In this article we will discuss about the mechanism of formation of CO2 with the help of suitable diagrams.
We have seen that hydration of CO2 occurs in the blood and the mechanism can be represented as CO2 + H2O ↔ H++ HCO3. Further the H+ is buffered by reduced Hb within the RBC and by plasma buffers outside the RBC. The reaction can be represented H+ + HCO–3+ HbO2↔ HHb + HCO–3+ O2 (liberated in the tissues). HHb represents H ion buffered by reduced Hb).
The negatively charged HCO3– left over in the reaction is neutralised by available bases in the blood. The most abundant available base in plasma being Na+ the HCO–3 in the plasma combines with Na+ to form NaHCO3. The most abundant base within the RBC being K+, KHCO3 is formed in that location. The reaction H2O + CO2 ↔ H+ + HCO–3 is accelerated tremendously due to presence of a specific enzyme carbonic anhydrase within the RBC.
Concentration of HCO–3 within the RBC, therefore, becomes very high within a short time and attains a level much higher than that in the plasma. Now since the red cell membrane is impermeable to positively charged ions some HCO–3 from within the RBC migrates into plasma and some Cl– from the plasma migrates within the RBC in exchange of HCO–3. This is ailed ‘chloride shift’ phenomenon (Fig. 8.26) and was discovered by Cumburger in 1927. Thus the concentration of HCO–3 in plasma becomes higher due to migration of this ion from within the RBC according to the law of Donan’s equilibrium.
(i) CO2 Transport in the Tissues:
Tension of CO2 in the tissue fluid is 46 mm Hg (at rest) and that in arterial end of the capillary is 40 mm Hg. CO2 therefore, diffuses from the tissue space to the capillary due to tension gradient.
It may be recalled that the coefficient of diffusion of CO2 is very high and in spite of the rather low tension gradient rapid and complete diffusion of CO2 occurs till tension equilibrium is established.
The H+ ion and HCO3 ion formed are disposed of as follows:
When equilibrium is established the plasma changes may be summarised:
i. Some free molecular CO2 in solution—which is responsible for CO2 tension.
ii. Some CO2 in solution in H2O as H2CO.
iii. Some CO2 buffered as NaHCO3.
iv. Some CO2 as carbaminoprotein.
Since formation of H2CO3 is accompanied by formation of almost equivalent quantities of NaHCO3 the ratio H2CO3/NaHCO3 is but little disturbed and the pH of the blood remains almost unaffected.
(ii) CO2 Transport in the RBC:
CO2 diffuses rapidly and the reaction CO2 + H2O ↔ H2CO3 ↔ H++ HCO–3 takes place 13,000 times quicker than in plasma because of the presence of the specific enzyme carbonic anhydrase.
Carriage of CO2 as Carbamino Compound:
CO2 combines directly with free amino group of the globin and forms carbamino compounds which may be represented as follows:
i. Independent of carbonic anhydrase and therefore the reaction is not inhibited by cynides.
ii. CO2 is not initially changed to H2CO3
iii. At a very rapid rate in the tissues where haemoglobin is desaturated. Carbamino compounds are also formed by direct union of CO2 with plasma proteins but since the concentration of haemoglobin within the RBC is high, a larger fraction of carbamino compounds are carried within the RBC than in the plasma.
Further an increase in PCO2 does not increase the formation of carbamino compounds since increased PCO2 means increased H+ concentration which leads to formation HbNH3+. This does not react with CO2 directly.
Oxygenation of haemoglobin inhibits carbamino compound formation because Oxy-haemoglobin by virtue of its greater acidity H+ which blocks carbamino compound formation. Reduced Hb, on the other hand, favours formation of carbino compound.
In the tissues Oxy-Hb is also being converted simultaneously to reduced Hb which is a weaker acid in comparison with the former and has got a weaker hold on the base (K) available within the RBC. If Oxy-Hb is represented symbolically by HbO2 its ‘salt’ with K (potassium) may be symbolised as KHbO2. With the ingress of CO2 and reduction Oxy-Hb the following changes occur.
The KHbO3, of course, ionises to K+ + HCO3–. Large quantities of carbamino-haemoglobin are also formed which ionises liberating H+ which are neutralised by imidazole group of histadine and β-amino group of valine of the globin polypeptide chains.
As already explained the HCO3– from within the RBC is exchanged for CI– of the plasma according to the law of Donan’s equilibrium (chloride shift). The chloride shift mechanism prevents accumulation of large amount of HCO3– within the RBC and thus prevents shifting of its pH to the alkaline side.
(iii) CO2 Transport in the Lungs (Fig. 8.27):
CO2 diffuses from plasma (PO2 = 46 mm Hg) to the alveolar air (PO2 = 40 mm Hg) and so the H2CO3 breaks down liberating further amount of CO2. Simultaneously oxy-haemoglobin is formed which being a stronger acid snatches off K within the RBC from its combination with acid ions and form KHbO2. Reversed chloride shift occurs and the HCO–3 ion enters the RBC and is broken down liberating further amount of CO2 which passes from RBC to plasma and then to the lungs.
Oxygenation of haemoglobin also breaks down carbamino compound liberating further quantity of CO2. The mechanism of gas transfer between the lungs → blood → tissues → venous blood and back to the lungs has been summarised in the diagram (Fig. 8.28).