The transport of oxygen is fundamental to aerobic respiration and the survival of complex organisms. The lungs, heart, vasculature, and red blood cells play essential roles in oxygen transport. Oxygen-carrying deficiencies or problems with oxygen transport or delivery are common sequelae of medical illness and must be promptly evaluated and corrected to prevent irreversible tissue damage.
Hemoglobin (Hgb or Hb) is the primary carrier of oxygen in humans. Approximately 98% of total oxygen transported in the blood is bound to hemoglobin, while only 2% is dissolved directly in plasma. Hemoglobin is a metalloprotein with four subunits composed of an iron-containing heme group attached to a globin polypeptide chain. One molecule of oxygen can bind to the iron atom of a heme group, giving each hemoglobin the ability to transport four oxygen molecules. One molecule of oxygen can bind to the iron atom of a heme group, giving each hemoglobin the maximum capacity to transport four oxygen molecules. This ability to sequentially bind oxygen to each subunit results in the unique sigmoidal shape of the oxyhemoglobin dissociation curve. Various defects in the synthesis or structure of erythrocytes, hemoglobin, or the globin polypeptide chain can impair the oxygen-carrying capacity of the blood and lead to hypoxia.
The body maintains adequate oxygenation of tissues in the setting of decreased PO or increased demand for oxygen. These changes are often expressed as shifts in the oxygen dissociation curve, representing the percentage of hemoglobin saturated with oxygen at varying levels of PO. Factors that contribute to a right shift in the oxygen dissociation curve and favor the unloading of oxygen correlate with exertion. These include increased body temperature, decreased pH (due to increased production of CO2), and increased 2,3-BPG. (Figure) This right shift of the oxyhemoglobin curve can be viewed as an adaptation for physical exertion. Regulation of the unloading of oxygen from the red blood cells to the target tissues is mainly by the concentration of 2,3-bisphosphoglycerate (2,3-BPG) within erythrocytes. 2,3-BPG preferentially binds to and stabilizes the deoxygenated form of hemoglobin, resulting in a lower affinity of hemoglobin for oxygen at a given oxygen tension and a subsequent increase in the availability of free oxygen for consumption by metabolically active tissues.
Another aspect of oxygen transport is the delivery of oxygen to the tissues each minute. This oxygen delivery depends on both cardiac output (CO) and the arterial oxygen content (CaO):
DO2 = CO * CaO
Note: the CaO calculation is given later in this article. Thus, changes in cardiac output, hemoglobin saturation, and hemoglobin concentration all affect oxygen delivery.
Oxygen is measured in the blood in three ways: partial pressure of dissolved oxygen, oxygen concentration, and hemoglobin saturation. Dissolved oxygen is obtained from arterial blood gas (ABG) measurements and is reported as partial pressure. Henry's law dictates that the amount of dissolved oxygen in plasma water equals the PO times the solubility constant of oxygen in the blood, which is determined to be 0.003 mL / mmHg O / dL blood. This PO is 40 mmHg in the venous and 100 mmHg in the arterial blood. Oxygen first has to dissolve in blood before it can bind to hemoglobin. The amount of dissolved O2 depends on the oxygen gradient between the alveoli and blood and the ease at which oxygen can move through the alveolar lung tissue itself, also known as the parameters involved in Fick's law of diffusion.
The most critical clinical test in assessing the efficacy of oxygen transportation is the concentration of oxygen (CaO). Most 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 1.34 mL O2 / g Hbg. Thus, when the hemoglobin concentration, hemoglobin saturation (SaO), and PO are known, we can calculate the total oxygen concentration of the blood using the following equation:
CaO = 1.34 * [Hgb] * (SaO / 100) + 0.003 * PaO2.
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. Saturation 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. Normal levels should be about 80-100% oxygen saturation of Hb. This technique's limitations are that 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 bound to carbon monoxide. Therefore, 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.
Carbon dioxide molecules are transported in the blood from body tissues to the lungs by one of three methods: dissolution directly into the blood, binding to hemoglobin, or carried as a bicarbonate ion. Several properties of carbon dioxide in the blood affect its transport. First, carbon dioxide is more soluble in blood than oxygen. About 5 to 7 percent of all carbon dioxide is dissolved in the plasma. Second, carbon dioxide can bind to plasma proteins or can enter red blood cells and bind to hemoglobin. This form transports about 10 percent of the carbon dioxide. When carbon dioxide binds to hemoglobin, a molecule called carbaminohemoglobin is formed. Binding of carbon dioxide to hemoglobin is reversible. Therefore, when it reaches the lungs, the carbon dioxide can freely dissociate from the hemoglobin and be expelled from the body.
Third, the majority of carbon dioxide molecules (85 percent) are carried as part of the bicarbonate buffer system. In this system, carbon dioxide diffuses into the red blood cells. Carbonic anhydrase (CA) within the red blood cells quickly converts the carbon dioxide into carbonic acid (H2CO3)(H2CO3). Carbonic acid is an unstable intermediate molecule that immediately dissociates into bicarbonate ions (HCO−3)(HCO3−) and hydrogen (H+) ions. Since carbon dioxide is quickly converted into bicarbonate ions, this reaction allows for the continued uptake of carbon dioxide into the blood down its concentration gradient. It also results in the production of H+ions. If too much H+ is produced, it can alter blood pH. However, hemoglobin binds to the free H+ ions and thus limits shifts in pH. The newly synthesized bicarbonate ion is transported out of the red blood cell into the liquid component of the blood in exchange for a chloride ion (Cl−); this is called the chloride shift. When the blood reaches the lungs, the bicarbonate ion is transported back into the red blood cell in exchange for the chloride ion. The H+ ion dissociates from the hemoglobin and binds to the bicarbonate ion. This produces the carbonic acid intermediate, which is converted back into carbon dioxide through the enzymatic action of CA. The carbon dioxide produced is expelled through the lungs during exhalation.
The benefit of the bicarbonate buffer system is that carbon dioxide is “soaked up” into the blood with little change to the pH of the system. This is important because it takes only a small change in the overall pH of the body for severe injury or death to result. The presence of this bicarbonate buffer system also allows for people to travel and live at high altitudes: When the partial pressure of oxygen and carbon dioxide change at high altitudes, the bicarbonate buffer system adjusts to regulate carbon dioxide while maintaining the correct pH in the body.
While carbon dioxide can readily associate and dissociate from hemoglobin, other molecules such as carbon monoxide (CO) cannot. Carbon monoxide has a greater affinity for hemoglobin than oxygen. Therefore, when carbon monoxide is present, it binds to hemoglobin preferentially over oxygen. As a result, oxygen cannot bind to hemoglobin, so very little oxygen is transported through the body (Figure 1).
Carbon monoxide is a colorless, odorless gas and is therefore difficult to detect. It is produced by gas-powered vehicles and tools. Carbon monoxide can cause headaches, confusion, and nausea; long-term exposure can cause brain damage or death. Administering 100 percent (pure) oxygen is the usual treatment for carbon monoxide poisoning. Administration of pure oxygen speeds up the separation of carbon monoxide from hemoglobin.
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