Rules 1 to 4 deal with respiratory acid-base disorders and provide a simple way to calculate the [HCO3-] that would be expected in a person who has a simple respiratory acid-base disorder. That is they predict the maximal amount of compensation that would occur.
Answer: By direct animal and human experimentation. For example, the pCO2 of the subjects was altered and the blood gases were measured. The data from these whole-body titrations allowed the normal physiological response and its time course to be quantified.
Answer: The rules allow calculation of the compensatory response that would be 'expected' if the primary respiratory or metabolic acid-base disorder were the only disorder present. That is, we predict the expected compensatory response so that we can separate what is expected (ie compensation) from the unexpected (ie a co-existent second disorder).
For example, consider a patient with a primary metabolic acidosis. Using rule 5, we calculate what we expect the arterial pCO2 will be in that person if this metabolic acidosis was the ONLY acid-base disorder present. We then compare this 'expected' pCO2 with the actual pCO2 (ie the measured value in the patient). If there is a significant difference between these two values, then this 'reveals' the presence of a second primary acid-base disorder (In this case, a discrepancy would reveal a co-existent respiratory acid-base disorder.)
Answer: Yes. Certain combinations of primary acid-base disorders cannot be revealed in this way.
In particular, if the patient has two types of primary metabolic acidosis, then this cannot be detected by this method (However, there are other ways to detect this as discussed elsewhere).
In general, the rules are useful for detecting a co-existent respiratory disorder in a patient with a metabolic disorder (or, conversely detecting a co-existent metabolic disorder in a patient with a respiratory disorder.)
A mixed acid-base disorder is present when two or more primary disorders are present simultaneously. Assessment of mixed disorders requires knowledge of the expected degree of compensation that is present with all of the simple acid-base disorders. This is the knowledge that is summmarised in the Interpretation Rules described in section 9.1. The history and examination are necessary to diagnose all acid-base disorders but are particularly useful in sorting out a mixed disorder.
A double disorder is present when any two primary acid-base disorders occur together, but not all combinations of disorders are possible.
You can however have a mixed acid base disorder with simultaneous metabolic acidosis and alkalosis. For example you could have a patient with gastric outlet obstruction who has been vomiting for several days to the extent they have become severely volume depleted with poor peripheral perfusion and pre-renal failure. Such a patient could have a severe metabolic alkalosis (from the loss of gastric acid from vomiting) and also a metabolic acidosis (eg lactic acidosis from poor perfusion & maybe an acidosis from the acute renal failure).
A triple disorder is present when a respiratory acid-base disorder occurs in association with a double metabolic disorder.