Red blood cells, or erythrocytes are tiny, biconcave discs that are involved in respiratory gas transport throughout the body. The biconcave shape creates maximal surface area of the cell for the diffusion of these gases through the plasma membrane. Mature RBCs lack a nucleus and other organelles, although these are present in immature RBCs.

Hemoglobin

About 33% of each red blood cell, by volume, consists of hemoglobin (he ‘-mo-glo-bin). Hemoglobin is so named because it consists of heme, an iron-containing pigment molecule, and a globin, a globe-like protein. Blood is red because heme is a reddish pigment. Hemoglobin combines reversibly with oxygen and plays a vital role in the transport of oxygen by RBCs. It also plays a minor role in carbon dioxide transport.

When blood flows through the lungs, oxygen diffuses from air spaces in the lungs into the blood. Oxygen enters RBCs and combines with hemoglobin to form oxyhemoglobin, which gives a bright red color to blood. After the release of some oxygen from oxyhemoglobin to body cells, the resultant deoxyhemoglobin carries a small amount of carbon dioxide from body cells back to the lungs for removal. The reduced amount of oxygen carried by the deoxyhemoglobin gives a dark red color to blood.

Concentration of Red Blood Cells

Red blood cells are by far the most abundant blood cells. An RBC count is a routine clinical test to determine the number of RBCs in a μl of blood. For adult males, healthy values range from 4.7 to 6.1 million RBCs per μl. For adult females, healthy values range from 4.2 to 5.4 million RBCs per μl. The hematocrit, another common clinical test to determine the concentration of RBCs, is the percentage by volume of RBCs in the blood. Average healthy values are 47% in adult males and 42% in adult females. The higher value in males results from the presence of testosterone, in order to meet the demands of a male’s higher metabolic rate. Testosterone increases levels of a hormone called erythropoietin.

The concentration of RBCs and the hemoglobin percentage of the blood are commonly measured to determine the blood oxygen-carrying capacity. Hemoglobin percentage is the hemoglobin content expressed in grams per 100 ml of blood. Average healthy values are 14.9 ± 1.5 g for adult males and 13.7 ± 1.5 g for adult females.

Normal values of RBCs per μl of blood also vary with altitude. The concentration of RBCs is greater in persons living at higher altitudes because of the reduced oxygen concentration in air. This reduces the rate at which oxygen can enter the blood, causing a decline in the concentration of oxygen in the blood, which, in turn, stimulates RBC production.

Production

Prior to birth, red blood cells are produced largely by the liver and spleen but, after birth, production occurs only in the red bone marrow (myeloid tissue). In infants, RBCs are formed in the red bone marrow of all bones but in adults RBC formation primarily occurs in the red bone marrow of the skull bones, ribs, sternum, vertebrae, and coxal bones, as red bone marrow becomes restricted to these areas.

Red blood cell production varies with the oxygen concentration of the blood in a negative-feedback mechanism. If the kidneys and liver sense low blood oxygen concentration (hypoxemia), such as occurs with blood loss, they release erythropoietin (EPO), a hormone that stimulates red bone marrow to produce more RBCs. When the newly made RBCs restore blood oxygen homeostasis, production of EPO declines, causing a decrease in RBC production. A small amount of EPO is always present to maintain RBC production at a basal rate. Note that the concentration of oxygen in blood triggers the negative-feedback mechanism, which regulates EPO secretion and, therefore, RBC production.

Iron, folic acid, and vitamin B12 are required for RBC production. Iron is required for hemoglobin synthesis because each hemoglobin molecule contains four iron ions. Folic acid and vitamin B12 are required for DNA synthesis during early stages of RBC formation in red bone marrow. Vitamin B12 is sometimes called the extrinsic factor because it is obtained from a source external to the body, such as the diet or an injection. Effective absorption of vitamin B12 from the digestive tract into the blood is facilitated by intrinsic factor, a glycoprotein secreted by the stomach.

All formed elements, including RBCs, develop from stem cells called hemocyto-blasts in red bone marrow in a process called hematopoiesis. Hemocyto-blasts divide to form myeloid stem cells and lymphoid stem cells, which, in turn, divide to produce the precursor cells that develop into specific types of blood cells and platelets. Note that RBCs lose their nuclei and other organelles as they mature.

Life Span And Destruction

The life span of red blood cells is about 120 days, and trillions of RBCs are destroyed and produced at a rate of about 2 million per second! Normally, destruction and production are kept in balance.

The plasma membranes of newly formed RBCs are flexible, which allows them to change shape as they pass through small blood vessels. However, with age the membranes lose their elasticity and become fragile and damaged because RBCs lack the organelles necessary to make membrane repairs. Worn-out RBCs are removed from circulation in the liver and spleen by phagocytic cells called macrophages (makiro-faj-es). Macrophages engulf and digest old and damaged RBCs in phagocytic vesicles.

The globin portion of hemoglobin is broken down into amino acids, which are reused for forming new hemoglobin and other proteins in the body. The heme portion of hemoglobin is broken down into an iron ion and a yellow pigment, bilirubin (bil-i-rtf-bin). The iron ion may be temporarily stored in the liver or spleen before being transported to the red bone marrow and used to form more hemoglobin. Bilirubin is secreted by the liver in bile, which is carried by the bile duct into the small intestine for disposal.