Blood is the essential red fluid that is pumped by the \Theart\t through the \Tcirculatory system\t of humans and all higher animals. It is complex in its composition and in its functions. Blood has two main constituents. The cells, or corpuscles, comprise about 45 percent, and the liquid portion, or \Tplasma\t, in which the cells are suspended comprises 55 percent. The blood cells comprise three main types: red blood cells, or erythrocytes; white blood cells, or leukocytes, which in turn are of many different types; and platelets, or thrombocytes. Each type of cell has its own individual functions in the body. The plasma is a complex colorless solution, about 90 percent \Twater\t, that carries different ions and molecules including \Tproteins\t, \Lenzyme\ls, \Lhormone\ls, nutrients, waste materials such as \Turea\t, and fibrinogen, the protein that aids in clotting. RED BLOOD CELLS The red blood cells are tiny, round, biconcave disks, averaging about 7.5 microns (0.003 in) in diameter. A normal 76.5-kg (170-lb) man has about 5 l (5.3 qt) of blood in his body, containing more than 25 trillion (25 X 10 to the power of 12) red cells. Because the normal life span of red cells in the circulation is only about 120 days, more than 200 billion cells are normally destroyed each day by the spleen and must be replaced. Red blood cells, as well as most white cells and platelets, are made by the \Tbone\t marrow. Large numbers of primitive red cells, or erythroblasts, grow here and divide repeatedly, each primitive cell normally producing 16 mature red cells. The maturing cells lose their nucleus before leaving the marrow, making the red blood cells the most numerous nonnucleated cells. The main function of the red blood cells is to transport \Toxygen\t from the \Tlungs\t to the tissues (see \Trespiratory system\t). Oxidation of various food substances to supply most of the energy requirements of the body results in \Tcarbon dioxide\t, one of the chief waste products, and red blood cells carry it to the lungs for release and to pick up more oxygen. The substance in the red blood cells that is largely responsible for their ability to carry oxygen and carbon dioxide is \Themoglobin\t, the material that gives the cells their red color. It is a protein complex comprising many linked \Lamino acid\ls, and occupies almost the entire volume of a red blood cell. Essential to its structure and function is iron. The red blood cell depends on its cell wall to protect it against the turbulent racing through kilometers of blood vessels. This cell wall has sufficient pliability to prevent prompt traumatic destruction but sufficient rigidity to maintain, under most circumstances, the normal disk shape of the cell. BLOOD TYPING The cell wall contains many antigenic proteins, which determine the blood type. Among these proteins are the antigens A and B (see \Tantigen\t), the major blood group factors. Blood containing the antigen A is called group A. Blood with antigen B is group B. Blood with both antigens is called AB, and blood with neither is called group O. Normally, the plasma of every person contains an antibody against the A or B antigen missing from the cell wall. In typing the blood, the antigens in the red cells are determined by mixing them with known typing serums. The \Lantibod\lies in the serum or plasma are determined by mixing it with cells of known A or B type. Such typing is necessary in preparation for blood transfusion. Antigens of the various Rh and Hr types, M and N, Kell, Duffy, and many others also exist in the red blood cell. All, like the A and B antigens, are inherited. When the red-cell antigens are determined, they show so many different combinations as to make a person's blood type almost as individual as a fingerprint. Antibodies against antigens other than A and B do not normally occur in the plasma. They may appear after transfusion, however, and may cause transfusion reactions and destruction of red blood cells or hemolytic disease of the newborn (erythroblastosis fetalis). The remainder of the red blood cell is the stroma, which contains a complex series of enzymes that derive energy from the \Tsugar\t in the plasma. It also acts as a chemical pump to keep out the \Tsodium\t, an excess of which would cause so much water to enter the cell that it would burst. WHITE BLOOD CELLS The leukocytes, or white blood cells, are of three types, all involved in defending the body against foreign organisms. The granulocytes comprise three types: neutrophils, eosinophils, and basophils, with neutrophils the most abundant. Neutrophils seek out bacteria and phagocytize, or engulf, them. The lymphocytes' chief function is to migrate into the connective tissue and build antibodies against \Tbacteria\t and \Lvirus\les. Leukocytes are almost colorless, considerably larger than red cells, have a nucleus, and are much less numerous; only one or two exist for every 1,000 red cells. The number increases in the presence of infection. Monocytes, representing only 4 to 8 percent of white cells, attack organisms not destroyed by granulocytes and leukocytes. The granulocytes, accounting for about 70 percent of all white blood cells, are formed in the bone marrow, where they mature from the primitive myeloblast, divide several times, and eventually become granulated cells with multilobed nuclei. The lymphocytes, on the other hand, are produced primarily by the lymphoid tissues of the body--the \Tspleen\t and lymph nodes. They are usually smaller than the granulocytes and have a round or oval nucleus. Monocytes are believed to originate from lymphocytes. Just as the oxygen-carrying function of red cells is necessary for survival, so do normal numbers of functioning leukocytes protect against infection (see also \Tlymphatic system\t). PLATELETS Platelets, or thrombocytes, are tiny bits of cytoplasm, much smaller than the red blood cells but lacking a nucleus. They are round or biconcave disks and are normally about 30 to 40 times more numerous than the white blood cells. They are produced as broken fragments of the cytoplasm of the giant cells of the bone marrow--the megakaryocytes. The platelets' primary function is to stop bleeding, with the help of certain clotting proteins in the plasma. When tissue is damaged, the platelets aggregate in clumps to obstruct blood flow through the smallest vessels, the capillaries. In the larger vessels, the clumps of platelets form a site around which a blood clot forms, aided by a clot-promoting factor freed by the platelets as they break down. PLASMA The plasma is more than 90 percent water and contains a large number of substances, many essential to life. Its major solute is a mixture of proteins. The most abundant plasma protein is \Talbumin\t. This material is normally kept inside the blood vessels. Its ability to attract water keeps a large portion of the body water in the blood. When the plasma albumin concentration becomes dangerously low, because of disease, free water collects in the tissues outside the blood vessels, producing a swelling known as edema. The \Lglobulin\ls are even larger protein molecules than albumin and are of many chemical structures and functions. The antibodies, produced by lymphocytes, are globulins and are carried throughout the body, where many of them fight bacterial or viral invasion. Other antibodies are related to the blood groups. One plasma globulin, transferrin, binds free iron, making it possible for the blood to pick up iron absorbed from food in the intestines and carry it to the bone marrow, where it is used for the production of hemoglobin. The lipoproteins bind fats, whereas haptoglobin ties up the free hemoglobin released by the destruction of red blood cells. An important function of plasma is to transport nutrients to the tissues. Glucose, absorbed from the bowels, constitutes a major source of body energy. Some of the plasma proteins and fats, for example, lipids, are also used by the tissues for cell growth and energy. Minerals essential to body function, although present only in trace amounts, are important elements of the plasma. The calcium ion, for example, is essential to the building of bone, as is phosphorus. Calcium is also essential to the clotting of blood. Copper, although toxic in more than trace concentrations, is also a necessary component of the plasma. BLOOD CLOTTING The first step in clot formation and, therefore, the cessation of bleeding, is the breakdown of platelets at the wound site. This triggers a series of reactions. Activated trace proteins, now known as factors VIII, IX, and XI, as well as factor VII, activated by junction with tissue factor, convert factor X to active thromboplastin with the help of calcium ions. Thus thromboplastin results from platelet breakdown or tissue damage or both. Thromboplastin, with the help of calcium, converts prothrombin, another plasma protein, into thrombin, the clotting enzyme. Thrombin, acting as a catalyst, converts soluble fibrinogen into insoluble protein fibrin. Fibrin is the basis of the final clot and is firmed by factor XIII, or fibrin-stabilizing factor. This process is reinforced by platelets, which attach to the fibrin, contract, and pull the clot together. Because minor injuries occur often, the platelets and the plasma clotting factors must constantly produce clots to stop bleeding. If all of these clots remained after the damaged tissue was healed, the body would soon be a mass of clots, and blood would not flow freely through the tissues. To prevent such a continuing clot, plasma proteins known as fibrinolysins, or plasmins, dissolve old clots and thus clear the blood vessels. BLOOD DISEASES Anemia Anemia is a deficiency of hemoglobin in the blood, and anemias are generally classified as caused by blood loss, abnormal destruction of the red cells, and inadequate red cell formation by the bone marrow. Anemia caused by acute or chronic blood loss, or abnormal bleeding, results from the inability of the bone marrow to make new cells as fast as they are needed. In acute, or massive, bleeding, the red blood cells and their hemoglobin are normal but are not abundant. Chronic, usually slow bleeding leads to a deficiency in iron stores needed for hemoglobin. This results in smaller red blood cells that are paler than normal. Abnormal destruction of red cells (the hemolytic anemias) leads to a shorter than normal red cell survival. For example, in the hereditary disease \Tsickle-cell\t \Tanemia\t the hemoglobin is built erroneously. Another hereditary hemolytic anemia is familial spherocytosis. In this disorder, the fault is not in the formation of the hemoglobin but in the structure of the red-cell membrane, which is not large enough for the volume of the cell. Such cells are more fragile and break more readily in circulation. Not all hemolytic anemias are congenital. In autoimmune hemolytic anemia, the person manufactures antibodies that attack and destroy the red cells. The blood of persons with this disease often shows spherocytes, and the disease resembles familial spherocytosis. Anemias caused by bone-marrow failure include aplastic anemia, in which the bone marrow lacks adequate numbers of some or all types of blood cells. Another classical anemia caused by failure of production is pernicious anemia. In this disease, the person's stomach fails to produce "intrinsic factor," which is necessary for the normal absorption of vitamin B-12 from the intestines. Because vitamin B-12 is essential for normal bone marrow function, red cells are not formed normally. In some persons, the concentration of red cells and of hemoglobin in the blood may be abnormally increased, rather than decreased, resulting in \Tpolycythemia\t. This is usually caused by an increased production of red cells, but in some persons it may be caused by a decreased volume of plasma. Neutropenia Deficiency of circulating granulocytes, with poor resistance to infection, may occur in many diseases. In general, if fewer than 500 neutrophiles exist for every cubic millimeter of blood, the chance of severe infection is greatly increased. One of the most common causes of severe neutropenia is the treatment, using X-ray irradiation and toxic drugs, of many malignant diseases, including acute leukemia. Leukemia A great increase in abnormal leukocytes may occur for unknown reasons, resulting in the diseases known as the \Lleukemia\ls. These range in severity from the chronic lymphocytic leukemia, in which a person may live for many years, to devastating acute leukemia, often causing death within months. Thrombocytopenia The number of platelets can severely decrease, with danger of bleeding. Perhaps the most common cause of platelet deficiency, or thrombocytopenia, is an autoimmune disease related to autoimmune hemolytic anemia. The difference is that, in these cases, the body produces antibodies that attack only the platelets. Platelet deficiency is also found in such diseases as aplastic anemia, in which some or all the normal bone marrow cells are decreased. Severe platelet deficiency may also occur in the severe bone-marrow depression of acute leukemia and of its treatment. Hemophilia Deficiencies of one or more of the plasma coagulation factors may also cause abnormal bleeding. The existence of many of the clotting factors was recognized only when persons were found who lacked such a factor. The best known such bleeding disorder is \Themophilia\t, in which a hereditary deficiency of factor VIII, or "antihemophilic globulin," exists. This disorder, like color blindness, is inherited as a sex-linked characteristic and occurs almost exclusively in males. Thromboembolic Disease More common than abnormal bleeding, however, is abnormal clotting in the blood vessels, known as thromboembolic disease. Such a tendency may be caused by an excess of one or more of the plasma clotting factors, or at times to a deficiency of one of the fibrinolytic factors. This group of disorders, caused by a relatively inactive life-style, or by a person's confinement to bed, is one of the most common causes of death in middle-aged and elderly persons. Paul G. Hattersley, M.D. Bibliography: Callender, S. T., Blood Disorders: The Facts (1986); Chanarin, Israel, The Blood and Its Diseases, 3d ed. (1984); Golde, D.W., and Gasson, J.C., "Hormones that Stimulate the Growth of Blood Cells," Scientific American, July 1988; Jandl, James, Blood (1987); Matthias, F. R., Blood Coagulation Disorders (1987); Russell, N. J., et al., Blood Biochemistry (1980); Weiss, Leon, The Blood Cells and Hematopoietic Tissues, 2d ed. (1984).