Blood tests


blood

blood has always held a great fascination, being regarded as a living substance, the very essence of life. The doctrine of the humours, which dominated Western medical thinking until the Renaissance, held that disease is the consequence of imbalance of the four components of which the human body is composed: blood; phlegm; black bile; and yellow bile. The English physician William Harvey (1578–1637) wrote that ‘blood acts above all the powers of the elements and is endowed with notable values and is also the instrument of the omnipotent creator.’ It is, he believed, ‘the fountain of life and the seat of the soul’.

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.
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COLIN BLAKEMORE and SHELIA JENNETT. "blood." The Oxford Companion to the Body. 2001. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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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 cellsnormally 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, 80100 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 patientif 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): 25442546.

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 435441.

Latagliata, R.; Petti, M. C.; and Mandelli, F. "Acute Myeloid Leukemia in the Elderly: 'per aspera ad astra'?" Leukemia Research 23 (1999): 603613.

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): 437442.

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): 639643.

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 7277.

Zauber, N. P., and Zauber, A. G. "Hematologic Data of Healthy Very Old People." Journal of the American Medical Association 257 (1987): 21812184.

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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 canaccidentially or otherwisemisinterpret 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 sceneand the matching DNA of the suspectis 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 truethere 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/>.

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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 55109 mg/dL. A glucose level equal to greater than 126 mg/dL is indicative of diabetes. A fasting plasma glucose level of 110125 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 140199 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: 55109 mg/dL
  • oral glucose tolerance test at two hours: less than 140 mg/dL
  • glycated hemoglobin: 36 percent
  • fructosamine: 1.62.7 mmol/L for adults (5% lower for children)
  • gestational diabetes screening test: less than 140 mg/dL
  • cerebrospinal glucose: 4080 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 303413724. Web site: <www.cdc.gov/diabetes>.

National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 208923560. 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 2087922560. 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

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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.

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Blood

Blood

Frequently, the forensic analysis of a crime or accident scene will involve the analysis of blood. Whether in the form of fresh liquid, dried blood, jelly-like coagulated blood, or patchy drops or stains, blood can be a treasure trove of information. As one example, the pattern of a bloodstain can tell a forensic investigator much about the nature of the accident or crime. Just as important is the composition of the blood.

A typical human body contains approximately ten pints (4.7 liters) of blood. Depending on the severity of a wound, blood can be lost slowly or, as in the case of a severed artery, can spurt quickly out of the body. A forensic examiner can tell a great deal about the nature of the accident or crime from the pattern of the blood residue. Additionally, knowledge of the composition of blood and properties of these components is also valuable in identifying a victim or implicating an assailant.

Human blood is made up of several different types of cells. Each has a distinctive appearance and function.

Red blood cells are absolutely vital for life. Each drop of blood contains millions of these cells. In the body, the circulating red blood cells deliver oxygen to cells and transport waste material from the cells.

Red blood cells are round, smooth-edged, and saucer-like in shape, typically having a slightly depressed center. In a disease like anemia or sickle cell anemia, the cells can be present in reduced numbers or can adopt an abnormal sickle shape. This reduces the oxygen carrying capacity of the blood. The presence of such abnormalities can alert a forensic investigator or medical examiner to the presence of disease or poison, or lack of constituents, including iron, vitamin B12, or folic acid, or other maladies.

The bright red color of a healthy red blood cell comes from the presence of an iron-containing compound called hemoglobin . The presence of iron makes hemoglobin an excellent molecule for the binding and transport of oxygen and carbon dioxide. As blood passes through the tiny channels that permeate the lung, the oxygen molecules that diffuse across the channel membrane bind to the hemoglobin. The oxygen is subsequently released to cells all through the body during the circulation of the red blood cells.

Once vacant, the binding site in the hemoglobin is able to accommodate the binding of carbon dioxides and other waste products of cellular metabolism. These products, which would become toxic to the cells if allowed to accumulate, are then transported away. As the red blood cells pass back through the lung, the carbon dioxide and other waste molecules are released from the hemoglobin and are exhaled.

Red blood cells are long-lived, but not immortal. The average lifetime is approximately 120 days. Although cells are continually dying and being replenished, the number of red blood cells remains constant in a properly-operating body.

In contrast to the smooth, plate-like red blood cells, white blood cells are spheres that have numerous knob-like projections sticking out from their surface.

White blood cells are part of the body's defense system against infection. When a microbial threat is recognized by the immune system , white blood cells are signaled and directed to the site of the threat. There, they attack the invading microorganisms, by producing antibodies directed against components of the microbe or by physically engulfing, ingesting, and dissolving the invader.

White blood cells are primed and ready for their defensive duties by means of a short life span. They live only a few days to several weeks.

Under normal conditions there are 7,00025,000 white blood cells per drop of blood. The determination of this number can provide an indication of the presence of disease. For example, if a bacterial, viral, or parasitic infection proves resistant to eradication, an increased number of white blood cells will be recruited to do battle with the invader, reducing the white blood cell count in the blood. Conversely, cancer of the blood (leukemia) causes the numbers of white blood cells to increase markedly. A leukemia patient can display upwards of 50,000 white blood cells per drop of blood.

The bloodstain that confronts a forensic investigator at the site of an accident or crime may be the result of a catastrophic injury that the body was unable to repair. Normally, the cuts and scrapes that occur during the normal course of life can be addressed by sealing up the wound.

The patching of a wound is the task of the colorless blood cells called platelets. Platelets do not have a uniform shape. Rather, they are reminiscent of an amoeba, being blob-like, with long and thin surface projections.

Platelets are recruited to the site of a cut or wound. Their shape and sticky surface facilitates their clumping together, along with calcium, vitamin K, and a protein called fibrinogen. The clump is known as a clot.

Clot formation is a complicated process that involves a cascade of biochemical reactions. Without platelets, clotting would not occur. When in the vicinity of the open wound, and so in the presence of an increased concentration of oxygen, the platelets dissolve. A consequence of the dissolution is the conversion of fibrinogen to fibrin. The tiny thread-like fibrin molecules collect to form a mesh that entraps intact and dissolved blood cells and other constituents. As this mass hardens, the clot forms. A hardened clot is also called a scab.

This effective wound patching system does have its limits, however. In the case of a catastrophic injury such as a knife or bullet wound, bleeding may continue unabated. If not treated, such a wound can be fatal.

The various blood cells are suspended in a straw-colored liquid called plasma. Plasma is composed mainly of water. Physiologically-important ions including calcium, sodium, potassium and magnesium also comprise plasma.

Plasma provides the medium in which the blood cells are suspended and transported around the body. As well, the disease-fighting antibodies produced by the immune system are also ferried to where they are needed via the plasma.

Blood, specifically the red blood cells, are also a valuable resource for a forensic investigator, as the cells can be used to determine what is known as the blood type of the victim or assailant.

The chemical residues present on the surface of red blood cells are the basis of blood typing. These were first described early in the twentieth century by the Austrian-born American immunologist Karl Landsteiner (18681943), who subsequently developed the typing criteria. For his achievements, Landsteiner was awarded the 1930 Nobel Prize in Medicine.

Landsteiner noted the presence of two distinct moleculesprotein antigens A and Bon the surface of red blood cells. Type A blood is comprised of red blood cells that have only the A molecule, whereas the red blood cells of type B blood have only the B molecule. The presence of both molecules occurs in type AB blood. Finally, red blood cells can be devoid of both molecules. This occurs in type O blood.

The determination of blood type can be easily done by mixing a sample of blood with antibodies to the A or B components. In the presence of the correct antibody , the blood cells will clump together, forming a visible precipitate.

Blood typing remains a powerful forensic tool in linking someone to the crime or accident scene. In addition, because blood type is a genetically acquired trait, blood typing can be useful in establishing familial relationships. However, because a great many people have the same blood type, this test alone is not a definitive identification .

Another very useful aspect of blood in forensic examinations involves a factor known as the Rh (for Rhesus) factor. The factor, which was also discovered by Landsteiner, derives its name from the Rhesus monkey, a species similar to us and so one that is used in medical studies. The Rh factor of human blood was discovered in blood comparisons between humans and the Rhesus monkey.

Rh factor is a protein that is present in the blood of some people (who are described as Rh positive, or Rh+. Some people lack the blood protein, and so are described as being Rh negative (Rh-).

The determination of the Rh status of a blood sample provides another piece of evidence that can help determine the identify of the victim or link someone to the crime or accident.

In addition to the A and B antigens and Rh factor, modern day blood typing includes over 150 blood-borne proteins and 250 enzymes located in blood cells.

This extensive form of blood typing, while still useful, is laborious and has been largely replaced by the molecular precision of genetic analysis.

As with every other cell in the body, blood cells contain genetic material in the form of deoxyribonucleic acid (DNA ). DNA can be isolated and subjected to a variety of sophisticated analyses to determine the sequence of the nucleotide building blocks that comprise the structure. As well, small sequences that tend to vary from person to person can be quickly copied over and over again, using the polymerase chain reaction (PCR ), to produce sufficient quantities for the sequence analysis. In this way, the pattern of DNA that is unique to an individual can be revealed.

Recovering the same DNA pattern in a blood sample of a suspect and from blood recovered at a crime scene is very powerful evidence tying the person to the crime scene. As seen in the trial of O.J. Simpson, however, even this evidence can fail to sway a jury if not convincingly presented or defended.

see also Blood spatter; Bloodstain evidence; Blood volume test; Blood, presumptive test; Cast-off blood; DNA; Toxins; Wound assessment.

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DNA Profiling

DNA Profiling

DNA is the material within every cell of the body and represents the blueprint of life. It allows physical traits to be passed on from one generation to the next. Although the majority of the human genome (the complete set of genes for an individual) is the same across all ethnic populations, people differ in their genetic makeup by a minuscule amount, and thus have their own unique DNA pattern. DNA profiling, also referred to as DNA typing, is the molecular genetic analysis that identifies DNA patterns. In forensic science , DNA profiling is used to identify those who have committed a crime. It is estimated that roughly one percent of all criminal cases employ this technique; however, DNA profiling has been used to acquit several suspects involved in serious crimes such as rape and murder and it has been used to convict individuals of crimes years after investigators closed the unsolved case. Aside from identifying an individual responsible for violent crimes, the judicial system also can use DNA profiling to determine family relationships in the case of disputed paternity or for immigration cases.

DNA molecular analysis has also been used in the diagnosis of clinical disorders. Many genetic diseases are caused by mutations in DNA within regions of the genome that code for protein, and scientist look in these regions for mutations to determine if a patient is affected or is a carrier of a genetic disease. Unlike clinical molecular genetics, DNA typing for forensics takes advantage of locations within the human genome that do not code for protein. These locations typically involve repetitive DNA sequences that are polymorphic, or have a variable number of repeat sizes. Because non-protein-coding DNA is used, DNA databanks that contain DNA typing information do not reveal any information about an individual's health status or whether the individual has or is a carrier of a genetic disease.

The sensitivity of DNA profiling tests have dramatically increased over the last two decades. It used to be necessary to have a sample roughly the size of the ink in an ink pen, skilled forensic scientists can now obtain enough DNA from saliva left on the end of a cigarette to get a DNA profile result. The speed at which results can be obtained has also dramatically improved. This is all, in part, due to the discovery of the polymerase chain reaction , a technique that can amplify large amounts of specific small sequences of DNA from the human genome. It is also due to the advent of various DNA fingerprinting tools. The effect of these advances has broadened the sample size and quality required for analysis.

DNA profiling uses a variety of DNA typing systems , including: restriction fragment length polymorphism (RFLP ) typing, short tandem repeat (STR) typing, single nucleotide polymorphism (SNP) typing, mitochondrial DNA (mtDNA) analysis, human leukocyte antigen (HLA)-typing, gender typing, and Y-chromosome typing.

The first approach to DNA typing used variable number tandem repeats, or VNTRs. VNTR's are repeating units of a DNA sequence, the number of which varies between individuals. They are analyzed as Restriction Fragment Length Polymorphisms (RFLPs). RFLPs are variations within specific regions of genomes that are detected by restriction enzymes. RFLP analysis originated in the 1970s after the discovery of restriction enzymes, or proteins that can cut DNA into smaller molecules (restriction fragments) based on specific DNA sequence recognition sites. A restriction enzyme recognizes and cuts DNA only at a particular sequence of nucleotides (the components of DNA). VNTR's are 2050 base pairs (pairs of nucleotides) long per repeat and a person can have anywhere from 50 to several hundred repeats. This repeat length is inherited. This DNA typing approach was first discovered by the British geneticist Alec Jeffreys in 1985 and is the principle behind today's DNA profiling systems.

The advantage of using a RFLP-based analysis for DNA profiling is that VNTR regions are highly variable in copy number from person to person. Therefore, it is highly unlikely that DNA profiles from unrelated individuals would be identical. However, there are also several drawbacks to this technique. Since these regions are large, it is often difficult to clearly separate the fragment using electrophoresis , which is a technique that uses a DNA sample loaded into a gel that migrates towards a positively charge electric field based on size. For example, larger fragments migrate slower than smaller fragments. This is problematic when the migration of one VNTR is indistinguishable from another VNTR, even if they differ in length. This is due to limited resolution of the gel matrix (only large differences can be detected). A larger amount of DNA (20 nanograms) of purified, high quality DNA is also required for this technique. Thus, DNA samples extracted from crime scene specimens may be not suitable in quality for this type of analysis. High purity in terms of DNA extractions can be compromised according to the source of the sample. If, for example, the sample is blood and is extracted from clothing, the dye from the cloth might alter the mobility of the extracted DNA in the gel, making the analysis difficult.

VNTR analysis has been replaced by Short Tandem Repeat (STR) analysis. STR regions are comprised of 24 base pair repeats that are repeated between 5 to 15 times. STR analysis is currently the standard approach to forensic DNA profiling. This is mainly because shorter repeat sequences are easier to analyze.

STR analysis is faster, less labor intensive, and can be automated. A single reaction can analyze 46 STR regions using very little DNA (only one nanogram is usually sufficient). If only a small amount of DNA is recovered or if it is degraded, it may be possible to use STR analysis, but not VNTR analysis.

Additionally, in VNTR analysis, genomic DNA is digested with restriction enzymes and then run on a gel. The fragments produced are transferred to a membrane and probed with a radiolabeled sequence of DNA that matches the VNTR sequence. The migration of the VNTR fragment on the gel determines their size and generates a pattern. The radiolabeled probe produces dark bands on x-ray film when exposed in a time-dependent and dose-dependant manner. Unlike VNTR analysis, STR analysis uses the polymerase chain reaction to amplify DNA in the region where the STR is located. These PCR products can then be run on a gel in the same manner as the VNTR fragment and using sophisticated computer software with laser controlled equipment, the migration of the PCR products can be compared to control DNA molecules that have a known size. If run together, the size of the unknown STR can be estimated. In this case, STRs are visualized by adding a DNA intercalator such as ethidium bromide into the gel, which intercalates into the DNA and fluoresces (emits) ultraviolet light.

STR analysis, however, is not without its drawbacks, as well. If very little DNA is recovered from a crime scene and it is degraded, not all regions in the genome will amplify, or there will be discriminatory amplification of DNA in only one chromosomal STR region, rather than both. This can significantly affect the results and lead forensic scientists to draw incorrect conclusions. Additionally, there may be substances in the sample that inhibit the PCR reaction. For these reasons, forensics scientists must use a standardized approach that is reproducible and includes all the necessary positive and negative controls for DNA profiling to be used as evidence during a court proceeding.

A significant problem in using DNA profiling as evidence in court proceedings is the possibility that a mistake was made in the sample extraction, preparation, or analysis. For this reason, investigators take precautions to reduce human error. Each forensics laboratory must maintain a high level of quality control and quality assurance standards to prevent this from happening. State and local mandates are being established to standardize these techniques.

Every cell, tissue, or organ in a person's body contains the same DNA pattern, so the United States law enforcement and armed forces has developed databases to collect information related to an individual's DNA identity. This information will be used for identification purposes in missing person cases or to identify the remains of deceased individuals. Other techniques previously used to identify individuals such as using dental records, dog tags, or blood typing have been superceded by DNA profiling, which provides more information and is more conclusive. For example, if two samples have the same blood type, it still is not clear that they came from the same person. Even dental records might not be helpful in cases where the integrity of the sample is compromised to a degree that makes it difficult to match it appropriately. In DNA profiling, even if the deceased person was significantly disfigured, it would still be possible to analyze the sample.

see also DNA databanks; DNA evidence, social issues; DNA fingerprint; DNA sequences, unique; DNA typing systems; Mitochondrial DNA typing.

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Blood

Blood

The life fluid of the body is blood. All animals, including humans, require that nutrients and oxygen be available for metabolism and that wastes be removed. In animals that measure 1 millimeter or less in diameter, these substances are transported within the body by diffusion between the cells and nearby body parts. In larger, more complex animals, circulatory systems have evolved with arteries, veins, and capillaries to transport respiratory gases, nutrients, waste products, hormones, antibodies, and salts to parts of the body.

Blood, the medium for transporting nutrients and waste products, is both a tissue and a fluid containing many specialized types of cells. It is a tissue because it is a collection of similar cells that serve a particular function. These cells are suspended in a liquid matrix called plasma, which allows the blood to act as a fluid.

Blood plays an important role in nearly all body functions. Oxygen is one of the crucial substances that enters the blood. Oxygen passes through the walls of the lungs, gills, or skin of the animal. The blood picks up and carries oxygen to all parts of the body. As the oxygen-laden blood moves through the circulatory system, it passes through cell walls and provides fuel for the working parts of the body.

Blood also carries digested food from the intestines to the muscle cells. When the muscles work, they produce waste products that must be disposed of. These waste products pass through the walls of the circulatory system into the blood. The blood then carries wastes to the kidneys, where they are eliminated from the body. The work of the muscles creates heat, which is transferred by blood throughout the body. In warm-blooded birds and mammals, blood maintains the temperature of the body.

Blood plays a critical part in the fight against diseases in animals. Blood contains many kinds of disease-fighting substances such as antibodies and white blood cells. Blood tests can reveal a great deal about how well the body is working.

Blood Composition

The blood of mammalsincluding humansis complex. About half of the volume of blood is made up of blood cells, which originate in the bone marrow. Blood cells begin as stem cells, then develop into many other kinds of cellsred cells, white cells, and platelets . Blood is composed of 55 percent plasma and 45 percent other elements.

Plasma is the watery part of the blood. Plasma is 90 percent water and carries most of the chemicals in the blood. These chemicals include minerals such as sodium, potassium, vitamins, hormones, enzymes, and glucose. Some of these substances are manufactured in the body; others enter through the lungs or with food. Plasma also carries dissolved gasses, especially oxygen, carbon dioxide, and nitrogen.

Most stem cells become red blood cells, or erythrocytes . Human blood contains 4.8 to 5.4 billion red blood cells per milliliter of blood. Red blood cells' primary function is to carry oxygen from the lungs to every cell throughout the body. The outer layer, or membrane, of the red blood cell is flexible and can bend in many different directions without breaking.

Red cells have an iron-containing substance or pigment known as hemoglobin . As hemoglobin passes through the lungs, it picks up oxygen, forming a red-colored compound known as oxyhemoglobin, which gives the blood a distinctive red color. As the blood passes through body tissues, hemoglobin releases oxygen to cells throughout the body. During this passage, the hemoglobin gives up some of its oxygen. In response, the tissues send a waste gas, carbon dioxide, into the blood.

White blood cells, or leukocytes , form a wandering system of protection for the body. Composed of granulocytes , monocytes , and lymphocytes , these cells originate in the bone marrow, where there is a ratio of one white cell to 700 red cells. Two-thirds of white cells are granulocytes, which travel to places in the body where bacteria or other foreign substances are located and swallow up these invaders. Monocytes, another type of white cell, also swallow up foreign substances and assist the body in overcoming and resisting infections. Lymphocytes produce antibodies, which are released into the blood to target and attach to foreign substances.

The smallest of the blood cells are called platelets. These cells assist in blood clotting by sticking together and plugging small holes in the walls of the blood vessels. As these tiny platelets flow out of a cut on the wall of the blood vessel, they release a chemical known as thromboplastin . This self-sealing characteristic of blood is critical to an animal's survival.

Differences among Animals

One-celled organisms have no need for blood. They are able to absorb nutrients, expel wastes, and exchange gases with their environment through a process called diffusion. In some invertebrates, such as flatworms and cnidarians , oxygen is dissolved in the plasma. Simple multicelled marine animals such as sponges, jellyfish, and anemones use seawater to bathe cells and perform the function of blood. The immune system of invertebrates is less developed than that of vertebrates, lacking the white blood cells and antibody system found in mammals.

Differing oxygen requirements play a significant role in the composition of blood and the design of animals' circulatory systems. Crustaceans and other arthropods have an open type of circulatory system, while more complex vertebratesincluding humanshave a closed circulatory system. Larger and more complex animals have greater oxygen needs and have developed respiratory pigments to help transport oxygen in the blood. These specialized compounds, hemoglobin or hemocyanin , are able to carry greater amounts of oxygen because of the metal atoms in the pigments reacting with and transporting additional atoms of oxygen.

The red pigment hemoglobin contains iron, transports oxygen, and is found in all vertebrates as well as some invertebrates with a closed circula-tory system, such as earthworms. The blue pigment hemocyanin, which contains copper, is found in some animals with an open circulatory system, including some crustaceans such as crabs, and in some mollusks. This pigment transports oxygen to body tissues and gives the blood a bluish color. The blood of insects is clear or yellow. The red fluid from some squashed insects actually comes from blood they have eaten, not from their own blood, as they have no pigments.

Although the blood of complex animals tends to be similar to human blood, there are differences at the cellular level. For example, reptiles, fish, and amphibians have red blood cells with a nucleus, unlike humans and other mammals. Some arctic fish are able to produce a specialized protein that acts as a type of antifreeze, allowing them to survive where the blood of other animals would freeze.

see also Circulatory System.

Leslie Hutchinson

Bibliography

Hickman, Cleveland, Larry Roberts, and Frances Hickman. Integrated Principles of Zoology, 8th ed. St. Louis, MO: Times Mirror/Mosby College Publishing, 1990.

Mill, P. J. Respiration in the Invertebrates. London: Macmillan Press, 1972.

Randall, David, Warren Burggren, and Kathleen French. Eckert Animal Physiology: Mechanisms and Adaptations, 4th ed. New York: W. H. Freeman and Company, 1997.

Plasma

Plasma is unquestionably essential for the survival of human beings. Along with carrying important minerals and dissolved salts like calcium, sodium, and potassium among others, disease-fighting antibodies are contained in plasma.

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Blood

Blood

Blood is a fluid connective tissue that performs many functions in the body. It carries oxygen and nutrients to the cells, hormones (chemical messengers) to the tissues, and waste products to organs that remove them from the body. Blood also acts as a defense against foreign microorganisms and helps to keep the body at a constant temperature in warm-blooded animals.

Blood consists of white blood cells, red blood cells, and platelets suspended in plasma, a watery, straw-colored fluid. Plasma makes up about 55 percent of the blood, while blood cells and platelets make up the remaining 45 percent. The average adult human body contains about 6 quarts (approximately 5.6 microliters) of blood.

Plasma

Plasma is made up of 92 percent water, 7 percent proteins, salts, and other substances it transports. Fibrinogen is an important protein involved in blood clotting. Albumins and globulins are proteins that aid in the regulation of fluid in and out of the blood vessels. Proteins called gamma globulins act as antibodies and help protect the body against foreign substances, called antigens.

The salts present in plasma include sodium, potassium, calcium, magnesium, chloride, and bicarbonate. They are involved in many important body functions such as muscle contraction, the transmission of nerve impulses, and regulation of the body's acid-base balance. The remaining substances in plasma include nutrients, hormones, dissolved gases, and waste products that are being transported to and from body cells. These materials enter and leave the plasma as blood circulates through the body.

Words to Know

Capillary: Microscopic vessels in the tissues that are involved in the exchange of nutrients and other substances between the blood and the tissues.

Clotting factor: A substance that promotes the clotting of blood (stoppage of blood flow).

Erythrocyte: A red blood cell.

Fibrin: A protein in plasma that functions in blood clotting by forming a network of threads that stop the flow of blood.

Hemoglobin: The protein pigment in red blood cells that transports oxygen to the tissues and carbon dioxide from them.

Hemophilia: A genetic disorder in which one or more clotting factors is absent from the blood, resulting in excessive bleeding.

Leukocyte: A white blood cell.

Plasma: The straw-colored liquid portion of the blood that contains water, proteins, salts, nutrients, hormones, and wastes.

Platelet: A disk-shaped cell fragment involved in blood clotting.

Proteins: Large molecules that are essential to the structure and functioning of all living cells.

Red bone marrow: The soft reddish tissue in the cavity of bones from which blood cells are produced.

Red blood cells

The main function of red blood cells, or erythrocytes (pronounced uh-REE-throw-sites), is the transport of oxygen from the lungs to body tissues. Erythrocytes are tiny disk-shaped structures that are hollowed out on either side. Their small size allows them to squeeze through microscopic blood vessels called capillaries. They number about 5 million per cubic millimeter of blood; in the entire human body, there are about 25 trillion red blood cells.

Red blood cells are formed in the red bone marrow of certain bones, where they produce a substance called hemoglobin. Hemoglobin is a protein pigment that contains iron and that gives red blood cells their color. The hemoglobin in red blood cells combines with oxygen in the lungs, transporting that oxygen to the tissues throughout the body. It also carries carbon dioxide from the tissues back to the lungs, where some of the carbon dioxide is exhaled. Each red blood cell lives only about four months. New red blood cells are constantly being produced in the bone marrow to take the place of old ones.

White blood cells

White blood cells, often called leukocytes (pronounced LUKE-oh-sites), are part of the body's immune system. They defend the body

against viruses, bacteria, and other invading microorganisms. There are five kinds of white blood cells in human blood: neutrophils, eosinophils, basophils, monocytes, and lymphocytes. Each plays a specific role in the body's immune or defense system. For example, during long-term infections such as tuberculosis (infectious disease of the lungs), monocytes increase in number. During asthma and allergy attacks, eosinophils increase in number.

Lymphocytes make up roughly one-fourth of all white blood cells in the body. They are divided into two classes: T lymphocytes and B lymphocytes. The letter T refers to the thymus, an organ located in the upper chest region where these cells mature. The letter B refers to the bone marrow where these specific lymphocytes mature. T lymphocytes are further divided into four types. Of these four, helper T lymphocytes are the most important. They direct or manage the body's immune response, not only at the site of infection but throughout the body. HIV, the virus that causes acquired immunodeficiency syndrome or AIDS, attacks and kills helper T lymphocytes. The disease cripples the immune system, leaving the body helpless to stave off infections. As AIDS progresses, the number of helper T lymphocytes drops from a normal 1,000 to 0.

All white blood cells are produced in the bone marrow. Some types are carried in the blood, while others travel to different body tissues. There are about 4,000 to 11,000 white blood cells per cubic millimeter of blood in the human body. This number can greatly increase when the body is fighting off infection.

Platelets

Platelets are small, disk-shaped fragments of cells that are broken off from other cells in the bone marrow. They help to control bleeding in a complex process called hemostasis. When an injury to a blood vessel causes bleeding, platelets stick to the ruptured blood vessel and release substances that attract other platelets. Together they form a temporary blood clot. Through a series of chemical reactions, the plasma protein fibrinogen is converted into fibrin. Fibrin molecules form threads that trap red blood cells and platelets, producing a clot that seals the cut blood vessel.

Platelets number about 300,000 per microliter of human blood. They have a short life span, surviving only about 10 days before being replaced.

In an inherited disorder called hemophilia, one or more clotting factors is missing in the blood. Persons with this disorder bleed excessively after injury because their blood does not clot properly.

Artificial blood: Running through the veins of the future?

Since the seventeenth century, doctors have experimented with substitutes for human blood. These substitutes have ranged from milk to oil to the blood from animals. At the beginning of the twenty-first century, with fears of HIV, mad cow disease, and other viruses contaminating the blood supply, the rush to create artificial blood intensified. Artificial or synthetic blood offers many pluses. In addition to helping relieve blood shortages, it could ease doctors' worries about mismatching the blood types of donors and patients. Artificial blood also stays fresher longer than normal blood and does not have to be refrigerated. In theory, artificial blood may be less likely to harbor viruses that infect donated blood. In 2001, having conducted research and testing for many years, several companies in the United States were close to the goal of creating an artificial human blood for use by the medical community.

[See also Circulatory system; Heart; Respiratory system ]

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Blood

Blood

Blood is the bodily fluid responsible for transport of materials and waste products throughout the body. It carries oxygen from and carbon dioxide to the lungs, nutrients from the digestive system or storage sites to tissues that require them, and waste products from the tissues to the liver for detoxification and to the kidneys for disposal. Blood delivers hormones to their sites of action and circulates numerous critical parts of the immune system throughout the body. Blood regulates its own pH , as well as that of the intercellular fluid in the body, and aids in thermoregulation by redistributing heat. Blood also carries the proteins and other factors it needs to clot, thereby preventing its own loss in the event of injury to the vessels in which it travels.

A human adult has 4 to 6 liters (1 to 1.5 gallons) of blood, approximately 92 percent of which is water. Nearly half its volume is red blood cells (RBCs, or erythrocytes). Proteins, sugars, salts, white blood cells, and platelets make up the remainder. The noncellular portion is termed plasma, while the cellular parts are collectively referred to as the formed elements. Blood forms in the bone marrow, a spongy tissue contained in the bones.

Red Blood Cells and Hemoglobin

Only a small amount of the oxygen needed for life can dissolve directly in plasma. Oxygen transport instead relies on red blood cells. At any one time, there are more than 25 trillion RBCs in circulation in an adult, more than the combined total of all other cell types in the body. As RBCs develop, they extrude their cell nucleus , so that at maturity they have almost nothing inside their membranes except the oxygen-carrying protein, hemoglobin . The absence of a nucleus contributes to the RBC's short life, as does the constant physical stress it experiences squeezing through capillaries that are narrower than it is. The average RBC circulates for approximately 120 days before being destroyed in the liver, bone marrow, or spleen. The iron from hemoglobin is recycled, while the cyclic nitrogen compound that holds it, called heme, is converted to bilirubin. Bilirubin is transported to the liver for elimination from the body as bile. Liver disease can cause jaundice, a yellowing of the skin due to bilirubin in the blood.

The iron in hemoglobin is critical for oxygen transport. Lack of dietary iron is one cause of anemia, a condition in which the blood cannot carry enough oxygen. The heme group binds oxygen tightly when the concentration of O2 is high (as it is in the lungs), but quickly releases it when the concentration is low, as it is in the tissues. The iron can also bind carbon monoxide (CO), which is produced by car engines and other combustion sources. CO binds much more tightly than oxygen does and prevents oxygen binding, making CO a deadly poison.

A genetic variant of the hemoglobin gene causes a single amino acid change in the hemoglobin molecule. This change causes the red blood cell to become sickle-shaped at low oxygen concentrations, so that it tends to become lodged in small capillaries, depriving tissues of oxygen. A person with one such variant hemoglobin gene does not suffer ill effects, but with two variants will develop sickle-cell anemia. Despite this, the sickling variant is common in populations historically exposed to malaria, because having one variant helps protect against malaria infection.

CO2 Transport and Blood Buffering

Carbon dioxide (CO2) does not bind to iron, but rather to the protein portion of hemoglobin. CO2 is a product of cell respiration, and is picked up in the tissues and transported to the lungs. Most of the CO2 transported is actually in the form of bicarbonate ion , HCO3. Bicarbonate is formed by the enzyme carbonic anhydrase, which is present in the red blood cells. This enzyme catalyzes the conversion of CO2 and H2O to carbonic acid (H2CO3), which immediately splits to form H and HCO3. Besides serving as a transport form of CO2, HCO3 also participates in blood buffering. It can react with excess H (acid ion) formed in other reactions. In this way, it prevents excess acidity in the blood. Similarly, HCO3 can react with excess OH (base ion) to form water and CO32, absorbing excess base. Along with phosphate, bicarbonate keeps the blood buffered at a pH of 7.4.

Nutrient Transport, Regulation, and Clotting

Blood also transports nutrients, hormones, and immune system components. Nutrients from the gut are dissolved directly in the plasma for transport, but are quickly shuttled to the liver for processing and storage of excess. Insulin and glucagon, hormones produced by the pancreas, control the level of blood sugar by promoting storage or release of glucose . The kidney performs the vital function of excreting excess salts and water, as well as metabolic wastes, helping to maintain blood levels of these substances within narrow limits. One waste product the kidneys cannot excrete is heat, produced by cell metabolism through out the body. Blood performs the vital function of carrying heat from the body core to the periphery, where it can be cooled before returning.


DREW, CHARLES (19041950)

African-American surgeon who invented a way to preserve blood plasma so that it could be stored. Drew's plasma saved the lives of thousands of Londoners during the Nazi bombings in World War II. But when the U.S. military refused to accept blood donated by black Americans, Drew resigned from his post as head of the Red Cross's "Plasma for Britain" program.


Hormones are released by endocrine organs directly into the bloodstream for wide and rapid circulation. White blood cells also use the circulatory system as a highway through the body, traveling in the blood until they exit in response to chemical signals from wounded or infected tissues. Platelets and clotting proteins in the blood work together to prevent blood loss when a vessel is broken. Clotting relies on chemical signals from damaged tissue and from platelets, and the activation of a complex cascade of more than a dozen different plasma proteins.

see also Blood Clotting; Heart and Circulation; Hormones; Respiration

Richard Robinson

Bibliography

Guyton, Arthur C., and John E. Hall. Textbook of Medical Physiology, 10th ed. Philadelphia, PA: W. B. Saunders, Co., 2000.

Stiene-Martin, E. Anne, Cheryl A. Lotspeich-Steininger, and John A. Koepke. Clinical Hematology: Principles, Procedures, Correlations, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1998.

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blood

blood in medieval science and medicine, blood was regarded as one of the four bodily humours, believed to be associated with a confident and optimistic, or sanguine, temperament.

Blood is traditionally used to denote the killing of a person, or guilt for a death, as in blood on one's hands.


blood and iron military force as distinguished from diplomacy; the phrase is a translation of German Blut und Eisen, and is particularly associated with the German statesman Otto von Bismarck (1815–98).
blood-and-thunder a story which features bloodshed and violence; the term is recorded from the mid 19th century.
blood is thicker than water in the end a family connection will outweigh other relationships. Recorded from the early 19th century, but a related 12th-century saying in German runs, ‘I hear it said that kin-blood is not spoiled by water’, and Lydgate in the Troy Book (1412) has, ‘For naturely blod will ay of kynde Draw vn-to blod, wher he may it fynde.’
the blood of the martyrs is the seed of the Church the Church thrives on persecution. Recorded in English as a saying from the mid 16th century; the 3rd century early Christian writer Tertullian has, ‘As often as we are mown down by you, the more we grow in numbers; the blood of Christians is the seed.’
blood on the carpet a serious disagreement or its aftermath; used hyperbolically to suggest that there has been bloodshed.
blood, toil, tears and sweat Winston Churchill's summary of what in May 1940 he could offer the country for its immediate future, in the words, ‘I have nothing to offer but blood, toil, tears and sweat.’
blood will have blood killing will provoke further killing. Recorded as an English saying from late Middle English, but ultimately, the saying refers to Genesis 9:6, ‘Whoso sheddeth man's blood, by man shall his blood be shed.’
blood will tell family characteristics or heredity cannot be concealed. Saying recorded from the mid 19th century.
first blood the first point or advantage gained in a contest. Also literally, ‘the first shedding of blood’, especially in a boxing match or formerly in duelling with swords.
make one's blood curdle fill one with horror. Like the alternative make one's blood run cold, originating in the medieval physiological scheme of the four humours in the human frame (melancholy, phlegm, blood, and choler). Blood was the hot, moist element, so the effect of horror or fear in making it run cold or curdling (solidifying) it was to make it unable to fulfil its proper function of supplying the body with vital heat or energy.
you cannot get blood from a stone often used, as a resigned admission, to mean that it is hopeless to try to extort money or sympathy from those who have none. Recorded from the mid 17th century, but a late Middle English poem by Lydgate has the related ‘Harde to likke hony out of a marbil stoon, For there is nouthir licour nor moisture’,

See also baptism of blood, blue blood, in cold blood, stir the blood.

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ELIZABETH KNOWLES. "blood." The Oxford Dictionary of Phrase and Fable. 2006. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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blood

blood / bləd/ • n. 1. the red liquid that circulates in the arteries and veins of humans and other vertebrate animals, carrying oxygen to and carbon dioxide from the tissues of the body: drops of blood. ∎  an internal bodily fluid, not necessarily red, that performs a similar function in invertebrates. ∎ fig. violence involving bloodshed: a commando operation full of blood and danger. ∎ fig. a person's downfall or punishment, typically as retribution: the press is baying for blood. 2. fig. temperament or disposition, esp. when passionate: a ritual that fires up his blood. 3. family background; descent or lineage: she must have Irish blood in her. ∎  [in comb.] a person of specified descent: a mixed-blood. PHRASES: be like getting blood out of (or from) a stone (or turnip) be extremely difficult (said in reference to obtaining something from someone): getting a story out of her is like getting blood out of a stone! blood and guts inf. violence and bloodshed, typically in fiction. blood, sweat, and tears extremely hard work; unstinting effort. first blood 1. the first shedding of blood, esp. in a boxing match or formerly in dueling with swords. 2. the first point or advantage gained in a contest: King drew first blood when he took the opening set. give blood allow blood to be removed medically from one's body in order to be stored for use in transfusions. have blood on one's hands be responsible for someone's death. in one's blood ingrained in or fundamental to one's character: racing is in his blood. in cold blood ruthlessly; without feeling: proving that he can kill in cold blood. make someone's blood boil inf. infuriate someone. make someone's blood run cold horrify someone. taste blood achieve an early success that stimulates further efforts: the speculators have tasted blood and could force a devaluation of the franc. young blood a younger member or members of a group, typically as an invigorating force.

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"blood." The Oxford Pocket Dictionary of Current English. 2009. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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blood test

blood test, examination of blood routinely or as an aid in diagnosing a suspected disease. Tests may be performed on whole blood or on the plasma portion only. Blood typing identifies the proteins at specific sites on red blood cells, a necessity in determining compatibility for blood transfusion. Human Lymphocyte Antigens (HLA) is a form of white blood cell typing prerequisite for organ and bone marrow transplants. The Coulter Cell Counter is widely used in electronic counts of red blood cells for the diagnosis of anemia and polycythemia. White cell counts are vital in detecting infections or in confirming leukemia. Serum or plasma may be collected, cultured, and inoculated with bacteria or other substances for the purpose of detecting the body's reaction to infections, cancer, or HIV, the virus that causes AIDS. Plasma may also be examined for evidence of functional disorders, e.g., for blood sugar in testing for diabetes mellitus. Blood tests for tumor markers, such as prostate-specific antigen, are effective in detecting cancer in high risk groups. Almost all blood tests are now performed by electronic equipment, and results are evaluated and printed out by computer.

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Blood

Blood. Commonly held in religions to be the sign and condition of life, and therefore a fundamental constituent of sacrifices. Because of its importance in relation to God's gift of life, the Jewish Bible contains an absolute prohibition against swallowing the blood of an animal (see Leviticus 3. 17; Deuteronomy 12. 15–16). The justification for this is the belief that the blood contained life (Leviticus 17. 11). The prohibition leads directly to laws of kashrut (see DIETARY LAWS) and sheḥitah (the method for slaughtering animals). Eating meat was itself a concession on the part of God after the Flood.

In Christianity, the shedding of the blood of Christ came to be understood as the continuation and culmination of the Temple sacrifices, achieving completely that which they had partially anticipated. From this developed devotion to the Precious Blood (from the Vulgate tr. of 1 Peter 1. 19), decreed as a feast day for the whole Church by Pius IX in 1859, though transferred to a votive mass after Vatican II.

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JOHN BOWKER. "Blood." The Concise Oxford Dictionary of World Religions. 1997. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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blood

blood Fluid circulating in the body that transports oxygen and nutrients to all the cells and removes wastes such as carbon dioxide. In a healthy human, it constitutes c.5% of the body's total weight; by volume, it comprises c.5.5 litres (9.7 pints). It is composed of a colourless, transparent fluid called plasma in which are suspended microscopic erythrocytes, leucocytes, and platelets.

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blood

blood (blud) n. a fluid that circulates throughout the body, via the arteries and veins, providing a vehicle by which an immense variety of different substances are transported between the various organs and tissues. It is composed of cells (see blood cell), which are suspended in a liquid medium (see plasma).

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blood

blood In animals, a fluid circulated through the body by muscular activity and usually containing respiratory pigments conveying oxygen, food materials, excretory products, cells that produce antibodies (lymphocytes), and cells that invade tissue to attack invading organisms.

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MICHAEL ALLABY. "blood." A Dictionary of Zoology. 1999. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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blood

blood OE. blōd = OS. blōd, OHG. bluot (G. blut). ON. blōō, Goth. blōp :- Gmc. *blōōam, of unkn. orig.
Hence bloodhound XIV, bloodthirsty XVI (Coverdale, after Luther's blutdürstig), bloody OE. blōdig; see -Y1.

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T. F. HOAD. "blood." The Concise Oxford Dictionary of English Etymology. 1996. Encyclopedia.com. 19 Apr. 2014 <http://www.encyclopedia.com>.

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blood test

blood test n. any test designed to discover abnormalities in a sample of a person's blood or to determine the blood group.

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DNA profiling

DNA profiling See DNA fingerprinting.

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blood

bloodblood, bud, crud, cud, dud, flood, Judd, mud, rudd, scud, spud, stud, sudd, thud •redbud • lifeblood •stick-in-the-mud

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