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Chapter: Biology of Disease: Disorders of Acid Base Balance

The Production and Transport of Carbon Dioxide

Body tissues produce about 20 moles of CO2 per day during oxidative metabolism. The CO2 diffuses from the cells into the extracellular fluid (ECF), that is the blood and tissue fluid, and eventually enters the plasma in quantities with the potential to form enough carbonic acid to disturb its pH.

THE PRODUCTION AND TRANSPORT OF CARBON DIOXIDE

Body tissues produce about 20 moles of CO2 per day during oxidative metabolism. The CO2 diffuses from the cells into the extracellular fluid (ECF), that is the blood and tissue fluid, and eventually enters the plasma in quantities with the potential to form enough carbonic acid to disturb its pH. However, in normal circumstances this does not occur because the CO2 is transported to the lungs and excreted. During transport, a substantial proportion of the CO2 enters the erythrocytes by diffusion. Within the erythrocytes, a small proportion of the CO2 remains dissolved or combines with proteins, mainly hemoglobin, to form carbamino compounds:


The major portion, however, combines with water to produce carbonic acid in a reaction catalyzed by carbonic anhydrase (Figure 9.2):


Carbonic acid dissociates to H+ and hydrogen carbonate (HCO3, ‘bicarbonate’)



Figure 9.3 shows how H+are removed from solution when they react withoxyhemoglobin (HbO8) and promote the release of its oxygen to the tissues and forms protonated hemoglobin (‘H+Hb’). The HCO3 formed diffuses down its electrochemical gradient out of the erythrocytes to the plasma in exchange for Cl, thus maintaining the electrochemical equilibrium of the erythrocyte. The exchange of HCO3 for Cl is normally called the chloride shift. Since both ions are charged, neither would pass freely across biological membranes, however, an anion exchanger protein facilitates their transport. This exchanger is a membrane protein that forms a pore through the membrane allowing the cotransport of the ions across the membrane. Given that the ions move in opposite directions, the anion exchanger or cotransporter is said to be an antiporter. The concentration of HCO3 in the plasma is normally kept between 21–28 mmol dm–3.




In the lungs, the partial pressure of oxygen is high while that of carbon dioxide is low. Thus oxygen enters the erythrocytes forming oxyhemoglobin, releasing the bound H+ and promoting the reverse of the events that occur in other body tissues (Figure 9.3). Thus, H+ associates with HCO3 to produce carbonic acid which then breaks down to carbon dioxide and water. The water enters the large body pool of water while the CO2 leaves the erythrocytes and is excreted on exhalation.

These events provide an interesting confirmation that enzymes catalyze reactions in either direction depending upon the position of equilibrium. Thus carbonic anhydrase promotes the formation of carbonic acid in most body tissues where the concentration of CO2 is relatively high. However, in the lungs, where the concentration of CO2 is reduced, the enzyme catalyzes the formation of CO2 and H2O from carbonic acid.



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