Blood is a vital fluid found in humans and other animals that provides important nourishment to all body organs and tissues and carries away waste materials. Sometimes referred to as “the river of life,” blood is pumped from the heart through a network of blood vessels collectively known as the circulatory system.
An adult human has about 5 to 6 liters (1 to 2 gal) of blood, which is roughly 7 to 8 percent of total body weight. Infants and children have comparably lower volumes of blood, roughly proportionate to their smaller size. The volume of blood in an individual fluctuates. During dehydration, for example while running a marathon, blood volume decreases. Blood volume increases in circumstances such as pregnancy, when the mother’s blood needs to carry extra oxygen and nutrients to the baby.
ROLE OF BLOOD
Blood carries oxygen from the lungs to all the other tissues in the body and, in turn, carries waste products, predominantly carbon dioxide, back to the lungs where they are released into the air. When oxygen transport fails, a person dies within a few minutes. Food that has been processed by the digestive system into smaller components such as proteins, fats, and carbohydrates is also delivered to the tissues by the blood. These nutrients provide the materials and energy needed by individual cells for metabolism, or the performance of cellular function. Waste products produced during metabolism, such as urea and uric acid, are carried by the blood to the kidneys, where they are transferred from the blood into urine and eliminated from the body. In addition to oxygen and nutrients, blood also transports special chemicals, called hormones, that regulate certain body functions. The movement of these chemicals enables one organ to control the function of another even though the two organs may be located far apart. In this way, the blood acts not just as a means of transportation but also as a communications system.
The blood is more than a pipeline for nutrients and information; it is also responsible for the activities of the immune system, helping fend off infection and fight disease. In addition, blood carries the means for stopping itself from leaking out of the body after an injury. The blood does this by carrying special cells and proteins, known as the coagulation system, that start to form clots within a matter of seconds after injury.
Blood is vital to maintaining a stable body temperature; in humans, body temperature normally fluctuates within a degree of 37.0° C (98.6° F). Heat production and heat loss in various parts of the body are balanced out by heat transfer via the bloodstream. This is accomplished by varying the diameter of blood vessels in the skin. When a person becomes overheated, the vessels dilate and an increased volume of blood flows through the skin. Heat dissipates through the skin, effectively lowering the body temperature. The increased flow of blood in the skin makes the skin appear pink or flushed. When a person is cold, the skin may become pale as the vessels narrow, diverting blood from the skin and reducing heat loss.
COMPOSITION OF BLOOD
About 55 percent of the blood is composed of a liquid known as plasma. The rest of the blood is made of three major types of cells: red blood cells (also known as erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes).
A. Plasma
Plasma consists predominantly of water and salts. The kidneys carefully maintain the salt concentration in plasma because small changes in its concentration will cause cells in the body to function improperly. In extreme conditions this can result in seizures, coma, or even death. The pH of plasma, the common measurement of the plasma’s acidity, is also carefully controlled by the kidneys within the neutral range of 6.8 to 7.7. Plasma also contains other small molecules, including vitamins, minerals, nutrients, and waste products. The concentrations of all of these molecules must be carefully regulated.
Plasma is usually yellow in color due to proteins dissolved in it. However, after a person eats a fatty meal, that person’s plasma temporarily develops a milky color as the blood carries the ingested fats from the intestines to other organs of the body.
Plasma carries a large number of important proteins, including albumin, gamma globulin, and clotting factors. Albumin is the main protein in blood. It helps regulate the water content of tissues and blood. Gamma globulin is composed of tens of thousands of unique antibody molecules. Antibodies neutralize or help destroy infectious organisms. Each antibody is designed to target one specific invading organism. For example, chicken pox antibody will target chicken pox virus, but will leave an influenza virus unharmed. Clotting factors, such as fibrinogen, are involved in forming blood clots that seal leaks after an injury. Plasma that has had the clotting factors removed is called serum. Both serum and plasma are easy to store and have many medical uses.
B. Red Blood Cells
Red blood cells make up almost 45 percent of the blood volume. Their primary function is to carry oxygen from the lungs to every cell in the body. Red blood cells are composed predominantly of a protein and iron compound, called hemoglobin, that captures oxygen molecules as the blood moves through the lungs, giving blood its red color. As blood passes through body tissues, hemoglobin then releases the oxygen to cells throughout the body. Red blood cells are so packed with hemoglobin that they lack many components, including a nucleus, found in other cells. Hemoglobin also takes up and releases nitric oxide, which plays an important role in regulating blood pressure.
The membrane, or outer layer, of the red blood cell is flexible, like a soap bubble, and is able to bend in many directions without breaking. This is important because the red blood cells must be able to pass through the tiniest blood vessels, the capillaries, to deliver oxygen wherever it is needed. The capillaries are so narrow that the red blood cells, normally shaped like a disk with a concave top and bottom, must bend and twist to maneuver single file through them.
C. White Blood Cells
White blood cells only make up about 1 percent of blood, but their small number belies their immense importance. They play a vital role in the body’s immune system—the primary defense mechanism against invading bacteria, viruses, fungi, and parasites. They often accomplish this goal through direct attack, which usually involves identifying the invading organism as foreign, attaching to it, and then destroying it. This process is referred to as phagocytosis.
White blood cells also produce antibodies, which are released into the circulating blood to target and attach to foreign organisms. After attachment, the antibody may neutralize the organism, or it may elicit help from other immune system cells to destroy the foreign substance. There are several varieties of white blood cells, including neutrophils, monocytes, and lymphocytes, all of which interact with one another and with plasma proteins and other cell types to form the complex and highly effective immune system.
D. Platelates and blood clotting
Mammalian platelets are nonnucleate cells produced by large bone marrow cells called megakaryocytes and circulate in the blood in a resting, inactive form for an average of 10 days. The normal platelet count in humans is between 150,000 and 400,000 platelets per cubic millimetre of blood. The inactive platelet contains three types of internal granules: the alpha granules, the dense granules, and the lysosomes. Each of these granules is rich in certain chemicals that have an important role in platelet function. For example, dense granules contain large quantities of calcium ions and adenosine diphosphate (ADP). Upon release from the platelet, ADP stimulates other platelets to activate when it binds to the ADP receptor on the platelet membrane. The alpha granules contain many proteins, including fibrinogen, thrombospondin, fibronectin, and von Willebrand factor. Upon platelet activation, platelets alter their shape from discoid to spherical and extend long footlike projections called pseudopodia. The alpha granules and dense granules move to the surface of the platelet, fuse with the platelet membrane, and release their contents into the blood surrounding the platelet. The lysosomes contain enzymes that digest spent proteins and other metabolites of the cell.
Activated platelets strongly adhere to surfaces other than the lining of blood vessels, such as collagen, glass, metals, and fabrics. Adherent platelets themselves become adhesive for other activated platelets so that, in a flow system, a platelet plug develops. The propagation of this adhesiveness from one layer to the next is probably due to chemicals, such as ADP and thromboxane A2, secreted into the blood from the granules of the activated platelets. The ADP released from the dense granules binds to a receptor on the platelet surface, initiating the biochemical and morphological changes associated with platelet activation and secretion. The property of adhesiveness for normal platelets requires a protein on the surface of the platelet membrane, known as glycoprotein Ib, to bind von Willebrand factor, a large multimeric plasma protein released from the alpha granules. Von Willebrand factor, when bound to glycoprotein Ib on the platelet surface, facilitates the interaction of platelets with a variety of other surfaces (e.g., the damaged vessel lining).
Platelet aggregation is the property of platelets to clump with each other to form a platelet plug. Two proteins on the platelet membrane play an important role in platelet aggregation: glycoprotein IIb and glycoprotein IIIa. These proteins form a complex in the membrane and expose a receptor site after platelet activation that binds fibrinogen (a bivalent molecule with two symmetrical halves that is found in relatively high concentration in plasma). Fibrinogen can bind simultaneously to two platelets. Thus, fibrinogen links platelets together (aggregation) through the glycoprotein IIb–IIIa complex that serves as the fibrinogen receptor.
Injury to the vessel lining and contact of the blood with tissues outside the vessel stimulates thrombin production by the activation of the clotting system. Thrombin causes platelet aggregation. Platelets exposed to thrombin secrete their granules and release the contents of these granules into the surrounding plasma.
BLOOD CLOTTING: Coagulation is the replacement of a relatively unstable platelet plug with a stronger, more resilient blood clot through a series of interdependent, enzyme-mediated reactions that bring about the generation of thrombin and the formation of fibrin from fibrinogen. The intrinsic and the extrinsic pathways of coagulation are involved in regulating coagulation; each is activated by a different trigger, although they share many steps in the course of the generation of thrombin.
Intrinsic pathway of blood coagulation:All the components necessary for the clotting process to proceed are found in the blood. As such, the proteins required for such clotting to take place are part of the intrinsic pathway of blood coagulation. This pathway involves a series of proteins, protein cofactors, and enzymes, which interact in reactions that take place on membrane surfaces. These reactions are initiated by tissue injury and result in the formation of a fibrin clot (Figure 1).
The intrinsic pathway is initiated by the activation of factor XII by certain negatively charged surfaces, including glass. High-molecular-weight kininogen and prekallikrein are two proteins that facilitate this activation. The enzyme form of factor XII (factor XIIa) catalyzes the conversion of factor XI to its enzyme form (factor XIa). Factor XIa catalyzes the conversion of factor IX to the activated form, factor IXa, in a reaction that requires calcium ions. Factor IXa assembles on the surface of membranes in complex with factor VIII; the factor IXa–factor VIII complex requires calcium to stabilize certain structures on these proteins associated with their membrane-binding properties. Factor X binds to the factor IXa–factor VIII complex and is activated to factor Xa. Factor Xa forms a complex with factor V on membrane surfaces in a reaction that also requires calcium ions. Prothrombin binds to the factor Xa–factor V complex and is converted to thrombin, a potent enzyme that cleaves fibrinogen to fibrin, a monomer. The monomer fibrin molecules then link together (polymerize) to form long fibres. Later, additional bonding between the units of the polymer is promoted by an enzyme known as factor XIIIa, which stabilizes the newly formed clot by cross-linkages. Although the detailed mechanisms are not known, this cascade, or waterfall, effect offers the possibility for amplification of a small signal associated with tissue injury into a major biologic event—the formation of a fibrin clot. Furthermore, careful regulation of this system is possible with the participation of two protein cofactors, factor VIII and factor V.
Certain negatively charged surfaces, including glass, kaolin, some synthetic plastics, and fabrics, activate factor XII to its enzyme form, factor XIIa. In contrast, certain materials have little tendency to activate factor XII. Inactive surfaces include some oils, waxes, resins, silicones, a few plastics, and endothelial cells, the most inert surface of all. The physicochemical properties that determine activity are not known. The problem is important, for modern surgery requires a perfectly inactive material to make substitutes (prostheses) for heart valves and sections of blood vessels. The formation of clots (thrombi) on these surfaces can lead to serious or even fatal complications. Open-heart surgery requires pumping of blood through equipment that does not activate the blood-clotting process significantly. Similarly, blood filtration of waste products during kidney dialysis must not lead to the generation of fibrin clots. To minimize the activation of blood coagulation when blood flows over foreign surfaces, special drugs (anticoagulants) such as heparin are employed.
The activity of the intrinsic pathway may be assessed in a simple laboratory test called the partial thromboplastin time (PTT), or, more accurately, the activated partial thromboplastin time. Plasma is collected and anticoagulated with citrate buffer; the citrate binds and effectively removes functional calcium ions from the plasma. Under these conditions, a fibrin clot cannot be generated. A negatively charged material, such as the diatomaceous material kaolin, is added to the plasma. Kaolin activates factor XII to its enzyme form, factor XIIa, which then activates factor XI. The process is blocked from further activation because of the lack of calcium ions, which are required for the next reaction, the activation of factor IX. Upon the addition of calcium ions and a phospholipid preparation (which serves as an artificial membrane for the assembly of the blood-clotting protein complexes), the duration of time is recorded until a visible clot is formed. This reaction takes place in a matter of 25 to 50 seconds, depending upon the formulation of chemicals used. In practice, the clotting time of a test plasma is compared to the clotting time of normal plasma. Delayed clotting, measured as a prolonged partial thromboplastin time, may be due to a deficiency in the activity of one or more of the blood-clotting factors or to a chemical inhibitor of blood coagulation.
The extrinsic pathway of blood coagulation:Upon the introduction of cells, particularly crushed or injured tissue, blood coagulation is activated and a fibrin clot is rapidly formed. The protein on the surface of cells that is responsible for the initiation of blood clotting is known as tissue factor, or tissue thromboplastin. Tissue factor is found in many of the cells of the body but is particularly abundant in those of the brain, lungs, and placenta. The pathway of blood coagulation activated by tissue factor, a protein extrinsic to blood, is known as the extrinsic pathway (Figure 1).
Tissue factor serves as a cofactor with factor VII to facilitate the activation of factor X. Alternatively, factor VII can activate factor IX, which, in turn, can activate factor X. Once activated, factor X proceeds to activate prothrombin to thrombin in a reaction requiring factor V. The thrombin converts fibrinogen to fibrin. With the exception of factor VII, all components of the extrinsic pathway are also components of the intrinsic pathway.
The activity of the extrinsic pathway may be assessed in the laboratory using a simple test known as the prothrombin time. Tissue extract, or tissue thromboplastin, is extracted from animal tissues rich in tissue factor. Plasma, anticoagulated with citrate buffer, is allowed to clot with the simultaneous addition of phospholipid, calcium, and thromboplastin. The duration of time until clot formation, known as the prothrombin time, is usually between 10 and 12 seconds. In practice, the clotting time of a test plasma is compared to the clotting time of normal plasma. Delayed clotting, measured as a prolonged prothrombin time, may be due to a deficiency in the activity of one or more of the blood-clotting factors in the extrinsic pathway or to a chemical inhibitor of blood coagulation that interferes with the extrinsic pathway.
In summary, there are two independent mechanisms for initiating blood coagulation and for activating factor X: (1) negatively charged surfaces that initiate blood clotting through the intrinsic pathway (factors XII, XI, IX, and VIII), and (2) tissue factor on cells outside the blood that participates in the extrinsic pathway (factor VII). The common pathway (factor X, factor V, prothrombin, and fibrinogen) is shared by both systems. Although both pathways provide the opportunity to acquire meaningful information about clotting proteins using the partial thromboplastin time and the prothrombin time, it is most likely that the physiologically important pathway of blood coagulation is the extrinsic pathway initiated by tissue factor.
PRODUCTION AND ELIMINATION OF BLOOD CELLS
Blood is produced in the bone marrow, a tissue in the central cavity inside almost all of the bones in the body. In infants, the marrow in most of the bones is actively involved in blood cell formation. By later adult life, active blood cell formation gradually ceases in the bones of the arms and legs and concentrates in the skull, spine, ribs, and pelvis.
Red blood cells, white blood cells, and platelets grow from a single precursor cell, known as a hematopoietic stem cell. Remarkably, experiments have suggested that as few as 10 stem cells can, in four weeks, multiply into 30 trillion red blood cells, 30 billion white blood cells, and 1.2 trillion platelets—enough to replace every blood cell in the body.
Red blood cells have the longest average life span of any of the cellular elements of blood. A red blood cell lives 100 to 120 days after being released from the marrow into the blood. Over that period of time, red blood cells gradually age. Spent cells are removed by the spleen and, to a lesser extent, by the liver. The spleen and the liver also remove any red blood cells that become damaged, regardless of their age. The body efficiently recycles many components of the damaged cells, including parts of the hemoglobin molecule, especially the iron contained within it.
The majority of white blood cells have a relatively short life span. They may survive only 18 to 36 hours after being released from the marrow. However, some of the white blood cells are responsible for maintaining what is called immunologic memory. These memory cells retain knowledge of what infectious organisms the body has previously been exposed to. If one of those organisms returns, the memory cells initiate an extremely rapid response designed to kill the foreign invader. Memory cells may live for years or even decades before dying.
Memory cells make immunizations possible. An immunization, also called a vaccination or an inoculation, is a method of using a vaccine to make the human body immune to certain diseases. A vaccine consists of an infectious agent that has been weakened or killed in the laboratory so that it cannot produce disease when injected into a person, but can spark the immune system to generate memory cells and antibodies specific for the infectious agent. If the infectious agent should ever invade that vaccinated person in the future, these memory cells will direct the cells of the immune system to target the invader before it has the opportunity to cause harm.
Platelets have a life span of seven to ten days in the blood. They either participate in clot formation during that time or, when they have reached the end of their lifetime, are eliminated by the spleen and, to a lesser extent, by the liver.
BLOOD DISEASES
Many diseases are caused by abnormalities in the blood. These diseases are categorized by which component of the blood is affected.
A. Red Blood Cell Diseases
One of the most common blood diseases worldwide is anemia, which is characterized by an abnormally low number of red blood cells or low levels of hemoglobin. One of the major symptoms of anemia is fatigue, due to the failure of the blood to carry enough oxygen to all of the tissues.
The most common type of anemia, iron-deficiency anemia, occurs because the marrow fails to produce sufficient red blood cells. When insufficient iron is available to the bone marrow, it slows down its production of hemoglobin and red blood cells. The most common causes of iron-deficiency anemia are certain infections that result in gastrointestinal blood loss and the consequent chronic loss of iron. Adding supplemental iron to the diet is often sufficient to cure iron-deficiency anemia.
SICKLE CELL ANEMIA: hereditary disease that destroys red blood cells by causing them to take on a rigid “sickle” shape. The disease is characterized by many of the symptoms of chronic anemia (fatigue, pale skin, and shortness of breath) as well as susceptibility to infection, jaundice and other eye problems, delayed growth, and episodic crises of severe pain in the abdomen, bones, or muscles. Sickle cell anemia occurs mainly in persons of African descent. The disease also occurs in persons of the Middle East, the Mediterranean, and India.
Sickle cell anemia is caused by a variant type of hemoglobin, the protein in red blood cells that carries oxygen to the tissues of the body, called hemoglobin S (Hb S). Hb S is sensitive to deficiency of oxygen. When the carrier red blood cells release their oxygen to the tissues and the oxygen concentration within those cells is reduced, Hb S, in contrast to normal hemoglobin (Hb A), becomes stacked within the red cells in filaments that twist into helical rods. These rods then cluster into parallel bundles that distort and elongate the cells, causing them to become rigid and assume a sickle shape. This phenomenon is to some extent reversible after the cells become oxygenated once more, but repeated sickling ultimately results in irreversible distortion of the red cells. The sickle-shaped cells become clogged in small blood vessels, causing obstruction of the microcirculation, which in turn results in damage to and destruction of various tissues.
Sickle cell anemia is caused by the inheritance of a variant hemoglobin (Hb S) gene from both parents. (This inheritance of variant genes from both parents is known as the homozygous state.) A person who inherits the sickle cell gene from one parent and a normal hemoglobin gene (Hb A) from the other parent (an inheritance known as the heterozygous state) is a carrier of the sickle cell trait. Because the red blood cells of heterozygous persons contain both Hb A and Hb S, such cells require much greater deoxygenation to produce sickling than do those of persons with sickle cell anemia. The great majority of persons with the sickle cell trait thus have no symptoms of disease, although certain manifestations—mainly associated with vigorous exertion at high altitudes—have been seen. The overall mortality rate of persons with the sickle cell trait is no different from that of a normal comparable population.
An estimated 1 in 12 blacks worldwide carries the sickle cell trait, while about 1 in 400 has sickle cell anemia. If both parents have the sickle cell trait, the chances are 1 in 4 that a child born to them will develop sickle cell anemia. However, through amniocentesis (analysis of amniotic fluid surrounding a fetus), a testing procedure done in the early stages of pregnancy, it is possible to detect sickle cell anemia in the fetus.
The Hb S gene is distributed geographically in a broad equatorial belt in Africa and also is found, though less often, in other parts of the continent and in the Americas. The persistence of Hb S has been explained by the fact that heterozygous persons are resistant to malaria. When the red cells of a person with the sickle cell trait are invaded by the malarial parasite, the red cells adhere to blood vessel walls, become deoxygenated, assume the sickle shape, and then are destroyed, the parasite being destroyed with them.
There is no cure for sickle cell anemia; most care is devoted to alleviating symptoms. Infants and young children with the disease are given regular daily doses of penicillin to prevent serious infection. In some cases blood transfusions are given regularly to prevent organ damage and stroke and to relieve the worst symptoms of red blood cell loss. In severe cases bone marrow transplantation has been of some benefit. The drug hydroxyurea reduces the principal symptoms of sickle cell anemia. Hydroxyurea apparently activates a gene that triggers the body's production of fetal hemoglobin. This type of hemoglobin, which is ordinarily produced in large amounts only by infants shortly before and after birth, does not sickle. Hydroxyurea therapy increases the proportion of fetal hemoglobin in the bloodstream of adult patients from 1 to about 20 percent, a proportion high enough to lessen markedly the circulatory problems that arise during crises.
B. White Blood Cell Diseases
Some white blood cell diseases are characterized by an insufficient number of white blood cells. This can be caused by the failure of the bone marrow to produce adequate numbers of normal white blood cells, or by diseases that lead to the destruction of crucial white blood cells. These conditions result in severe immune deficiencies characterized by recurrent infections.
Any disease in which excess white blood cells are produced, particularly immature white blood cells, is called leukemia, or blood cancer. Many cases of leukemia are linked to gene abnormalities, resulting in unchecked growth of immature white blood cells. If this growth is not halted, it often results in the death of the patient. These genetic abnormalities are not inherited in the vast majority of cases, but rather occur after birth. Although some causes of these abnormalities are known, for example exposure to high doses of radiation or the chemical benzene, most remain poorly understood.
Treatment for leukemia typically involves the use of chemotherapy, in which strong drugs are used to target and kill leukemic cells, permitting normal cells to regenerate. In some cases, bone marrow transplants are effective. Much progress has been made over the last 30 years in the treatment of this disease. In one type of childhood leukemia, more than 80 percent of patients can now be cured of their disease.
C. Coagulation Diseases
One disease of the coagulation system is hemophilia, a genetic bleeding disorder in which one of the plasma clotting factors, usually factor VIII, is produced in abnormally low quantities, resulting in uncontrolled bleeding from minor injuries. Although individuals with hemophilia are able to form a good initial platelet plug when blood vessels are damaged, they are not easily able to form the meshwork that holds the clot firmly intact. As a result, bleeding may occur some time after the initial traumatic event. Treatment for hemophilia relies on giving transfusions of factor VIII. Factor VIII can be isolated from the blood of normal blood donors but it also can be manufactured in a laboratory through a process known as gene cloning.
BLOOD PRESSURE
Blood Pressure is the pressure of circulating blood against the walls of the arteries (blood vessels that carry blood from the heart to the rest of the body). Blood pressure is an important indicator of the health of the circulatory system. Any condition that dilates or contracts the arteries or affects their elasticity, or any disease of the heart that interferes with its pumping power, affects blood pressure.
In a healthy human being, blood pressure remains within a certain average range. The complex nervous system mechanisms that balance and coordinate the activity of the heart and arterial muscles permit great local variation in the rate of blood flow without disturbing the general blood pressure.
Hemoglobin, the iron-protein compound that gives blood its red color, also plays a role in regulating local variation in blood pressure. Hemoglobin carries nitric oxide, a gas that relaxes the blood vessel walls. Hemoglobin controls the expansion and contraction of blood vessels, and thus blood pressure, by regulating the amount of nitric oxide to which the vessels are exposed.
Two measurements are used to describe blood pressure. Systolic pressure measures blood pressure when the heart contracts to empty its blood into the circulatory system. Diastolic pressure measures blood pressure when the heart relaxes and fills with blood. Systolic and diastolic pressure are measured in millimeters of mercury (abbreviated mm Hg) using an instrument called a sphygmomanometer. This instrument consists of an inflatable rubber cuff connected to a pressure-detecting device with a dial. The cuff is wrapped around the upper arm and inflated by squeezing a rubber bulb connected to it by a tube. Meanwhile, a health-care professional listens to a stethoscope applied to an artery in the lower arm. As the cuff inflates, it gradually compresses the artery. The point at which the cuff stops the circulation and at which no pulsations can be heard through the stethoscope is read as the systolic pressure. As the cuff is slowly deflated, a spurting sound can be heard when the heart contraction forces blood through the compressed artery. The cuff is then allowed gradually to deflate further until the blood is flowing smoothly again and no further spurting sound is heard. A reading at this point shows the diastolic pressure that occurs during relaxation of the heart. Normal blood pressure in an adult is less than 120/80 mm Hg. The first number describes systolic pressure, while the second number describes diastolic pressure.
Blood pressure is influenced by a wide range of factors and varies between individuals and in the same individual at different times. For instance, blood pressure naturally increases with age because the arteries lose the elasticity that, in younger people, absorbs the force of heart contractions. Other factors, such as emotions, exercise, or stress, may temporarily raise blood pressure.
Abnormally high blood pressure, known as hypertension, that remains untreated can lead to stroke, heart attack, and kidney or heart failure. Hypertension may have no known cause or it may result from heart or blood vessel disorders or from diseases affecting other parts of the body. Abnormally low blood pressure, known as hypotension, may be caused by shock, malnutrition, or some other disease or injury.
An adult human has about 5 to 6 liters (1 to 2 gal) of blood, which is roughly 7 to 8 percent of total body weight. Infants and children have comparably lower volumes of blood, roughly proportionate to their smaller size. The volume of blood in an individual fluctuates. During dehydration, for example while running a marathon, blood volume decreases. Blood volume increases in circumstances such as pregnancy, when the mother’s blood needs to carry extra oxygen and nutrients to the baby.
ROLE OF BLOOD
Blood carries oxygen from the lungs to all the other tissues in the body and, in turn, carries waste products, predominantly carbon dioxide, back to the lungs where they are released into the air. When oxygen transport fails, a person dies within a few minutes. Food that has been processed by the digestive system into smaller components such as proteins, fats, and carbohydrates is also delivered to the tissues by the blood. These nutrients provide the materials and energy needed by individual cells for metabolism, or the performance of cellular function. Waste products produced during metabolism, such as urea and uric acid, are carried by the blood to the kidneys, where they are transferred from the blood into urine and eliminated from the body. In addition to oxygen and nutrients, blood also transports special chemicals, called hormones, that regulate certain body functions. The movement of these chemicals enables one organ to control the function of another even though the two organs may be located far apart. In this way, the blood acts not just as a means of transportation but also as a communications system.
The blood is more than a pipeline for nutrients and information; it is also responsible for the activities of the immune system, helping fend off infection and fight disease. In addition, blood carries the means for stopping itself from leaking out of the body after an injury. The blood does this by carrying special cells and proteins, known as the coagulation system, that start to form clots within a matter of seconds after injury.
Blood is vital to maintaining a stable body temperature; in humans, body temperature normally fluctuates within a degree of 37.0° C (98.6° F). Heat production and heat loss in various parts of the body are balanced out by heat transfer via the bloodstream. This is accomplished by varying the diameter of blood vessels in the skin. When a person becomes overheated, the vessels dilate and an increased volume of blood flows through the skin. Heat dissipates through the skin, effectively lowering the body temperature. The increased flow of blood in the skin makes the skin appear pink or flushed. When a person is cold, the skin may become pale as the vessels narrow, diverting blood from the skin and reducing heat loss.
COMPOSITION OF BLOOD
About 55 percent of the blood is composed of a liquid known as plasma. The rest of the blood is made of three major types of cells: red blood cells (also known as erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes).
A. Plasma
Plasma consists predominantly of water and salts. The kidneys carefully maintain the salt concentration in plasma because small changes in its concentration will cause cells in the body to function improperly. In extreme conditions this can result in seizures, coma, or even death. The pH of plasma, the common measurement of the plasma’s acidity, is also carefully controlled by the kidneys within the neutral range of 6.8 to 7.7. Plasma also contains other small molecules, including vitamins, minerals, nutrients, and waste products. The concentrations of all of these molecules must be carefully regulated.
Plasma is usually yellow in color due to proteins dissolved in it. However, after a person eats a fatty meal, that person’s plasma temporarily develops a milky color as the blood carries the ingested fats from the intestines to other organs of the body.
Plasma carries a large number of important proteins, including albumin, gamma globulin, and clotting factors. Albumin is the main protein in blood. It helps regulate the water content of tissues and blood. Gamma globulin is composed of tens of thousands of unique antibody molecules. Antibodies neutralize or help destroy infectious organisms. Each antibody is designed to target one specific invading organism. For example, chicken pox antibody will target chicken pox virus, but will leave an influenza virus unharmed. Clotting factors, such as fibrinogen, are involved in forming blood clots that seal leaks after an injury. Plasma that has had the clotting factors removed is called serum. Both serum and plasma are easy to store and have many medical uses.
B. Red Blood Cells
Red blood cells make up almost 45 percent of the blood volume. Their primary function is to carry oxygen from the lungs to every cell in the body. Red blood cells are composed predominantly of a protein and iron compound, called hemoglobin, that captures oxygen molecules as the blood moves through the lungs, giving blood its red color. As blood passes through body tissues, hemoglobin then releases the oxygen to cells throughout the body. Red blood cells are so packed with hemoglobin that they lack many components, including a nucleus, found in other cells. Hemoglobin also takes up and releases nitric oxide, which plays an important role in regulating blood pressure.The membrane, or outer layer, of the red blood cell is flexible, like a soap bubble, and is able to bend in many directions without breaking. This is important because the red blood cells must be able to pass through the tiniest blood vessels, the capillaries, to deliver oxygen wherever it is needed. The capillaries are so narrow that the red blood cells, normally shaped like a disk with a concave top and bottom, must bend and twist to maneuver single file through them.
C. White Blood Cells
White blood cells only make up about 1 percent of blood, but their small number belies their immense importance. They play a vital role in the body’s immune system—the primary defense mechanism against invading bacteria, viruses, fungi, and parasites. They often accomplish this goal through direct attack, which usually involves identifying the invading organism as foreign, attaching to it, and then destroying it. This process is referred to as phagocytosis.White blood cells also produce antibodies, which are released into the circulating blood to target and attach to foreign organisms. After attachment, the antibody may neutralize the organism, or it may elicit help from other immune system cells to destroy the foreign substance. There are several varieties of white blood cells, including neutrophils, monocytes, and lymphocytes, all of which interact with one another and with plasma proteins and other cell types to form the complex and highly effective immune system.
D. Platelates and blood clotting
Mammalian platelets are nonnucleate cells produced by large bone marrow cells called megakaryocytes and circulate in the blood in a resting, inactive form for an average of 10 days. The normal platelet count in humans is between 150,000 and 400,000 platelets per cubic millimetre of blood. The inactive platelet contains three types of internal granules: the alpha granules, the dense granules, and the lysosomes. Each of these granules is rich in certain chemicals that have an important role in platelet function. For example, dense granules contain large quantities of calcium ions and adenosine diphosphate (ADP). Upon release from the platelet, ADP stimulates other platelets to activate when it binds to the ADP receptor on the platelet membrane. The alpha granules contain many proteins, including fibrinogen, thrombospondin, fibronectin, and von Willebrand factor. Upon platelet activation, platelets alter their shape from discoid to spherical and extend long footlike projections called pseudopodia. The alpha granules and dense granules move to the surface of the platelet, fuse with the platelet membrane, and release their contents into the blood surrounding the platelet. The lysosomes contain enzymes that digest spent proteins and other metabolites of the cell.
Activated platelets strongly adhere to surfaces other than the lining of blood vessels, such as collagen, glass, metals, and fabrics. Adherent platelets themselves become adhesive for other activated platelets so that, in a flow system, a platelet plug develops. The propagation of this adhesiveness from one layer to the next is probably due to chemicals, such as ADP and thromboxane A2, secreted into the blood from the granules of the activated platelets. The ADP released from the dense granules binds to a receptor on the platelet surface, initiating the biochemical and morphological changes associated with platelet activation and secretion. The property of adhesiveness for normal platelets requires a protein on the surface of the platelet membrane, known as glycoprotein Ib, to bind von Willebrand factor, a large multimeric plasma protein released from the alpha granules. Von Willebrand factor, when bound to glycoprotein Ib on the platelet surface, facilitates the interaction of platelets with a variety of other surfaces (e.g., the damaged vessel lining).
Platelet aggregation is the property of platelets to clump with each other to form a platelet plug. Two proteins on the platelet membrane play an important role in platelet aggregation: glycoprotein IIb and glycoprotein IIIa. These proteins form a complex in the membrane and expose a receptor site after platelet activation that binds fibrinogen (a bivalent molecule with two symmetrical halves that is found in relatively high concentration in plasma). Fibrinogen can bind simultaneously to two platelets. Thus, fibrinogen links platelets together (aggregation) through the glycoprotein IIb–IIIa complex that serves as the fibrinogen receptor.
Injury to the vessel lining and contact of the blood with tissues outside the vessel stimulates thrombin production by the activation of the clotting system. Thrombin causes platelet aggregation. Platelets exposed to thrombin secrete their granules and release the contents of these granules into the surrounding plasma.
BLOOD CLOTTING: Coagulation is the replacement of a relatively unstable platelet plug with a stronger, more resilient blood clot through a series of interdependent, enzyme-mediated reactions that bring about the generation of thrombin and the formation of fibrin from fibrinogen. The intrinsic and the extrinsic pathways of coagulation are involved in regulating coagulation; each is activated by a different trigger, although they share many steps in the course of the generation of thrombin.Intrinsic pathway of blood coagulation:All the components necessary for the clotting process to proceed are found in the blood. As such, the proteins required for such clotting to take place are part of the intrinsic pathway of blood coagulation. This pathway involves a series of proteins, protein cofactors, and enzymes, which interact in reactions that take place on membrane surfaces. These reactions are initiated by tissue injury and result in the formation of a fibrin clot (Figure 1).
The intrinsic pathway is initiated by the activation of factor XII by certain negatively charged surfaces, including glass. High-molecular-weight kininogen and prekallikrein are two proteins that facilitate this activation. The enzyme form of factor XII (factor XIIa) catalyzes the conversion of factor XI to its enzyme form (factor XIa). Factor XIa catalyzes the conversion of factor IX to the activated form, factor IXa, in a reaction that requires calcium ions. Factor IXa assembles on the surface of membranes in complex with factor VIII; the factor IXa–factor VIII complex requires calcium to stabilize certain structures on these proteins associated with their membrane-binding properties. Factor X binds to the factor IXa–factor VIII complex and is activated to factor Xa. Factor Xa forms a complex with factor V on membrane surfaces in a reaction that also requires calcium ions. Prothrombin binds to the factor Xa–factor V complex and is converted to thrombin, a potent enzyme that cleaves fibrinogen to fibrin, a monomer. The monomer fibrin molecules then link together (polymerize) to form long fibres. Later, additional bonding between the units of the polymer is promoted by an enzyme known as factor XIIIa, which stabilizes the newly formed clot by cross-linkages. Although the detailed mechanisms are not known, this cascade, or waterfall, effect offers the possibility for amplification of a small signal associated with tissue injury into a major biologic event—the formation of a fibrin clot. Furthermore, careful regulation of this system is possible with the participation of two protein cofactors, factor VIII and factor V.
Certain negatively charged surfaces, including glass, kaolin, some synthetic plastics, and fabrics, activate factor XII to its enzyme form, factor XIIa. In contrast, certain materials have little tendency to activate factor XII. Inactive surfaces include some oils, waxes, resins, silicones, a few plastics, and endothelial cells, the most inert surface of all. The physicochemical properties that determine activity are not known. The problem is important, for modern surgery requires a perfectly inactive material to make substitutes (prostheses) for heart valves and sections of blood vessels. The formation of clots (thrombi) on these surfaces can lead to serious or even fatal complications. Open-heart surgery requires pumping of blood through equipment that does not activate the blood-clotting process significantly. Similarly, blood filtration of waste products during kidney dialysis must not lead to the generation of fibrin clots. To minimize the activation of blood coagulation when blood flows over foreign surfaces, special drugs (anticoagulants) such as heparin are employed.The activity of the intrinsic pathway may be assessed in a simple laboratory test called the partial thromboplastin time (PTT), or, more accurately, the activated partial thromboplastin time. Plasma is collected and anticoagulated with citrate buffer; the citrate binds and effectively removes functional calcium ions from the plasma. Under these conditions, a fibrin clot cannot be generated. A negatively charged material, such as the diatomaceous material kaolin, is added to the plasma. Kaolin activates factor XII to its enzyme form, factor XIIa, which then activates factor XI. The process is blocked from further activation because of the lack of calcium ions, which are required for the next reaction, the activation of factor IX. Upon the addition of calcium ions and a phospholipid preparation (which serves as an artificial membrane for the assembly of the blood-clotting protein complexes), the duration of time is recorded until a visible clot is formed. This reaction takes place in a matter of 25 to 50 seconds, depending upon the formulation of chemicals used. In practice, the clotting time of a test plasma is compared to the clotting time of normal plasma. Delayed clotting, measured as a prolonged partial thromboplastin time, may be due to a deficiency in the activity of one or more of the blood-clotting factors or to a chemical inhibitor of blood coagulation.
The extrinsic pathway of blood coagulation:Upon the introduction of cells, particularly crushed or injured tissue, blood coagulation is activated and a fibrin clot is rapidly formed. The protein on the surface of cells that is responsible for the initiation of blood clotting is known as tissue factor, or tissue thromboplastin. Tissue factor is found in many of the cells of the body but is particularly abundant in those of the brain, lungs, and placenta. The pathway of blood coagulation activated by tissue factor, a protein extrinsic to blood, is known as the extrinsic pathway (Figure 1).
Tissue factor serves as a cofactor with factor VII to facilitate the activation of factor X. Alternatively, factor VII can activate factor IX, which, in turn, can activate factor X. Once activated, factor X proceeds to activate prothrombin to thrombin in a reaction requiring factor V. The thrombin converts fibrinogen to fibrin. With the exception of factor VII, all components of the extrinsic pathway are also components of the intrinsic pathway.
The activity of the extrinsic pathway may be assessed in the laboratory using a simple test known as the prothrombin time. Tissue extract, or tissue thromboplastin, is extracted from animal tissues rich in tissue factor. Plasma, anticoagulated with citrate buffer, is allowed to clot with the simultaneous addition of phospholipid, calcium, and thromboplastin. The duration of time until clot formation, known as the prothrombin time, is usually between 10 and 12 seconds. In practice, the clotting time of a test plasma is compared to the clotting time of normal plasma. Delayed clotting, measured as a prolonged prothrombin time, may be due to a deficiency in the activity of one or more of the blood-clotting factors in the extrinsic pathway or to a chemical inhibitor of blood coagulation that interferes with the extrinsic pathway.
In summary, there are two independent mechanisms for initiating blood coagulation and for activating factor X: (1) negatively charged surfaces that initiate blood clotting through the intrinsic pathway (factors XII, XI, IX, and VIII), and (2) tissue factor on cells outside the blood that participates in the extrinsic pathway (factor VII). The common pathway (factor X, factor V, prothrombin, and fibrinogen) is shared by both systems. Although both pathways provide the opportunity to acquire meaningful information about clotting proteins using the partial thromboplastin time and the prothrombin time, it is most likely that the physiologically important pathway of blood coagulation is the extrinsic pathway initiated by tissue factor.
PRODUCTION AND ELIMINATION OF BLOOD CELLS
Blood is produced in the bone marrow, a tissue in the central cavity inside almost all of the bones in the body. In infants, the marrow in most of the bones is actively involved in blood cell formation. By later adult life, active blood cell formation gradually ceases in the bones of the arms and legs and concentrates in the skull, spine, ribs, and pelvis.
Red blood cells, white blood cells, and platelets grow from a single precursor cell, known as a hematopoietic stem cell. Remarkably, experiments have suggested that as few as 10 stem cells can, in four weeks, multiply into 30 trillion red blood cells, 30 billion white blood cells, and 1.2 trillion platelets—enough to replace every blood cell in the body.
Red blood cells have the longest average life span of any of the cellular elements of blood. A red blood cell lives 100 to 120 days after being released from the marrow into the blood. Over that period of time, red blood cells gradually age. Spent cells are removed by the spleen and, to a lesser extent, by the liver. The spleen and the liver also remove any red blood cells that become damaged, regardless of their age. The body efficiently recycles many components of the damaged cells, including parts of the hemoglobin molecule, especially the iron contained within it.
The majority of white blood cells have a relatively short life span. They may survive only 18 to 36 hours after being released from the marrow. However, some of the white blood cells are responsible for maintaining what is called immunologic memory. These memory cells retain knowledge of what infectious organisms the body has previously been exposed to. If one of those organisms returns, the memory cells initiate an extremely rapid response designed to kill the foreign invader. Memory cells may live for years or even decades before dying.
Memory cells make immunizations possible. An immunization, also called a vaccination or an inoculation, is a method of using a vaccine to make the human body immune to certain diseases. A vaccine consists of an infectious agent that has been weakened or killed in the laboratory so that it cannot produce disease when injected into a person, but can spark the immune system to generate memory cells and antibodies specific for the infectious agent. If the infectious agent should ever invade that vaccinated person in the future, these memory cells will direct the cells of the immune system to target the invader before it has the opportunity to cause harm.
Platelets have a life span of seven to ten days in the blood. They either participate in clot formation during that time or, when they have reached the end of their lifetime, are eliminated by the spleen and, to a lesser extent, by the liver.
BLOOD DISEASES
Many diseases are caused by abnormalities in the blood. These diseases are categorized by which component of the blood is affected.
A. Red Blood Cell Diseases
One of the most common blood diseases worldwide is anemia, which is characterized by an abnormally low number of red blood cells or low levels of hemoglobin. One of the major symptoms of anemia is fatigue, due to the failure of the blood to carry enough oxygen to all of the tissues.
The most common type of anemia, iron-deficiency anemia, occurs because the marrow fails to produce sufficient red blood cells. When insufficient iron is available to the bone marrow, it slows down its production of hemoglobin and red blood cells. The most common causes of iron-deficiency anemia are certain infections that result in gastrointestinal blood loss and the consequent chronic loss of iron. Adding supplemental iron to the diet is often sufficient to cure iron-deficiency anemia.
SICKLE CELL ANEMIA: hereditary disease that destroys red blood cells by causing them to take on a rigid “sickle” shape. The disease is characterized by many of the symptoms of chronic anemia (fatigue, pale skin, and shortness of breath) as well as susceptibility to infection, jaundice and other eye problems, delayed growth, and episodic crises of severe pain in the abdomen, bones, or muscles. Sickle cell anemia occurs mainly in persons of African descent. The disease also occurs in persons of the Middle East, the Mediterranean, and India.Sickle cell anemia is caused by a variant type of hemoglobin, the protein in red blood cells that carries oxygen to the tissues of the body, called hemoglobin S (Hb S). Hb S is sensitive to deficiency of oxygen. When the carrier red blood cells release their oxygen to the tissues and the oxygen concentration within those cells is reduced, Hb S, in contrast to normal hemoglobin (Hb A), becomes stacked within the red cells in filaments that twist into helical rods. These rods then cluster into parallel bundles that distort and elongate the cells, causing them to become rigid and assume a sickle shape. This phenomenon is to some extent reversible after the cells become oxygenated once more, but repeated sickling ultimately results in irreversible distortion of the red cells. The sickle-shaped cells become clogged in small blood vessels, causing obstruction of the microcirculation, which in turn results in damage to and destruction of various tissues.
Sickle cell anemia is caused by the inheritance of a variant hemoglobin (Hb S) gene from both parents. (This inheritance of variant genes from both parents is known as the homozygous state.) A person who inherits the sickle cell gene from one parent and a normal hemoglobin gene (Hb A) from the other parent (an inheritance known as the heterozygous state) is a carrier of the sickle cell trait. Because the red blood cells of heterozygous persons contain both Hb A and Hb S, such cells require much greater deoxygenation to produce sickling than do those of persons with sickle cell anemia. The great majority of persons with the sickle cell trait thus have no symptoms of disease, although certain manifestations—mainly associated with vigorous exertion at high altitudes—have been seen. The overall mortality rate of persons with the sickle cell trait is no different from that of a normal comparable population.
An estimated 1 in 12 blacks worldwide carries the sickle cell trait, while about 1 in 400 has sickle cell anemia. If both parents have the sickle cell trait, the chances are 1 in 4 that a child born to them will develop sickle cell anemia. However, through amniocentesis (analysis of amniotic fluid surrounding a fetus), a testing procedure done in the early stages of pregnancy, it is possible to detect sickle cell anemia in the fetus.
The Hb S gene is distributed geographically in a broad equatorial belt in Africa and also is found, though less often, in other parts of the continent and in the Americas. The persistence of Hb S has been explained by the fact that heterozygous persons are resistant to malaria. When the red cells of a person with the sickle cell trait are invaded by the malarial parasite, the red cells adhere to blood vessel walls, become deoxygenated, assume the sickle shape, and then are destroyed, the parasite being destroyed with them.
There is no cure for sickle cell anemia; most care is devoted to alleviating symptoms. Infants and young children with the disease are given regular daily doses of penicillin to prevent serious infection. In some cases blood transfusions are given regularly to prevent organ damage and stroke and to relieve the worst symptoms of red blood cell loss. In severe cases bone marrow transplantation has been of some benefit. The drug hydroxyurea reduces the principal symptoms of sickle cell anemia. Hydroxyurea apparently activates a gene that triggers the body's production of fetal hemoglobin. This type of hemoglobin, which is ordinarily produced in large amounts only by infants shortly before and after birth, does not sickle. Hydroxyurea therapy increases the proportion of fetal hemoglobin in the bloodstream of adult patients from 1 to about 20 percent, a proportion high enough to lessen markedly the circulatory problems that arise during crises.
B. White Blood Cell Diseases
Some white blood cell diseases are characterized by an insufficient number of white blood cells. This can be caused by the failure of the bone marrow to produce adequate numbers of normal white blood cells, or by diseases that lead to the destruction of crucial white blood cells. These conditions result in severe immune deficiencies characterized by recurrent infections.
Any disease in which excess white blood cells are produced, particularly immature white blood cells, is called leukemia, or blood cancer. Many cases of leukemia are linked to gene abnormalities, resulting in unchecked growth of immature white blood cells. If this growth is not halted, it often results in the death of the patient. These genetic abnormalities are not inherited in the vast majority of cases, but rather occur after birth. Although some causes of these abnormalities are known, for example exposure to high doses of radiation or the chemical benzene, most remain poorly understood.
Treatment for leukemia typically involves the use of chemotherapy, in which strong drugs are used to target and kill leukemic cells, permitting normal cells to regenerate. In some cases, bone marrow transplants are effective. Much progress has been made over the last 30 years in the treatment of this disease. In one type of childhood leukemia, more than 80 percent of patients can now be cured of their disease.
C. Coagulation Diseases
One disease of the coagulation system is hemophilia, a genetic bleeding disorder in which one of the plasma clotting factors, usually factor VIII, is produced in abnormally low quantities, resulting in uncontrolled bleeding from minor injuries. Although individuals with hemophilia are able to form a good initial platelet plug when blood vessels are damaged, they are not easily able to form the meshwork that holds the clot firmly intact. As a result, bleeding may occur some time after the initial traumatic event. Treatment for hemophilia relies on giving transfusions of factor VIII. Factor VIII can be isolated from the blood of normal blood donors but it also can be manufactured in a laboratory through a process known as gene cloning.
BLOOD PRESSURE
Blood Pressure is the pressure of circulating blood against the walls of the arteries (blood vessels that carry blood from the heart to the rest of the body). Blood pressure is an important indicator of the health of the circulatory system. Any condition that dilates or contracts the arteries or affects their elasticity, or any disease of the heart that interferes with its pumping power, affects blood pressure.
In a healthy human being, blood pressure remains within a certain average range. The complex nervous system mechanisms that balance and coordinate the activity of the heart and arterial muscles permit great local variation in the rate of blood flow without disturbing the general blood pressure.
Hemoglobin, the iron-protein compound that gives blood its red color, also plays a role in regulating local variation in blood pressure. Hemoglobin carries nitric oxide, a gas that relaxes the blood vessel walls. Hemoglobin controls the expansion and contraction of blood vessels, and thus blood pressure, by regulating the amount of nitric oxide to which the vessels are exposed.
Two measurements are used to describe blood pressure. Systolic pressure measures blood pressure when the heart contracts to empty its blood into the circulatory system. Diastolic pressure measures blood pressure when the heart relaxes and fills with blood. Systolic and diastolic pressure are measured in millimeters of mercury (abbreviated mm Hg) using an instrument called a sphygmomanometer. This instrument consists of an inflatable rubber cuff connected to a pressure-detecting device with a dial. The cuff is wrapped around the upper arm and inflated by squeezing a rubber bulb connected to it by a tube. Meanwhile, a health-care professional listens to a stethoscope applied to an artery in the lower arm. As the cuff inflates, it gradually compresses the artery. The point at which the cuff stops the circulation and at which no pulsations can be heard through the stethoscope is read as the systolic pressure. As the cuff is slowly deflated, a spurting sound can be heard when the heart contraction forces blood through the compressed artery. The cuff is then allowed gradually to deflate further until the blood is flowing smoothly again and no further spurting sound is heard. A reading at this point shows the diastolic pressure that occurs during relaxation of the heart. Normal blood pressure in an adult is less than 120/80 mm Hg. The first number describes systolic pressure, while the second number describes diastolic pressure.
Blood pressure is influenced by a wide range of factors and varies between individuals and in the same individual at different times. For instance, blood pressure naturally increases with age because the arteries lose the elasticity that, in younger people, absorbs the force of heart contractions. Other factors, such as emotions, exercise, or stress, may temporarily raise blood pressure.
Abnormally high blood pressure, known as hypertension, that remains untreated can lead to stroke, heart attack, and kidney or heart failure. Hypertension may have no known cause or it may result from heart or blood vessel disorders or from diseases affecting other parts of the body. Abnormally low blood pressure, known as hypotension, may be caused by shock, malnutrition, or some other disease or injury.