RBCs play a critical role in the transport of oxygen and carbon dioxide in the body. Chapter 27 includes a detailed discussion of how oxygen is transported from air in the lungs to the body cells and how carbon dioxide moves from body cells to the lungs for removal. Both of these functions depend on hemoglobin. In addition to hemoglobin, the presence of an enzyme, carbonic anhydrase (CA), in RBCs catalyzes a reaction that joins carbon dioxide and water to form carbonic acid. Dissociation of the acid then generates bicarbonate ions (HCO₃⁻) and hydrogen ions (H⁺), which diffuse out of the RBCs. Because carbon dioxide (CO₂) is chemically incorporated into the newly formed bicarbonate ions, it can be transported in this new form in the blood plasma until it is excreted from the body. Bicarbonate ions also have an important role in maintaining normal blood pH levels (see Chapter 33).

Considered together, the total surface area of all the RBCs in an adult is enormous. It provides an area larger than a football field for the exchange of respiratory gases between hemoglobin found in circulating erythrocytes and interstitial fluid that bathes the body cells. This is an excellent example of the relationship between form and function.

Packed within each RBC are an estimated 200 to 300 million molecules of hemoglobin, which make up about 95% of the dry weight of each cell. Each hemoglobin molecule is composed of four protein chains. Each chain, called a globin, is bound to a red pigment, identified in Figure 20-5, as a heme group. Each heme group contains one iron atom. Therefore one hemoglobin molecule contains four iron atoms. This structural fact enables one hemoglobin molecule to unite with four oxygen molecules to form oxyhemoglobin (a reversible reaction). Hemoglobin can also combine with carbon dioxide to form carbaminohemoglobin (also reversible). But in this reaction the structure of the globin part of the hemoglobin molecule, rather than its heme part, makes the combining possible.

A man’s blood usually contains more hemoglobin than a woman’s. In most normal men, 100 ml of blood contains 14 to 16 grams of hemoglobin. The normal hemoglobin content of a woman’s blood is a little less—specifically, in the range of 12 to 14 grams/100 ml. Recall that testosterone in the male tends to stimulate erythrocyte production and cause an increase in RBC numbers. Increased levels of hemoglobin in males are directly related to increased erythrocyte numbers. An adult who has a hemoglobin content of less than 10 grams/100 ml of blood is diagnosed as having anemia. If you dissect the word parts, you see that anemia literally means “lack of blood.” The term anemia also may be used to describe a reduction in the number or volume of functional RBCs in a given unit of whole blood. Anemias are classified according to the size and hemoglobin content of RBCs. Box 20-2 describes a type of anemia that results from production of an abnormal type of hemoglobin.

Box 20-2

FYI

Sickle cell anemia.

Sickle cell anemia is a severe, sometimes fatal, hereditary disease that is characterized by an abnormal type of hemoglobin. A person who inherits only one defective gene develops a form of the disease called sickle cell trait, in which red blood cells contain a small proportion of a hemoglobin type that is less soluble than normal. This hemoglobin forms solid crystals when the blood oxygen level is low, causing distortion and fragility of the red blood cell. If two defective genes are inherited (one from each parent), more of the defective hemoglobin is produced, and the distortion of red blood cells becomes severe. In the United States, about 1 in every 500 African-American and 1 in every 1000 Hispanic newborns are affected each year. In these individuals, the distorted red blood cell membranes can be damaged by drastic changes in shape. Red blood cells damaged in this way tend to stick to vessel walls, and if a blood vessel in the brain is affected, a stroke may occur because of the decrease in blood flow velocity or blockage of blood flow.

Stroke is one of the most devastating problems associated with sickle cell anemia in children and will affect about 10% of the 2500 youngsters who have the disease in the United States. Studies have shown that frequent blood transfusions in addition to standard care can dramatically reduce the risk of stroke in many children suffering from sickle cell anemia. Recent advances in bone marrow transplants in children and hemopoietic stem cell transplants in adults show the promise of long-term reversal of the effects of sickle cell anemia.

The illustration shows the characteristic shape of a red cell containing the abnormal hemoglobin.

The entire process of RBC formation is called erythropoiesis. In the adult, erythrocytes begin their maturation sequence in the red bone marrow from nucleated cells known as hematopoietic stem cells, or adult blood-forming stem cells. Adult stem cells are cells that have the ability to maintain a constant population of newly differentiating cells of a specific type. These adult blood-forming stem cells divide by mitosis; some of the daughter cells remain as undifferentiated adult stem cells, whereas others go through several stages of development to become erythrocytes. Figure 20-6 shows the developmental stages that can be identified as transformation from the immature forms to the mature red blood cell occurs. The entire maturation process requires about 4 days and proceeds from step to step by gradual transition. Just what influences direct embryonic stem cells (found in the embryo and in umbilical cord blood) to develop into a specific type of adult stem cell (e.g., hematopoietic stem cells) and then eventually differentiate into a specific cell type, such as an RBC, is a topic of intense research.

As you can see in Figure 20-6, all blood cells are derived from hematopoietic stem cells. In RBCs, differentiation begins with the appearance of proerythroblasts. Mitotic divisions then produce basophilic erythroblasts. The next maturation division produces polychromatic erythroblasts, which produce hemoglobin. These cells subsequently lose their nuclei and become reticulocytes. Once released into the circulating blood, reticulocytes lose their delicate reticulum and become mature erythrocytes in about 24 to 36 hours. Note in Figure 20-6 that overall cell size decreases as the maturation sequence progresses.

RBCs are formed and destroyed at a breathtaking rate. Every day of our adult lives we produce more than 200 billion RBCs to replace an equal number destroyed during that brief time. Because in health the number of RBCs remains relatively constant, efficient homeostatic mechanisms must operate to balance the number of cells formed against the number destroyed.

The rate of RBC production soon speeds up if blood oxygen levels reaching the tissues decrease. Oxygen deficiency increases RBC numbers by increasing the secretion of a glycoprotein hormone named erythropoietin (eh-RITH-roh-POY-eh-tin), or EPO. An inactive form of this hormone, called an erythropoietinogen, is released into the blood primarily from the liver on an ongoing basis. If oxygen levels decrease, the kidneys release increasing amounts of erythropoietin, which in turn stimulates bone marrow to accelerate its production of red blood cells. With increasing numbers of RBCs, oxygen delivery to tissues increases, and less erythropoietin is produced, and consequently less is available to stimulate RBC production in the red bone marrow. Figure 20-7 shows how erythropoietin production is controlled by a negative feedback loop that is activated by decreasing oxygen concentration in the tissues.

Stay updated, free articles. Join our Telegram channel

Join