Physiology 5th Ed.


Forms of CO2 in Blood

CO2 is carried in the blood in three forms: as dissolved CO2, as carbaminohemoglobin (CO2 bound to hemoglobin), and as bicarbonate (HCO3), which is a chemically modified form of CO2. By far, HCO3is quantitatively the most important of these forms.

Dissolved CO2

As with O2, a portion of the CO2 in blood is in the dissolved form. The concentration of CO2 in solution is given by Henry’s law, which states that the concentration of CO2 in blood is the partial pressure multiplied by the solubility of CO2. The solubility of CO2 is 0.07 mL CO2/100 mL blood/mm Hg; thus, the concentration of dissolved CO2 in arterial blood, as calculated by Henry’s law, is 2.8 mL CO2/100 mL blood (40 mm Hg × 0.07 mL CO2/100 mL blood/mm Hg), which is approximately 5% of the total CO2 content of blood. (Recall that because of the lower solubility of O2, compared with CO2, dissolved O2 is only 2% of the total O2 content of blood.)


CO2 binds to terminal amino groups on proteins (e.g., hemoglobin and plasma proteins such as albumin). When CO2 is bound to hemoglobin, it is called carbaminohemoglobin, which accounts for about 3% of the total CO2.

CO2 binds to hemoglobin at a different site than O2 binds to hemoglobin. As discussed previously, CO2 binding to hemoglobin reduces its affinity for O2 and causes a right-shift of the O2-hemoglobin dissociation curve (Bohr effect). In turn, O2 bound to hemoglobin changes its affinity for CO2, such that when less O2 is bound, the affinity of hemoglobin for CO2 increases (the Haldane effect). These mutual effects of O2 and CO2 on each other’s binding to hemoglobin makes sense—in the tissues, as CO2 is produced and binds to hemoglobin, hemoglobin’s affinity for O2 is decreased and it releases O2 to the tissues more readily; in turn, release of O2 from hemoglobin increases its affinity for the CO2 that is being produced in the tissues.


Almost all of the CO2 carried in blood is in a chemically modified form, HCO3, which accounts for more than 90% of the total CO2. The reactions that produce HCO3 from CO2 involve the combination of CO2 and H2O to form the weak acid H2CO3. This reaction is catalyzed by the enzyme carbonic anhydrase, which is present in most cells. In turn, H2CO3 dissociates into H+ and HCO3. Both reactions are reversible, and carbonic anhydrase catalyzes both the hydration of CO2 and the dehydration of H2CO3. Thus,


In the tissues, CO2 generated from aerobic metabolism is added to systemic capillary blood, converted to HCO3 by the reactions described previously, and transported to the lungs. In the lungs, HCO3 is reconverted to CO2 and expired. Figure 5-25 shows the steps that occur in systemic capillaries. The circled numbers shown in the figure correspond to the following steps:


Figure 5–25 Transport of carbon dioxide (CO2) in the blood. CO2 and H2O are converted to H+ and HCO3 inside red blood cells. H+ is buffered by hemoglobin (Hb-H) inside the red blood cells. HCO3 exchanges for Cl and is transported in plasma. The circled numbers correspond to the numbered steps discussed in the text.

1.          In the tissues, CO2 is produced from aerobic metabolism. CO2 then diffuses across the cell membranes and across the capillary wall, into the red blood cells. The transport of CO2 across each of these membranes occurs by simple diffusion, driven by the partial pressure gradient for CO2.

2.          Carbonic anhydrase is found in high concentration in red blood cells. It catalyzes the hydration of CO2 to form H2CO3. In red blood cells, the reactions are driven to the right by mass action because CO2 is being supplied from the tissue.

3.          In the red blood cells, H2CO3 dissociates into H+ and HCO3. The H+ remains in the red blood cells, where it will be buffered by deoxyhemoglobin, and the HCO3 is transported into the plasma in exchange for Cl (chloride).

4.          If the H+ produced from these reactions remained free in solution, it would acidify the red blood cells and the venous blood. Therefore, H+ must be buffered so that the pH of the red blood cells (and the blood) remains within the physiologic range. The H+ is buffered in the red blood cells by deoxyhemoglobin and is carried in the venous blood in this form. Interestingly, deoxyhemoglobin is a better buffer for H+ than oxyhemoglobin: By the time blood reaches the venous end of the capillaries, hemoglobin is conveniently in its deoxygenated form (i.e., it has released its O2 to the tissues).

  There is a useful reciprocal relationship between the buffering of H+ by deoxyhemoglobin and the Bohr effect. The Bohr effect states that an increased H+ concentration causes a right shift of the O2-hemoglobin dissociation curve, which causes hemoglobin to unload O2 more readily in the tissues; thus, the H+ generated from tissue CO2 causes hemoglobin to release O2 more readily to the tissues. In turn, deoxygenation of hemoglobin makes it a better buffer for H+.

5.          The HCO3 produced from these reactions is exchanged for Cl across the red blood cell membrane (to maintain charge balance), and the HCO3 is carried to the lungs in the plasma of venous blood.Cl-HCO3exchange, or the Cl shift, is accomplished by an anion exchange protein called band three protein (so called because of its prominence in an electrophoretic profile of blood).

All of the reactions previously described occur in reverse in the lungs (not shown in Fig. 5-25). H+ is released from its buffering sites on deoxyhemoglobin, HCO3 enters the red blood cells in exchange for Cl, H+ and HCO3combine to form H2CO3, and H2CO3 dissociates into CO2 and H2O. The regenerated CO2 and H2O are expired by the lungs.