What condition is characterized by an anion gap metabolic acidosis?

Conditions Characterized by Anion Gap Metabolic Acidosis

High anion gap metabolic acidosis (HAGMA) is characterized by several conditions including severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock, severe dehydration, extracorporeal circulation of blood, cardiac arrest, and severe primary lactic acidosis. 1

Understanding Anion Gap Metabolic Acidosis

Anion gap metabolic acidosis occurs when there is accumulation of acids in the body that are not measured by routine electrolyte panels. The anion gap is calculated using the formula:

Anion Gap = [Na⁺] - ([Cl⁻] + [HCO₃⁻]) 2

Normal anion gap is typically 8-12 mmol/L. An elevated anion gap (>12 mmol/L) indicates the presence of unmeasured anions in the blood.

Common Causes of High Anion Gap Metabolic Acidosis

The most frequent causes of HAGMA can be remembered using the mnemonic GOLD MARK 3:

• G: Glycols (ethylene and propylene)
• O: Oxoproline (5-oxoproline/pyroglutamic acidosis)
• L: L-lactate (lactic acidosis)
• D: D-lactate
• M: Methanol
• A: Aspirin (salicylates)
• R: Renal failure
• K: Ketoacidosis (diabetic, alcoholic, starvation)

Clinical Presentation and Diagnosis

Patients with HAGMA may present with:

• Hyperventilation (Kussmaul breathing)
• Altered mental status
• Nausea and vomiting
• Signs of the underlying condition

Diagnostic approach:

1. Calculate the anion gap using the formula above
2. Correct the anion gap for serum albumin level (for each 1 g/dL decrease in albumin, add 2.5 mmol/L to the calculated anion gap) 4
3. Determine the delta ratio (change in anion gap divided by change in bicarbonate) to identify if there is a pure HAGMA or mixed acid-base disorder 4
4. Identify the underlying cause through targeted laboratory testing

Management Principles

Management depends on the underlying cause but generally includes:

1. Treating the underlying condition:

   • Insulin therapy for diabetic ketoacidosis
   • Fluid resuscitation for shock or dehydration
   • Discontinuation of offending agents (e.g., salicylates, methanol)
   • Dialysis for severe renal failure

2. Sodium bicarbonate therapy:

   • Reserved for severe acidosis (pH < 7.2) or symptomatic cases 2
   • Initial dosing: 1-2 vials (44.6-100 mEq) IV in cardiac arrest 1
   • For less urgent metabolic acidosis: 2-5 mEq/kg over 4-8 hours 1
   • Avoid rapid correction to prevent paradoxical CNS acidosis, iatrogenic alkalosis, hypokalemia, and hypocalcemia 2

3. Monitoring:

   • Serial arterial blood gases
   • Electrolytes
   • Clinical status
   • Target bicarbonate level ≥22 mmol/L 2

Special Considerations

• In cases of toxic alcohol ingestion, both increased osmolal gap and high anion gap may be present, though this depends on the stage of metabolism 5
• Multiple causes of HAGMA can coexist, as seen in complex cases with combinations of ketones, lactate, renal failure, and 5-oxoproline 6
• Severe hyperphosphatemia can contribute to anion gap acidosis 7
• Consider extracorporeal therapy (ECTR) if anion gap >27 mmol/L or severe clinical features (coma, seizures, AKI) are present 2

Pitfalls to Avoid

• Failing to correct anion gap for albumin levels, which can mask a high anion gap in hypoalbuminemic patients
• Overlooking less common causes of HAGMA when common causes are ruled out
• Attempting full correction of low bicarbonate too rapidly (within 24 hours), which can lead to alkalosis 1
• Neglecting to monitor for complications of bicarbonate therapy, including volume overload, hypertension, hypokalemia, and hypocalcemia 2