Gas Transport in the Blood



Gas Transport in the Blood



Key Points


Oxygen transport


1. A small amount of oxygen is transported in solution in plasma, but most is in combination with hemoglobin.


2. A molecule of hemoglobin can reversibly combine with four molecules of oxygen.


3. The binding of oxygen and hemoglobin is determined by oxygen tension.


4. The oxyhemoglobin dissociation curve can be displayed with percent saturation of hemoglobin as a function of oxygen tension.


5. The affinity of hemoglobin for oxygen varies with blood temperature, pH, carbon dioxide tension, and the intracellular concentration of certain organic phosphates.


6. As hemoglobin is depleted of oxygen, its color changes from bright red to bluish red.


7. Carbon monoxide has 200 times the affinity of oxygen for hemoglobin.


8. Methemoglobinemia occurs in certain toxic states, notably nitrite poisoning.


Carbon dioxide transport


1. Carbon dioxide is transported in the blood both in solution in plasma and in chemical combination.


Gas transport during exercise


1. Oxygen demands of exercise are met by increases in blood flow, in hemoglobin levels, and in oxygen extraction from blood.



Oxygen Transport


A Small Amount of Oxygen Is Transported in Solution in Plasma, but Most Is in Combination with Hemoglobin


Oxygen is poorly soluble in water and therefore in plasma. Because of this low solubility, most animals need an oxygen-carrying pigment to transport sufficient oxygen to the tissues. The only animals that can exist without hemoglobin live deep in the ocean in the cold parts of the world. The depth at which they live results in a high ambient pressure and thus a high oxygen tension (PO2). In addition, the cold environment results in a low metabolic rate and therefore little need for oxygen. The high PO2 and low oxygen demand enable them to exist without an oxygen-carrying pigment. All land-dwelling animals seen by veterinarians have such a pigment, and in mammals and birds, that pigment is hemoglobin.


When blood in the pulmonary capillaries flows past the alveoli, oxygen diffuses from the alveoli into the blood until the partial pressures (tensions) equilibrate: that is, there is no further driving pressure difference. Because oxygen is poorly soluble in water, only a very small amount dissolves in the plasma, and hemoglobin is necessary for delivery of sufficient oxygen to the tissues. Without hemoglobin, which transports the majority of the oxygen, the cardiac output would have to be inordinately high to maintain the oxygen supply to the body organs.


Even though the amount of oxygen dissolved in plasma is small, it increases directly as the partial pressure of oxygen increases; 0.003 mL of oxygen dissolves in each 100 mL (1 dL) of plasma at an oxygen tension (PO2) of 1 mm Hg (Figure 48-1). The pulmonary capillary blood equilibrates with the alveolar oxygen tension (PAO2) of 100 mm Hg; therefore, 0.3 mL of oxygen dissolves in each deciliter of blood. If an animal breathes pure oxygen its PAO2 increases to at least 600 mm Hg and 1.8 mL of oxygen (600 × 0.003) dissolves in each deciliter of plasma.


image
FIGURE 48-1 Amount of oxygen (in ml/dl) dissolved in plasma as a function of oxygen tension (PO2).


A Molecule of Hemoglobin Can Reversibly Combine with Four Molecules of Oxygen


Mammalian hemoglobin consists of four units, each containing one heme and its associated protein (globin). Globin is a polypeptide composed of 140 to 150 amino acids. Heme is a protoporphyrin consisting of four pyrroles with a ferrous iron at the center. Each ferrous iron can combine reversibly with a single molecule of oxygen. The complete hemoglobin molecule has four hemes each with its associated globin and thus can combine reversibly with up to four molecules of oxygen (Figure 48-2). The type and sequence of amino acids that compose globin are critical to oxygen binding. Without the presence of globin, oxygen would irreversibly oxidize the ferrous iron to ferric iron. The amino acids in globin cradle the heme and limit access of oxygen to the ferrous iron. This prevents oxidation and allows uptake and release of oxygen in response to local PO2. The type and sequence of amino acids that compose globin define the different types of mammalian hemoglobin. Adult hemoglobin contains two alpha (α) and two beta (β) amino acid chains; fetal hemoglobin contains two α and two gamma (γ) chains. Closely related species, such as humans and anthropoid apes, have similar amino acid sequences on the side chains, whereas more divergent species have more differences in amino acid sequences.


image
FIGURE 48-2 Structure of the hemoglobin molecule showing the two pairs of polypeptide chains. Within each chain is a heme, four in all. The ferrous iron in the center of each heme provides the binding site for molecular oxygen. (From Mader SS: Inquiry into life, ed 8, New York, 1997, McGraw-Hill.)

Each hemoglobin molecule can reversibly bind up to four molecules of oxygen, one with each heme. The reversible combination of oxygen with hemoglobin is shown in the oxyhemoglobin dissociation curve (Figure 48-3). The binding of oxygen is a four-step process, and the oxygen affinity of a particular heme is influenced by the oxygenation of the others. This means that when the first heme unit is oxygenated, oxygen affinity of the second heme unit is increased, and so on. These heme-heme interactions are responsible for the sigmoid shape of the oxyhemoglobin dissociation curve.


image
FIGURE 48-3 Oxyhemoglobin dissociation curve of normal (hemoglobin [Hb] = 15 g/dL), anemic (Hb = 10 g/dL), and polycythemic (Hb = 20 g/dL) blood. The amount of oxygen combined with hemoglobin (i.e., the oxygen content) is plotted as a function of oxygen tension (Po2). A, Arterial; V, venous.


The Binding of Oxygen and Hemoglobin Is Determined by Oxygen Tension


Figure 48-3 shows that the oxygen content of blood—that is, the amount of oxygen combined with hemoglobin—is determined by PO2. At a PO2 of more than approximately 70 mm Hg, the oxyhemoglobin dissociation curve is virtually flat, which indicates that further increases in PO2 add little oxygen to hemoglobin. At this point, the hemoglobin is saturated with oxygen because each iron atom is associated with an oxygen molecule. The fact that hemoglobin becomes virtually saturated with oxygen at a PO2 of more than 70 mm Hg has important clinical consequences. Many animals live at altitudes considerably above sea level, where the lower barometric pressure results in a low PIO2 (inspired oxygen tension). Although these animals have a lower PaO2 (arterial oxygen tension) than their sea-level–dwelling counterparts, they are still able to transport sufficient oxygen to their tissues because their hemoglobin is well saturated with oxygen. Clearly, at extreme altitudes, hemoglobin begins to desaturate.


One gram of saturated hemoglobin can hold 1.36 to 1.39 mL of oxygen; therefore, average mammalian blood with 10 to 15 g of hemoglobin per deciliter has an oxygen capacity of 13.6 to 21 mL of oxygen per deciliter (volume percentage [vol%]) when hemoglobin is saturated with oxygen. The oxygen capacity of the blood is the maximal amount of oxygen that can be carried in the blood at any given time. Anemia, a reduction in the number of circulating erythrocytes (red blood cells) with a consequent reduction in the amount of hemoglobin in the blood, decreases oxygen capacity. When the hemoglobin content of blood increases, oxygen capacity increases as well. The latter occurs during exercise; contraction of the spleen forces more erythrocytes into the circulation. More erythrocytes than normal in the blood is known as polycythemia, and these red blood cells increase the oxygen capacity of the blood.


When the PO2 is less than 60 mm Hg, the oxyhemoglobin dissociation curve has a steep slope. This is in the range of tissue Po2 at which oxygen is unloaded from the blood. Tissue PO2 varies in accordance with the blood flow/metabolism ratio, but average tissue PO2 is 40 mm Hg. Blood exposed to such a PO2 loses 25% of its oxygen to the tissues. In rapidly metabolizing tissues in which tissue PO2 is lower, more oxygen is unloaded from the blood. The oxygen remaining in combination with hemoglobin forms a reserve that can be tapped in emergencies.


Oxygen content is a term that describes the amount of oxygen in the blood, most bound to hemoglobin. When hemoglobin is saturated with oxygen, oxygen content and oxygen capacity are equal. When oxygen leaves the blood in the tissues, oxygen content decreases, but the oxygen capacity remains the same.



The Oxyhemoglobin Dissociation Curve Can Be Displayed with Percent Saturation of Hemoglobin as a Function of Oxygen Tension


Percent saturation of hemoglobin is the ratio of oxygen content to oxygen capacity. Hemoglobin is more than 95% saturated with oxygen when it leaves the lungs of an animal at sea level. Percent saturation of mixed venous blood averages 75%; venous oxygen tension (image) averages 40 mm Hg. Although all mammals have similarly shaped oxyhemoglobin dissociation curves, the position of the curve with regard to PO2 varies (Figure 48-4). This can be described by measurement of P50, the partial pressure at which hemoglobin is 50% saturated with oxygen. A higher P50 is generally found in small mammals and allows unloading of oxygen at a high PO2 to satisfy their higher metabolic demands.


image
FIGURE 48-4 Oxyhemoglobin dissociation curve of three species of mammal. Percent saturation of hemoglobin is plotted as a function of oxygen tension (Po2). Although the curves have similar shapes in all mammals, they are not superimposed. The differences between the curves can be expressed by the partial pressure (tension) at which hemoglobin is 50% saturated with oxygen (P50). P50 for each species is indicated as E (elephant), H (horse), and R (rabbit).


The Affinity of Hemoglobin for Oxygen Varies with Blood Temperature, pH, Carbon Dioxide Tension, and the Intracellular Concentration of Certain Organic Phosphates


An increase in tissue metabolism produces heat, which elevates blood temperature and shifts the oxyhemoglobin dissociation curve to the right (increases P50). Such a shift facilitates dissociation of oxygen from hemoglobin and releases oxygen to the tissues; hemoglobin is then said to have “less affinity” for oxygen. Conversely, excessive cooling of the blood, as occurs in hypothermia, shifts the dissociation curve to the left. Because of this increased affinity of hemoglobin for oxygen, tissue PO2 must be lower than usual to release oxygen from hemoglobin.


Changes in carbon dioxide tension (PCO2) and pH also affect the affinity of hemoglobin for oxygen. The shift in the oxyhemoglobin dissociation curve resulting from a change in PCO2 is called the Bohr shift. This shift results in part from the combination of carbon dioxide with hemoglobin, but mostly from the production of hydrogen ions, which decrease the pH. A change in pH alters the oxygen binding by changing the structure of hemoglobin. As a result, a higher, more alkaline pH shifts the oxyhemoglobin dissociation curve to the left, and a lower, more acidic pH shifts the curve to the right (Figure 48-5). The Bohr effect is not constant among species; a given change in pH produces a greater shift in the dissociation curve for small mammals than for large mammals, supposedly ensuring the delivery of oxygen during high rates of metabolic activity, when carbon dioxide production is greatest.


image
FIGURE 48-5 Effect of pH on the oxyhemoglobin dissociation curve. A decrease in pH shifts the dissociation curve to the right and therefore assists in unloading oxygen at the tissues. The shift in the dissociation curve has much less effect on the percent saturation of hemoglobin when oxygen is being loaded into the blood in the lungs (i.e., Po2 = 100 mm Hg) than when oxygen is being unloaded in the tissues (i.e., Po2 = 40 mm Hg).

A solution of mammalian hemoglobin generally has a higher affinity for oxygen than does whole blood until organic phosphates, such as 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP), are added to the solution. In erythrocytes, DPG has a molar content equivalent to that of hemoglobin, much higher than in other cells. This DPG regulates the combination of oxygen with hemoglobin. When concentrations of DPG are high, as occurs under the anaerobic conditions imposed by altitude or anemia, the oxyhemoglobin dissociation curve is shifted to the right (P50 increases), and the unloading of oxygen is facilitated. In contrast, a reduction in DPG levels, as can occur in stored blood, shifts the dissociation curve to the left. Not all forms of hemoglobin bind DPG equally. Ruminant hemoglobin in general is unresponsive to DPG; elephant hemoglobin binds DPG weakly; and some forms of fetal hemoglobin do not bind DPG.

< div class='tao-gold-member'>

You may also need

Tags:
Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Gas Transport in the Blood

Full access? Get Clinical Tree
Get Clinical Tree app for offline access