What causes high anion gap (electrolyte imbalance) and metabolic alkalosis (elevated blood pH)?

Causes of High Anion Gap with Metabolic Alkalosis

The combination of high anion gap and metabolic alkalosis is most commonly caused by vomiting in a patient with an underlying high anion gap acidosis, or from surreptitious ingestion of alkali substances like baking soda in patients with certain underlying conditions. 1

Pathophysiological Mechanisms

The simultaneous presence of these two seemingly contradictory acid-base disturbances occurs through specific mechanisms:

1. Primary high anion gap acidosis with secondary metabolic alkalosis:

   • A patient develops a high anion gap acidosis (from conditions like diabetic ketoacidosis, lactic acidosis, toxic ingestion, or uremia) 2, 3
   • Concurrent vomiting or nasogastric suction leads to loss of gastric acid, generating a metabolic alkalosis
   • The mixed disorder results when the alkalosis partially or completely offsets the acidosis

2. Alkali ingestion in specific contexts:

   • Surreptitious ingestion of baking soda (sodium bicarbonate) or other alkali substances 1
   • This is particularly relevant in patients with alcoholism, eating disorders, or psychiatric conditions
   • The excessive alkali causes metabolic alkalosis while underlying conditions may contribute to anion gap elevation

Common Clinical Scenarios

• Diabetic ketoacidosis with vomiting:

  • DKA generates ketoacids (acetoacetate, β-hydroxybutyrate) causing high anion gap acidosis 2
  • Vomiting (common in DKA) causes loss of hydrochloric acid, generating metabolic alkalosis
  • The arterial pH may be near normal despite severe ketosis due to these opposing forces

• Alcoholic ketoacidosis with vomiting:

  • Alcohol metabolism produces ketoacids causing high anion gap
  • Persistent vomiting from gastritis or withdrawal generates metabolic alkalosis

• Lactic acidosis with volume depletion:

  • Conditions causing lactic acidosis (shock, sepsis, tissue hypoxia) create high anion gap 3
  • Associated volume depletion activates renin-angiotensin-aldosterone system
  • Increased aldosterone promotes H+ secretion, contributing to metabolic alkalosis

• Toxic ingestions with vomiting:

  • Ingestion of methanol, ethylene glycol, or salicylates causes high anion gap acidosis 3, 4
  • Vomiting (either from toxicity or induced for treatment) creates metabolic alkalosis

• Chronic alkali abuse:

  • Seen in patients with eating disorders or psychiatric conditions
  • Chronic ingestion of sodium bicarbonate (baking soda) or calcium carbonate (antacids) 1
  • May be associated with milk-alkali syndrome

Diagnostic Approach

1. Laboratory evaluation:

   • Arterial blood gas analysis (may show normal or elevated pH despite acidosis)
   • Serum electrolytes with calculated anion gap
   • Serum ketones, lactate, glucose, renal function tests 2
   • Toxicology screen if indicated
   • Urine pH and urine anion gap (helpful in cases of surreptitious vomiting or alkali ingestion) 1

2. Clinical clues to investigate:

   • History of diabetes, alcohol use, or renal disease
   • Evidence of volume depletion
   • Signs of vomiting (may be denied in eating disorders)
   • Access to medications or substances that could cause either condition
   • Psychiatric history suggesting potential for surreptitious behaviors 1

Management Considerations

• Treat the underlying high anion gap acidosis:

  • For DKA: IV insulin infusion, electrolyte replacement, glucose monitoring 2
  • For lactic acidosis: Improve tissue perfusion and oxygenation 2
  • For toxic ingestions: Specific antidotes (fomepizole for toxic alcohols), consider dialysis 2, 4

• Address the metabolic alkalosis:

  • Volume repletion with isotonic fluids
  • Potassium replacement (alkalosis often associated with hypokalemia)
  • Discontinuation of alkali ingestion if present

• Monitor for complications:

  • Hypokalemia (worsened by both conditions and insulin treatment)
  • Hypocalcemia (can occur with severe alkalosis)
  • Respiratory compensation changes

Clinical Pitfalls

• Misdiagnosis risk: The opposing acid-base disorders may partially neutralize each other, resulting in a near-normal pH that masks the severity of the underlying conditions
• Missed diagnosis: Failure to recognize surreptitious behaviors like self-induced vomiting or alkali ingestion can lead to persistent unexplained metabolic alkalosis 1
• Treatment complications: Aggressive bicarbonate therapy for presumed acidosis can dangerously worsen an unrecognized concurrent alkalosis
• Laboratory interpretation: The anion gap may be falsely elevated by severe alkalosis due to the effect on albumin charge

Remember that the combination of high anion gap and metabolic alkalosis represents a mixed acid-base disorder that requires careful clinical assessment to identify all contributing factors.