Mixed Acid Base Disorders

Mixed acid base disorders occur when there is more than one primary acid base disturbance present simultaneously. They are frequently seen in hospitalized patients, particularly in the critically ill.

When to suspect a mixed acid base disorder:

  1. The expected compensatory response does not occur
  2. Compensatory response occurs, but level of compensation is inadequate or too extreme
  3. Whenever the PCO2 and [HCO3-] becomes abnormal in the opposite direction. (i.e. one is elevated while the other is reduced). In simple acid base disorders, the direction of the compensatory response is always the same as the direction of the initial abnormal change.
  4. pH is normal but PCO2 or HCO3- is abnormal
  5. In anion gap metabolic acidosis, if the change in bicarbonate level is not proportional to the change of the anion gap. More specifically, if the delta ratio is greater than 2 or less than 1.
  6. In simple acid base disorders, the compensatory response should never return the pH to normal. If that happens, suspect a mixed disorder.

Mixed metabolic disorders

  1. Anion Gap and Normal Anion Gap Acidosis.
    This mixed acid base disorder is identified in patients with a delta ratio less than 1 which signifies that the reduction in bicarbonate is greater than it should be, relative to the change in the anion gap. Thus, implicating that there must be another process present requiring buffering by HCO3-, i.e a concurrent normal anion gap acidosis.
    • Lactic acidosis superimposed on severe diarrhea. (note: the delta ratio is not particularly helpful here since the diarrhea will be clinically obvious)
    • Progressive Renal Failure
    • DKA during treatment
    • Type IV RTA and DKA

  1. Anion Gap Acidosis and Metabolic Alkalosis
    This mixed acid base disorder is identified in patients with a delta ratio greater than 1, which signifies a reduction in bicarbonate less than it should be, relative to the change in the anion gap. This suggests the presence of another process functioning to increase the bicarbonate level without affecting the anion gap, i.e. metabolic alkalosis.

    • Lactic acidosis, uremia, or DKA in a patient who is actively vomiting   or who requires nasogastric suction.
    • Patient with lactic acidosis or DKA given sodium bicarbonate therapy.
  1. Normal Anion Gap Acidosis and Metabolic Alkalosis
    This diagnosis can be quite difficult, because the low HCO3- and low PCO2 both move back toward normal when metabolic alkalosis develops. Also, unlike elevated anion gap acidosis, the anion gap will not indicate the presence of the acidosis.
    • In patients who are vomiting and with diarrhea (note: all acid base parameters may fall within the normal range)

Mixed respiratory and respiratory–metabolic disorders
        Having a good knowledge of compensatory mechanisms and extent of compensation will aid in identifying these disorders. Remember; compensation for simple acid-base disturbances always drives the compensating parameter (ie, the PCO2, or [HCO3-]) in the same direction as the primary abnormal parameter (ie, the [HCO3-] or PCO2). Whenever the PCO2 and [HCO3] are abnormal in opposite directions, ie, one above normal while the other is reduced, a mixed respiratory and metabolic acid-base disorder exists. 

Rule of thumb:

The above examples both produce very extreme acidemia or alkalemia and are relatively easy to diagnose. However more often, the disorder is quite subtle. For example, in cases of metabolic acidosis, the HCO3- is low and PCO2 low. If the PCO2 is normal or not aqequately reduced, this may indicate a subtle coexisting respiratory acidosis.

Mixed acid base disorders usually produce arterial blood gas results that could potentially be explained by other mixed disorders. Oftentimes, the clinical picture will help to distinguish. It is important to distinguish mixed acid base disorders because work up and management will depend on accurate diagnosis.

  1. Chronic Respiratory Acidosis with superimposed Acute Respiratory Acidosis
    • Acute exacerbation of COPD secondary to acute pneumonia
    • COPD patient with worsening hypoventilation secondary to oxygen therapy or sedative administration
  1. Chronic Respiratory Acidosis and Anion Gap Metabolic Acidosis
    • COPD patient who develops shock and lactic acidosis
  1. Chronic Respiratory Acidosis and Metabolic Alkalosis
    • Pulmonary insufficiency and diuretic therapy
    • or COPD patient treated with steroids or ventilation (important to recognize as alkalemia will reduce acidemic stimulus to breathe)
  1. Respiratory Alkalosis and Metabolic Acidosis
    • Salicylate intoxication
    • Gram negative sepsis
    • Acute cardiopulmonary arrest
    • Severe pulmonary edema


Please note that it is impossible to have more than one respiratory disorder in the same mixed disorder(i.e. concurrent respiratory alkalosis and respiratory acidosis)