details the reader is referred to text books of biochemislry Carbonic anhydrase is powerfully

the RBC to form KHCO3. A small amounl of CO2 forms carbamino Hb compound with the Hb Another fraction of CO2 is dissolved withm the fluid of the RBC to form CO2 in physical solution within the RBC. Some further details will now be discussed: Bicarbonates Chloride shift From the tissues, when the CO2 enters the capillary, it first passes through plasma, but CO2 does not form H2CO3 in plasma (because carbonic anhydrase is absent in plasma). As the CO2 next enters the inside of the RBC, it forms the H2CO3 Within the RBC, there is an enzyme carbonic anhydrase. It calalyzes the reaction CO2 + H2O = = H2C03 without the carbonic anhydrase, theoretically, the H2O can combine with CO2 to form H2C03 but that reaclion is so slow and the amount of H2CO3 formed is so poor that it may be ignored. As the H2CO3 is formed within the RBC, it sphts into H+and HCO-3 ions. The H+are quickly taken up by the Hb, so Ihe reaction continuously moves from left to the right, and large quantities of HCO-3 are formed withm the RBC. This HCO-3 is permeable through the RBC membrane and moves out of the RBC to enter plasma according to the e quation of Gibbs-Donnan In the plasma, it replaces Clfrom NaCI and combines with Na+ to form NaHC03. So ultimately a good portion of Ihe C02 taken up, is converted into plasma NaHC03. The released chloride ions as mentioned above, move into the RBC from the plasma so that the Cl-concentration within RBC rises as the CO2 is laken up by the blood. This (= rise of Cl-ions in RBC) is, thus, due to the shift of the 07 ions from the plasma and discovered by Hamburger in 1918 and hence spoken of as Hamburger's chloride shift The entire sequence of events is diagramatically shown in figure 4.5.3. Some HCO-3 stay back within the RBC to form KHCO3 Recall that, inside any cell including the RBC, the concentration of Na+ is very poor but that of K+ is very high whereas in the plasma concentration of Na+ ion is high but that of K+ is very low. Further, Na+ cannot ordinarily enter into the RBC and K+ ions cannot leave the RBC. For all these reasons one finds KHCO3 withm the RBC and NaHCO3 withm the plasma. Fig. 4.5.3. CO2 exchange and Ihe associated reactions at the tissue; the chloride shift For these reactions to proceed smoolhly, therefore the enzyme carbonic anhydrase is essential. Further, as so many steps are involved, the total time taken to develop the whole reaction, compared with the formation of carbaminohemoglobin is somewhat greater.The chloride shift of Hamburger is reversed in the lungs. Because of the fact that oxy hemoglobin is less basic (or more acidic) than reduced Hb, the reduced Hb can catch more H+ ions. Therefore in the tissue levels, as HbO2 rapidly loses oygen, its ability to catch H+ also increases. As a result as H and HCO-3 ions are being formed from H2C03, the H+ ions are mopped up. Conversely, in the lung capillaries, the conversion of HHb (reduced) into HbO2 causes release of H+from the hemoglobin The released H+ joms with Ihe HCO-3 released from KHCO3 (the K+ ion of KHCQ3 goes lo join with Ihe Hb, see below) forming H2CO3 and this, because of carbonic anhydrase, splits into H20 and C02; as the CO2 is continuously going out into the alveoli (because of the pressure gradient) the reaction now moves from right to the left. Now the HCO-3 ions of NaHC03 from plasma enters the RBC, converted into H20 and CO2 and the C02 goes out. In exchange of HCO-3 the Clfrom the RBC goes out from the RBC to enter Ihe plasma and NaCI of plasma is now reconstituted. When the Hb was reduced, the K+ ions were engaged by both Cl- ions (i.e. , concentration of KCI in the RBC's became high) and also to some extent by the HCO-3. Recall (Table 4.5.2) that HCO-3 concentration in RBC of venous blood is higher than that of arterial blood. When HHb becomes Hb02, the K+ ions begin to combine with the Oxyhe-moglobin and Cl-ions are released from KCI. Carbonic anhydrase. This enzyme which contains Zn, are found in the RBC, gastric mucosa, renal tubules and pancreas. Its aclion is to speed up the reaction, h2O + COO2 H2CO3 Subsequently as shown in the previous paragraphs of this chapter, H2CO3 may break up into H+ and HCO3 ions but that splitting is not due to any enzyme action. Much of the chemislry of carbonic anhydrase of human origin is now known and for details the reader is referred to text books of biochemislry Carbonic anhydrase is powerfully depressed by the drug acetazolamide (Diamox) which is clinically used as a diuretic. Carbammo hemoglobin compound A part of CO2 can and does combine straighl with the Hb to form carbammohemoglobin compound. The ultimate reaclion is: CO2 HbNH2 The highlights of carbammohemoglobin compound are: 1. For its formation it requires no enzyme. 2. The rate of its formation is exlremely rapid. The formation of NaHC03 in the peripheral capillaries from CO2 or the breakdown of NaHC03 to produce, ultimately, the CO2 is time consuming requiring between 0.75 to 1 sec. The total stay of a single RBC in the lung capillary being nearly 1 sec. at rest, the time for the reaction may be reasonably sufficient bul during exercise, the transit time of an erythrocyle may be only 0.3 sec. (In the capillaries of the peripheral tissue, however, blood moves slowly). Because of the fact that carbammo hemoglobin compounds are formed or broken down very rapidly the