It was believed that the peripheral chemoreceptors alone acted as the initial sensor responding to the rise in blood pH but further animal studies have indicated that metabolic acid-base disorders do cause a slow change in brain ISF [H+] and this change allegedly could be sufficient for account for the change in ventilation that occurs. This view is not accepted by all - see discussion in Section 2.3)
The hypoventilation causes a compensatory rise in arterial pCO2 but the magnitude of the response has generally been found to be quite variable. More recent studies have almost invariably shown that hypoventilation does reliably occur in metabolic alkalosis.
This has been attributed to various problems with some of the older studies which did not account for the presence of conflicting factors, particularly those causing hyperventilation:
This common association of metabolic alkalosis with factors causing hyperventilation probably accounts for most of the past findings of variability of the change in arterial pCO2. In effect, this is saying that many of these patients had a co-existent respiratory alkalosis.
It was also widely believed that the maximum value of arterial pCO2 due to compensatory hypoventilation was 55 to 60mmHg. There is no doubt that this is wrong.
Arterial pCO2 can rise higher than this and values up to 86mmHg have been reported in severe cases of metabolic alkalosis!
If hypoventilation is sufficient to cause hypoxaemia, this also may stimulate respiration via the peripheral chemoreceptors. As mentioned above, associated hypoxaemia is probably responsible for variability in the measured arterial pCO2 in patients who also have a sufficiently low arterial pO2. Patients who present with hypoxaemia and hypercapnia may be diagnosed with respiratory failure if the association with metabolic alkalosis is not appreciated. It is usually best in these patients to administer oxygen and to avoid intubation and ventilation.
A couple of cautions for severe cases:
The expected pCO2 due to appropriate hypoventilation in simple metabolic alkalosis can be estimated from the following formula:
Note the wide variation allowed (ie a 10 mmHg range) because of the conflicting factors that affect ventilation (discussed above). This formula is used to determine if a coexistent respiratory acid-base disorder is present. For example, if pCO2 is much lower than expected, a respiratory alkalosis is also present.