This rise has immediate and slow components as two different processes are involved. The immediate component is due to a resetting of the physicochemical equilibrium point (by law of mass action) and this raises the bicarbonate slightly.
Next is a slower component where a further rise in plasma bicarbonate due to enhanced renal retention of bicarbonate. The additional effect on plasma bicarbonate of the renal retention is what converts an "acute" respiratory acidsosis into a "chronic" respiratory acidosis.
As can be seen by inspection of the Henderson-Hasselbalch equation (below), an increased [HCO3-] will counteract the effect (on the pH) of an increased pCO2 because it returns the value of the [HCO3]/0.03 pCO2 ratio towards normal.
pH = pKa + log([HCO3]/0.03 pCO2)
By the law of mass action, the increased arterial pCO2 causes a shift to the right in the following chermical reaction:
CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
In the blood, this reaction occurs rapidly inside red blood cells because of the presence of carbonic anhydrase. The hydrogen ion produced is buffered by intracellular proteins and by phosphates. Consequently, in the red cell, the buffering is mostly by haemoglobin. This buffering, by removing hydrogen ions, pulls the above reaction to the right resulting in an increased bicarbonate production. The bicarbonate exchanges for chloride ion across the erythrocyte membrane and the plasma bicarbonate level rises. In an acute acidosis, there is insufficient time for the kidneys to respond to the increased arterial pCO2 so this is the only cause of the increased plasma bicarbonate in this early phase. The increase in bicarbonate only partially returns the extracellular pH towards normal.
Empirically, the [HCO3] rises by 1 mmol/l for every 10mmHg increase in pCO2 above its reference value of 40mmHg. For example, if arterial pCO2 has risen acutely from 40mmHg to 60mmHg (due to decreased alveolar ventilaton) then this acute rise of 2 tens (i.e. 60-40 = 20mmHg rise) results in a rise of plasma bicarbonate by 2 from its reference value of 24 mmol/l up to 26 mmol/l. Consequently, we would predict that if this acute respiratory acidosis was the only base disorder present, then plasma bicarbonate would be 26 mmol/l.
Though very important for carriage of carbon dioxide in the blood, the bicarbonate system is not itself responsible for any buffering of a respiratory acid-base disorder. This is because a buffer system cannot buffer itself. If HCO3 were to react with H+ produced from the dissociation of H2CO3 this would just produce H2CO3 again - reversing the reaction is not 'buffering'.
Ninety-nine percent of the buffering of an acute respiratory acidosis occurs intracellularly. Proteins (especially haemoglobin in red cells) and phosphates are the most important buffers involved. These take up the H+ produced from the dissociation of H2CO3. This intracellular buffering results in a further increase in intracellular [HCO3] because it pulls the CO2 hydration reaction to the right. The HCO3 that leaves the cell causes the rise in extracellular HCO3. The amount of buffering is limited by the concentration of protein as that is low relative to the amount of carbon dioxide requiring buffering.
In summary: Compensation for an acute respiratory acidosis is by intracellular buffering (mostly by proteins) and plasma bicarbonate rises slightly as it leaves the cell down its concentration gradient. The bicarbonate system does not contribute to this buffering.
If the respiratory acidosis persists then the plasma bicarbonate rises to an even higher level because of renal retention of bicarbonate.
Thus in a chronic respiratory acidosis there are TWO factors present which elevate the plasma bicarbonate:-
Studies have shown that an average 4 mmol/l increase in [HCO3-] occurs for every 10mmHg increase in pCO2 from the reference value of 40mmHg. For example, if arterial pCO2 has risen from 40mmHg to 60mmHg (due to decreased alveolar ventilaton) and remained elevated for several days, then this chronic rise of 2 "tens" (i.e. 60-40 = 20mmHg = 2 tens) results in a rise of plasma bicarbonate by 8 from its reference value of 24 mmol/l up to 32 mmol/l. Consequently, we would predict that if this chronic respiratory acidosis was the only acid base disorder present, then plasma bicarbonate would be 32 mmol/l.
The renal response in underway by 6 to 12 hours with a maximal effect reached by 3 to 4 days. This maximal effect is not sufficient to return plasma pH to normal, but because of the additional renal contribution, the pH is returned towards normal much more than occurs in an acute respiratory acidosis.
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 differing time courses of compensation and correction can cause some confusion when interpreting blood gas results. This is because correction of the hypoventilation can occur rapidly but the elevated bicarbonate level of chronic respiratory acidosis corrects much more slowly. Consider a couple of typical situations which sometimes cause confusion in interpretation:
Rapid correction of a chronic respiratory acidosis (by increased alveolar ventilation) means that the blood gases in an individual patient may appear to show 'full compensation' because of the slow renal readjustment in bicarbonate excretion. The stressful event of being in a hospital Emergency Room may result in sufficient hyperventilation and the snapshot provided by a single set of gases may reveal such a situation. This is not 'full compensation' but 'slow recovery' of an elevated bicarbonate level.
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'.)