Porth's Essentials of Pathophysiology, 4e

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Respiratory Function

U N I T 6

at which oxygen is released from hemoglobin is deter- mined largely by tissue uptake. During strenuous exer- cise, for example, the muscle cells may remove as much as 15 mL of oxygen per dL of blood from hemoglobin. Hemoglobin can be regarded as a buffer system that regulates the delivery of oxygen to the tissues. In order to function as a buffer system, the affinity of hemoglobin for oxygen must change with the metabolic needs of the tissues. This change is represented by a shift to the right or left in the dissociation curve (Fig. 21-17B). A shift to the right indicates that the affinity of hemoglobin for oxygen is decreased and the PO 2 that is available to the tissues at any given level of hemoglobin satura- tion is increased. It usually is caused by conditions that produce an increase in tissue metabolism, such as fever or acidosis, or by an increase in PCO 2 . High altitude and conditions such as pulmonary insufficiency, heart failure, and severe anemia also cause the oxygen dis- sociation curve to shift to the right. A shift to the left indicates that the affinity of hemoglobin for oxygen is increased and the PO 2 that is available to the tissues at any given level of hemoglobin saturation is decreased. It occurs in situations associated with a decrease in tis- sue metabolism, such as alkalosis, decreased body tem- perature, and decreased PCO 2 levels. The degree of shift can be determined by the P 50 , or the partial pressure of oxygen that is needed to achieve a 50% saturation of hemoglobin. Returning to Figure 22-17B, the dissocia- tion curve on the left has a P 50 of approximately 20 mm Hg; the normal curve, a P 50 of 26; and the curve on the right, a P 50 of 39 mm Hg. The oxygen content (measured in mL/dL) of blood represents the total amount of oxygen that is car- ried in the blood, including the dissolved oxygen and that carried by the hemoglobin. It is the oxygen con- tent rather than the PO 2 or hemoglobin saturation that determines the amount of oxygen that is carried in the blood and delivered to the tissues. Thus, an anemic per- son may have a normal PO 2 and hemoglobin satura- tion level but decreased oxygen content because of the decreased amount of hemoglobin that is available for binding of oxygen (Fig. 21-17C). Carbon DioxideTransport Carbon dioxide is transported in the blood in three forms: dissolved in plasma (10%), attached to hemo- globin (30%), and as bicarbonate (60%). Acid–base balance is influenced by the amount of dissolved car- bon dioxide and the bicarbonate level in the blood (see Chapter 8, Understanding Carbon Dioxide Transport). As carbon dioxide is formed during metabolism, it diffuses out of cells into the tissue spaces and then into the capillaries. The amount of dissolved carbon diox- ide that can be carried in plasma is determined by the partial pressure of the gas and its solubility coefficient (0.3 mL/dL blood/mm Hg PCO 2 ). Carbon dioxide is 20 times more soluble in plasma than oxygen. Thus, the dissolved state plays a greater role in transport of car- bon dioxide compared with oxygen.

Most of the carbon dioxide diffuses into the red blood cells, where it either forms carbonic acid or combines with hemoglobin. Carbonic acid (H 2 CO 3 ) is formed when carbon dioxide combines with water (CO 2 + H 2 O = H + + HCO 3 – ). The process is catalyzed by an enzyme called carbonic anhydrase , which is present in large quantities in red blood cells. Carbonic anhydrase increases the rate of the reaction between carbon dioxide and water approximately 5000-fold. Carbonic acid read- ily ionizes to form bicarbonate (HCO 3 – ) and hydrogen (H + ) ions. The hydrogen ions combine with hemoglobin, which is a powerful acid–base buffer, and the bicarbon- ate ion diffuses into plasma in exchange for a chloride (Cl – ) ion. This exchange is made possible by a special bicarbonate-chloride carrier protein in the red blood cell membrane. As a result of the bicarbonate-chloride shift, the chloride and water content of the red blood cell is greater in venous blood than in arterial blood. In addition to the carbonic anhydrase-mediated reac- tion with water, carbon dioxide reacts directly with hemoglobin to form carbaminohemoglobin. The com- bination of carbon dioxide with hemoglobin is a revers- ible reaction that involves a loose bond, which allows transport of carbon dioxide from tissues to the lungs, where it is released into the alveoli for exchange with the external environment. The release of oxygen from hemoglobin in the tissues enhances the binding of car- bon dioxide to hemoglobin; in the lungs, the combining of oxygen with hemoglobin displaces carbon dioxide. ■■ Although the lungs are responsible for the exchange of gases with the environment, it is the blood that transports oxygen from the lungs to the tissues and returns carbon dioxide to the lungs. Most of the oxygen (97% to 99%) in the blood is carried in chemical combination with hemoglobin in red blood cells, with the remaining 1% to 3% being carried in the plasma as a dissolved gas. ■■ The oxygen dissociation curve is S shaped with a plateau area, above which an increase in dissolved oxygen (PO 2 ) has minimal or no effect on hemoglobin saturation.This insures adequate hemoglobin saturation over a wide range of dissolved oxygen values. ■■ The oxygen content or amount of oxygen that is carried in the blood is equal to amount of oxygen that is carried bound to hemoglobin plus the dissolved form. Since each gram of hemoglobin carries approximately 1.34 mL oxygen, it is the hemoglobin content of the blood rather than the hemoglobin saturation that determines the amount of oxygen that the blood can carry. SUMMARY CONCEPTS