CARBON DIOXIDE

Large quantities of CO 2 produced in tissues must be efficiently transferred into blood and transported to the lungs where CO 2 is excreted. Transport of CO 2 dissolved in solution alone is not adequate to meet these requirements. Carbon dioxide is transported as three different, but interrelated, entities in blood. A small portion of total CO 2 content in blood exists as dissolved carbon dioxide. Although small in absolute quantity, dissolved CO 2 has a key role in exchange because it is the only form that rapidly crosses membranes separating blood from tissues and alveolar gas. The largest quantity of CO 2 exists in blood as bicarbonate ion. This ion is a product of the dissociation of carbonic acid, a compound formed when CO 2 combines with water. A modest amount of carbon dioxide is transported as carbamate, a compound formed by binding of CO 2 to amino groups of the hemoglobin molecule. Exchange of oxygen augments simultaneous CO 2 exchange through changes in the molecular configuration of hemoglobin. This structural change increases buffering of hydrogen ions and binding of CO 2 as carbamate. The time required for completion of these interrelated processes is critical because blood remains in the pulmonary capillaries for less than 1 s. Two processes overcome this limitation. The natural rate of conversion between CO 2 and carbonic acid is quite slow, but is catalyzed in vivo by carbonic anhydrase. In addition, a specialized transporter protein facilitates bicarbonate transfer across the erythrocyte membrane. Reactions of CO 2 play a major compensatory role in diseases that cause metabolic acidosis. Hydrogen ions combine with bicarbonate ions and are converted into CO 2, which is subsequently excreted in the lungs. This process reduces circulating hydrogen ions and is an important factor in defense of acid-base homeostasis. Although the rare congenital absence of isomers of carbonic anhydrase have been previously associated with abnormalities in the brain, bones, and kidneys, recent evidence raises the possibility that CO 2 excretion may also be impaired in these patients.