Gas Exchange and Transport

Hemoglobin

Most oxygen is transported on hemoglobin molecules in the erythrocytes (red blood cells); carbon dioxide is carried through the blood in three ways: dissolved in plasma, converted to carbonic acid, or bound to protein, particularly hemoglobin.

Oxygen can be carried in the blood in one of two ways. First, it can bind to hemoglobin, a protein found in the red blood cells responsible for carrying 98.5 percent of all oxygen in the blood. The remaining 1.5 percent of the oxygen is dissolved in the plasma. Plasma makes up 55 percent of total blood volume and is 91 percent water, seven percent blood proteins (i.e., albumin, globulin), and two percent nutrients (i.e., glucose, lipids). The percentage of dissolved oxygen is low due to oxygen’s low solubility in water, which makes up most of the plasma. Hemoglobin is made of four polypeptide chains (chains made up of amino acids linked together) bound to an iron-containing heme group. There are four heme groups, each of which contains an iron atom capable of binding one oxygen molecule, per hemoglobin molecule. The iron atom binds to the oxygen, so each hemoglobin molecule can combine with four oxygen molecules. This reaction happens very quickly and is also reversible. The molecule formed when oxygen binds with a hemoglobin molecule is called oxyhemoglobin, written as HbO2. Hemoglobin that is no longer attached to an oxygen molecule is called deoxyhemoglobin, written as HHb.

The first thing that happens is that the oxygen binds to the iron, which causes the hemoglobin molecule to change shape. This new shape allows it to easily take up two more oxygen molecules. Having three molecules attached to it encourages the binding of the fourth oxygen molecule. Conversely, when releasing the oxygen molecules, the release of one causes the release of the next and so on, like a cascade. Factors such as temperature, pH, and partial pressure of carbon dioxide, all play a role in determining the rate of uptake and release of the oxygen molecules. As pH increases and as temperature and partial pressure of carbon dioxide decrease, there is an increased affinity for oxygen to bind to hemoglobin. Conversely, as pH decreases and temperature and partial pressure of carbon dioxide increase, there is decreased affinity for oxygen to bind to hemoglobin.

The removal of carbon dioxide from the cells is accomplished in one of three ways. First, carbon dioxide can travel in the form of bicarbonate ions in the plasma. This makes up about 70 percent of all the carbon dioxide that is moved in the blood. The entrance of the carbon dioxide molecules into the plasma causes them to change into a weak acid called carbonic acid after combining with water for transport inside the red blood cells. The carbonic acid (H2CO3) will break down into hydrogen ions (H+) and bicarbonate ions (HCO3-) through the actions of an enzyme called carbonic anhydrase. Once created, bicarbonate ions move from the red blood cells into the plasma, where the ions are carried to the lungs for expulsion as carbon dioxide. Second, carbon dioxide can be carried through the bloodstream by dissolving in the blood plasma. Carbon dioxide dissolves much better than oxygen in the plasma, so it is easier for it to be transported this way than oxygen. Still, only small amounts of carbon dioxide are transported this way. Third, carbon dioxide may be found attached to hemoglobin. This binding happens very quickly and does not require the use of enzymes. The binding of the carbon dioxide does not create competition with the binding of oxygen. This is because carbon dioxide connects directly to the amino acids in the hemoglobin protein, while oxygen attaches to the heme group. The attachment and release of carbon dioxide is directly related to the partial pressure of the gas and how much oxygen is present on the hemoglobin.

Exchange of Gases in the Alveoli

Oxygen and carbon dioxide are carried in the blood using the protein hemoglobin. Oxygen binds to the heme groups of the hemoglobin, while carbon dioxide binds to the amino acids.

Oxyhemoglobin-Dissociation Curve

The oxyhemoglobin-dissociation curve describes hemoglobin's affinity for oxygen at different partial pressures of oxygen; changes in pH, temperature, and bisphosphoglycerate levels will shift the oxyhemoglobin-dissociation curve.

To model how the partial pressure of oxygen influences how much oxygen can attach and detach from hemoglobin, hematologists (doctors specializing in blood) have created the oxyhemoglobin-dissociation curve. Hemoglobin affinity for oxygen is how readily hemoglobin acquires and releases oxygen to the surrounding fluid. The oxyhemoglobin-dissociation curve is a graph that shows how partial pressures in the lungs and tissues change in their oxygen saturation based on oxygen concentrations in the blood. For example, in the lungs, when high partial pressure of oxygen is present, if the partial pressure of oxygen changes from 80 percent to 60 percent, the saturation of hemoglobin changes very little (i.e., 95 percent to 90 percent). Therefore, a 20 percent change in partial pressure only results in a five percent change in hemoglobin saturation, at high partial pressures. On the other hand, if the partial pressure is low, for example, 20 percent, an increase in partial pressure will result in a 40 percent increase in hemoglobin saturation. This is because hemoglobin has a safety mechanism in place to make sure it is always fully saturated with oxygen, even when the partial pressure drops by a significant amount. Conversely, when there is low partial pressure in the tissues, there are large changes in the amount of hemoglobin saturation. This happens because tissues other than the lungs have a low partial pressure and need the hemoglobin to make sure that oxygen is delivered to all the places where it is needed, such as the heart during exercise.

There are several environmental factors that can alter the oxyhemoglobin-dissociation curve. These include changes in temperature, pH, the partial pressure of carbon dioxide, and the amount (within the red blood cells) of 2,3-bisphosphoglycerate (BPG), a 3-carbon isomer that binds with deoxygenated hemoglobin and decreases hemoglobin's ability to bind with oxygen. All these factors change the structure of hemoglobin, thereby altering its ability to bind with oxygen. As temperature, BPG, and blood pH decreases, hemoglobin's affinity for oxygen decreases. This increases the rate at which hemoglobin releases oxygen. As a result, the oxyhemoglobin-dissociation curve shifts the curve to the right. When there is an increase in temperature, BPG, or pH, the affinity of hemoglobin for oxygen increases, which causes a shift to the left of the curve, indicating more oxygen is acquired by hemoglobin.

During metabolic activities, glucose is broken down and oxygen is used up. This causes carbon dioxide to be released into the blood. Higher amounts of carbon dioxide in the blood cause a condition called acidosis, which is a decrease in blood pH level. Higher amounts of carbon dioxide in the blood also increase the partial pressure of carbon dioxide. Both of these factors cause the bonds between hemoglobin and oxygen to weaken, an event called the Bohr effect. Conversely, high partial pressure of oxygen in the lung alveoli will cause hemoglobin to release carbon dioxide, thereby expelling carbon dioxide to be expired from the lungs. The weakening of the bonds between hemoglobin and carbon dioxide is called the Haldane effect.
The partial pressure of oxygen in the lungs and the tissues is what drives the amount of oxygen saturation of hemoglobin in the blood. Temperature, pH, and 2,3-bisphosphoglycerate levels can alter the saturation curve by changing the structure of hemoglobin and its ability to bind oxygen.

Fetal Hemoglobin

Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin; as a result, the fetus has increased access to oxygen from the maternal bloodstream.

Before birth, human beings have a form of hemoglobin called hemoglobin F, or fetal hemoglobin. Hemoglobin F is a special form of hemoglobin found in a fetus that has a higher affinity for oxygen than adult hemoglobin. This is because fetal hemoglobin exhibits a lower affinity for BPG, which results in a higher binding affinity for oxygen. This benefits the developing fetus because it can take oxygen from its mother should the need arise. After birth, the amounts of hemoglobin F drop off dramatically, usually around six months of age. The liver produces enzymes that destroy the fetal hemoglobin. At this age, the baby starts to produce the adult form of the protein.

The presence of hemoglobin F in adults can be a sign of a serious blood disease. There are tests that can be done to determine if levels of hemoglobin F are too high. If this is the case, then the person may have thalassemia, a disease where the blood has limited oxygen-carrying proteins, myeloid leukemia, a type of blood cancer that produces an excess of white blood cells, or sickle cell anemia, a blood disease that causes misshapen red blood cells. The presence of hemoglobin F alone does not necessarily indicate disease, as some people normally have higher levels of the protein than others.