Transport of Carbon Dioxide
The purpose of breathing is to supply oxygen to the tissues and get rid of the carbon dioxide (CO2) produced during metabolism, which can sometimes be at the rate of 200 mL/ min, thus stabilising the biochemical environment necessary to maintain the vital metabolic process.
Carbon dioxide occurs in three different forms in the body, i.e. (a) dissolved, (b) as bicarbonate and (c) as carbamate.
7.8.1 Transport as Dissolved Carbon Dioxide
Only 5% of total arterial content is present in dissolved CO2, and the contribution of dissolved CO2 to the total arteriovenous CO2 concentration difference is only 10%. During heavy exercise, the CO2 in the dissolved state can rise up to sevenfold that may contribute to one-third of the total CO2 exchange.
Though carbon dioxide is 20 times more soluble than oxygen because of its high solubility and diffusing capacity, carbon dioxide partial pressure of alveolar and pulmonary end-capillary blood is virtually the same. At the same time, arterial blood will contain about 2.5 mL of dissolved carbon dioxide per 100 mL and venous blood 3 mL per 100 mL.
7.8.2 TransportasBicarbonate
The majority of CO2 is transported as HCO3 The Henderson- Hasselbalch equation gives the ratio of HCO3 over dissolved CO2:
In humans, the plasma value of pKa is 6.10 at 37 °C, which varies with changes in temperature and ionic strength.
Carbon dioxide and water can easily enter the red blood cell by diffusion. They form carbonic acid, a reversible reaction favoured by carbonic anhydrase, dissociating into hydrogen and bicarbonate ions. The ratio of H2CO3 to HCO3- is 1: 20 at a physiological pH of 7.4.
However, during exercise, the lactic acid produced in addition to CO2 will reduce the blood pH, resulting in a drop in the ratio of H2CO3 to HCO3- from 1:20 to 1:13:
The bicarbonate ions formed in RBC diffuse out to the plasma, and chloride ions move in. This phenomenon is known as the chloride shift (or Hamburger effect). This is facilitated by an ion-exchange transporter protein in the cell membrane called capnophorin or Band 3 for Cl-HCO3 that allows chloride shift at a 1:1 ratio. As the process of carbonic acid production and further dissociation continues, there is a danger of building up hydrogen ions in the RBC, which can further prevent this process. But this does not happen since hydrogen ions bind to reduced haemoglobin formed by unloading oxygen at the tissue level. This reduced haemoglobin is less acidic than oxygenated haemoglobin and can accommodate hydrogen ions. Therefore, the degree of oxygenation determines the CO2-binding capacity of haemoglobin, a phenomenon known as the Christiansen- Douglas-Haldane effect (CDH effect) or simply the Haldane effect, named after the three physiologists who first demonstrated this phenomenon in 1914.
The chloride shift has a major impact on the volume of the red blood cells. The chloride shift increases the intercellular osmolarity of the cells which along with the hydrogen ion buffering increases the volume of the red blood cells by drawing in water. As a result, the mean corpuscular volume (MCV) rises. This process gets reversed as the blood passes through the lungs.
At the level of the lung, as O2 enters RBCs and binds to Hb, it promotes the release of Hb-bound CO2 and H+ that deoxy-Hb buffered. The H+ binds to HCO3- to form H2CO3,
which dissociates to form CO2 and water.
The CO2 is expired out by the lungs, thereby decreasing the CO2 and H+ concentrations, which increases the affinity of Hb for oxygen in the RBCs passing through pulmonary capillaries. Because CO2 and H+ effects are interrelated and additive, the combined change in Hb oxygen affinity has been called the classical Bohr effect. In contrast, the change in Hb oxygen affinity produced only by H+ is called the Bohr effect:
7.8.3 TransportasCarbamate
Carbon dioxide tends to bind rapidly to terminal uncharged amino groups (R-NH2), resulting in the formation of carb- amino compounds. The combination of CO2 with NH2 groups is called carbamate. When carbamate is formed from haemoglobin, it is called carbaminohaemoglobin. The carbamino form comprises a very small amount of the carbon dioxide transported by the blood, about one-third of the difference in the amount of carbon dioxide between the veins and arteries.
The amount of CO2 bound as carbamate to haemoglobin or plasma proteins depends on several factors such as the saturation of haemoglobin with O2, the
2,3-diphosphoglycerate (2,3-DPG) concentration of RBC and the concentration of H+ ions in red blood cells and plasma. Deoxygenation of haemoglobin facilitates the binding of the increased amount of CO2 to haemoglobin, while an increase in H+ ions or acidification decreases the carbamate formation by haemoglobin.
In general, carbaminohaemoglobin has a lower affinity for oxygen. In sheep and goats, a type of haemoglobin HbC exists prominently in newborns and anaemic and hypoxemic adults, which binds twice as much CO2 as HbA in goats. This produces a marked reduction in the binding affinity of oxygen to HbC in goats and sheep than that in normal adult Hbs.
The carbamino formation also produces H+, which further lowers Hb oxygen affinity.
7.8.4 Carbon Dioxide Dissociation Curve
The carbon dioxide dissociation curve depicts variations in the total CO2 carried by the blood with the changes in partial pressures of carbon dioxide. The curve shifts to the right when the Hb is oxygenated, which means that the blood begins to release carbon dioxide as the Hb becomes oxygenated. It is known as the Haldane effect.
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