Blood
Blood
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 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.
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 animals without vertebrae,
called invertebrates, have circulatory systems that do not contain blood vessels. In these open circulatory systems, the fluid analogous to blood is called hemo-lymph (Greek, hemo, blood + lympha, water). Examples of animals that circulate hemolymph include insects and aquatic arthropods such as lobsters and crawfish. Like blood, hemolymph transports oxygen and carbon dioxide and has a limited clotting ability. Unlike blood, hemolymph is colorless. Other invertebrates have no true circulatory system. In these animals, it is not possible to distinguish blood or hemolymph from the watery fluid that bathes the tissues. This fluid contains a few defensive cells, proteins, and salts. However, oxygen and carbon dioxide are not transported in this fluid.
Human blood
The human body contains about 4-6.3 quarts (4-6 liters) 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%.
Plasma contains mostly water, which accounts for about 92% of the plasma content. The water acts as a solvent (the fraction that compounds can dissolve in) for carrying other substances.
Proteins account for 7% of plasma. The most prevalent of these proteins in plasma 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. 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 interstitial fluid into the blood, diluting the plasma and swelling the blood volume. A high blood volume could have disastrous consequences, because the circulatory system can only pump so much blood before it becomes overloaded.
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 other immune cells. Fibrinogen is a protein that functions in a complex series of reactions that leads to the formation of blood clots.
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 solutions of water and salts or by having the patient drink solutions of salts and water.
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, or 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.
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; about five million per microliter (10-6 of blood. The structure of a red blood cell enables it to transport oxygen from the lungs to body tissues. Red blood cells are very small (about 6 nanometers wide; a nanometer is 10-9 meters), 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 aerobicmetabolism (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.
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 the last 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.
KEY TERMS
ABO blood groups— Blood types established by the A and B antigens present on the plasma membrane of red blood cells; ABO blood groups include A, B, AB, and O.
Aerobic metabolism— Metabolic processes that require oxygen.
Agranular leukocyte— A white blood cell without granules in its cytoplasm; these white blood cells include the monocytes and lymphocytes.
Albumin— A protein found in plasma.
Antibody— A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.
Antigen— A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.
B lymphocyte— Immune system white blood cell that produces antibodies.
Basophil— A type of white blood cell; functions in the inflammatory response by releasing histamines and other chemicals that have specific effects on tissues.
Capillary— The smallest blood vessel, which connects an artery to a vein.
Centrifugation— A laboratory procedure in which a test tube of blood or other liquid is spun at a high speed to separate components of differing densities.
Circulatory system— The body system that circulates blood pumped by the heart through the blood vessels to the body tissues.
Clotting factor— A set of substances released by platelets that function in the clotting mechanism.
Cytotoxic T lymphocyte— A type of white blood cell that attacks and kills cells infected by a foreign microorganism.
Electrolytes— The salts and other substances present in the plasma that function in crucial body processes.
Eosinophil— A type of white blood cell that counteracts the effects of histamine and other inflammatory chemicals; also phagocytizes bacteria tagged by antibodies.
Erythrocyte— A red blood cell.
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.
Formed elements— The cells present in blood.
Granular leukocyte— A white blood cell that contains granules in its cytoplasm; includes basophils, eosinophils, and neutrophils.
Helper T lymphocyte— The “lynch pin” of specific immune responses; helper T cells bind to APCs (antigen-presenting cells), activating both the antibody and cell-mediated immune responses.
Hemoglobin— An iron-containing, protein complex carried in red blood cells that binds oxygen for transport to other areas of the body.
Hemolymph— The blood-like liquid present in the open circulatory systems of certain invertebrates.
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.
Human leukocyte antigen (HLA)— A type of antigen present on white blood cells; divided into several distinct classes; each individual has one of these distinct classes present on their white blood cells.
Immunoglobulin— The protein molecule that serves as the primary building block of antibodies.
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.
Leukocyte— A white blood cell.
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.
Lymphoid stem cell— The cell from which B and T lymphocytes are derived.
Lysozyme— An enzyme released by neutrophils that kills cells.
Macrophage— A type of phagocytic cell derived from monocytes.
Monocyte— A type of white blood cell that phagocytizes foreign microorganisms.
Neutrophil— A type of white blood cell that phagocytizes foreign microorganisms; also releases lysozyme.
Phagocytosis— The engulfment and digestion of a cell.
Plasma— The straw-colored liquid portion of blood that contains water, proteins, salts, nutrients, hormones, and metabolic wastes.
Plasma cell— The cell derived from the B lymphocyte, which secretes antibodies.
Platelet— A cell that contains clotting factors.
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.
Thymus— The organ in which T cells undergo further development and maturation.
Resources
BOOKS
Kimbell, Ann Marie. Risky Trade: Infectious Disease in the Era of Global Trade. Aldershot, UK: Ashgate Publishing, 2006.
Sibinga, Smit and Roger Y. Dodd (eds.). Transmissible Diseases and Transfusion. New York: Springer, 2002.
Winslow, Robert M. Blood Substitutes. New York: Academic Press, 2005.
PERIODICALS
Moen, Christian H. “Companies knowingly sold virus-tainted blood products abroad, class action claims.” Trial. 39 (2003): 72-75.
Kathleen Scogna
Blood
BLOOD
BLOOD . Among the religions of the world one finds many ambivalent or contradictory attitudes toward blood. Blood is perceived as being simultaneously pure and impure, attractive and repulsive, sacred and profane; it is at once a life-giving substance and a symbol of death. Handling blood is sometimes forbidden, sometimes mandatory, but usually dangerous. Rites involving blood require the intervention of individual specialists (warriors, sacrificers, circumcisers, butchers, or executioners) and always the participation of the group or community.
In many primitive societies, blood is identified as a soul substance: of men, of animals, and even of plants. The Romans said that in it is the sedes animae ("seat of life"). In pre-Islamic times, Arabs considered it the vegetative, liquid soul that remains in the body after death, feeding on libations. For the Hebrews, "the life of the flesh is in the blood" (Lv. 17:4).
The spilling of blood is often forbidden. This ban applies to certain categories of humans and animals: sacrificial victims, royalty, game, and so on. The Iroquois, the Scythians (Herodotus, 4.60–61), and the old Turco-Mongols, as well as the rulers of the Ottoman empire, forbade shedding the blood of persons of royal lineage. There is reason to believe that the Indian Hindu religions that have abolished sacrifices, and the feasting that goes with sacrifice, have done so more to avoid the shedding of blood than to comply with the dogmas of nonviolence and reincarnation. According to Genesis 9:4, the eating of raw meat is forbidden: "But you must not eat the flesh with the life, which is the blood, still in it." The Islamic tradition has similar restrictions.
Attitudes toward blood can be divided into two general categories: toward the blood of strangers, foreigners, or enemies and toward the blood of members of one's own community.
The blood of enemies usually is not protected by any taboo. It has been suggested that one justification for war is the perceived necessity of shedding blood in order to water the earth. One frequently encounters the idea that the earth is thirsty for blood—but only for licit blood. It can refuse blood that is not licit or cry out for vengeance against such illicit bloodshed, as the biblical passages Isaiah 26:21 and Job 16:18 illustrate. In pre-Columbian America blood was essential to the survival of the Sun, and in other countries it was demanded by the gods.
The killing of enemies is sometimes mandatory. Among the Turkic peoples in ancient times and again during the Islamic period in the sixteenth century, an adolescent did not acquire his adulthood, his name, and thus his soul until he committed his first murder. Killing—and being killed—has been the raison d'être for the Ojibwa and Dakota Indian tribes, as well as, to a certain extent, the Muslim "martyrs" of holy war and the Japanese samurai. At one time, a bloody death at the hand of an enemy seemed more to be envied than a natural death. However, concerning the caste of Hindu warriors in India, it was believed that one whose vocation was killing awaited his own immolation.
The blood of the enemy is rarely dangerous, even though the qualities and strengths of the soul remain in it. In antiquity people attempted to appropriate these qualities of blood by drinking it or washing themselves in it. Herodotus (17.64) notes that the Scythians drank the blood of the first victims they killed.
Within the community, however, attitudes toward blood and killing are different. Members of the community are connected by consanguinity, and they share collective responsibility for one another; the blood of each is the blood of all. The group's totemic animals may be included in this community, which is connected to the animals by adoption or alliance. A stranger can enter the group through marriage or "blood brotherhood," a custom practiced among the Fon of West Africa and among Central Asian peoples. Relations between blood brothers can be established in various ways, often through the juxtaposition of cuts made in their wrists or by pouring a few drops of blood into a cup, mixing it with wine (called "the blood of the vine" in antiquity), and drinking it. The Turkic peoples, Scythians, and Tibetans used the tops of skulls for drinking cups.
Murder within the community is forbidden. To kill one's relative is tantamount to shedding one's own blood; it is a crime that draws a curse that lasts for generations. When Cain murdered Abel, Abel's "blood cried out for vengeance," and Cain's descendants suffered as a result. When Oedipus unknowingly killed his father, he gouged out his own eyes to confess his blindness, but his punishment fell upon his children. After Orestes executed his mother, Clytemnestra, he was followed by the Furies, spiritlike incarnations of blood. The death of the just and innocent brings vengeance. King David protested: "I and my kingdom are guiltless before the Lord forever from the blood of Abner.… Let it rest on the head of Joab, and on all his father's house" (2 Sm. 3:28–29). According to Matthew, after the sentencing of Jesus to be crucified the Jews cried: "Let his blood be upon us and upon our children" (27:25).
A murder between families or between clans is a grave wrong that must be avenged by killing the guilty party. The latter, who in turn becomes the victim, will have his own avenger from among his relatives. Thus develops the cycle of vendetta killing, which can be broken only by "paying the blood price." Vendetta killing is found in ancient Greece, pre-Islamic Arabia, modern Corsica, and among the Nuer of the Sudan. The Jewish and Muslim demands of "an eye for an eye" may be similar to this phenomenon.
Under certain circumstances killing is perceived as a creative act, especially in the realm of the gods, where suicide or parricide sometimes leads to birth or new life. Mesopotamian and Babylonian cosmogonies feature gods who were slain in order to give life. The Greek Kronos severed the testicles of his father Ouranos (Sky) with a billhook while the latter lay in a tight embrace with Gaia (Earth). The blood of Ouranos's genital organs gave birth to new beings and, according to some traditions, to Aphrodite herself. This kind of suicide—relinquishing a part to preserve the whole—was sometimes magnified into a supreme act of love or redemption: Odin gave up one eye for the sake of supernatural "vision"; Attis emasculated himself; Abraham was prepared to slit the throat of his only son; Jesus accepted death volun-tarily.
Some kinds of sacrifice are centered around blood. Blood is the drink of the gods or the drink shared by mortals with the gods. Blood sacrifices are varied in form and function. In Jewish sacrifice (abolished since the destruction of the Temple), the victim is not human but animal; its death has reconciliatory and expiatory value. In Muslim sacrifices, the gift of meat is the price paid by the genuinely guilty; there is no blessing or grace expected, and reconciliation and expiation are not involved.
In the Christian concept of sacrifice, the slitting of an animal's throat is abolished, and the animal is replaced by the "Lamb of God," Jesus on the cross. Crucifixion and asphyxiation, although not bloody in themselves, are perceived as fundamentally bloody. The sacrifice (at least, as it is understood outside Protestantism) is renewed daily; it is both expiatory and redemptory. The sacrifice is accompanied by a communal meal (Eucharist) where the believer is invited to eat bread, symbolizing the body of Christ, and to drink wine, symbolizing his blood. Charles Guignebert has noted that the bread has been of less interest than the wine; the wine "is the symbolism of blood that dominates in the Eucharist … and affirms its doctrinal richness" (Guignebert, 1935, p. 546). Christ, who offers the cup to his disciples, says, "This is the blood of the new testament that is shed for many for the remission of sins."
Judaism had already established that the covenant between God and his people was one of blood, of circumcision and sacrifice. Moses sprinkled the people with the blood of sacrificed bulls, saying, "Behold the blood of the covenant which the Lord hath made with you" (Ex. 24:8).
The idea of establishing a covenant through blood is found in many cultures. People create covenants among themselves as well as between their gods and themselves. Some peoples in Central Asia, in Siberia, and on the steppes of eastern Europe cut a dog or other animal in two to seal a treaty or to take a solemn oath, thus guaranteeing their loyalty. The protective force of blood is illustrated in the covenant between God and Israel in Exodus 13:7–13; the Israelites, remaining in their homes, which were marked with blood, were spared from the death that struck the Egyptians. A similar idea is expressed in Indonesia when the doors and pillars of houses are smeared with blood during sacrifices of domestic dedication.
Blood can eliminate flaws and weaknesses. In Australia, a young man would spread his blood on an old man in order to rejuvenate him. Some Romans, in honor of Attis, emasculated themselves and celebrated the dendrophoria by beating their backs, hoping thus to escape the disease of death and to wash themselves of its stain. Similarly, Shīʿī flagellants relive the martyrdom of Ḥusayn ibn ʿAlī, grandson of the prophet Muḥammad.
The most common type of self-inflicted wound is circumcision. In the female the incision of the clitoris sometimes corresponds with this rite. Male circumcision is required in Hebrew tradition, where it is the sign of a covenant with God. It is common also in Islam. Many explanations have been given for this almost universal rite. It is seen primarily as a manifestation of the desire to eliminate any traces of femininity in the male. It is doubtful that circumcision is an attempt to imitate the menses. If the sexual act is considered a defilement, the removal of the foreskin could, in effect, rid the sexual organ of impurity transmitted from the mother. Yet there are some societies where the circumcised male is considered to be as impure as the menstruating female and where he is treated as if he were one.
The menses are universally considered the worst impurity, due to the involuntary and uncontrollable flowing of blood. Menstruating women are believed to pose great dangers to men, and for this reason many peoples of New Guinea, Australia, Polynesia, Africa, Central Asia, and the Arctic have feared them and imposed innumerable bans on them. One finds similar fears in the Hebrew (Lv. 20:18), Islamic, and Hindu traditions. Researchers have not yet properly emphasized the implications of the interruption of menstruation during pregnancy; one can surmise that the fetus, believed to be fed with the impure blood, acquires this impurity, which has to be removed at birth. The impurity only indirectly appears to be a function of the sexual act or of the vaginal bleeding at delivery.
See Also
Circumcision; Clitoridectomy; Human Sacrifice; Mortification; Omophagia; Revenge and Retribution; Sacrifice.
Bibliography
Nearly all works on the history of religions mention blood, but there are no valuable monographs on the subject other than G. J. M. Desse's Le sang dans le rite (Bordeaux, 1933). The reader is referred also to Lucien Lévy-Bruhl's The "Soul" of the Primitive (New York, 1928) and to Mircea Eliade's Rites and Symbols of Initiation (New York, 1958). Numerous facts on the topic are found in Bronislaw Malinowski's Sex and Repression in Savage Society (London, 1927) and Crime and Custom in Savage Society (New York, 1926). W. Robertson Smith's Lectures on the Religion of the Semites, 3d ed. (London, 1927), is still fundamental in the study of sacrifice. Charles Guignebert discusses the symbolism of blood as found in the Christian Eucharist in Jesus (London, 1935). On circumcision, see B. J. F. Laubscher's Sex, Custom and Psychopathology (London, 1937). On blood brotherhood, see Georges Davy's La foi jurée (Paris, 1922). Bruno Bettelheim's Symbolic Wounds: Puberty Rites and the Envious Male (Glencoe, Ill., 1954) and Paul Hazoumé's Le pacte de sang au Dahomey (Paris, 1937) are also worth consulting.
New Sources
Jean-Paul Roux has published Le sang. Mythes, symboles et réalités (Paris, 1988), which is the only monograph tackling this subject in a cross-cultural perspective. There is a plentiful bibliography but the approach is old-fashioned and the style not very scholarly. An indispensable tool for any further research is represented by the imposing series "Sangue e antropologia," edited for nine years in twenty two volumes by Francesco Vattioni under the auspices of the Centro Studi Sanguis Christi (Rome, 1981–1996). Philologists, historians and theologians present and discuss a host of materials related to blood functions and symbolism in various cultural contexts, with focus on Christianity in Biblical and patristic times.
Jean-Paul Roux (1987)
Translated from French by Sherri L. Granka
Revised Bibliography
Blood
BLOOD
The blood is a complex organ composed of cells of diverse form that perform diverse functions. Red blood cells or erythrocytes deliver oxygen to the tissues of the body. Platelets govern primary hemostasis, plugging damaged blood vessels after trauma to stop bleeding. The white blood cells (neutrophils, macrophages, eosinophils, basophils, and B- and T-lymphocytes ) are all involved in different aspects of immunity from infection. Although most aspects of blood physiology do not change throughout adult life, some disorders of the blood, particularly anemia and neoplastic diseases, do occur more frequently with increasing age.
Aging and blood cell production
In mammals, the cells of the blood are produced in the bone marrow. Blood cell production depends upon a small population of cells known as hematopoietic stem cells (HSCs). In the bone marrow milieu, these cells can differentiate to give rise to mature cells of any of the eight blood cell lineages. This process, the development of these eight highly specialized cell types from the pluripotent HSC, is called hematopoiesis.
Most mature blood cells are rather short-lived. For example, red blood cells (erythrocytes) survive for three to four months after they are released into the blood from the bone marrow; neutrophils last only about a week. To maintain appropriate numbers of blood cells the bone marrow continuously produces new blood cells—normally about 1 percent of the red blood cells and 10 percent of the granulocytes of the body are replaced each day. Thus, unlike most adult body tissues, which may lose the capacity to undergo cell division (e.g., nerve tissue) or divide only in response to stress (e.g., liver and kidney), the cells of the bone marrow divide actively throughout life; this may have implications for blood homeostasis in aging humans. In the early 1960s, Leonard Hayflick observed that human diploid cells grown in the laboratory could divide only a finite number of times even under optimal conditions. This phenomenon, known as the "Hayflick Limit," is caused in part by erosion of tandem repeat DNA sequences at the telomeres of chromosomes. These sequences are added to the ends of chromosomes by a specific enzyme, telomerase, which is not active in adult cells. Every time a cell divides there is loss of part of the telomeric repeat array, resulting in progressive loss of these sequences and eventually in impairment of essential cell functions. It has been suggested that the requirement for continuous cell division in the bone marrow may therefore result, in older adults, in "exhaustion" of HSCs.
Some observations in humans and in laboratory animals lend support to the notion of HSC exhaustion. The cellularity of the human bone marrow diminishes with increasing age. At birth, 80–100 percent of the marrow is made up of hematopoietic cells, with the balance occupied by fat, whereas in adults younger than sixty-five years the marrow cellularity is approximately 50 percent, further declining to 30 percent by age seventy-five. Furthermore, hemoglobin levels, which indicate the number of circulating red blood cells, are lower, on average, in older adults (see below). In human and mouse bone marrow, hematopoietic progenitor cells from older individuals exhibit reduced capacity to proliferate in vitro. A more physiologic assessment of HSC function may be obtained from transplantation studies. In mice, bone marrow cells from older donors work as well as those from young mice in restoring hematopoiesis in irradiated recipients, while in humans, bone marrow transplants are successfully performed from donors in their seventies. Old HSCs appear, therefore, to be of equal quality to younger ones, insofar as this can be estimated, but to be fewer in number with age. Overall, theoretical considerations combined with the laboratory and clinical data suggest that aging does reduce the proliferative capacity of HSCs. This reduction is too small to be clinically significant under normal circumstances, although it may result in a reduction in the reserve capacity of the marrow, and could account for an increased susceptibility to anemia in older adults.
Aging and anemia
The chief function of red blood cells is to deliver oxygen to the metabolizing tissues of the body. To ensure adequate performance of this essential function, the quantity of circulating red blood cells or red cell mass (as reflected by the blood hemoglobin level) is tightly regulated. If the red cell mass falls then the amount of oxygen delivered to body tissues is reduced. The peritubular cells of the kidney are particularly sensitive to reductions in oxygen delivery. Under such conditions, these cells are stimulated to release the hormone erythropoietin, which in turn acts upon the bone marrow to increase the production of red blood cells. This leads to improvement in oxygen delivery to body tissues, including the kidney, and thus secretion of erythropoietin is suppressed and the rate of red blood cell production reduced. In this way, red cell production may increase as much as tenfold in times of need, and the red cell mass is usually maintained in a very narrow range.
When these regulatory mechanisms fail, and the red cell mass falls to an abnormally low level, anemia results. Anemia may be caused by an increased rate of red cell loss or from a decreased rate of red cell production. Blood loss may be caused by bleeding or by a shortening of the red blood cell life span (known as hemolysis ). Red cell production may be suppressed by exposure to various toxins (e.g., certain drugs or radiation), by nutritional deficiencies (e.g., of iron, folic acid, or vitamin B12), by bacterial or viral infections, or by involvement of the marrow by primary or metastatic cancer.
It has been shown in numerous population studies that older adults have, on average, lower hemoglobin levels than do younger adults. These observations have led some investigators to conclude that a decline in red cell mass is inherent to the aging process, and that age-specific normal ranges ought to be employed in diagnosing anemia in older people. This issue is complicated, however, by the fact that disorders associated with anemia occur more frequently with increasing age. When only healthy subjects are studied, however, the difference in mean hemoglobin between older and younger adults largely disappears. Therefore anemia in an elderly person cannot be ascribed simply to "old age"; an underlying cause should be sought.
Neoplastic diseases of the blood
With the exception of acute lymphoblastic leukemia, which has its peak incidence in childhood, cancer of the blood is a disease of older adults. While the "cause" of cancer is not entirely understood, great advances in our understanding of the nature of this disease were made in the last two decades of the twentieth century. It is now apparent that in most, and likely in all, cancers, genetic mutations lead to alterations in the normal cellular programs of differentiation, proliferation, and programmed cell death (apoptosis ). Many of these discoveries have come from research on the cancers of the blood.
Myelodysplasia
The synonymous terms myelodysplasia and preleukemia refer to acquired abnormalities of the bone marrow that precede the onset of acute leukemia. These conditions are characterized by chronic anemia, often in combination with reduced white blood cell and platelet counts. Accordingly, patients with myelodysplasia experience symptoms of fatigue, recurrent infections, and easy bruising or bleeding. Paradoxically, despite the reduced numbers of mature blood cells in the peripheral blood, the bone marrow in myelodysplasia shows increased proliferation of developing blood cells. The development of these blood cells is abnormal, however, and their fate is to be destroyed before they can leave the marrow and enter the blood. Myelodysplasia is rarely diagnosed in patients younger than fifty years, and the peak incidence of this disease is seen in the age range eighty to eighty-four years. No cure for myelodysplasia is known, but the symptoms of this condition can be alleviated by transfusions of red cells and platelets and in some cases by injections of the hormone erythropoietin, which stimulates red cell production. These therapies do not alter the natural progression of myelodysplasia to acute leukemia, which may occur over the course of months or years, and which is heralded by the accumulation of cells called blasts in the marrow. These cells are the hallmark of acute leukemia.
Acute leukemia
The term leukemia comes from the Greek, meaning "white blood," and refers to a set of diseases in which neoplastic white blood cells (blasts) accumulate in the blood and bone marrow. These cells fail to differentiate into mature, functional cells of the eight normal lineages, and furthermore suppress the growth of normal blood cells. The symptoms of acute leukemia are a consequence of a lack of normal red blood cells (anemia), white blood cells (leukopenia ), and platelets (thrombocytopenia ), deficiencies that result, respectively, in fatigue, susceptibility to infection, and bruising or bleeding. This disease progresses rapidly, and without treatment is invariably fatal, usually within weeks or months. The treatment of acute leukemia is based upon the use of chemotherapy and radiation therapy, sometimes with the addition of bone marrow transplantation. The goal of these treatments is to destroy all of the leukemic blasts, and to allow the residual normal HSCs to repopulate the bone marrow and restore normal blood production. The first aim of treatment is to eradicate all detectable leukemic blasts in a patient—if this is achieved, the disease is said to be in remission. Remission is not, however, tantamount to cure; almost invariably a small number of leukemic cells survive the therapy and eventually the leukemia returns or relapses. Acute leukemia may develop from preexisting myelodysplasia, or it may arise de novo. Like myelodysplasia, acute leukemia is more common in older adults than in younger adults; approximately 60 percent of cases are diagnosed in patients older than sixty years. Numerous clinical studies have shown, however, that older adults with acute leukemia are significantly less likely to achieve remission or cure than are younger patients. Currently, even with the best available therapy, few people older than sixty years diagnosed with acute leukemia survive longer than three years. There are likely two reasons for this poorer prognosis. First, the therapies for acute leukemia are themselves toxic and harsh. Older patients are more likely to have other significant health problems, and are therefore more susceptible to the adverse effects of therapy and are less likely to receive as high a dose. Second, the biology of acute leukemia appears to be different in older adults, perhaps because of accumulation of additional genetic mutations in HSCs over time. In older adults, acute leukemia is more likely to follow a period of myelodysplasia (see above), or to occur after previous exposure to chemotherapy for another malignancy. Leukemia in older patients is also more likely to exhibit certain characteristic chromosomal abnormalities in the leukemic clone. These features are associated with a poorer response to therapy, whether in younger or older patients.
Chronic leukemia
In contrast to acute leukemia, the chronic leukemias are slowly developing conditions and may be present for years while causing minimal symptoms. The two main forms of chronic leukemia seen in adults are chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL).
Chronic myeloid leukemia is characterized by the accumulation of an abnormal clone of cells of the neutrophil lineage (a type of white blood cell), in various stages of differentiation, in the bone marrow, the peripheral blood, and the spleen, which typically becomes massively enlarged. In the chronic phase of CML there are few symptoms, but this phase inevitably gives way, after a period of two to five years, to an acute phase or blast crisis, which resembles acute leukemia and carries a grave prognosis. CML cells invariably carry a chromosomal translocation affecting chromosomes 9 and 22, which is known as the Philadelphia chromosome; this translocation results in the fusion of two genes, BCR and ABL. The presence of the BCR-ABL fusion appears to be necessary and sufficient for the development of CML. Currently, the mainstays of therapy for CML are interferon alpha, a natural substance that can induce long-term remissions in this disease, and allogeneic bone marrow transplantation. A recently developed drug that specifically inhibits the action of BCR-ABL shows tremendous promise as a CML treatment.
In chronic lymphocytic leukemia, there is accumulation of a clone of abnormal lymphocytes. This initially causes no symptoms, but over time there is progressive accumulation of the malignant cells in the lymph nodes, bone marrow, and spleen. Anemia and thrombocytopenia result, with symptoms of fatigue and bruising or bleeding. Normal lymphocytes are suppressed, and susceptibility to infections is increased. CLL runs an indolent course, and often no treatment is needed for several years following diagnosis. No cure for CLL is currently available, and treatment comprises supportive measures, such as red cell transfusion, and chemotherapy with oral or intravenous agents to control bulky disease in lymph nodes and spleen.
Cancers of the lymphatic system
Lymphoma is cancer of the lymphocytes and arises outside the bone marrow, in the lymph nodes, the spleen, or the lymphatic tissue of the gut. This disease typically causes enlargement of the lymph nodes and constitutional symptoms such as fever, sweats, and weight loss. Frequently, lymphoma invades the bone marrow, causing anemia, thrombocytopenia, and leukopenia. There exists a great number of subtypes of lymphoma that differ substantially in their clinical behavior, ranging from indolent or "low grade" lymphomas that may cause minimal symptoms to aggressive "high grade" lymphomas that run a stormy course and require urgent treatment. Lymphoma is treated with chemotherapy, sometimes combined with radiation therapy. Although some cases of lymphoma can be cured, these remain in the minority.
Multiple myeloma is a neoplastic disease affecting the antibody-producing cells, or plasma cells. Like other malignancies of the blood, the incidence of this condition increases with age; 98 percent of cases occur in patients older than forty years. In myeloma, malignant plasma cells accumulate in the bone marrow. These malignant cells produce great quantities of an antibody, known as a monoclonal paraprotein. This antibody is not produced in response to infection and is useless to the body. Indeed, the paraprotein may injure the kidney, and as malignant plasma cells accumulate, normal plasma cells, and other bone marrow cells, are suppressed and the production of normal antibodies is severely impaired. Anemia is also frequently present. In addition, the malignant cells secrete chemicals, known as cytokines, which cause the bones to lose calcium and weaken. Hence, patients with myeloma may experience fatigue, frequent infections, pain and fractures of bone, and kidney failure. No cure for multiple myeloma is known, although treatment with chemotherapy may temporarily reduce the burden of malignant cells and alleviate symptoms. Drugs that stimulate the bones to retain calcium have been proven effective in reducing bone loss and its complications.
The presence of a paraprotein is not sufficient to establish the diagnosis of myeloma. Indeed, monoclonal paraproteins are common in older adults, but usually occur in the absence of the accumulation of malignant plasma cells, anemia, bone destruction, and kidney damage characteristic of myeloma. These cases are referred to as "monoclonal gammopathy of unknown significance" (MGUS). Some cases of MGUS probably represent early myeloma, or a pre-malignant condition that leads to myeloma. In most cases, however, this condition remains entirely benign.
Richard A. Wells
See also Cancer, Biology; Cancer, Diagnosis and Management; Cellular aging.
BIBLIOGRAPHY
Baldwin, J. G. "Hematopoietic Function in the Elderly." Archives of Internal Medicine 148 (1988): 2544–2546.
Cohen, H. J."Disorders of the Blood." In Oxford Textbook of Geriatric Medicine. Edited by J. G. Evans and T. F. Williams. Oxford, U.K.: Oxford University Press, 1992. Pages 435–441.
Latagliata, R.; Petti, M. C.; and Mandelli, F. "Acute Myeloid Leukemia in the Elderly: 'per aspera ad astra'?" Leukemia Research 23 (1999): 603–613.
Nilsson-Ehle, H.; Jagenburg, R.; Landhal, S.; Svanborg, A.; and Westin, J. "Decline of Blood Haemoglobin in the Aged: A Longitudinal Study of an Urban Swedish Population from Age 70 to 81." British Journal of Haematology 71 (1989): 437–442.
Timiras, M. L., and Brownstein, H. "Prevalence of Anemia and Correlation of Hemoglobin with Age in a Geriatric Screening Population." Journal of the American Geriatrics Society 35 (1987): 639–643.
Whittaker, J. A., and Holmes J. A., eds. Leukaemia and Related Disorders, 3d ed. Oxford, U.K.: Blackwell Science Ltd., 1998.
Williams, W. J. "Hematology in the Aged." In Hematology, 5th ed. Edited by E. Beutler, M. A. Lichtman, B. S. Collier, and T. J. Kipps. New York: McGraw-Hill Inc., 1995. Pages 72–77.
Zauber, N. P., and Zauber, A. G. "Hematologic Data of Healthy Very Old People." Journal of the American Medical Association 257 (1987): 2181–2184.
Blood
Blood
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 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.
Kinds of blood found in the animal kingdom
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 animals without vertebrae, called invertebrates , have circulatory systems that do not contain blood vessels. In these open circulatory systems, the fluid analogous to blood is called hemolymph (Greek, hemo, blood + lympha, water ). Examples of animals that circulate hemolymph include insects and aquatic arthropods such as lobsters and crawfish. Like blood, hemolymph transports oxygen and carbon dioxide and has a limited clotting ability. Unlike blood, hemolymph is colorless. Other invertebrates have no true circulatory system . In these animals, it is not possible to distinguish blood or hemolymph from the watery fluid that bathes the tissues. This fluid contains a few defensive cells, proteins, and salts. However, oxygen and carbon dioxide are not transported in this fluid.
The composition of human blood
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%.
Plasma
Plasma contains mostly water, which accounts for 91.5% of the plasma content. The water acts as a solvent for carrying other substances.
Proteins account for 7% of plasma. The most prevalent of these proteins in plasma 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. 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 interstitial fluid into the blood, diluting the plasma and swelling the blood volume . A high blood volume could have disastrous consequences, because the circulatory system can only pump so much blood before it becomes overloaded.
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 other immune cells. Fibrinogen is a protein that functions in a complex series of reactions that leads to the formation of blood clots.
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 solutions of water and salts or by having the patient drink solutions of salts and water.
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, or 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.
Formed elements, or blood cells
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.
See also Anemia; Anticoagulants; Blood gas analysis; Blood supply; Heart; Hematology; Respiratory system.
Resources
books
Agre, Peter C., and Jean-Pierre Cartron, eds. Protein BloodGroup Antigens of the Human Red Cell: Structure, Function, and Clinical Significance. Baltimore: Johns Hopkins University Press, 1992.
Belcher, Anne E. Blood Disorders. St. Louis: Mosby Year-Book, 1993.
Kapff, Carola R. Blood: Atlas and Sourcebook of Hematology. 2nd edition. Boston: Little, Brown. 1991.
Long, Michael W., and Max S. Wicha, eds. The HematopoieticMicroenvironment: The Functional and Structural Basis of Blood Cell Development. Baltimore: Johns Hopkins University Press, 1993.
Periodicals
Roush, Wade. "An 'Off-Switch' for Red Blood Cells." Science. 268 (April 7, 1995): 27.
Ware, Anthony J., and Donald D. Heistad. "Platelet-Endothelium Interactions." New England Journal of Medicine,, 328 (March 4, 1993): 628.
Weller, Peter F. "The Immunobiology of Eosinophils." NewEngland Journal of Medicine 324 (April 18, 1991): 110.
Kathleen Scogna
KEY TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .- ABO blood groups
—Blood types established by the A and B antigens present on the plasma membrane of red blood cells; ABO blood groups include A, B, AB, and O.
- Aerobic metabolism
—Metabolic processes that require oxygen.
- Agranular leukocyte
—A white blood cell without granules in its cytoplasm; these white blood cells include the monocytes and lymphocytes.
- Albumin
—A protein found in plasma.
- Antibody
—A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.
- Antigen
—A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.
- B lymphocyte
—Immune system white blood cell that produces antibodies.
- Basophil
—A type of white blood cell; functions in the inflammatory response by releasing histamines and other chemicals that have specific effects on tissues.
- Capillary
—The smallest blood vessel; it connects artery to vein.
- Centrifugation
—A laboratory procedure in which a test tube of blood or other liquid is spun at a high speed.
- Circulatory system
—The body system that circulates blood pumped by the heart through the blood vessels to the body tissues.
- Clotting factor
—A set of substances released by platelets that function in the clotting mechanism.
- Cytotoxic T lymphocyte
—A type of white blood cell that attacks and kills cells infected by a foreign microorganism.
- Electrolytes
—The salts and other substances present in the plasma that function in crucial body processes.
- Eosinophil
—A type of white blood cell that counteracts the effects of histamine and other inflammatory chemicals; also phagocytizes bacteria tagged by antibodies.
- Erythrocyte
—A red blood cell.
- 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.
- Formed elements
—The cells present in blood.
- Granular leukocyte
—A white blood cell that contains granules in its cytoplasm; includes basophils, eosinophils, and neutrophils.
- Helper T lymphocyte
—The "lynch pin" of specific immune responses; helper T cells bind to APCs (antigen-presenting cells), activating both the anti-body and cell-mediated immune responses.
- Hemoglobin
—An iron-containing, protein complex carried in red blood cells that binds oxygen for transport to other areas of the body.
- Hemolymph
—The blood-like liquid present in the open circulatory systems of certain invertebrates.
- 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.
- Human leukocyte antigen (HLA)
—A type of antigen present on white blood cells; divided into several distinct classes; each individual has one of these distinct classes present on their white blood cells.
- Immunoglobulin
—The protein molecule that serves as the primary building block of antibodies.
- 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.
- Leukocyte
—A white blood cell.
- 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.
- Lymphoid stem cell
—The cell from which B and T lymphocytes are derived.
- Lysozyme
—An enzyme released by neutrophils that kills cells.
- Macrophage
—A type of phagocytic cell derived from monocytes.
- Monocyte
—A type of white blood cell that phagocytizes foreign microorganisms.
- Neutrophil
—A type of white blood cell that phagocytizes foreign microorganisms; also releases lysozyme.
- Phagocytize
—To engulf and digest a cell.
- Plasma
—The straw-colored liquid portion of blood that contains water, proteins, salts, nutrients, hormones, and metabolic wastes.
- Plasma cell
—The cell derived from the B lymphocyte, which secretes antibodies.
- Platelet
—A piece of a cell that contains clotting factors.
- 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.
- T cells
—Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.
- Thymus
—The organ in which T cells undergo further development and maturation.
Blood
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 of 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 hemolymph.)
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 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 for 91.5% 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 3-8% 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 0.5-1% 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 2-4% 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 (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.
Role in human health
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:
- A person with A antigens is type A and has antibodies to B antigens.
- A person with B antigens is type B and has antibodies to A antigens.
- A person with both antigens is type AB and does not have antibodies to either antigen.
- A person with none of the antigens is type O and has antibodies to both A and B antigens.
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.
Common diseases and disorders
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 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 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.
Resources
BOOKS
Long, Michael W., and Max S. Wicha, eds. The Hematopoietic Microenvironment: The Functional and Structural Basis of Blood Cell Development. Baltimore: Johns Hopkins University Press, 1993.
Shin, Linda, and Karen Belliner. Blood and Coagulation Disorders Sourcebook: Basic Information about Blood and Its Components. Omnigraphics, 1998.
PERIODICALS
Creteur, Jacques, William Sibbald, and Jean-Louis Vincent. "Hemoglobin Solutions: Not Just Red Blood Cell Substitutes." Critical Care Medicine 28 (August 2000): 3025-34.
Delves, P. J. and I. M. Roitt. "The Immune System: First of Two Parts." New England Journal of Medicine 343 (6 July 2000): 37-49.
Delves, P. J. and I. M. Roitt. "The Immune System: Second of Two Parts." New England Journal of Medicine 343 (13 July 2000): 108-17.
Tremper, Kevin K. "Perfluorochemical Blood Substitutes: Indications for an Oxygen-Carrying Colloid." Anesthesiology 91 (November 1999): 1185.
ORGANIZATIONS
American Sickle Cell Anemia Association. 10300 Carnegie Avenue, East Office Building (EEb18), Cleveland, OH 44106. (216) 229-8600. 〈http://www.ascaa.org〉.
America's Blood Centers. 725 15th Street NW, Suite 700, Washington, DC 20005. (202) 393-5725. 〈http://www.americasblood.org〉.
National Hemophilia Foundation. 116 West 32nd Street, 11th Floor, New York, NY 10001. (800) 42-HANDI. 〈http://www.hemophilia.org〉.
OTHER
"Blood Work: A Useful Tool for Monitoring HIV." Project Inform Website. April 2001. 7 July 2001. 〈http://www.projinf.org/fs/HIVDiagTest.html〉.
"Sickle Cell Anemia." KidsHealth Website. 2001. 7 July 2001. 〈http://kidshealth.org/parent/medical/heart/sickle_cell_anemia.html〉.
blood
Blood is of immense cultural significance. We talk of blood ‘being thicker than water’ to signify the strength of family loyalty, as also reflected in ‘blood brothers’. A massacre is a ‘blood bath’, the reward for assassination ‘blood money’. Blood signifies power, for good or evil; the consumption of blood, metaphorically, lies at the heart of the Christian sacrament, yet many societies produce legends of vampires, whose evil is signified by their taste for human blood. Blood is often equated with strength: the monthly loss of blood through menstrual flow frequently led doctors (mostly male) to assume an inherent weakness in women. But too much blood could also be troublesome: ruddy-faced, plethoric men would make an annual visit to the barber-surgeon each spring (blood's season, according to the doctrine of the humours) to be bled. Barbers and surgeons went their separate ways in the seventeenth and eighteenth centuries, but the red stripe down the barber's pole still commemorates this annual blood-letting ritual.
Knowledge of the structure of blood (such as the notion that it consists of cells suspended in a protein-rich fluid called plasma) slowly accumulated from the seventeenth century onwards. The Dutch microscopist Anton van Leeuwenhoek (1632–1723), examining his own blood under a simple microscope, first described the red corpuscles (cells), and measured their diameter. White corpuscles were first observed by the British physician William Hewson (1739–74), who also discovered the essential features of how blood coagulates, showing that it is due to the clotting of plasma rather than changes in the cellular constituents. In the latter half of the nineteenth century it was found that blood cells are the progeny of more primitive cells in the bone marrow. The modern science of haematology stemmed from the work of the German pharmacologist Paul Ehrlich (1854–1915), who developed a stain that led to a clear distinction between the different types of cells in the blood.
An understanding of the function of blood also evolved over several centuries. William Harvey described its circulation in 1628, and a few years later the English physician Richard Lower (1631–91) observed the change from the dark blue colour of venous to the bright red of arterial blood after its passage through the lungs. In 1790 the French chemist Antoine Lavoisier (1743–94) discovered oxygen and found that it was the constituent of air that is responsible for the change of the colour of blood. In the mid nineteenth century it was found that oxygen combines with a substance in the red cells, which was identified as the protein haemoglobin by the German biochemist Felix Hoppe-Seyler (1825–95). By 1900 it was also appreciated that the white cells play a crucial role in defence against infection, an idea first proposed by the Russian zoologist Ilya Metchnikoff (1845–1916).
Blood is the body's major transport system, carrying vital substances to all the tissues and removing their waste products. It delivers oxygen from the lungs and collects carbon dioxide to be excreted there; it takes up nutrients from the gut, and distributes them for use or storage; and by virtue of its passage through the kidneys it provides an important mechanism for the excretion of toxic waste products of metabolism. The blood also distributes hormones from their sites of secretion to their sites of action, and likewise the cells, antibodies, and other substances which combat injury and infection. In performing these functions, the blood continually exchanges substances across the capillary walls with the fluids that bathe all body cells. The total volume of blood, which remains remarkably constant in adults, is approximately 70 ml/kg body weight, or about 5 litres. It consists of a fluid component, plasma, in which are suspended red cells, white cells, and platelets (see figure). In health, the cells comprise about 45% of the total volume of blood: this value is known as the haematocrit, and reflects mainly the bulk of the red blood cells.
Red blood cells
The number of circulating red cells in a unit volume of blood — the red cell count — varies at different stages of development. It is relatively high in fetal life and falls quickly after birth, before gradually rising to reach its adult level by the age of 20 (about 5 million/mm3 of blood). Although it is approximately the same in males and females during childhood, it is higher in males after adolescence. Red cells survive for only about three months in the circulating blood, so production continues throughout life.The major role of red cells (erythrocytes) is to transfer oxygen from the lungs to the tissues. Their rate of production is beautifully adapted to this function. It is regulated by a hormone called erythropoietin, produced in the kidney in the adult and in the liver in the fetus. Close to the gene that regulates erythropoietin production are regions of DNA that sense oxygen tension; when this falls, erythropoietin synthesis is stimulated, and more red cells are produced in the bone marrow. When adequate oxygenation of the tissues is achieved, erythropoietin production is reduced. By this biological feedback loop the body is able to respond to varying oxygen demands by modifying the rate of red cell production. In addition to erythropoietin, there is probably some fine tuning of the rate of erythropoiesis by other hormones and protein growth factors.
The site of red cell production changes during development. In the embryo, they are made in the yolk sac, in the fetus in the liver and spleen, and in adult life in the bone marrow. These sites all contain a primitive, self-renewing population of blood-cell precursors, the haemopoietic stem cells, which are capable of producing all the different cells of the blood. Red cell production (erythropoiesis) takes about 7 days. The progeny of stem cells destined to become red cells start out as large, nucleated cells; during their development haemoglobin synthesis begins and, after several divisions, their nucleus is condensed and eventually extruded from the cell. This red cell precursor is now called a reticulocyte. Reticulocytes are released from the marrow into the blood; they undergo fine quality control in the spleen, where unwanted nuclear remnants are removed. (This process is different in birds and amphibians; the nucleus is not removed and is retained throughout the life of the red cell in the peripheral blood.) An adequate dietary supply of iron and of specific vitamins is necessary for the synthesis of haemoglobin and the production of normal red cells.
After their release from the bone marrow, red cells spend approximately 120 days in the circulation. During this time they travel over 100 miles, are buffeted at high velocities during their passage through the heart, and have to negotiate tiny capillaries narrower than their own diameter. As they age, subtle structural changes occur which render them identifiable to scavenger cells in the spleen and elsewhere, and they end their days being devoured and digested by these predators.
The red cells of most species are biconcave discs, a shape that offers maximum surface area for exchange of oxygen and carbon dioxide. They consist of a protein and lipid membrane, which encases haemoglobin together with water and a variety of enzymes and salts. Their chemistry is beautifully adapted to their function as an oxygen transporter and to protect them and their haemoglobin from chemical damage.
The oxygen-carrying protein of red cells, haemoglobin, is also closely adapted to its function. In most mammals, adult haemoglobin (haemoglobin A) comprises two unlike pairs of chains of amino acids, or globin chains, called a and b, each of which is folded round one iron-containing haem molecule, to which oxygen can bind. The resulting molecule is designated a2b2. In humans, and some other species, there is a different fetal haemoglobin, haemoglobin F, which has a chains combined with g chains (a2g2). In most species adult and fetal haemoglobins are preceded by an embryonic haemoglobin. These different haemoglobins are adapted to particular oxygen requirements at different stages of development. While taking up and giving off oxygen, subtle spatial alterations occur between the globin chains which are responsible for the oxygen dissociation properties of haemoglobin, essential for normal oxygen transport. These functions can be modified by carbon dioxide, pH, and intracellular substances such as 2,3-diphosphoglycerate, the control of which is itself regulated by intracellular pH and oxygen levels. Hence there is an elegant intracellular control network relating oxygen delivery to red cell metabolism which, in turn, reflects the oxygen requirements of the tissues.
White blood cells
The white blood cells, much less abundant than red cells, play a key role in the body's defence against environmental pathogens. They are subdivided — on the basis of their microscopic structure, differences in taking up stains, and functions — into phagocytic (‘eater’) cells (which include neutrophils, monocytes, and eosinophils), and non-phagocytic cells (lymphocytes and basophils).Phagocytic white cells derive from precursors in the bone marrow. Their production and maturation is controlled by a family of proteins called haemopoietic growth factors. Following their release into the blood, many of them remain in a so-called storage pool, stuck to the wall of blood vessels. The numbers circulating freely in the blood therefore represent just a fraction of the total body content.
The main function of the neutrophils is to kill microorganisms. They are attracted to areas of damaged tissue, where they internalize bacteria and other foreign particles, killing any invaders by a complex combination of oxidative and non-oxidative mechanisms. Monocytes have similar properties to neutrophils, and play an important role as part of the macrophage (‘big eater’) system by presenting foreign proteins (antigens) to T cells (see below). Eosinophils, which are particularly active against parasitic infections, exert their action by discharging highly active elements from preformed granules. Basophils, and tissue cells called mast cells, to which they are related, also play an important role in combating parasitic infection.
The other important class of white cells is the lymphocytes. These cells play a major role in the body's immune system. They are also derived from haemopoietic stem cells and disseminated in the bloodstream; some migrate to sites known as the ‘primary lympho-epithelial organs’, including the thymus gland, where they differentiate further and eventually populate the ‘secondary lymphoid tissues’, including the spleen, lymphoid tissue in the alimentary canal, and the lymph nodes. One set of lymphocytes, thymus-derived or T cells, migrate to specific areas within these tissues and pass through them into the lymphatic vessels; thus they recirculate from the blood to the lymph, and then back to the blood where the lymphatic system drains into it via the thoracic duct. The Tcells are responsible for cellular immune responses. The other class of lymphocytes, B cells, populate different regions of the lymphatic system. Some of them also recirculate. They are the precursors of antibody-forming cells.
The immune system of a human can differentiate more than one million different foreign proteins, or antigens. T and B cells identify antigen by exposing receptor molecules on their surface: immunoglobulin for B cells, and T cell receptors for T cells. Before their first encounter each lymphocyte can only produce receptors to one particular antigen. When a lymphocyte binds to an antigen, it starts to divide to produce a clone of daughter cells, all with the same specificity — a process known as clonal selection. B cells produce immunoglobulins, or antibodies, in response to particular antigens, while T cells, after being activated by antigen presented to them by macrophages, either kill invading organisms directly, or play more subtle roles in co-ordinating other immune defence mechanisms. The extraordinary specificity and diversity of action of B and T cells is a reflection of a complex series of developmental rearrangements of the genes for immunoglobulins and the T cell receptor.
Platelets and blood clotting
It is vital to have ways to prevent the loss of blood after damage to blood vessels. It is equally important, however, that these processes occur only when they are needed, and do not spread from the site of injury to block off normal healthy vessels. These aims are achieved by the complicated series of cellular and biochemical interactions that constitutes blood clotting. Platelets, the other cellular elements of the blood, play a central role. These small, enucleate cells are produced from large parent cells, the megakaryocytes, in the bone marrow.When a blood vessel ruptures there is immediate reflex constriction, thus narrowing the opening through which blood can escape. Platelets then aggregate at the site of the disruption. The adhesion of platelets to the exposed tissues beneath the wall of the blood vessel requires the action of a plasma protein called von Willebrand factor, which binds to specific receptors on the outer membrane of the platelet. As platelets adhere they release a variety of chemicals that cause further aggregation, leading to the production of a temporary haemostatic plug.
At the same time as platelets are forming aggregates in the damaged vessel wall, a sequence of reactions — the coagulation ‘cascade’ — is activated. The objective of this complex process is to convert a soluble plasma protein, fibrinogen, to an insoluble fibrin mesh, or blood clot. This conversion requires the action of the enzyme thrombin, which is normally present in the blood in its inactive form, prothrombin. Thrombin also stimulates platelets to release several clotting factors and aggregating agents.
The activation of prothrombin results from the action of a remarkable biological amplification system in which circulating, inactive blood clotting factors are converted to catalytically active forms. The properties, and potential dangers, of this system are phenomenal: a sufficient amount of thrombin can be generated from the prothrombin in 2 ml of blood to clot the entire circulating volume. One of the inactive precursors in the clotting cascade is defective in the blood in haemophilia. Four of the factors require vitamin K for their production in the liver. Ionized calcium is one of the necessary factors.
This system is further complicated by the fact that activation of thrombin can occur through the intrinsic coagulation system, that is by the interaction of circulating factors, as well as by an extrinsic system which requires a factor from the tissues to interact with some of the circulating factors.
There is continual minor damage to the lining of blood vessels, so that blood clotting is continually being activated. Therefore mechanisms must exist for terminating the clotting cascade or dealing with the consequences of its activation. These involve either the inactivation of some of the protein co-factors by the enzymatic action of other plasma proteins (such as protein C or antithrombin III), or the digestion of unwanted fibrin (fibrinolysis) by the enzyme plasmin, activated from the plasminogen which is normally present in the blood.
Haemostasis — the prevention of blood loss — and blood coagulation are thus dynamic processes in which there is continual activation of the complex coagulation pathways, kept in check by inactivation mechanisms together with the removal of unwanted blood clot by the fibrinolytic system.
Plasma
The liquid plasma, in which all the cells of the blood are suspended, contains a variety of substances both in solution and as colloidal particles. There are salts, nutrients from the food (lipids, sugars, and amino acids) and hormones. A complex mixture of proteins includes albumin — the main bulk of the plasma proteins, and of considerable importance in maintaining osmotic homeostasis, as it prevents the accumulation of excess fluid in the body tissues; globulins — some acting as ‘carriers’ for substances such as hormones, and others (gamma-globulins) which are part of the immune system; and also fibrinogen and other substances necessary for clotting.The main functions of plasma are to transport nutrients, waste materials, and hormones; to provide an appropriate environment for different blood cells; to ensure, by exchange of water and solutes across capillary walls, that the chemical composition of the body fluids, both outside and inside cells, remains within normal, physiological concentrations; and — by carrying the coagulation proteins and their antagonists — to ensure that blood loss is prevented promptly after injury.
Mark Weatherall, and D. J. Weatherall
See also anaemia; blood circulation; blood transfusion;body fluids; haemoglobin; homeostasis; immune system; lymphatic system; menstruation; thymus.
DNA Profiling
DNA Profiling
DNA profiling is a molecular testing method used to uniquely identify people and other organisms. In many ways, it is similar to blood typing and fingerprinting, and it is sometimes called "DNA fingerprinting." Because every organism's DNA is unique, DNA can be examined to identify people who might be related to each other, to compare suspected criminals to DNA left at the scene of a crime, or even to identify certain strains of disease-causing bacteria.
Blood Typing and the ABO Groupings
Before the development of the molecular biology tools that make DNA testing possible, investigators identified people through blood typing. This method hails from 1900, when Karl Landsteiner first discovered that people inherited different blood types. Several decades later, researchers determined that the basis for those blood types was a set of proteins on the surface of red blood cells.
The main proteins on the surface of red blood cells used in blood typing come in two varieties: A and B. Every person inherits from their parents either the genes for the A protein, the B protein, both, or neither. Someone who inherits the A gene from one parent and neither gene from the other parent has blood type A. If a person inherits both genes, they are AB. A person who inherits neither is type O. Another protein group found on red blood cells is referred to collectively as the Rh factor. People either have the Rh factor or they do not, regardless of which of the A and B genes they inherited. To type a person's blood, antibodies against these various proteins (A, B, and Rh) are mixed with a blood sample. If the proteins are present, the blood cells will stick together and the sample will get cloudy.
Blood typing can be used to exclude the possibility that a blood sample came from a particular person, if the person's type does not match that of the sample. However, it cannot be used to claim that any particular person is the source of the sample, because there are so few blood types, and they are shared by so many people. About 45 percent of people in the United States are type O, and another 40 percent are type A. If four people were physically present at the scene of a murder, and the candlestick found nearby had type O blood spilled on it, chances are good that two of those individuals could be found guilty of the crime, based solely on the blood typing evidence. Most court cases, however, rely on more evidence than just blood or DNA typing, such as whose fingerprints are also found on the candlestick (see Statistics and the Prosecutor's Fallacy, below).
DNA Polymorphism Offers High Resolution
DNA is the molecule that contains all the genetic information of an individual. One person's DNA is made up of about three billion building blocks known as nucleotides or bases. Every organism in the world has a unique DNA sequence except for identical twins. Although identical twins accrue changes as they develop, they generally do not accumulate enough genetic differences for DNA typing to be useful. Portions of the DNA, called genes, encode proteins within the sequence of bases. Genes are separated by long stretches of noncoding DNA. Because these sequences do not have to code for functional proteins, they are free to accumulate more differences over time, and thus provide more variation than genes. Thus, they are more useful than gene sequences in distinguishing individuals.
Polymorphisms are differences between individuals that occur in DNA sequences which occupy the same locus in the chromosome. An individual will have only one sequence at a particular polymorphic locus in each chromosome, but if the population bears several to dozens of different possible sequences at the site in question, then the locus is considered "highly variable" within the population. DNA profiling determines which polymorphisms a person has at a small number of these highly variable loci. Because of this, DNA profiling can provide high resolution in distinguishing different individuals. The chances of one person having the same DNA profile as another are typically much less than the chances of winning a lottery.
STR Analysis
The technology of DNA profiling has advanced from its beginnings in the 1980s. Today, DNA profiling primarily examines "short tandem repeats," or STRs. STRs are repetitive DNA elements between two and six bases long that are repeated in tandem, like GATAGATAGATAGATA. These repeat sequences often exist in a chromosomal region called heterochromatin, a largely unused portion of DNA found in each chromosome.
Different STR sequences (also called genetic markers) occur at different loci. While their positions are fixed, the number of repeated units varies within the population, from four to forty depending on the STR. Therefore, one genetic marker may have between four and forty different variations, and each variation is referred to as an allele of that marker. Each person has at most two alleles of each marker, one inherited from each parent. The two alleles for a particular marker may be identical, if both parents had the same form.
The United States Federal Bureau of Investigation has designated thirteen of these sequences to use with STR analysis. These thirteen markers are all four-base repeats, and were chosen because multiple alleles of each exist throughout the population. The FBI system, called CODIS (Combined DNA Indexing System), has become the standard DNA profiling system in use today.
STR analysis begins with sample collection. Because of the often small samples involved and the legal weight that will be given to them, it is vital that the sample not be contaminated by other DNA. This may occur for instance if skin cells from the person collecting the sample are mixed with skin cells under the fingernails of a victim. Once the sample is collected, it must be kept secure at all times, to prevent any possibility of tampering.
In the laboratory, the DNA is isolated and purified, and then multiple copies of it are made using the polymerase chain reaction (PCR ). Technicians can specify which DNA sequences to multiply, so that only the thirteen core STR sequences will be amplified (multiple copies produced), leaving the rest of the billions of irrelevant bases alone.
In order to specify which DNA to amplify, "primers" are used. The primers are DNA sequences that recognize a nonrepeated sequence in the genetic markers, and which are used by the DNA polymerase that does the actual copying. After the DNA has been copied, the new DNA molecules are separated by size, by gel electrophoresis. A fluorescent molecule previously attached to each primer will send a light signal to the machine that measures the length of the molecule, or allele.
VNTR Analysis
An early form of DNA profiling, rarely used today, is based on VNTRs, or "variable number of tandem repeats." VNTRs requires extensive sample processing: The DNA is chopped up with restriction enzymes, separated by size, and probes are applied to the fragmented DNA to view only the relevant DNA pieces. In the DNA of two different individuals, different spacing between two cut sites for the restriction enzymes gives a unique pattern of DNA size fragments, called "restriction fragment length polymorphisms," or RFLPs.
Making a Match
To understand how DNA profiling is used to identify a person, imagine a sample of blood collected at a crime scene that doesn't match the victim's blood, and is presumably from the unknown perpetrator. DNA from the blood is isolated and its set of STRs are analyzed. The results will be a list of the alleles found at each of the markers (for example, VWA-12, 13; TH01-6, 7, and so on), where the initial symbol is the abbreviation for the markers and the last two are the numbers of the alleles found in the sample for that marker. The full set of thirteen markers may or may not be analyzed in each case. When a suspect is identified, his or her DNA can be analyzed for these same markers. If the set of alleles are different, the investigators can be sure that the two DNAs came from different sources, and the suspect is not the source of the blood. Since the introduction of DNA profiling, an absence of matching DNA has been used to free dozens of wrongly convicted prisoners.
If the samples do match, the question becomes whether the blood is actually from the suspect, or from someone else with the same set of alleles. As with blood typing, this is a matter of statistics, and depends on how frequently each allele occurs in the population. This information has been tabulated and is kept on file in the FBI CODIS database. If two samples share a very rare allele, that increases the likelihood they came from the same source.
Matching multiple alleles increases the certainty they came from the same source. Since the thirteen STRs are inherited independently of each other, the likelihood that one person's DNA will include specific alleles of all thirteen STR sites is the product of the individual allele frequencies. For example, if each allele a person carries occurs in 25 percent of the population, then the probability that all thirteen alleles will occur in one individual is (0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25 × 0.25) or 1 in more than 67 million. This analysis can discriminate between millions of people, far better than is possible using the four blood groups. Since many alleles are even rarer than 25 percent, their presence in both samples further increases the probability that they came from the same source.
Statistics and the Prosecutor's Fallacy
Despite the persuasiveness of such figures, it is quite possible to misuse DNA evidence to incorrectly argue that an innocent suspect must be the perpetrator of the crime, or that a guilty suspect should go free. Both defense and prosecution attorneys can—accidentially or otherwise—misinterpret data to make a highly likely event seem improbable, or a highly unlikely event seem probable. Jurors can be confused because DNA testing reveals the probability that an innocent person's DNA profile matches the sample at the scene of the crime. Jurors must decide, however, what the probability is that a person is innocent, if his DNA matches that sample. The prosecutor's fallacy occurs when investigators focus on the existence of the match, rather than the possibility that the match could be a coincidence.
Let's assume the DNA profile found at the crime scene—and the matching DNA of the suspect—is expected to occur once in every million people. The correct statement of probability arising from these facts is, "If the suspect is innocent, there is a one-in-one-million chance of obtaining this DNA match." The fallacy is to reverse these clauses, and state, "If the DNA matches, there is a one in one million chance that the suspect is innocent." To understand the logical fallacy, imagine the statement, "If it's Tuesday, it must be a school day." The reverse is not true—there are other school days besides Tuesday.
Similarly, there are other ways of misusing statistics in DNA profiling. Let's assume the suspect in the above case is actually guilty. If the suspect hails from a city with a population of ten million, there are ten people in the city whose DNA matches the DNA at the crime scene. Therefore, his defense lawyers could argue there is a 90 percent chance that the suspect is innocent, because he is 1 out of 10 individuals with that same DNA profile. If the defense can convince the jury to ignore other incriminating evidence, such as the suspect's bloody glove left behind at the scene, then the attorney may introduce reasonable doubt. Only by considering DNA typing within the context of other evidence can the probability of a DNA match improve the integrity of the justice system.
DNA Profiling Comes of Age
Although DNA profiling was viewed with some skepticism when it first made its way into the courts, DNA typing is now used routinely, in and out of the courthouse. It is commonly used in rape and murder cases, where the assailant generally leaves behind some personal evidence such as hair, blood, or semen. In paternity tests, the child's DNA profile will be a combination of the profiles of both parents. DNA profiling has also been used to identify victims in disasters where large numbers of people died at once, such as in airplane crashes, large fires, or military conflicts.
DNA testing can also used in organisms other than humans. For instance, it has been used to type cattle in a cattle-stealing case. It can also be used to identify pathogenic strains of bacteria to track the outbreak of disease epidemics.
see also Biotechnology and Genetic Engineering, History; Gel Electrophoresis; Polymerase Chain Reaction; Polymorphisms; Repetitive DNA Elements.
Mary Beckman
Bibliography
Bloom, Mark V., Greg A. Freyer, and David A. Micklos. Laboratory DNA Science: An Introduction to Recombinant DNA Techniques and Methods of Genome Analysis. Menlo Park, CA: Addison-Wesley, 1996.
Evert, Ian W., and Bruce S. Weir. Interpreting DNA Evidence: Statistical Genetics for Forensic Scientists. Sunderland, MA: Sinauer Associates, 1998.
Steward, Ian. "The Interrogator's Fallacy." Scientific American (September 1996): 172-175.
Internet Resources
"13 CODIS Core STR Loci with Chromosomal Positions." National Institute of Standards and Technology. <http://www.cstl.nist.gov/biotech/strbase/images/codis.jpg>.
The Biology Project. The University of Arizona. <http://www.biology.arizona.edu/human_bio/activities/blackett2/gifs/sample2.gif>.
FBI Core STR Markers. <http://www.cstl.nist.gov/biotech/strbase/fbicore.htm>.
The Innocence Project. <http://www.innocenceproject.org/>.
Blood Sugar Tests
Blood sugar tests
Definition
Blood sugar or plasma glucose tests are used to determine the concentration of glucose in blood. These tests are used to detect an increased blood glucose (hyperglycemia ) or a decreased blood glucose (hypoglycemia ).
Purpose
Blood glucose tests are used in a variety of situations, including the following:
- Screening persons for diabetes mellitus : The American Diabetes Association (ADA) recommends that a fasting plasma glucose (fasting blood sugar) be used to diagnose diabetes. If the person already has symptoms of diabetes, a blood glucose test without fasting, called a casual plasma glucose test, may be performed. In difficult diagnostic cases, a glucose challenge test called a two-hour oral glucose tolerance test is recommended. If the result of any of these three tests is abnormal, it must be confirmed with a second test performed on another day. The same test or a different test can be used, but the result of the second test must be abnormal as well in order to establish a diagnosis of diabetes.
- Blood glucose monitoring: Daily measurement of whole blood glucose identifies diabetics who require intervention to maintain their blood glucose within an acceptable range as determined by their physician. The Diabetes Control and Complications Trial (DCCT) demonstrated that persons with diabetes who maintained blood glucose and glycated hemoglobin (hemoglobin with glucose bound to it) at or near normal decreased their risk of complications by 50 to 75 percent. Based on results of this study, the American Diabetes Association (ADA) recommends routine glycated hemoglobin testing to measure long-term control of blood sugar.
- Diagnosis and differentiation of hypoglycemia: Low blood glucose may be associated with symptoms such as confusion, memory loss, and seizure. Demonstration that such symptoms are the result of hypoglycemia requires evidence of low blood glucose at the time of symptoms and reversal of the symptoms by glucose. In documented hypoglycemia, blood glucose tests are used along with measurements of insulin and C-peptide (a fragment of proinsulin) to differentiate between fasting and postprandial (after a meal) causes.
Description
The body uses glucose to produce the majority of the energy it needs to function. Glucose is absorbed from the gastrointestinal tract directly and is also derived from digestion of other dietary carbohydrates. It is also produced inside cells by the processes of glycogen breakdown (glycogenolysis) and reverse glycolysis (gluconeogenesis). Insulin is made by the pancreas and facilitates the movement of glucose from the blood and extracellular fluids into the cells. Insulin also promotes cellular production of lipids and glycogen and opposes the action of glucagons, which increases the formation of glucose by cells.
Diabetes may result from a lack of insulin or a subnormal response to insulin. There are three forms of diabetes: Type I or insulin dependent (IDDM), type II or noninsulin dependent (NIDDM), and gestational diabetes (GDM). Type I diabetes usually occurs in childhood and is associated with low or absent blood insulin and production of ketones even in the absence of stressed metabolic conditions. It is caused by autoantibodies to the islet cells in the pancreas that produce insulin, and persons must be given insulin to control blood glucose and prevent ketosis. Type II accounts for 85 percent or more of persons with diabetes. It usually occurs after age 40 and is usually associated with obesity . Persons who have a deficiency of insulin may require insulin to maintain glucose, but those who have a poor response to insulin may not. Ketosis does not develop under normal metabolic conditions but may occur with stress. Gestational diabetes is a form of glucose intolerance that first appears during pregnancy. It usually ends after delivery, but over a 10-year span approximately 30 to 40 percent of females with gestational diabetes go on to develop noninsulin dependent diabetes.
There are a variety of ways to measure a person's blood glucose.
Whole blood glucose tests
Whole blood glucose testing can be performed by a person in his or her home, or by a member of the healthcare team outside the laboratory. The test is usually performed using a drop of whole blood obtained by finger puncture. Care must be taken to wipe away the first drop of blood because this is diluted with tissue fluid. The second drop is applied to the dry reagent test strip or device.
Fasting plasma glucose test
The fasting plasma glucose test requires an eight-hour fast. The person must have nothing to eat or drink except water. The person's blood is usually collected by a nurse or phlebotomist by sticking a needle into a vein. Either serum, the liquid portion of the blood after it clots, or plasma may be used. Plasma is the liquid portion of unclotted blood that is collected. The ADA recommends a normal range for fasting plasma glucose of 55–109 mg/dL. A glucose level equal to greater than 126 mg/dL is indicative of diabetes. A fasting plasma glucose level of 110–125 gm/dL is referred to as "impaired fasting glucose."
Oral glucose tolerance test (OGTT)
The oral glucose tolerance test is done to see how well the body handles a standard amount of glucose. There are many variations of this test. A two-hour OGTT as recommended by the ADA is described below. The person must have at least 150 grams of carbohydrate each day, for at least three days before this test. The person must take nothing but water and abstain from exercise for 12 hours before the glucose is given. At 12 hours after the start of the fast, the person is given 75 grams of glucose to ingest in the form of a drink or standardized jelly beans. A healthcare provider draws a sample of venous blood two hours following the dose of glucose. The serum or plasma glucose is measured. A glucose concentration equal to or greater than 200 mg/dL is indicative of diabetes. A level below 140 mg/dL is considered normal. A level of 140–199 mg/dL is termed "impaired glucose tolerance."
The glycated (glycosylated) hemoglobin test is used to monitor the effectiveness of diabetes treatment. Glycated hemoglobin is a test that indicates how much glucose was in a person's blood during a two- to three-month window beginning about four weeks prior to sampling. The test is a measure of the time-averaged blood glucose over the 120-day life span of the red blood cells. The normal range for glycated hemoglobin measured as HbA 1c is 3 to 6 percent. Values above 8 percent indicate that a hyperglycemic episode occurred sometime during the window monitored by the test (two to three months beginning four weeks prior to the time of blood collection).
The ADA recommends that glycated hemoglobin testing be performed during a person's first diabetes evaluation, again after treatment is begun and glucose levels are stabilized, then repeated semiannually. If the person does not meet treatment goals, the test should be repeated quarterly.
A related blood test, fructosamine assay, measures the amount of albumin in the plasma that is bound to glucose. Albumin has a shorter half-life than red blood cells, and this test reflects the time-averaged blood glucose over a period of two to three weeks prior to sample collection.
Precautions
Diabetes must be diagnosed as early as possible. If left untreated, it results in progressive vascular disease that may damage the blood vessels, nerves, kidneys, heart, and other organs. Brain damage can occur from glucose levels below 40 mg/dL and coma from levels above 450 mg/dL. For this reason, plasma glucose levels below 40 mg/dL or above 450 mg/dL are commonly used as alert values. Point-of-care and home glucose monitors measure glucose in whole blood rather than plasma and are accurate generally within a range of glucose concentration between 40 and 450 mg/dL. In addition, whole blood glucose measurements are generally 10 percent lower than serum or plasma glucose.
Other endocrine disorders and several medications can cause both hyperglycemia and hypoglycemia. For this reason, abnormal glucose test results must be interpreted by a physician.
Glucose is a labile (affected by heat) substance; therefore, plasma or serum must be separated from the blood cells and refrigerated as soon as possible. Splenectomy can result in an increase and hemolytic anemia can result in a decrease in glycated hemoglobin.
Exercise, diet, anorexia, and smoking affect the results of the oral glucose tolerance test. Drugs that decrease tolerance to glucose and affect the test include steroids, oral contraceptives , estrogens, and thiazide diuretics.
Preparation
Blood glucose tests require either whole blood, serum, or plasma collected by vein puncture or finger puncture. No special preparation is required for a casual blood glucose test. An eight-hour fast is required for the fasting plasma or whole-blood glucose test. A 12-hour fast is required for the two-hour OGTT and three-hour OGTT tests. In addition, the person must abstain from exercise in the 12-hour fasting period. Medications known to affect carbohydrate metabolism should be discontinued three days prior to an OGTT test if possible, and the person must maintain a diet of at least 150 grams of carbohydrate per day for at least three days prior to the fast.
Aftercare
After the test or series of tests is completed (and with the approval of his or her doctor), the person should eat, drink, and take any medications that were stopped for the test.
The patient may feel discomfort when blood is drawn from a vein. Bruising may occur at the puncture site, or the person may feel dizzy or faint. Pressure should be applied to the puncture site until the bleeding stops to reduce bruising. Warm packs can also be placed over the puncture site to relieve discomfort.
Risks
The patient may experience weakness, fainting, sweating, or other reactions while fasting or during the test. If this occurs, he or she should immediately inform the physician or nurse.
Normal results
Normal values listed below are for children. Results may vary slightly from one laboratory to another depending upon the method of analysis used.
- fasting plasma glucose test: 55–109 mg/dL
- oral glucose tolerance test at two hours: less than 140 mg/dL
- glycated hemoglobin: 3–6 percent
- fructosamine: 1.6–2.7 mmol/L for adults (5% lower for children)
- gestational diabetes screening test: less than 140 mg/dL
- cerebrospinal glucose: 40–80 mg/dL
- serous fluid glucose: equal to plasma glucose
- synovial fluid glucose: within 10 mg/dL of the plasma glucose
- urine glucose (random semiquantitative): negative
For the diabetic person, the ADA recommends an ongoing blood glucose goal of less than or equal to 120 mg/dL.
The following results are suggestive of diabetes mellitus and must be confirmed with repeat testing:
- fasting plasma glucose test: greater than or equal to 126 mg/dL
- oral glucose tolerance test at two hours: equal to or greater than 200 mg/dL
- casual plasma glucose test (nonfasting, with symptoms): equal to or greater than 200 mg/dL
Parental concerns
The needle used to withdraw the blood only causes pain for a moment. If a child needs to take glucose tests regularly at home, the parent will need to keep track of the testing schedule and the results.
When to call a doctor
If the needle puncture site continues to bleed, or if hours or days later the site looks infected (red and swollen), then a doctor should be contacted.
KEY TERMS
Diabetes mellitus —The clinical name for common diabetes. It is a chronic disease characterized by the inability of the body to produce or respond properly to insulin, a hormone required by the body to convert glucose to energy.
Glucose —A simple sugar that serves as the body's main source of energy.
Glycated hemoglobin —A test that measures the amount of hemoglobin bound to glucose. It is a measure of how much glucose has been in the blood during a two to three month period beginning approximately one month prior to sample collection.
See also Diabetes.
Resources
BOOKS
Chernecky, Cynthia C., and Barbara J. Berger. Laboratory Tests and Diagnostic Procedures, 3rd ed. Philadelphia: Saunders, 2001.
Henry, John B., ed. Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia: Saunders, 2001.
Kee, Joyce LeFever. Handbook of Laboratory and Diagnostic Tests, 4th ed. Upper Saddle River, NJ: Prentice Hall, 2001.
Wallach, Jacques. Interpretation of Diagnostic Tests, 7th ed. Philadelphia: Lippincott Williams & Wilkens, 2000.
ORGANIZATIONS
American Diabetes Association (ADA). National Service Center, 1660 Duke St., Alexandria, VA 22314. Web site: <www.diabetes.org/>.
Centers for Disease Control and Prevention (CDC). Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion. TISB Mail Stop K-13, 4770 Buford Highway NE, Atlanta, GA 30341–3724. Web site: <www.cdc.gov/diabetes>.
National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892–3560. Web site: <www.niddk.nih.gov/health/diabetes/ndic.htm>.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health, Building 31, Room 9A04, 31 Center Drive, MSC 2560, Bethesda, MD 208792–2560. Web site: <www.niddk.nih.gov>.
WEB SITES
"Glucose Test." Medline Plus. Available online at <www.nlm.nih.gov/medlineplus/ency/article/003482.htm< (accessed November 29, 2004).
Mark A. Best
Blood Sugar Tests
Blood Sugar Tests
Definition
Blood sugar tests include several different tests that measure the amount of sugar (glucose) in a person's blood. These tests are performed either on an empty stomach, or after consuming a meal or pre-measured glucose drink. Blood sugar tests are done primarily to diagnose and evaluate a person with diabetes mellitus.
Purpose
The body uses sugar, also called glucose, to supply the energy it needs to function. People get sugar from their diet and from their body tissues. Insulin is made by the pancreas and affects the outer membrane of cells, making it easy for glucose to move from the blood into the cells. When insulin is active, blood glucose levels fall. Sugar from body tissues is stored in the form of glycogen. When glycogen is active, blood glucose levels rise.
After a meal, blood glucose levels rise sharply. The pancreas responds by releasing enough insulin to take care of all the newly added sugar found in the body. The insulin moves the sugar out of the blood and into the cells. Only then does the blood sugar start to level off and begin to fall. A person with diabetes mellitus either does not make enough insulin, or makes insulin that does not work properly. The result is blood sugar that remains high, a condition called hyperglycemia.
Diabetes must be diagnosed as early as possible. If left untreated, it can damage or cause failure of the eyes, kidneys, nerves, heart, blood vessels, and other body organs. Hypoglycemia, or low blood sugar, also may be discovered through blood sugar testing. Hypoglycemia is caused by various hormone disorders and liver disease, as well as by too much insulin.
Description
There are a variety of ways to measure a person's blood sugar.
Whole blood glucose test
Whole blood glucose testing can be performed by a person in his or her home, and kits are available for this purpose. The person pricks his or her finger (a finger stick) with a sterile sharp blade from the kit. A single drop of blood is placed on a strip in a portable instrument called a glucometer. The glucometer quickly determines the blood sugar and shows the results on a small screen in usually a few seconds.
New technologies for monitoring glucose levels will help diabetics better control their glucose levels. These tests are particularly important for children and adolescents. In mid-2002, the U.S. Food and Drug Administration (FDA) approved a new home test for use by children and adolescents (it had already been approved for adults) called the Cygnus GlucoWatch biographer that helped better detect hypoglycemia. Studies show that more frequent checks are better; new monitors such as this allow for simpler frequent testing. Continuous monitoring was in development in early 2004, as a company called TheraSense, Inc. received preapproval from the FDA for clinical trials on its home continuous glucose monitor. The monitor was designed to provide users with real-time glucose data, alarms for hypoglycemia and hyperglycemia and to show trends in their blood sugar levels.
Fasting plasma glucose test
The fasting plasma glucose test is done on an empty stomach. For the eight hours before the test, the person must fast (nothing to eat or drink, except water). The person's blood is drawn from a vein by a health care worker. The blood sample is collected into a tube containing an anticoagulant. Anticoagulants stop the blood from clotting. In the laboratory, the tube of blood spins at high speed within a machine called a centrifuge. The blood cells sink to the bottom and the liquid stays on the top. This straw-colored liquid on the top is the plasma. To measure the glucose, a person's plasma is combined with other substances. From the resulting reaction, the amount of glucose in the plasma is determined.
Oral glucose tolerance test
The oral glucose tolerance test is conducted to see how well the body handles a standard amount of glucose. This test measures the amount of glucose in a person's plasma before and two hours after drinking a large premeasured beverage containing glucose. The person must eat a consistent diet, containing at least 5.25 oz (150g) of carbohydrates each day, for three days before this test. For eight hours before the test, the person must fast. A health care provider draws the first sample of blood at the end of the fast to determine the glucose level at the start of the test. The health care provider then gives the person a beverage containing 2.6oz (75g) of glucose. Two hours later, the person's blood is drawn again. These blood samples are centrifuged and processed in the laboratory. A doctor can then compare the before and after glucose levels to see how well the patient's body processed the sugar.
Two-hour postprandial blood glucose test
The two-hour postprandial blood glucose test measures the amount of glucose in plasma after a person eats a specific meal containing a certain amount of sugar. Although the meal follows a predetermined menu, it is difficult to control many factors associated with this testing method.
Blood sugar tests can be used in a variety of situations including:
- Testing people suspected for diabetes. The American Diabetic Association (ADA) recommends that either a fasting plasma glucose test or an oral glucose tolerance test be used to diagnose diabetes. If the person already has symptoms of diabetes, a blood glucose test without fasting (called a casual plasma glucose test) may be done. If the test result is abnormal, it must be confirmed with another test performed on another day. The two tests can be different or they can be the same, but they must be done on different days. If the second test also is abnormal, the person has diabetes. A two-hour postprandial test is not recommended by the ADA as a test to use for the diagnosis of diabetes. A doctor may order this test, and follow it with the oral glucose tolerance test or the fasting plasma glucose test if the results are abnormal.
- Testing pregnant women. Diabetes that occurs during pregnancy (gestational diabetes) is dangerous for both the mother and the baby. Women who may be at risk are screened when they are 24-28 weeks pregnant. A woman is considered at risk if she is older than 25 years, is not at her normal body weight, has a parent or sibling with diabetes, or if she is in an ethnic group that has a high rate of diabetes (Hispanics, Native Americans, Asians, African Americans). The blood sugar test to screen for gestational diabetes is a variation of the oral glucose tolerance test. Fasting is not required. If the result is abnormal, a more complete test is done on another day.
- Testing healthy people. Healthy people without symptoms of diabetes should be screened for diabetes when they are 45 years old and again every three years. Either the fasting plasma glucose or oral glucose tolerance test is used for screening. People in high risk groups should be tested before the age of 45 and tested more frequently.
- Testing of people already diagnosed with diabetes. The ADA recommends that a person with diabetes keep the amount of glucose in the blood at a normal level as much as possible. This can be done by the diabetic person testing his or her own blood at home one or more times a day.
Preparation
Each blood sugar test that uses plasma requires a 5 mL blood sample. A healthcare worker ties a tight band (tourniquet) on the person's upper arm, locates a vein in the inner elbow region, and inserts a needle into the vein. Vacuum action draws the blood through the needle into an attached tube. Collection of the sample takes only a few minutes.
When fasting is required, the person should have nothing to eat or drink (except water) for eight hours before the test and until the test or series of tests is completed. The person should not smoke before or during the testing period because this can temporarily increase the amount of glucose in the blood. Other factors that can cause inaccurate results are a change in diet before the test, illness or surgery two weeks before the test, certain drugs, and extended bed rest. The doctor may tell a person on insulin or taking pills for diabetes to stop the medication until after the test.
Aftercare
After the test or series of tests is completed (and with the approval of his or her doctor), the person should eat, drink, and take any medications that were stopped for the test.
The patient may feel discomfort when blood is drawn from a vein. Bruising may occur at the puncture site or the person may feel dizzy or faint. Pressure to the puncture site until the bleeding stops will reduce bruising. Warm packs to the puncture site will relieve discomfort.
Risks
If the person experiences weakness, fainting, sweating, or any other unusual reaction while fasting or during the test, he or she should immediately tell the person giving the test.
Normal results
Normal results are:
- fasting plasma glucose test less than 120 mg/dL
- oral glucose tolerance test, 2 hours less than 140 mg/dL
For the diabetic person, the ADA recommends an ongoing blood sugar goal of less than or equal to 120 mg/dL.
Abnormal results
These abnormal results indicate diabetes and must be confirmed with repeat testing:
- fasting plasma glucose test less than or equal to 126 mg/dL
- oral glucose tolerance test, 2 hours less than or equal to 200 mg/dL
- casual plasma glucose test (nonfasting, with symptoms) less than or equal to 200 mg/dL
- gestational oral glucose tolerance test, 1 hour less than or equal to 140 mg/dL
Brain damage can occur from glucose levels below 40 mg/dL and coma from levels above 470 mg/dL.
A condition known as prediabetes or impaired glucose tolerance, which may lead to Type 2 diabetes, usually is indicated with a reading of 100 mg/dL. Other hormone disorders can cause both hyperglycemia and hypoglycemia. Abnormal results must be interpreted by a doctor who is aware of the person's medical condition and medical history.
Resources
PERIODICALS
"New Guidelines Set Lower Threshold for Precursor to Diabetes." RN (January 2004): 17.
Plotnick, Leslie P. "The Next Step in Blood Glucose Monitoring?" Pediatrics (April 2003): 885.
"Premarket Approval Application Filed for Continuous Glucose Monitor." Medical Letter on the CDC & FDA (January 4, 2004): 26.
ORGANIZATIONS
American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. 〈http://www.diabetes.org〉.
Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.
National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747. 〈http://www.niddk.nih.gov/health/diabetes/ndic.htm〉.
Blood
Blood
As the fluid of life, blood has abundant literal and metaphorical meanings that vary across cultures and genders. Women's blood and men's blood differ in both composition and cultural associations, and this distinction is most often linked to women's menstruation. In sexual practice, blood can be an erotic fluid comparable to other bodily fluids. Blood also designates family relations and racial distinctions, both based on genetic material in blood.
PHYSIOLOGY
The heart pumps blood throughout the body, where the blood delivers nutrients and oxygen to organs and tissues and removes waste products such as carbon dioxide and lactic acid. Physiologically, the blood of men and women differs in the amount of hemoglobin, which carries iron and oxygen to the body's cells. This difference is due largely to women's loss of blood through menstruation and to men's greater muscle mass. It also means that women are more likely to become anemic, and this illness is a particular danger to pregnant women. Babies born to anemic mothers are at high risk of being developmentally retarded. Leonard Shlain (2003) argues that women's need for iron, most readily available in red meat, encouraged the development of hunting in pre-modern society.
FEMININE AND MASCULINE BLEEDING
Cultural connotations of blood reveal its relation to gender stereotypes, so that women's blood is feminine and weak, whereas men's blood is masculine and virile. Women's blood is most often associated with their reproductive ability and is thus linked to menstruation, the loss of virginity, childbirth, and menopause.
Menstruation has disparate meanings in different cultures. It is considered variously as a simple act of elimination, a positive experience linked to fertility of women and of the earth, and an unclean process that is regulated by taboos. One euphemism used in the United States and elsewhere, "the curse of Eve," reflects sentiments that menstruation is an unwelcome experience for women and an uncomfortable topic of discussion for men. A symbol of the arrival of puberty, a woman's first menstruation is called the menarche. As a rite of initiation, some cultures celebrate this flowing of blood; in many Western cultures, this event goes largely unacknowledged. In tribal cultures such as the Loango of East Africa, menstruating women are isolated from the rest of the community in menstruation huts. The Bible, in Leviticus, warns against associating with or having sex with menstruating women for fear of contamination with the unclean fluid. Some feminist critics argue that the taboos on and fear of menstruation are a suppressive reaction to the implicit procreative power to which menstruation attests.
Many women bleed when they lose their virginity, since sexual intercourse can break the hymen, a membrane covering the vaginal opening. However, other activities, including the use of tampons and involvement in sports, may stretch or break the hymen before initial intercourse. Despite knowledge that the existence of the hymen is not an infallible indicator of virginity, many Mediterranean, African, and Islamic cultures require proof that a woman is a virgin on her wedding night, asking for evidence of the broken hymen by such means as a bloody sheet displayed to wedding guests. Other feminine bleeding occurs during and after childbirth due to straining and tearing of the genital area and the uterus. Women thus bleed both at regular intervals—through menstruation—and at significant moments in their reproductive lives. At menopause, with the cessation of menstruation, women's sexually associated bleeding ceases.
Men's blood is generally associated with wounds resulting from physical conflicts and war, and thus is a symbol of heightened masculinity, virility, or dominance. Representations of violence normally include blood, and film and television may be censored for extreme violence as demonstrated by excessive amounts of blood. Barbara Ehrenreich (1997) argues that the link between violence, blood, and masculinity, supported by the prevalence of phallic weapons, may have replaced previous mythical representations of vaginas as both bleeding wounds and predatory, bloody mouths.
Some tribal cultures have rituals for men that parallel menstruation, in which men make a small incision on their penises and allow a certain amount of blood to flow out before bandaging the wound. In Judaism, as Lawrence A. Hoffman (1996) points out, the circumcision of infants is a similar male initiation rite that involves the symbolic loss of blood from the genitals. Ehrenreich (1997, p. 106-107) lists many other cultural practices that compare women's vaginal bleeding with ritual acts of bloodletting for men:
In Papua New Guinea, the self-induced ritual nosebleeds are seen as parallel to menstruation; the Australian Aborigines who subincise their penises reopen the wounds regularly in order, they say, to simulate menstruation. In ancient Hawaii blood sacrifice was understood to be a "man's childbearing," just as childbearing was a "woman's sacrifice," and the Aztecs similarly equated men's death in war to women's death in childbirth. War as a kind of ritual bloodletting is linked to menstruation in the myths of the Ndembu people of Africa, and the Plains Indian mythology studied by Claude Lévi-Strauss.
SEXUAL PRACTICES AND BLOOD
Sexual fetishes involving blood are termed blood play or blood sports; these involve individuals licking or drinking the blood of their sexual partners after cutting or otherwise wounding them. This practice is related to bloodletting, vampirism, and self-mutilation. Such practices are grouped with other sexual activities based on sadomasochist tendencies or sexual dominance and submissiveness.
Vampires, mythic figures who drink the blood of the living to maintain their own lives after death, are highly sexualized in cultural representations. The act of drinking another person's blood involves seduction to attain physical proximity and a life-threatening "kiss" that transfers bodily fluid. While representations of female vampires exist, most are men, a stereotype that relies on the connection between violence, sexual aggression, and masculinity.
In Japanese anime and manga, male characters who are sexually aroused are shown to have nosebleeds. The exact reason for this connection is unclear, but one theory is that the rush of blood to the genitals is so intense that it floods the whole body and spills out through the nose. The depiction of blood and sex is common in Japanese culture, which is notable for its eroticization of violence, usually against women.
BLOOD-BORNE SEXUALLY TRANSMITTED DISEASE
Many sexually transmitted diseases, such as herpes and AIDS, are carried in the blood as well as in other bodily fluids like semen. Beginning in the late twentieth century, AIDS became a major concern for citizens of all countries. Originally considered a gay male disease, due to its initial prevalence among gay men and the ease with which gay sex transmits the virus, AIDS was rarely spoken of nor were treatments readily available. After discovering this disease can be transmitted through heterosexual encounters and blood transfusions, the United States took a more active role in educating the public about the virus, including advocating safe sex with condoms. In Africa, AIDS is an epidemic due to a lack of knowledge about virus transmission and ineffective folk remedies. One such remedy, the belief that an infected man may cure himself by having sex with a virgin female, has led to the mass rape and infection of young women.
BLOOD RELATIONS: KINSHIP AND BLOODLINES
As the carrier of genetic material, blood is linked to family or clan identity and racial groups. Thus, kinship is often referred to as bloodlines, distinguishing bonds of blood relationship from friendship or marriage. People who are not related by blood but who want to symbolize their strong connection with each other may become blood brothers or blood sisters by partaking in various rituals that may involve sharing or commingling their blood.
Bloodlines establish taboos on marrying or having sex within one's immediate family, a practice known as incest, or within larger groups or relations such as clans, also defined as endogamy. Such taboos are practical for cultural and health reasons. Culturally, the ban on endogamous relations helps create connections among multiple clans or families, which can increase wealth or form protective alliances. In addition, bans on incest maintain harmony within smaller family units by both discouraging any natural sexual attraction to one's immediate relatives, such as the Oedipal desire of a son for his mother, or the Electra complex (in which a daughter is sexually attracted to her father), and reinforcing natural aversions to such sexuality. Physiologically, continued incestuous relations lead to problems such as a diminished gene pool and increased susceptibility to disease. One such disease is hemophilia, or the inability for blood to clot properly, which notoriously affected members of the royal families of Europe beginning with Queen Victoria of England (r. 1837–1901). It can also be traced back to the Talmud and other Jewish religious texts, dating from the second to fifth centuries ce, that regulate circumcision based on previous family members who bled to death following the act. Hemophilia is most often manifested in men, while women are almost always only carriers.
In Western society, bloodlines and kinship are marked by patrilineal naming, so that fathers pass their surnames on to their children and thus show the continuation of their bloodlines. Several anthropologists argue that patriliny has not always been the standard mode of determining kinship. In 1861, J. J. Bachofen published Das Mutterrecht (Mother right), in which he argued that matriliny, which figures the mother-child relation as the basic social unit, preceded patriarchy and patriliny. Patriliny and patriarchy followed to demonstrate and secure the father's role in reproduction, family, and society.
In the United States, the historical preoccupation with racial difference, particularly the distinction between white and black Americans, resulted in the "one drop of blood" rule, which holds that a single drop of blood from a non-white ancestor results in a non-white person. During slavery, this rule kept many mixed-race individuals in bondage, and often the white male slave owners had sex with or raped their female slaves to increase their property and wealth. Following slavery, racial discrimination continued to categorize mixed-race individuals as black and relegate them to an inferior social status. Due to increased mixed-race births, such emphasis on racial groups as categories of identity has waned. To account for this demographic and social change, the 2000 U.S. census was the first census to offer respondents the opportunity to classify themselves as belonging to more than one racial group.
see also Female Genital Mutilation; Incest; Menstruation; Miscegenation; Vagina; Vampirism.
BIBLIOGRAPHY
Bradburne, James M., ed. 2001. Blood: Art, Power, Politics and Pathology. New York: Prestel.
Buckley, Thomas, and Alma Gottlieb, eds. 1988. Blood Magic: The Anthropology of Menstruation. Berkeley: University of California Press.
Ehrenreich, Barbara. 1997. Blood Rites: Origins and History of the Passions of War. New York: Metropolitan Books.
Hoffman, Lawrence A. 1996. Covenant of Blood: Circumcision and Gender in Rabbinic Judaism. Chicago: University of Chicago Press.
Pasternak, Burton; Carol R. Ember; and Melvin Ember. 1997. Sex, Gender, and Kinship: A Cross-Cultural Perspective. Upper Saddle River, NJ: Prentice Hall.
Shlain, Leonard. 2003. Sex, Time, and Power: How Women's Sexuality Shaped Human Evolution. New York: Viking.
Wolf, Arthur P., and William H. Durham, eds. 2004. Inbreeding, Incest, and the Incest Taboo: The State of Knowledge at the Turn of the Century. Stanford, CA: Stanford University Press.
Michelle Veenstra