What is the relationship between blood and blood disorders?
Blood provides a common communication channel for all organs in the body. It is responsible for the transport of oxygen, enzymes, hormones, drugs, and many other substances, as well as for the transfer of heat produced by chemical reactions in the body. The average-sized adult has about ten pints of blood. At rest, ten pints a minute (and up to forty pints during exercise) are pumped by the heart via the arteries to the lungs and all other tissues. This blood then returns to the heart through the veins, in a continuous circuit.
About half the volume of blood consists of cells, which include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). The remainder is a fluid called plasma, which contains dissolved proteins, sugars, fats, and minerals.
All types of blood cells are formed within the bone marrow by a series of divisions from a single type of cell called a stem cell. Red blood cells, or erythrocytes (from the Greek eruthros, “red”), are very small, have no nucleus, and consist almost completely of hemoglobin. Very little oxygen is needed for the survival of these cells. They have a large surface relative to their volume, which allows oxygen and carbon dioxide to diffuse in and out of the cell rapidly. This large surface also allows the cell to swell and shrink and to be squashed through narrow capillaries without its surface being subjected to shearing or bursting. Red blood cells cannot repair themselves, and after three or four months in circulation they are eliminated and replaced. Their main function is to act as containers for hemoglobin; as such, they are among the most highly specialized cells in the body.
Hemoglobin, the red, iron-containing pigment responsible for the color of blood, has a great affinity for oxygen. It will release the oxygen in a situation where free oxygen is scarce, as it is among the live cells of working tissues. Hemoglobin gives blood an oxygen-carrying capacity eighty times greater than if the oxygen were merely dissolved in plasma. When hemoglobin gives up its oxygen, it becomes capable of taking up carbon dioxide, which it carries to the lungs. Thus this substance provides a sophisticated oxygen delivery system that provides the proper amount of oxygen to the tissues under a wide variety of circumstances. Hemoglobin occupies 33 percent of the volume of the red cell and accounts for 90 percent of its dry weight.
Leukocytes, or white blood cells (from the Greek leukos, meaning “clear” or “white”), are larger and less plentiful than red blood cells and can also be found outside the blood. Their purpose is to clean the system of wastes and foreign material and to act as defense against living germs. They travel through the circulatory system and can pass through the walls of blood vessels to do their work in the surrounding tissues. White blood cells play an important role in the defense against infection by viruses, bacteria, fungi, parasites, and inflammation of any cause. There are three main types: granulocytes, monocytes, and lymphocytes. Granulocytes, or polymorphonuclear leukocytes, contain granules and have an oddly shaped nucleus; they are themselves of three types: neutrophils, basophils, and eosinophils. The most important are the neutrophils, which are responsible for isolating and killing invading bacteria (pus consists largely of neutrophils). They are also called phagocytes (“engulfing cells”) because of their capability to swallow bacteria and other foreign materials. They normally remain in the blood for only six to nine hours and then travel to the tissues where they spend a few more days and then move to sites of infection. Eosinophils are involved in allergic reactions. Monocytes circulate in the blood for six to nine days and are also a type of phagocyte important in the immune system.
Lymphocytes are the entities responsible for immune response, such as the production of antibodies and the rejection of tissue grafts. They direct the activity of all other cells in the immune response. Many of them are formed in the lymph nodes rather than in the bone marrow. Their lifetime is between three months and ten years. Unlike granulocytes and monocytes, they do not engulf solid particles but instead play a part in antibody production. An antibody is a protein that may dissolve freely in the blood plasma or in other body fluids and may affix to other cells. Antibodies can be regarded as disinfectants since they kill or specifically mark foreign material so that it is more readily noticed, caught, digested, or swept away by scavenger cells. There are many different types of lymphocytes, each of which has a different function. T lymphocytes are responsible for delayed hypersensitivity phenomena and produce substances called lymphokines, which affect the function of many cells. They also moderate the activity of other lymphocytes called B lymphocytes. These cells form the antibodies that protect against a second attack of a disease. Most of these cells are in a state of patrol and form an early warning system that moves out of the circulation, into the tissue fluids, and back to the blood. If these cells encounter foreign material that fits a specific molecular pattern in their structure, or receive such material from another cell, they move to a lymph node or similar area. There they divide to produce a line of daughter cells, all of which manufacture an antibody specifically active against that foreign or irregular material.
Platelets, or thrombocytes, are the smallest cells in blood; they can survive there for about nine days. They circulate in the blood in an inactive state, but under certain circumstances they begin to adhere to blood vessels and one another, producing and releasing chemicals that begin the process of blood clotting. Thus they are critical in hemostasis (the arresting of bleeding).
Plasma is the straw-colored fluid in which blood cells are suspended. It is composed mainly of water (95 percent), with a salt content that is similar to salt water. Some of its other important constituents are nutrients, waste products, proteins, and hormones. Nutrients are transported to the tissues after absorption from the intestinal tract or following release from storage places such as the liver. They include sugars, fats, vitamins, minerals, and the amino acids required to make proteins. The main waste product of tissue metabolism is urea, which is transported in the plasma to the kidneys. The waste product from the destruction of hemoglobin is a yellow pigment called bilirubin, which is normally removed from the plasma by the liver and turned into bile. Among the proteins in plasma are substances such as fibrinogen (involved in the process of coagulation and clotting), immunoglobulins and their complements (bacteria fighters that are part of the immune system), and albumin. Hormones are chemical messengers transported from various glands to their target organs.
The term blood group refers to the classification of blood according to differences in the makeup of its red blood cells. The ABO system consists of three blood group substances, the A, B, and H antigens (substances that induce the production of an antibody when injected into an animal), which are components of erythrocyte surface substances. Individuals with type A cells carry anti-B antibodies in their serum; those with type B cells carry anti-A antibodies; those with type AB cells (which bear both A and B antigens) carry neither anti-A nor anti-B antibodies; and type O individuals, whose cells bear neither antigen, carry both anti-A and anti-B antibodies. The transfusion of type A blood into a type B individual, for example, clumps together the transfused erythrocytes and results in an often fatal blockage of blood vessels, which indicates the importance of blood typing before a transfusion is performed.
Another blood group system is based on the rhesus (or Rh) factor. The system involves several antigens, but the most important is called factor D. It is found in 85 percent of the population; those individuals are called Rh positive. If it is not present, the person is classified as Rh negative. Based on this system, individuals are therefore classified as O positive or AB negative, for example, on the basis of their ABO and Rh blood groups. The main importance of the Rh group is during pregnancy. An Rh-negative women who is pregnant with an Rh-positive baby may form antibodies against the baby’s blood. Such women are given antibodies directed against factor D after delivery to prevent the development of anti-D antibodies, which would cause hemolytic disease of the newborn in successive Rh-positive infants. The transfusion of Rh-positive blood into an Rh-negative patient can cause a serious reaction if the patient has had a previous blood transfusion that contained the Rh antigen.
About four hundred other antigens have been discovered, but they are widely scattered throughout the population and rarely cause transfusion problems. Only the ABO and the Rh blood group systems have major clinical importance.
Blood typing is used to categorize blood for transfusion. Knowledge of blood group substances and of their inheritance has been useful for legal, historical, and medical purposes. The ABO blood groups are found in all people, but the frequency of each group varies with race and geographical distribution. This fact can aid anthropologists who are involved in investigating, for example, early population migrations. The blood group of an individual is determined by the genes inherited from his or her parents. Identification of a blood group can be used in a paternity case to establish that a man could not have been the father of a particular child, although it cannot be shown positively that a man is the father by blood grouping. Blood found at the scene of a crime can be typed and used to exclude suspects if the type does not match. Some blood groups are associated with particular disorders. For example, blood group A has been found to be more common in people suffering from cancer of the stomach, while group O is found more often in people suffering from peptic ulcers.
Blood tests can be used to check on the health of major organs as well as respiratory functions, hormonal balance, the immune system, and metabolism. They can reveal not only the blood cell abnormalities characteristic of some diseases but also healthy variations in blood induced by response to infections. Blood tests can be classified into three categories. Hematological tests involve studying the components of blood itself by looking at the number, shape, size, and appearance of its cells, as well as by testing the function of clotting factors. The most important tests of this type are the blood count, blood smear, and blood-clotting tests. Biochemical tests look at chemicals in the blood such as sodium, potassium, uric acid, urea, vitamins, gases, and drugs. In microbiological tests, blood is examined for microorganisms, such as bacteria, viruses and viral particles, fungi, and parasites, and for antibodies that form against them.
Known causes of blood disorders include genetic reasons (an inherited abnormality in the production of some blood component), nutritional disorders (such as a vitamin deficiency), infections by microorganisms, tumors (such as bone marrow cancer), poisons (carbon monoxide, lead, and snake and spider venoms), drugs (which can produce blood abnormalities as a side effect), and radiation.
Abnormalities can occur in any of the components of blood, including some constituents of plasma. Leukemias are disorders in which the number of white blood cells is abnormally high. In acquired immunodeficiency syndrome (AIDS), the T lymphocytes are infected by a virus, resulting in dysfunction and an increased risk for certain types of infections and cancers. Abnormal platelets or the lack of platelets can lead to some types of bleeding disorders, such as hemophilia (an inability of the blood to clot properly). Unwanted clot formation (thrombosis) can occur from circumstances that over activate the blood’s clotting mechanisms. Anemia results from a deficiency of hemoglobin and a corresponding reduction in the blood’s oxygen-carrying capacity; this is the most common blood disorder. Deficiencies of the proteins in blood plasma include albuminemia (albumin deficiency).
Blood is a liquid of complex structure and vital functions that has been considered the essence of life for centuries. There is no shortage of irrational or unscientific ideas about the supposed properties of human blood—one can speak of “blood brotherhood,” “blood feuds,” “blood relations,” and of someone being “bloodthirsty.”
The present medical understanding of blood has developed over the past two or three thousand years. The study of blood began in Egypt and Mesopotamia, around 500 bce., and it moved to the countries around the Mediterranean that had become intellectually active. Ancient Greek thinkers noted that there were differences between arteries and veins and that the blood moved through them. According to whether the heart, the liver, or the brain was thought to be the prime organ controlling the rest of the body, various functions were tentatively ascribed to blood, such as its relation to sleep, the distribution of heat, and the animation of the body.
The Greek school of medicine became personified in Hippocrates. He denied the widely accepted theory of the existence of spirits and proposed that the body followed natural laws. He presented the concept of body juices, or humors. There were four of them: blood, lymph or phlegm, yellow bile (or choler), and black bile (or melancholy), with blood being the most important one. The philosopher Aristotle accepted the humoral hypothesis. One of his pupils was Alexander the Great, whose military conquests spread Greek influence widely. A notable medical school developed in Alexandria, Egypt, and the ideas of Hippocrates and Aristotle were taught there. There was, however, a variation in regard to blood; namely, the theory of plethora, in which it was postulated that an excess of blood in the circulatory system or one organ caused illness.
Four hundred years later, Galen, a product of the Alexandria School of Medicine, denied the doctrine of plethora and went back to the humoral approach. Health and disease were thought to occur as a result of an upset in the equilibrium of these humors. Bloodletting to restore the balance of the humors by purging the body of its contaminated fluids was practiced from the time of Hippocrates until the nineteenth century. During Galen’s time, animal dissection was widely practiced and provided a better concept of blood and its functions. It was proposed that the liver changed food to blood, which was distributed to the body along the veins. At the same time, impurities from the body were thought to be absorbed into the venous blood and to be returned to the liver and then to the right side of the heart, where they supposedly ascended in the pulmonary artery to the lungs to be exhaled.
The weakening of medieval ideas set the stage for English doctor William Harvey’s discovery of the circulation of blood. He used the analogy of the heart as a pump and veins and arteries as pipes, where blood is moving around and is being driven in some kind of continuous circuit. Four years after Harvey died in 1661, the Italian anatomist Marcello Malpighi observed the capillary blood vessels with the aid of the microscope. The cellular composition of blood was also recognized with the aid of this device, as Antoni van Leeuwenhoek, a Dutch naturalist, accurately described and measured red blood cells. The discovery of white blood cells and platelets followed after microscope lenses were improved. William Hewson first observed leukocytes in the eighteenth century. He thought that these cells came from the nucleated cells in the lymph and that they eventually emerged from the spleen as red blood cells. In the nineteenth century, the interest in leukocytes intensified with studies on inflammation and microbial infection.
In 1852, Karl Vierordt published the first quantitative results of blood cell analysis after several attempts were made to correlate blood cell counts with various diseases. The observation of crystalline hemoglobin was first reported in 1849. In 1865, Felix Hoppe-Seyler discovered the oxygen-carrying capacity of the red pigment (hemoglobin) in the cells. The early history of protein chemistry is essentially that of hemoglobin, because it was one of the first molecules to have its molecular weight accurately determined and the first to be associated with a specific physiological function (that of carrying oxygen).
In 1900, the German pathologist Karl Landsteiner began mixing blood taken from different people and found that some mixtures were compatible and others were not. This incompatibility resulted in illness and sometimes death after transfusions. He discovered two types of marker proteins, or antigens, on the surface of red blood cells, which he called A and B. According to whether a person’s blood contains one or the other antigen, both, or neither, it is classified as type A, B, AB, or O. He also discovered the Rh factor in 1940 during experiments with rhesus monkeys. Improved methods of blood examination in the 1920s and the growth of knowledge of blood physiology in the 1930s allowed anemias and other blood disorders to be studied on a rational basis.
Modern hematology recognizes that alterations in the components of blood are a result of disease, and research is conducted continually for a better understanding of this relationship and of blood itself.
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