Anemia

• Carbon monoxide

An increase in PCO2, a decrease in pH, and an increase in temperature shift the oxyhemoglobin dissociation curve to the right. As a result, at any given PO2, the hemoglobin releases more oxygen to the tissue (see Figure 17.6). Carbon dioxide and hydrogen ion can bind to hemoglobin; the binding of these substances changes the conformation of the hemoglobin and reduces its affinity for oxygen. An increase in temperature also reduces the affinity of hemoglobin for oxygen. This effect benefits a metabolically active tissue. As the rate of metabolism increases, as it does during exercise, oxygen consumption, and therefore the demand for oxygen, increases. In addition, the carbon dioxide, hydrogen ions, and heat produced by the tissue are increased. These products of metabolism facilitate the release of oxygen from the hemoglobin to the tissue that needs it.

2,3-Bisphosphoglycerate (2,3-BPG) is produced by red blood cells. This substance binds to hemoglobin, shifting the oxyhemoglobin dissociation curve to the right. Once again, the rightward shift of the curve reduces the affinity of hemoglobin for oxygen so that more oxygen is released to the tissues. Levels of 2,3-BPG are increased when the hemoglobin in the arterial blood is chronically undersaturated or, in other words, during hypoxemia. Decreased arterial PO2 may occur at altitude or as the result of various cardiovascular or pulmonary diseases. The rightward shift of the curve is beneficial at the level of the tissues because more of the oxygen bound to the hemoglobin is released to the tissues. However, the shift of the curve may be detrimental in the lungs because loading of hemoglobin may be impaired. Levels of 2,3-BPG may be decreased in blood stored in a blood bank for as little as 1 week. A decrease in 2,3-BPG shifts the oxyhemoglobin dissociation curve to the left. In this case, at any given PO2, unloading of oxygen to the tissues is decreased. The progressive depletion of 2,3-BPG can be minimized by storing the blood with citrate-phosphate-dextrose.

Anemia decreases the oxygen content of the blood and therefore the supply of oxygen to tissues. It is characterized by a low hematocrit that may be caused by a number of pathological conditions, such as a decreased rate of erythropoiesis (red blood cell production), excessive loss of erythrocytes, or a deficiency of normal hemoglobin in the erythrocytes. Although the oxygen content of the blood decreases, it is important to note that anemia has no effect on the PO2 of the blood or on the oxyhemoglobin dissociation curve (see Figure 17.7). Arterial PO2 is determined only by the amount of oxygen dissolved in the blood, which is unaffected. Furthermore, the affinity of hemoglobin for oxygen has not changed; what has changed is the amount of hemoglobin in the blood. If less hemoglobin is available to bind with oxygen, then less oxygen is in the blood.

Carbon monoxide interferes with the transport of oxygen to the tissues by way of two mechanisms:

• Formation of carboxyhemoglobin

• Leftward shift of the oxyhemoglobin dissociation curve

Carbon monoxide has a much greater affinity (240 times) for hemoglobin than does oxygen, so carboxyhemoglobin is readily formed. Therefore, even small amounts of carbon monoxide can tie up the hemoglobin and prevent loading of oxygen. Furthermore, formation of carboxyhemoglobin causes a leftward shift of the oxyhemoglobin dissociation curve (see Figure 17.7). As a result, at any given PO2, unloading of oxygen to the tissues is impaired. Therefore, the hemoglobin not only carries less oxygen, but also does not release this oxygen to the tissues that need it. The concentration of hemoglobin in the blood and the PO2 of the blood are normal.

Carbon monoxide poisoning is particularly insidious. An individual exposed to carbon monoxide is usually unaware of it because this gas is odorless, colorless, and tasteless. Furthermore, it does not elicit any irritant reflexes that result in sneezing, coughing, or feelings of dyspnea (difficulty in breathing). Finally, carbon monoxide does not stimulate ventilation. As will be discussed in a subsequent section, the peripheral chemoreceptors are sensitive to decreases in PO2, not oxygen content.

Transport of carbon dioxide. Carbon dioxide is carried in the blood in three forms:

• Physically dissolved

• Carbamino hemoglobin

20 40 60 80

Blood PO2 (mmHg)

20 40 60 80

Blood PO2 (mmHg)

Figure 17.7 Effect of anemia and carbon monoxide poisoning on oxygen transport. Anemia results from a deficiency of normal hemoglobin. The PO2 of the blood and the percent of hemoglobin saturation remain normal. However, because less hemoglobin is present to transport oxygen, oxygen content of the blood is decreased. Carbon monoxide impairs transport of oxygen to the tissues by two mechanisms. First, it binds preferentially with hemoglobin and prevents it from binding with oxygen. As a result, the hemoglobin remains fully saturated (although with carbon monoxide instead of oxygen) and the oxygen content of the blood is decreased. Second, it shifts the oxyhemoglobin dissociation curve to the left and inhibits the release of oxygen from the hemoglobin. As with anemia, the PO2 of the blood is unaffected.

As with oxygen, the amount of carbon dioxide physically dissolved in the plasma is proportional to its partial pressure. However, carbon dioxide is 20 times more soluble in plasma than is oxygen. Therefore, approximately 10% of carbon dioxide in blood is transported in the dissolved form.

Carbon dioxide can combine chemically with the terminal amine groups (NH2) in blood proteins. The most important of these proteins for this process is hemoglobin. The combination of carbon dioxide and hemoglobin forms carbamino hemoglobin:

Deoxyhemoglobin can bind more carbon dioxide than oxygenated hemoglobin. Therefore, unloading of oxygen in the tissues facilitates loading of carbon dioxide for transport to the lungs. Approximately 30% of carbon dioxide in the blood is transported in this form.

The remaining 60% of carbon dioxide is transported in the blood in the form of bicarbonate ions. This mechanism is made possible by the following reaction:

The carbon dioxide produced during cellular metabolism diffuses out of the cells and into the plasma. It then continues to diffuse down its concentration gradient into the red blood cells. Within these cells, the enzyme carbonic anhydrase (CA) facilitates combination of carbon dioxide and water to form carbonic acid (H2CO3). The carbonic acid then dissociates into hydrogen ion (H+) and bicarbonate ion (HCO-).

As the bicarbonate ions are formed, they diffuse down their concentration gradient out of the red blood cell and into the plasma. This process is beneficial because bicarbonate ion is far more soluble in the plasma than carbon dioxide. As the negatively charged bicarbonate ions exit the red blood cell, chloride ions, the most abundant anions in the plasma, enter the cells by way of HCO--Cl- carrier proteins. This process, referred to as the chloride shift, maintains electrical neutrality. Many of the hydrogen ions bind with hemoglobin. As with carbon dioxide, deoxyhemoglobin can bind more readily with hydrogen ions than oxygenated hemoglobin.

This entire reaction is reversed when the blood reaches the lungs. Because carbon dioxide is eliminated by ventilation, the reaction is pulled to the left. Bicarbonate ions diffuse back into the red blood cells. The hemoglobin releases the hydrogen ions and is now available to load up with oxygen. The bicarbonate ions combine with the hydrogen ions to form carbonic acid, which then dissociates into carbon dioxide and water. The carbon dioxide diffuses down its concentration gradient from the blood into the alveoli and is exhaled. A summary of the three mechanisms by which carbon dioxide is transported in the blood is illustrated in Figure 17.8.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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