About 99% of this buffering occurs intracellularly. Proteins are the most important intravascular buffers for CO2 but their concentration is low relative to the amount of carbon dioxide requiring buffering.
Though very important for carriage of carbon dioxide in the blood, the bicarbonate system is not responsible for any buffering of a respiratory acid-base disorder. This is basically because a system cannot buffer itself. Consider: For the bicarbonate system to 'buffer' H+ produced from the dissociation of H2CO3 would just result in the production of an equal amount of CO2. The production of bicarbonate is instead the reaction that produces the H+ that requires buffering.
Intracellularly, proteins (including haemoglobin) and phosphates are the most important buffers involved. These take up the H+ produced from the dissociation of H2CO3. The amount of this extracellular buffering is assessed by the amount of acute rise in [H2CO3] that occurs because for every H+ produced there is one H2CO3 produced also. Most of the buffering occurs intracellularly and this cannot be assessed by this method.
This response to a chronic respiratory acidosis is slower and takes 3 or 4 days to reach its maximum.
The response occurs because increased arterial pCO2 increases intracellular pCO2 in proximal tubular cells and this causes increased H+ secretion from the PCT cells into the tubular lumen. This results in:
The increase in plasma [HCO3] results in an increase in amount of bicarbonate filtered in the kidney and this amount increases as plasma bicarbonate continues to increase. Eventually a new steady state is reached which is referred to as ‘maximal compensation’. This level of compensation rarely if ever returns the arterial pH 'fully' back to normal (ie ‘maximal’ compensation is always less then ‘full’ compensation). Renal excretion of NH4Cl returns to normal once the maximal state has been reached.
In summary, the compensation for hypercapnia is:
The situation may be complicated because of the differing time courses of compensation & correction. Consider a couple of typical situations which sometimes cause confusion in interpretation:
Correction of a chronic respiratory acidosis can occur more rapidly than correction of the renal compensation so it is possible that the blood gases in an individual patient may appear to show 'full compensation' if the alveolar ventilation has increased and before the kidneys have had time to adjust. The stimulation of being in the Emergency Room may result in such a situation and the snapshot provided by a single set of gases may reveal such a situation. (Remember this when the junior doctor alights upon such a set of results and says, "But I thought you said that compensation never 'fully' returns the pH to normal but this is what has happened here?")
If a patient with chronic respiratory acidosis is intubated and ventilated, the arterial pCO2 can be rapidly corrected (by adjusting the ventilator parameters). This can occur quite rapidly, but the elevated bicarbonate takes longer longer than this to fall. The situation can be more complicated because some such patients have additional factors which inhibit the ready excretion of the elevated bicarbonate, as occurs in 'post-hypercapnic metabolic alkalosis'.)