Transport of oxygen and carbon dioxide

Hemoglobin and oxygen transport

Oxygen has a low solubility coefficient, so it does not readily dissolve in blood. Instead, over 98% of O₂ is bound to hemoglobin. The heme portion of hemoglo­bin contains four atoms of iron, each able to bind to one molecule of O₂.

Adult hemoglobin consists of two alpha and two beta chains. Fetal hemoglobin contains two alpha and two gamma chains. More than 400 different types of abnormal hemoglobin have been identified, but the most common associated with diseases in humans are the following:

• Hemoglobin S. This type of hemoglobin is present in sickle cell anemia.

• Hemoglobin C. This is another type of hemoglo­bin found in sickle cell anemia.

• Hemoglobin E. This type of hemoglobin is found in people of Southeast Asian descent.

• Hemoglobin D. This type of hemoglobin may be present with sickle cell anemia or thalassemia.

• Hemoglobin H (heavy hemoglobin). This type of hemoglobin may be present in certain types of thalassemia (Box 14.4).

Oxygen bound to hemoglobin forms oxyhemoglo­bin. Hemoglobin that has released O₂ is called reduced hemoglobin, or deoxyhemoglobin. Because it picks up a H⁺ ion after releasing O₂, reduced hemoglobin is abbreviated as HHb:

Box 14.4 Onion toxicity in cats and dogs

Allium species (meadow garlic, nodding onion, Pacific onion, and wild garlic) contain Organosulfur compounds that can be very toxic when consumed by cats or dogs. These compounds can cause oxidative hemolysis, which results in cell lysis of erythrocytes. Consuming as little as 5g∕kg or 15-30 g/kg of onions in cats and dogs, respectively, can cause this problem. Treatment includes induc­ing emesis in asymptomatic dogs and cats known to have ingested these products.

Fig. 14.9. Oxygen-Iiemoglobin dissociation curve. The saturation of hemoglobin is affected by changes in P_θ2. At the lungs, hemoglobin is 100% saturated. As the blood passes through tissue in which the P_θ2 is lower, hemoglobin is able to rapidly unload O₂

P_θ2 is the most important factor controlling how much O₂ is bound to hemoglobin. When reduced hemoglobin is converted to oxyhemoglobin, it is fully saturated. When only a portion of hemoglobin exists as oxyhemoglobin, it is partially saturated. This can be graphically represented as an oxygen-hemoglobin dissociation curve (Fig. 14.9). At the level of the lungs, hemoglobin becomes fully saturated. As blood passes through tissue where the Pq₂ drops to 40 mmHg, hemoglobin unloads its oxygen and is only 75% saturated.

The oxygen-hemoglobin dissociation curve has a steep slope between 10 and 50 mmHg P_θ2. When an animal is at rest, hemoglobin releases approximately only 25% of its oxygen. It maintains a reserve that is available when needed. If the animal begins vigorous exercise, hemoglobin is able to respond by releasing a greater amount of O₂.

Other factors affecting the oxygen- hemoglobin dissociation curve

Although the Pj₂ is the most important factor affecting hemoglobin's affinity for oxygen, other factors can also influence this association. These factors can shift the oxygen-hemoglobin curve to either side of normal (Fig. 14.10):

1. pH of the blood. Increasing the acidity of blood, that is, lowering the pH, lowers the affinity of hemoglobin for O₂. Therefore, as the metabolism of tissue increases, resulting in increased lactic and carbonic acid at the same P_θ2, hemoglobin releases

Po₂ (mmHg)

Fig. 14.10.

more O₂ at that site. Mechanistically, this occurs because the binding of H⁺ to hemoglobin causes a conformational change decreasing hemoglobin's O₂-Carrying capacity. This shift of the curve to the right is termed the Bohr effect. The reverse reac­tion can also occur in which binding of O₂ to hemoglobin causes the liberation of H⁺. Decreas­ing the acidity shifts the oxygen-hemoglobin dis­sociation curve to the left.

2. Temperature. An increase in temperature also shifts the oxygen-hemoglobin dissociation curve to the right. Like increased acidity, increased temperature is a by-product of increased metab­olism. Increased metabolism requires additional O₂, so shifting this curve to the right provides necessary O₂.

3. 2,3-Bisphosphoglycerate (BPG). An increase in the production of BPG, formerly called diphospho­glycerate, also shifts the curve to the right, thus liberating more O₂. Increased production of BPG is also associated with increased metabolism.

4. Pco-,- A decrease in pH acts similarly to an increase in Pqo-,- As shown next, CO₂ can react with water to form carbonic acid, which then dissociates to form bicarbonate and H⁺. Thus, increased P_co-, is associated with decreased pH.

Hemoglobin-nitric oxide

Nitric oxide (NO), a gas, plays an important role in vasomotor tone. It is a potent vasodilator. Produced in lung and endothelial cells, NO can be carried by hemoglobin. The binding of O₂ to hemoglobin causes a change in the conformation of hemoglobin allowing NO to bind to the cysteine of hemoglobin. This protects NO from being broken down by the Fe in hemoglobin. As oxyhemoglobin releases its O₂, it simultaneously releases NO.

Carbon dioxide transport

Carbon dioxide is a waste product of metabolism. It is transported in the blood to the lungs in three forms:

1. Dissolved CO₂. Accounting for the smallest amount of transported CO₂, 7-10% is carried dis­solved in the plasma.

2. Carbamino compounds. Approximately 20% of CO₂ is transported in the red blood cells attached to the amino acids of globin forming Carbamino- hemoglobin. Since CO₂ is bound to globin, and not the heme molecule, the CO₂ does not compete with O₂ or NO transport:

The formation of Carbaminohemoglobin is influ­enced by P_co, and the degree of oxygenation of hemoglobin. In the lungs, where Pqo-, in alveolar air is low, carbon dioxide dissociates from hemo­globin and is exhaled. At the tissue level, where Pco, is high, the formation of Carbaminohemoglo- bin is favored since deoxygenated hemoglobin readily combines with CO₂.

3. Bicarbonate ions. Most carbon dioxide, about 70%, is transported in the blood as bicarbonate ions (HCO₃ ) (Fig. 14.11). As tissues produce CO₂, it diffuses into the systemic capillaries where most of it enters the red blood cells and, in the presence of carbonic anhydrase, it combines with water to produce carbonic acid. Carbonic acid dissociates to bicarbonate and hydrogen ions. The hydrogen ions bind to hemoglobin, causing the Bohr effect and enhancing the release of O₂. HCOy diffuses from the red blood cells into the plasma and is transported to the lungs. As HCOy leaves the red blood cells, chloride ions (CL) enter, a process called the chloride shift.