This disorder can be seen in two clinical settings:

Note that electrolyte and ABG values vary depending on the dominant acid–base disorder. The effect on pH by these acid–base disorders is to bring it to near normal (counterbalancing). One consistent abnormality is serum AG, which is elevated. If diarrhea is the cause for metabolic acidosis, the AG may not be that high .

The clinical setting is usually renal failure, ketoacidosis, or lactic acidosis with sepsis. Salicylate overdose or pulmonary embolism can produce both metabolic acidosis and respiratory alkalosis. The representative electrolyte and ABG are shown in the following table. The AG is elevated. The effect on pH is counterbalancing, so that the pH is brought to near normal, but the fall in pCO₂ is greater with both disorders. In salicylate overdose, the initial acid–base disorder is respiratory alkalosis due to direct central nervous system (CNS) stimulation followed by the development of metabolic acidosis. The presence of dominant disorder can be identified by calculation of appropriate secondary response. For example, if metabolic acidosis is the dominant acid–base disorder, the superimposed respiratory alkalosis can be diagnosed by a greater fall in pCO₂ than expected for a simple metabolic acidosis. If respiratory alkalosis is the dominant disturbance, a coexisting metabolic acidosis can be identified by a greater fall in serum [HCO₃ ⁻] than expected for a simple respiratory alkalosis .

The laboratory values shown in the following table indicate that metabolic acidosis is the dominant acid–base disturbance. The expected pCO₂ should be 26 ± 2 mmHg (1.5 × serum HCO₃ ⁻ + 8 ± 2 = 18 + 8 = 26 ± 2). Instead, the reported pCO₂ is 22 mmHg, indicating that the patient is more hypocapnic than expected. Thus, respiratory alkalosis is superimposed on metabolic acidosis .

This acid–base disorder occurs in the clinical setting of cardiac arrest, renal failure, or lactic acidosis with sedatives or narcotics, or COPD. The effect on pH is additive, as both acid–base disorders lower pH. The electrolyte pattern and ABG (see table below) suggest that the primary acid–base disorder is chronic respiratory acidosis and the coexisting disturbance is metabolic acidosis due to lactic acidosis. The AG is high. The AG may be normal, if the cause of metabolic acidosis is diarrhea or renal tubular defect.

The conditions that predispose to this mixed acid–base disorder are vomiting or diuretic therapy with metabolic alkalosis complicated by respiratory alkalosis due to pneumonia, or hepatic failure. Pregnant individuals usually have respiratory alkalosis because of progesterone and elevated diaphragm, however, when they develop profuse vomiting, a superimposed metabolic alkalosis develops.

When patients on mechanical ventilator develop respiratory alkalosis because of increased respiratory rate, they are predisposed to metabolic alkalosis, if nasogastric suction is applied. The effect on pH is additive. The following electrolyte and ABG pattern was observed in a patient with alkali ingestion and pneumonia: