Harvey's Garden

Mixed acid-base disorder

4 min read

Pathophysiology/Etiology

Mixed disorders arise from the coexistence of any combination of the four primary disturbances: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. They are often seen in patients with multiple underlying health problems.

  • Metabolic Acidosis + Respiratory Acidosis: Often seen in critical illness such as cardiac arrest (lactic acidosis from hypoperfusion and respiratory arrest) or severe pneumonia/COPD with sepsis.
  • Metabolic Acidosis + Respiratory Alkalosis: A classic example is salicylate toxicity, which directly stimulates the respiratory center (causing respiratory alkalosis) and later causes a high anion gap metabolic acidosis. Sepsis is another common cause.
  • Metabolic Alkalosis + Respiratory Acidosis: Commonly occurs in a patient with COPD (chronic respiratory acidosis) who develops vomiting or is on diuretic therapy (metabolic alkalosis).
  • Metabolic Alkalosis + Respiratory Alkalosis: Can be seen in a patient with liver cirrhosis and ascites on diuretics who is also hyperventilating.
  • High Anion Gap Metabolic Acidosis + Normal Anion Gap Metabolic Acidosis: Can occur in a patient with diabetic ketoacidosis (high anion gap) who also has severe diarrhea (normal anion gap acidosis).
  • Triple Disorder: A combination of respiratory acidosis or alkalosis with two co-existing metabolic disorders (e.g., high anion gap metabolic acidosis and metabolic alkalosis). An example is a patient with septic shock (lactic acidosis) and vomiting (metabolic alkalosis) who is also hypoventilating (respiratory acidosis).

Diagnosis

A stepwise approach involving the patient’s history, physical exam, and laboratory data is essential.

  1. Analyze the Arterial Blood Gas (ABG) & Basic Metabolic Panel (BMP)

    • pH: Determines if there is acidemia (<7.35) or alkalemia (>7.45). A normal pH in the setting of abnormal PCO2 and HCO3⁻ strongly suggests a mixed disorder.
    • PCO2: Indicates the respiratory component. A high PCO2 suggests respiratory acidosis; a low PCO2 suggests respiratory alkalosis.
    • HCO3⁻: Reflects the metabolic component. A low HCO3⁻ suggests metabolic acidosis; a high HCO3⁻ suggests metabolic alkalosis.

  2. Determine the Primary Disorder

    • Look at the pH. If acidemic, the primary process must be an acidosis (either respiratory or metabolic). If alkalemic, the primary process is an alkalosis. Match the pH with the PCO2 or HCO3⁻ that explains the derangement.

  3. Check for Appropriate Compensation

    • A key to identifying a mixed disorder is to determine if the compensatory response is appropriate. If the compensation is either more or less than expected, a second primary disorder is present.
    • Winter’s Formula for Metabolic Acidosis: Expected PaCO2 = (1.5 x [HCO3-]) + 8 ± 2. If the actual PaCO2 is significantly different, there is a concurrent respiratory disorder.
    • For other primary disorders, there are established rules for expected compensation in both acute and chronic settings.

  4. Calculate the Anion Gap (AG)

    • AG = Na⁺ - (Cl⁻ + HCO3⁻). The normal range is typically 8-12 mEq/L.
    • An elevated AG indicates the presence of a metabolic acidosis, even if the pH and bicarbonate are normal.

  5. Calculate the Delta Gap (Δ-Gap) / Delta Ratio

    • This is used when a high anion gap metabolic acidosis is present to check for an underlying second metabolic disorder.
    • Delta Gap = (Measured AG - Normal AG) - (Normal HCO3⁻ - Measured HCO3⁻)
    • An alternative is the Delta Ratio: (Measured AG - Normal AG) / (Normal HCO3⁻ - Measured HCO3⁻).
      • A ratio of 1-2 suggests a pure high anion gap metabolic acidosis.
      • A ratio < 1 suggests a concurrent normal anion gap metabolic acidosis.
      • A ratio > 2 suggests a concurrent metabolic alkalosis.

Management/Treatment

Treatment should be directed at the underlying causes of each primary disorder. It is crucial to address each component of the mixed disturbance.

  • Fluid resuscitation to improve tissue perfusion in cases of lactic acidosis.
  • Insulin and fluids for diabetic ketoacidosis.
  • Mechanical ventilation to correct respiratory acidosis or alkalosis.
  • Bronchodilators for COPD exacerbations.
  • Antiemetics to stop vomiting causing metabolic alkalosis.
  • Careful therapeutic intervention is required, as correcting one disorder can sometimes worsen the effects of another.

Key Associations/Buzzwords

  • Normal pH with abnormal PCO2 and HCO3⁻: Classic sign of a mixed disorder where an acidosis and alkalosis are counterbalancing each other.
  • Salicylate toxicity: Mixed respiratory alkalosis and high anion gap metabolic acidosis.
  • COPD patient who is vomiting: Mixed respiratory acidosis and metabolic alkalosis.
  • “Triple Disorder”: Presence of a respiratory disorder plus a high anion gap metabolic acidosis and a metabolic alkalosis.

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