bicarbonate empirically in high anion gap metabolic acidosis—treat the underlying cause first 1, 2
• Monitor serum potassium frequently during treatment, as correction of acidosis drives potassium intracellularly and can cause life-threatening hypokalemia 1, 2

Hypertension-Specific Considerations

The presence of hypertension in a 19-year-old with high anion gap metabolic acidosis is unusual and should raise particular concern for:

• Salicylate toxicity, which can cause both metabolic acidosis and hypertension 1
• Sympathomimetic co-ingestion with toxic alcohols
• Severe volume depletion causing compensatory vasoconstriction in diabetic ketoacidosis