BLOOD

Definition
Blood is a liquid connective tissue that performs many functions in the body, including transport of oxygen, carbon dioxide, nutrients, waste products, and hormones; clotting; and defense against microorganisms. Blood consists blood cells suspended in plasma, a fluid 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.

Description
All vertebrates circulate blood within blood vessels. Because blood is enclosed within blood vessels, the circulatory systems of vertebrates are called closed circulatory systems. (Some invertebrates have open circulatory systems that do not contain blood vessels and circulate a blood-like fluid called hem lymph.)

The human body contains about 4 to 6.3 qt (4 to 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 red blood cell formation. Plasma makes up 55% of the blood, while the blood cells constitute the other 45%. The various types of blood cells are red blood cells (erythrocytes), white blood cells (leukocytes or leucocytes), and platelets.

Plasma
Plasma contains mostly water, which accounts for91.5% of the plasma content. The water acts as a solvent for carrying other substances.

PLASMA PROTEINS. Proteins account for 7% of plasma. The higher concentration of protein in blood prevents water from moving from the blood into the interstitial fluid. Without this osmotic protection, water would move from the blood into the interstitial fluid, causing a rapid loss of blood volume.

The most abundant of the plasma proteins is albumin, a protein also found in egg white. Albumin concentration is four times higher in the blood than in the interstitial fluid (the watery fluid that bathes tissues, but is located outside and between cells). This high concentration of albumin in plasma serves an important osmotic function.

Other proteins that are present in plasma are immunoglobins and fibrinogen. Immunoglobins, also called antibodies, are proteins that function in the immune response. Antibodies attach to invading bacteria and other microorganisms, marking them for destruction by immune cells. Fibrinogen is a protein that functions in a complex series of reactions that leads to the formation of blood clots.

OTHER PLASMA COMPONENTS. The other components of plasma are salts, nutrients, enzymes, hormones, and nitrogenous waste products. Together, these substances account for 1.5% of plasma. The salts present in plasma include sodium, potassium, calcium, magnesium, chloride, and bicarbonate. These salts function in many important body processes. For instance, calcium functions in muscle contraction; sodium, chloride, and potassium function in nerve impulse transmission in nerve cells; and bicarbonate regulates pH. These salts are also called electrolytes. An imbalance of electrolytes, which can be caused by dehydration, can be a serious medical condition. Many gastrointestinal illnesses, such as cholera, cause a loss of electrolytes through severe diarrhea. When electrolytes are lost, they must be replaced with intravenous or oral solutions of water and salts.

The remaining substances present in plasma are elements that the plasma is transporting from one place to another. For instance, plasma contains nutrients that nourish tissues. The nutrients found in plasma include amino acids, the building blocks of proteins; glucose and other sugars; and fatty acids and glycerol, the components of lipids (fats). In addition to nutrients, plasma also contains enzymes, or small proteins that function in chemical reactions, and hormones, which are transported from glands to body tissues. Waste products from the breakdown of proteins are also found in plasma. These waste products include creatinine, uric acid, and ammonium salts. Blood transports these waste products from the body tissues to the kidneys, where they are filtered from the blood and excreted in the urine.

Red blood cells
The human body contains an estimated 25 trillion red blood cells; approximately 4.8 million to 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), shaped like a disk, and contain a small depression on either side. Their small size allows them to squeeze through the tiniest of blood vessels (capillaries). In addition, their size 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, their combined surface areas translate into an extremely large surface area for the diffusion of oxygen. The disk shape and the depressions on either side also contribute to a greater surface area.

TRANSPORT OF OXYGEN. Red blood cells are unusual in that they do not contain nuclei or mitochondria, the cellular organelles 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.

HEMOPOIESIS. 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 (alternatively, hematopoiesis). In adults hemopoiesis takes place in the marrow of ribs, vertebrae, the breastbone, and the pelvis. On average, a red blood cell lives only three to four months. Constant wear and tear on the red blood cell membrane, caused by squeezing through tiny capillaries, contributes 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.

White blood cells
White blood cells are less numerous than red blood cells in the human body; each microliter of blood contains 5,000 to 10,000 white blood cells. The number of white blood cells increases, however, when the body is fighting off infection. Their numbers are maintained 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.

TYPES OF WHITE BLOOD CELLS. 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 granulocytes. The granules are specific chemicals that are released 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% to 8% of the white blood cells, and neutrophils, which comprise 60% to 70% of white blood cells, are called phagocytes. 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 in 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% to 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, 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% to 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% to 25% of the total composition of white blood cells, are divided into two types: B lymphocytes (also called B cells) and T lymphocytes (also called T cells). 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. These stem cells undergo further development and maturation in the spleen, tonsils, thymus, adenoids, and lymph nodes.

Platelets
Platelets are not cells; they are fragments of cells that function in blood clotting. Platelets number about 250,000 to 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 five to nine days before being replaced. Platelets are produced in red bone marrow and are broken off from other red blood cells.

Blood substitutes
Researchers hope to create synthetic blood substitutes to ease the burden of dwindling blood donations that are needed to meet the demand for surgeries, transfusions, and emergencies. Currently under development are blood substitutes that use perfluorocarbons or modified hemoglobin to carry oxygen to tissues.

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 is a mixture of 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.

Hemoglobin solutions contain hemoglobin that has been isolated from red blood cells and chemically altered to increase its lifespan in the bloodstream and to ensure adequate oxygen-carrying capabilities.

Strictly, these substances are not whole blood substitutes since they only have the ability to carry oxygen and cannot replace the other important functions of blood. However, they would be valuable in eliminating the risk of transmitting disease during transfusions as well as preventing accidental blood type mismatches.

ABO  BLOOD GROUPS. 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:

These combinations are necessary to know when performing a blood transfusion. 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.

HLA ANTIGEN GROUPS. 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.

Sickle cell anemia
Sickle cell anemia is an inherited disorder caused by a defect in one of hemoglobin's four protein chains. The defective hemoglobin distorts the shape of the red blood cells and injuries the red blood cell membrane. Water and potassium leak from the cells, causing the red blood cells to become rigid and "sickle-shaped." 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. Although the prognosis for individuals with sickle cell anemia was historically poor, improvements in life expectancy and quality have been made due to early diagnosis and treatment.

Hemophilia
Hemophilia is hereditary group of bleeding disorders that results in insufficient clotting and excessive bleeding. Types are hemophilia A, hemophilia B, and von Willebrand's disease. Hemophilia A is the most common type. It results from a deficiency in clotting factor VIII. Only males have this sex-linked disease, but women may be carriers. Uncontrolled bleeding, both internal and
external, may be caused by the smallest of injuries. Treatment involves clotting factor supplementation, and tranfusions are common when blood is lost, or prophylactically.

Human immunodeficiency virus
Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS), attacks and kills T lymphocytes. This dis-ease 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 per cubic millimeter to below 200.

KEY TERMS

Aerobic metabolism—Metabolic processes that require oxygen.
Antibody— an immune protein that marks foreign microorganisms in the body for destruction by other immune cells.
Antigen— A protein that is attached to a cell’s plasma membrane.
Centrifugation—A laboratory procedure in which a test tube of blood or other liquid is spun at a high speed.
Clotting factor—A set of substances released by platelets that function in the clotting mechanism.
Electrolytes—The salts and other substances present in the plasma that function in crucial body processes.
Fibrin—A protein that functions in the clotting mechanism; forms mesh-like threads that trap red blood cells.
Fibrinogen—The inactive form of fibrin present in plasma; activated by clotting factors released by platelets.
Hemoglobin—The protein found in red blood cells that binds oxygen; consists of four protein chains surrounding an iron core.
Hemophilia—A genetic disorder in which one or more clotting factors are not released by the platelets; causes severe bleeding from even minor cuts and bruises.
Hemopoiesis—The process of red blood cell formation in the bone marrow.
Histamine—A chemical released by basophils during the inflammatory response; causes blood vessels to dilate.
Immunoglobin—An antibody.
Inflammatory response—A type of non-specific immune response; involves the release of chemicals from basophils that increase blood circulation and white blood cell migration to the affected area.
Interstitial fluid—The fluid that bathes cells.
Lymph node—A small structure located at several points in the body; consists of lymphatic tissue that filters blood and removes microorganisms.
Lymphocyte—A type of white blood cell; includes B and T lymphocytes.
Lysozyme—An enzyme released by neutrophils that kills cells.
Lymphoid stem cell—The cell from which B and T lymphocytes are derived.
Phagocytize—To engulf and digest a cell.
Plasma cell—The cell derived from the B lymphocyte, which secretes antibodies.
Pluripotent stem cell—the type of stem cell from which red blood cells and more white blood cells are derived in the bone marrow.
Sickle cell anemia—A genetic disorder caused by a defect in one of hemoglobin's four protein chains; causes red blood cells to be sickle-shaped.

THIS IS GENERAL INFORMATION ON DISEASE. PLEASE CONTACT YOUR DOCTOR FOR MORE DETAILS AND TREATMENT.
Compiled by –Santosh  Ghodinde ,Community Pharmacist, Dhanwantari Medical, Panvel.