The Red Blood Cells (Erythrocytes)
Functions of red blood cells
1.The major function is to transport hemoglobin, which in turn carries oxygen from the lungs to the tissues. In some lower animals hemoglobin circulates as free protein in the plasma, not enclosed in red blood cells. However, when it is free in the plasma of the human being, approximately 3 per cent of it leaks through the capillary membrane into the tissue spaces or through the glomerular membrane of the kidney into the glomerular filtrate each time the blood passes through the capillaries. Therefore, for hemoglobin to remain in the blood stream, it must exist inside red blood cells.
2. The red blood cells have other functions besides simply transport of hemoglobin. For instance, they contain a large quantity of carbonic anhydrase, which catalyzes the reaction between carbon dioxide and water, increasing the rate of this reaction many thousand fold. The rapidity of this reaction makes it possible for the water in blood to react with large quantities of carbon dioxide and thereby transport it from the tissues to the lungs in the form of the bicarbonate ion (HCO-3).
3. Also, the hemoglobin in the cells is an excellent acid-base buffer (as is true of most proteins), so that the red blood cells are responsible for most of the buffering power of whole blood.
The Shape and Size of Red Blood Cells. Normal erythrocytes are small cells shaped like biconcave discs—flattened discs with depressed center on both sides (fig.3).They have a mean diameter of approximately 7.5 micrometers and a thickness at the thickest point of 1.9 micrometer and in the center of 1 micrometer or less. Their small size and peculiar shape provide a large surface area relative to their volume, making them ideally suited for gas exchange.
RBCs differ from other blood cells because they are anucleate , they lack a nucleus. They also contain very few organelles.
Moreover, because erythrocytes lack mitochondria and make ATP by anaerobic mechanisms, they do not use up any of the oxygen they are transporting, making them very efficient oxygen transporters indeed.
RBCs outnumber white blood cells by about 1000 to 1 and are the major factor contributing to blood viscosity. Although the numbers of RBC in the circulation do vary, there are normally about 5 million cells per cubic millimeter of blood. (A cubic millimeter [mm3] is a very tiny drop of blood, almost not enough to be seen.) When the number of RBC/mm3 increases, blood viscosity increases. Similarly, as the number of RBCs decreases, blood thins and flows more rapidly.
Concentration of Red Blood Cells in the Blood.
In normal men the average number of red blood cells per cubic millimeter is 5,200,000 (±300,000) and in normal women 4,700,000 (± 300,000).
The more hemoglobin molecules the RBCs contain, the more oxygen they will be able to carry. Perhaps the most accurate way of measuring the oxygen-carrying capacity of the blood is to determine how much hemoglobin it contains.
Although the numbers of erythrocytes are important, it is the amount of hemoglobin in the bloodstream at any time that really determines how well the erythrocytes are performing their role of oxygen transport.
Since a single red blood cell contains about 250 million hemoglobin molecules, each capable of binding 4 molecules of oxygen, each of these tiny cells can carry about 1 billion molecules of oxygen!
Hemoglobin (Hb), an iron-bearing protein, transports the bulk of the oxygen that is carried in the blood. It also binds with a small amount of carbon dioxide.
Normal blood contains 12-18 g hemoglobin per ml blood. The hemoglobin content is slightly higher in men (13-18 g) than in women
Production of Red Blood Cells (Erythropoiesis)
A- Areas of the Body That Produce Red Blood Cells:
In the early few weeks of embryonic life, primitive, nucleated red blood cells are produced in the yolk sac. During the middle trimester of gestation the liver is the main organ for production of red blood cells, though reasonable numbers of red blood cells are also produced by the spleen and lymph nodes. Then, during the latter part of gestation and after birth, red blood cells are produced exclusively by the bone marrow.
B- Genesis of Blood Cells
Pluripotential Hemopoietic Stem Cells:
In the bone marrow are cells called pluripotential hemopoietic stem cells (PHSCs), from which all the cells in the circulating blood are derived. As these cells reproduce, continuing throughout the life of the person, a portion of them are exactly like the original pluripotential cells and are retained in the bone marrow to maintain a supply of these, though their numbers do diminish with age. The larger portion of the reproduced stem cells, however, differentiate to form the other cells called committed stem cells.
The different committed stem cells, when grown in culture, will produce colonies of specific types of blood cells. Therefore, a committed stem cell that produces erythro-cytes is called a colony-forming unit-erythrocyte (CFU-E).
Growth Inducers and Differentiation Inducers:
Growth and reproduction of the different stem cells are controlled by multiple proteins called growth inducers. Four major growth inducers have been described, each having different characteristics. One of these, interleukin-3, promotes growth and reproduction of virtually all the different types of stem cells, whereas the others induce growth of only specific types of committed stem cells.
The growth inducers promote growth but not differentiation of the cells. Instead, this is the function of still another set of proteins, called differentiation inducers. Each of these causes one type of stem cell to differentiate one or more steps toward a final type of adult blood cell.
Formation of the growth inducers and differentiation inducers is itself controlled by factors outside the bone marrow. For instance, in the case of red blood cells, exposure to low oxygen for a long period of time results in growth induction, differentiation, and production of greatly increased numbers of erythrocytes.
C- Stages of Differentiation of Red Blood Cells
The first cell that can be identified as belonging to the red blood cell series is the proerythroblast, (Fig.4). Under appropriate stimulation, large numbers of these cells are formed from the CFU-E stem cells.
Once the proerythroblast has been formed, it divides several more times, eventually forming many mature red blood cells. The first-generation cells are called bosophilic erythroblosts because they stain with basic dyes; the cell at this time has accumulated very little hemoglobin. However, the cells become filled with hemoglobin to a concentration of approximately 34 per cent, the nucleus condenses to a small size, and its final remnant is extruded from the cell and these cells are called orthochromatic erythroblast. At the same time the endoplasmic reticulum is reabsorbed. The cell at this stage is called a reticulocyte because it still contains a small amount of basophilic material, consisting of remnants of the Golgi apparatus, mitochondria, and a few other cytoplasmic organelles. It is during this reticulocyte stage that the cells pass into the blood capillaries by diapedesis (squeezing through the pores of the membrane).
D- Regulation of RBCs Production
The rate of erythrocyte production is controlled by a hormone called erythropoietin. Normally a small amount of erythropoietin circulates in the blood at all times, and red blood cells are formed at a fairly constant rate. Although the liver produces some, the kidneys play the major role in producing this hormone. When blood levels of oxygen begin to decline for any reason, the kidneys step up their release of erythropoietin (Fig.5). Erythropoietin targets the bone marrow, prodding it into "high gear" to turn out more RBCs. As you might expect, an overabundance of erythrocytes, or an excessive amount of oxygen in the bloodstream, depresses erythropoietin release and red blood cell production. An important point to remember is that it is not the relative number of RBCs in the blood that controls RBC production. Control is based on their ability to transport enough oxygen to meet the body s demands.
— Requirement for Maturation of Red Blood Cells
Because of the continuing need to replenish red blood cells, the cells of the bone marrow are among the most rapidly growing and reproducing cells of the entire body. Therefore, as would be expected, their maturation and rate of production is affected greatly by a person s nutritional status.
Especially important for final maturation of the red blood cells are the two vitamins vitamin B12(Cyanocobalamin) and folic acid. Both of these are essential for the synthesis of DNA, for each in a different way is required for the formation of thymidine triphosphate, one of the essential building blocks of DNA. Therefore, lack of either vitamin B12 or folic acid causes diminished DNA and consequently failure of nuclear maturation and division. Furthermore, the erythroblastic cells of the bone marrow, in addition to failing to proliferate rapidly, become larger than normal, developing into so-called megaloblasts, and the adult erythrocyte has a flimsy membrane and is often irregular, large, and oval instead of the usual biconcave disc. These poorly formed cells, after entering the circulating blood, are capable of carrying oxygen normally but their fragility causes them to have a short life, one half to one third of normal. Therefore, it is said that vitamin B12 or folic acid deficiency causes maturation failure in the process of erythropoiesis.
-The cause of the abnormal cells seems to be as follows:
The inability of the cells to synthesize adequate quantities of DNA leads to slow reproduction of the cells but does not prevent formation of RNA by the DNA. Therefore, the quantity of RNA in each cell becomes much greater than normal, leading to excess production of cytoplasmic hemoglobin and other constituents, which causes the cells to enlarge. Yet because of abnormalities of some of the genes (the DNA), the structural components of the cell membrane and cyto-skeleton are malformed, which leads to abnormal cell shapes and especially greatly increased cell membrane fragility.