Mixed acid-base disturbances

These are quite common and can be detected by non-parallel changes in HCO3 and the anion gap, chloride and pCO2. The following features give you an indication that a mixed acid-base disturbance is present:
  1. The pH is normal but there is an abnormal pCO2 and/or bicarbonate. (Remember that compensation rarely results in a normal pH.)
  2. Changes in pCO2 and bicarbonate occur in opposing directions. (Remember that with compensation, changes in pCO2 and bicarbonate parallel each other.)
  3. Change in pH is opposite to that predicted from the pCO2 and HCO3.
  4. Compensation exceeds upper or lower limits.
There are easy formulas used to determine if there is a mixed acid-base disturbance present. These formulas depend on whether there is an elevated anion gap or not. For all these formulas, the change in the parameter is compared to the midpoint of the reference range for the parameter (normal), i.e.
  • Change in AG = Measured AG - Normal AG
  • Change in bicarbonate = Measured bicarbonate - Normal bicarbonate
  • Change in chloride = corrected chloride concentration - Normal chloride
Remember that all of these are generalizations. There are exceptions to every rule.

High anion gap

In an uncomplicated high anion gap acidosis, the change in AG is equivalent to the change in bicarbonate. If the change in anion gap is greater or less (usually by 2:1) than the change in bicarbonate, a mixed acid-base disturbance is present.
  • If the decrease in bicarbonate is greater than the increase in anion gap, this indicates that there is a mixed disturbance, with something lowering the bicarbonate greater than expected. In this instance, this is compatible with a mixed high anion gap and hyperchloremic (normal anion gap) acidosis,e.g. renal failure, resolving diabetic ketoacidosis, diarrhea with a high anion gap acidosis (e.g. lactic acidosis).

  • If the decrease in bicarbonate is less than the increase in anion gap, this indicates that there is a mixed disturbance, with something preventing the bicarbonate from being as low as it should be. This is compatible with a mixed high anion gap acidosis and metabolic alkalosis, e.g. GDV (lactic acidosis with sequestration of chloride-rich fluid), renal failure with vomiting/diuretics, vomiting and diarrhea/diabetic ketoacidosis/lactic acidosis. In this case, the bicarbonate and chloride will be low and the anion gap will be high.
Normal anion gap acidosis or alkalosis

In an uncomplicated normal anion gap acidosis or a metabolic alkalosis, the change in chloride is equivalent to the change in bicarbonate. If the change in chloride is greater or less (usually by 2:1) than the change in bicarbonate, a mixed acid-base disturbance is present.
  • If the decrease in chloride is greater than the increase in bicarbonate, this indicates that there is a mixed disturbance, with something decreasing the bicarbonate. In this instance, this is compatible with a mixed normal anion gap acidosis and a metabolic alkalosis. This can occur renal failure with vomiting/diuretics, vomiting and diarrhea, and liver disease.

  • If the increase in chloride is less than the decrease in bicarbonate, this indicates that there is a mixed disturbance, with something enhancing the decrease in bicarbonate. This is compatible with a mixed high anion gap and normal anion gap acidosis.
Summary
  • High anion gap with change in anion gap > change in bicarbonate. This indicates:
    1) Mixed high anion gap metabolic acidosis and metabolic alkalosis. Most common causes include renal failure and vomiting, renal failure and diuretics, diabetic ketoacidosis and vomiting, lactic acidosis and vomiting.
    2) Non acidotic high anion gap with normal or increased bicarbonate. This occurs in a pure metabolic alkalosis, carbenicillin therapy and dehydration (increased albumin).
    3) Mixed high anion gap metabolic acidosis plus respiratory acidosis, e.g. cardiopulmonary arrest.

  • High anion gap with change in anion gap < change in bicarbonate. This indicates:
    1) Mixed high anion gap and normal anion gap acidosis.
    2) High anion gap acidosis masked by low anion gap (decreased albumin, paraproteins).
    3) Combined high anion gap acidosis and chronic respiratory alkalosis.

    Remember: There can be more than 2 mixed acid-base disturbances. There can be three primary acid-base disturbances, e.g. mixed high and normal anion gap acidosis and respiratory acidosis occurs with cardiopulmonary arrest.
Exceptions

The change in anion gap can be greater than the change in bicarbonate without there being a mixed acid-base abnormality in the following situations: Alkalemia, sodiium containing drugs, changes in albumin, changes in unmeasured cations. However the changes in anion gap induced by these conditions are usually mild.

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