Musculoskeletal System. Basic Concepts. Genetic Disorders. Oxygen Transport. Overview Oxygen is transported within the blood in a simple dissolved form as well as a chemically-bound form associated with hemoglobin See: Gases in Liquids. Oxygen transport in the body occurs in two basic steps involving the reversible loading and unloading of hemoglobin with oxygen. Hemoglobin is loaded with oxygen as it passes through the pulmonary capillaries and is then transported to the peripheral tissues where the oxygen is unloaded.
The primary factor determining whether oxygen is loaded or unloaded onto hemoglobin is the surrounding partial pressure of oxygen. The quantitative relationship between oxygen partial pressure and the percent of hemoglobin molecules bound to oxygen is provided by the "Oxygen-Hemoglobin Dissociation Curve" described below.
Careful analysis of this dissociation curve can provide valuable insights into how oxygen transport is regulated. Oxygen Transport in Outline Oxygen is loaded in blood in the pulmonary capillaries where the oxygen tension is mm Hg as a result of alveolar ventilation. Oxygen is unloaded from the blood in the peripheral tissues where the oxygen tension is roughly 40 mm Hg as a result of peripheral tissue oxygen consumption. The curve can be generated by placing a sample of human blood in an oxygen-free environment and then slowly increasing the partial pressure of oxygen from 0 mm Hg to roughly mm Hg.
The percent of hemoglobin within the sample bound to oxygen can be measured using optical techniques, allowing for an assessment of the hemoglobin oxygen-saturation for every value of oxygen partial pressure. The Oxygen-Hemoglobin Dissociation Curve is obtained by plotting the hemoglobin saturation against the oxygen partial pressure. Qualitative Features The key feature of the dissociation curve is its non-linear, sigmoid shape. As observed, the saturation of hemoglobin changes substantially when the partial pressure of oxygen ranges between 20 - 60 mm Hg but tends to plateau at oxygen partial pressures above 80 mm Hg.
Consequently, the amount of oxygen released from blood may be very different given the starting and ending partial pressures of oxygen. For example, a drop in oxygen partial pressure from mm Hg to 80 mm Hg will result in little release of hemoglobin-bound oxygen; however, a drop in oxygen partial pressure from 60 mm Hg to 40 mm Hg will result in an enormous release of hemoglobin bound oxygen even though in both cases the oxygen partial pressure was reduced by 40 mm Hg.
The sigmoid shape of the oxygen-hemoglobin dissociation curve is the result of hemoglobin's unique biochemistry which allows for oxygen binding in a cooperative fashion. Hemoglobin, or Hb, is a protein molecule found in red blood cells erythrocytes made of four subunits: two alpha subunits and two beta subunits. Each subunit surrounds a central heme group that contains iron and binds one oxygen molecule, allowing each hemoglobin molecule to bind four oxygen molecules. Molecules with more oxygen bound to the heme groups are brighter red.
As a result, oxygenated arterial blood where the Hb is carrying four oxygen molecules is bright red, while venous blood that is deoxygenated is darker red.
Hemoglobin : The protein inside red blood cells a that carries oxygen to cells and carbon dioxide to the lungs is hemoglobin b. Hemoglobin is made up of four symmetrical subunits and four heme groups. Iron associated with the heme binds oxygen. It is the iron in hemoglobin that gives blood its red color.
It is easier to bind a second and third oxygen molecule to Hb than the first molecule. This is because the hemoglobin molecule changes its shape, or conformation, as oxygen binds. The fourth oxygen is then more difficult to bind.
The binding of oxygen to hemoglobin can be plotted as a function of the partial pressure of oxygen in the blood x-axis versus the relative Hb-oxygen saturation y-axis. The resulting graph, an oxygen dissociation curve, is sigmoidal, or S-shaped. As the partial pressure of oxygen increases, the hemoglobin becomes increasingly saturated with oxygen. Oxygen dissociation curve : The oxygen dissociation curve demonstrates that as the partial pressure of oxygen increases, more oxygen binds hemoglobin.
However, the affinity of hemoglobin for oxygen may shift to the left or the right depending on environmental conditions. The oxygen-carrying capacity of hemoglobin determines how much oxygen is carried in the blood. In addition, other environmental factors and diseases can also affect oxygen-carrying capacity and delivery; the same is true for carbon dioxide levels, blood pH, and body temperature. The increase in carbon dioxide and subsequent decrease in pH reduce the affinity of hemoglobin for oxygen.
The oxygen dissociates from the Hb molecule, shifting the oxygen dissociation curve to the right. Therefore, more oxygen is needed to reach the same hemoglobin saturation level as when the pH was higher. A similar shift in the curve also results from an increase in body temperature. Increased temperature, such as from increased activity of skeletal muscle, causes the affinity of hemoglobin for oxygen to be reduced. In sickle cell anemia, the shape of the red blood cell is crescent-shaped, elongated, and stiffened, reducing its ability to deliver oxygen.
In this form, red blood cells cannot pass through the capillaries. This is painful when it occurs. Thalassemia is a rare genetic disease caused by a defect in either the alpha or the beta subunit of Hb. Patients with thalassemia produce a high number of red blood cells, but these cells have lower-than-normal levels of hemoglobin.
The most important clinical test in assessing the efficacy of oxygen transportation is the concentration of oxygen CaO ; this is because the vast majority of oxygen in the blood is bound to hemoglobin, while a minimal amount dissolves in plasma water.
Furthermore, the oxygen-carrying capacity of hemoglobin is empirically determined to be 1. The saturation of hemoglobin SaO2 is another measure of the efficacy of oxygen transport and is the ratio of oxygen bound to hemoglobin divided by the total hemoglobin. This can be determined noninvasively in a clinical setting through the use of pulse oximetry, which measures differences in absorption of specific wavelengths o flight by oxygenated and deoxygenated hemoglobin in the blood. The limitations of this technique are because it is a ratio tied to total hemoglobin and thus cannot detect anemia or polycythemia.
Additionally, pulse oximetry cannot detect anemia or that oxygenated hemoglobin is indistinguishable from hemoglobin that is bound to carbon monoxide. Thus, a person who has suffered exposure to high levels of carbon monoxide may have a normal oxygen saturation as indicated by pulse oximetry, despite lower levels of oxygen bound to hemoglobin.
A persistent reduction in oxygen transportation capacity is most often the result of anemia. The definition of anemia is a decrease in the total amount of hemoglobin in the blood generally less than Anemia can result from disorders leading to the impaired production of hemoglobin e.
Thalassemias are an important class of inherited disorders resulting in defective production of hemoglobin. An individual with thalassemia has a mutation which impairs production of the globin polypeptide chain of hemoglobin.
Thalassemias are classified based upon the number of genes mutated or absent, and whether they encode the alpha globin chain or the beta globin chain.
While the presentations and severity of thalassemias vary significantly, they all result in a quantitative defect in hemoglobin production. Sickle cell anemia ranks as one of the more notable disorders of hemoglobin structure. While the quantity of hemoglobin produced may be normal, a single amino acid substitution of valine for glutamic acid results in a structural defect that promotes the polymerization of deoxygenated hemoglobin.
When deoxyhemoglobin polymerizes, it forms fibers that alter the shape of erythrocytes in a process known as sickling. While sickle cell anemia can remain asymptomatic for a significant time, severe hypoxia may precipitate a sickling crisis, leading to symptoms of generalized pain, fatigue, headache, and jaundice.
Other defects in oxygen transportation may be the result of an environmental toxin, with one example being carbon monoxide poisoning, also known as carboxyhemoglobinemia.
The affinity of carbon monoxide for hemoglobin is times that of oxygen. It is important to note that in the setting of carboxyhemoglobinemia, it is not a reduction in oxygen-carrying capacity that causes pathology, but an impaired delivery of bound oxygen to target tissues.
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