Blood

Blood is a liquid connective tissue that performs many functions in the body, including transport of oxygen, Red blood cells alongside the wall of the blood vessel. Photograph by Dennis Kunkel. Phototake NYC. Reproduced by permission. carbon dioxide, nutrients, waste products, and hormones; clotting; and defense against microorganisms. Blood consists of formed elements, or blood cells suspended in plasma, a watery liquid that contains proteins, salts, and other substances. When a blood sample is placed in a test-tube and spun rapidly (a process called centrifugation), the heavier blood cells sink to the bottom of the test tube, while the straw-colored plasma floats on top.

The human body contains about 4-6.3 qt (4-6 L) of blood. Men have more blood than women, due to the presence of higher levels of testosterone, a hormone that regulates sex characteristics and function and also stimulates blood formation. Plasma makes up 55% of the blood, while the blood cells constitute the other 45%.

Blood cells make up 45% of the total composition of blood. The various types of blood cells are erythrocytes, or red blood cells; leukocytes (also spelled leucocytes), or white blood cells; and platelets.

Red blood cells

The human body contains an estimated 25 trillion red blood cells; approximately 4.8-5.4 million are found in every microliter of blood. The structure of a red blood cell is eminently suited to its primary function, the transport of oxygen from the lungs to body tissues. Red blood cells are very small (about 6 nanometers wide), disk-shaped, and contain a small depression on either side. Their small size allows them to squeeze through the tiniest blood vessels, called capillaries. In addition, the small size of red blood cells allows a greater diffusion of oxygen across the blood cells' plasma membranes than if the cells were larger. Because blood contains so many of these small cells, the combined surface area of these many blood cells translates into an extremely large amount of surface area for the diffusion of oxygen. The disk shape and the depressions on either side also contribute to a greater surface area.

Red blood cells are unusual in that they do not contain nuclei or mitochondria, the cellular organelle in which aerobic metabolism (the breakdown of nutrients that requires oxygen) is carried out. Instead, red blood cells acquire energy through metabolic processes that do not require oxygen. The lack of nuclei and mitochondria therefore allow the red blood cell to function without depleting its cargo of oxygen, leaving more oxygen for the body tissues.

The molecule that binds oxygen in red blood cells is called hemoglobin. Hemoglobin is a large, globular protein consisting of four protein chains surrounding an iron core. Hemoglobin is densely packed inside the red blood cell; in fact, hemoglobin accounts for a third of the weight of the entire red blood cell. Each red blood cell contains about 250 molecules of hemoglobin. In the lungs, oxygen diffuses across the red blood cell membrane and binds to hemoglobin. As blood circulates to the tissues, oxygen diffuses out of the red blood cells and enters tissues. The waste product of aerobic metabolism, carbon dioxide, then diffuses across red blood cells and binds to hemoglobin. Once circulated back to the lungs, the red blood cells discharge their load of carbon dioxide, which is then breathed out of the lungs. However, only 7% of carbon dioxide generated from metabolism is transported back to the lungs for exhalation by red blood cells; the majority is transported in the form of bicarbonate, a component of plasma.

The complexity of blood is apparent. Still, researchers hope to create synthetic blood substitutes, which will ease the burden of dwindling donations to meet the demand for surgeries, transfusions, and emergency use. Currently under development is an artificial blood that uses perfluorocarbons to carry oxygen to tissues, replacing the function of hemoglobin. Perfluorocarbons are long, fatty hydrocarbon chains containing fluorine that have the ability to pick up oxygen in lungs, and release it into tissues. The artificial blood made with these molecules is a mixture of the perfluorocarbons with saline (physiological salt water) using surfactants, substances that allow the mixing of oil and water. The solution then can be administered to patients. Over time, as the artificial blood helps deliver oxygen to tissues, the perflourocarbon molecules are exhaled from the body. Strictly, this substance is not a whole blood substitute since it only has the ability to carry oxygen and cannot replace the other important functions of blood. However, it is valuable because it eliminates the risk of transmitting disease during transfusions as well as preventing accidental blood type mismatches.

Sickle cell anemia is an inherited disorder caused by a defect in one of hemoglobin's four protein chains. The sickle hemoglobin distorts the shape of the red blood cells and injures the red blood cell membrane. Water and potassium leak from the cells, causing the red blood cells to become "sickle-shaped." The cells also become inflexible and rigid. As a result of these changes, oxygen transport is severely interrupted and circulation of the blood through the blood vessels can become blocked. These irregular blood cells do not carry as much oxygen as their normally-shaped counterparts. Sickle cell anemia is invariably fatal; most people with the disease die in early adulthood.

Red blood cells are formed in red bone marrow from precursor cells called pluripotent stem cells. The process of red blood cell formation is called hemopoiesis, or hematopoiesis. In adults, hemopoiesis takes place in the marrow of ribs, vertebrae, breast bone, and pelvis. On average, a red blood cell lives only 3-4 months. Constant wear and tear on the red blood cell membrane, caused by squeezing through tiny capillaries, contribute to the red blood cell's short life span. Worn out red blood cells are destroyed by phagocytic cells (cells that engulf and digest other cells) in the liver. Parts of red blood cells are recycled for use in other red blood cells, such as the iron component of hemoglobin.

An interesting aspect of red blood cells is that they carry certain proteins, called antigens, on their plasma membranes. These antigens are responsible for the various blood groups known as A, B, AB, and O. A person with A antigens is type A; a person with B antigens is type B; a person with both antigens is type AB; and a person with none of the antigens is type O. A individuals have antibodies to B antigens; B individuals have antibodies to A antigens; AB individuals do not have antibodies to the antigens, and O individuals have antibodies to both A and B antigens. These combinations are necessary to know for blood transfusions. For instance, if a type A individual donates blood to a type B individual, the A antibodies in the recipient's B blood will react with the A antigens of the donor's A blood. This reaction, called the agglutination reaction, causes the blood cells to clump together. Agglutination can be fatal. Until blood typing was worked out early in this century, many deaths from blood transfusions occurred due to incompatibility of antigens and antibodies.

White blood cells

White blood cells are less numerous than red blood cells in the human body; each microliter of blood contains 5,000-10,000 white blood cells. The number of white blood cells increases, however, when the body is fighting off infection. White blood cells, therefore, are maintained at a stable number until the immune system detects the presence of a foreign invader. When the immune system is activated, chemicals called lymphokines stimulate the production of more white blood cells.

White blood cells function in the body's defense against invasion and are key components of the immune system. They usually do not circulate in the blood vessels, and are instead found in the interstitial fluid and in lymph nodes. Lymph nodes are composed of lymphatic tissue and are located at strategic places in the body. Blood filters through the lymph nodes, and the white cells present in the nodes attack and destroy any foreign invaders.

The human body contains five types of white blood cells: monocytes, neutrophils, basophils, eosinophils, and lymphocytes. Each type of white blood cell plays a specific role in the body's immune defense system.

Under a microscope, three kinds of white blood cells appear to contain granules within their cytoplasm. These three types are the neutrophils, basophils, and eosinophils. Together, these three types of white blood cells are called the granular leukocytes. The granules are specific chemicals released by these white blood cells during the immune response. The other two types of white blood cells, the monocytes and lymphocytes, do not contain granules. These types are known as the agranular leukocytes.

Monocytes, which comprise 3-8% of the white blood cells, and neutrophils, which comprise 60-70% of white blood cells, are phagocytic cells. They ingest and digest cells, including foreign microorganisms such as bacteria. Monocytes differentiate into cells called macrophages. Macrophages can be fixed in one place, such as the brain and lymph nodes, or can "wander" to areas where they are needed, such as the site of an infection. Neutrophils have an additional defensive property: they release granules of lysozyme, an enzyme that destroys cells.

Basophils comprise 0.5-1% of the total composition of white blood cells and function in the body's inflammatory response. Allergies are caused by an inflammatory response to relatively harmless substances, such as pollen or dust, in sensitive individuals. When activated in the inflammatory response, basophils release various chemicals that cause the characteristic symptoms of allergies. Histamines, for instance, cause the runny nose and watery eyes associated with allergic reactions; heparin is an anticoagulant that slows blood clotting and encourages the flow of blood to the site of inflammation, inducing swelling.

Eosinophils, which comprise 2-4% of the total composition of white blood cells, are believed to counteract the effects of histamine and other inflammatory chemicals. They also phagocytize bacteria tagged by antibodies.

Lymphocytes, which comprise 20-25% of the total composition of white blood cells, are divided into two types: B lymphocytes and T lymphocytes. The names of these lymphocytes are derived from their origin. T lymphocytes are named for the thymus, an organ located in the upper chest region where these cells mature; and B lymphocytes are named for the bursa of Fabricus, an organ in birds where these cells were discovered. T lymphocytes play key roles in the immune response. One type of T lymphocyte, the helper T lymphocyte, activates the immune response when it encounters a macrophage that has ingested a foreign microorganism. Another kind of T lymphocyte, called a cytotoxic T lymphocyte, kills cells infected by foreign microorganisms. B lymphocytes, when activated by helper T lymphocytes, become plasma cells, which in turn secrete large amounts of antibodies.

All white blood cells arise in the red bone marrow. However, the cells destined to become lymphocytes are first differentiated into lymphoid stem cells in the red bone marrow; from the red bone marrow, these stem cells undergo further development and maturation in the spleen, tonsils, thymus, adenoids, and lymph nodes.

HIV, the virus that causes Acquired Immune Deficiency syndrome (AIDS), attacks and kills T lymphocytes. This disease cripples the immune system and leaves the body helpless to stave off infections. As AIDS progresses, the number of helper T lymphocytes drops from a normal 1,000 to zero.

Like red blood cells, the plasma membranes of white blood cells also contain antigens. These surface antigens are called the human leukocyte associated (HLA) antigens. Like the red blood cell types, these HLA antigens represent different white blood cell "groups." When a person receives an organ transplanted from a donor, the recipient and the donor must have the same HLA antigen group for the transplant to be successful. If the donor and recipient are two different HLA antigen groups, the recipient's body will "reject" the organ; in other words, the recipient's immune system will be activated by the foreign cells of the organ and initiate an immune response against the organ.

Platelets

Platelets are not cells; they are fragments of cells that function in blood clotting. Platelets number about 250,000-400,000 per liter of blood. Blood clotting is a complex process that involves a cascade of reactions that leads to the formation of a blood clot. Platelets contain chemicals called clotting factors. These clotting factors first combine with a protein called prothrombin. This reaction converts prothrombin to thrombin. Thrombin, in turn, converts fibrinogen (present in plasma) to fibrin. Fibrin is a thread-like protein that traps red blood cells as they leak out of a cut in the skin. As the clot hardens, it forms a seal over the cut. This process works for relatively small cuts in the skin. When a cut is large, or if an artery is severed, blood loss is so severe that the physical pressure of the blood leaving the body prevents clots from forming. In addition, in the inherited disorder called hemophilia, one or more clotting factors are lacking in the platelets. This disorder causes severe bleeding from even the most minor cuts and bruises.

Platelets have a short life span; they survive for only 5-9 days before being replaced. Platelets are produced in red bone marrow and are broken off from other red blood cells.