ANATOMY AND PHYSIOLOGY The Circulatory System The circulatory system is responsible for the transport of water and

dissolved materials throughout the body, including oxygen, carbon dioxide, nutrients, and waste. The circulatory system transports oxygen from the lungs and nutrients from the digestive tract to every cell in the body, allowing for the continuation of cell metabolism. The circulatory system also transports the waste products of cell metabolism to the lungs and kidneys where they can be expelled from the body. Without this important function toxic substances would quickly build up in the body.

The human circulatory system is organized into two major circulations. Each has its own pump with both pumps being incorporated into a single organthe heart. The two sides of the human heart are separated by partitions, the interatrial septum and the interventricular septum. Both septa are complete so that the two sides are anatomically and functionally separate pumping units. The right side of the heart pumps blood through the pulmonary circulation (the lungs) while the left side of the heart pumps blood through the systemic circulation (the body).

The Heart

The human heart is a specialized, four-chambered muscle that maintains the blood flow in the circulatory system. It lies immediately behind the sternum, or breastbone, and between the lungs. The apex, or bottom of the heart, is tilted to the left side. At rest, the heart pumps about 59 cc (2 oz) of blood per beat and 5 l (5 qt) per minute. During exercise it pumps 120-220 cc (4-7.3 oz) of blood per beat and 20-30 l (21-32 qt) per minute. The adult human heart is about the size of a fist and weighs about 250-350 gm (9 oz). The human heart begins beating early in fetal life and continues regular beating throughout the life span of the individual. If the heart stops beating for more than 3 or 4 minutes permanent brain damage may occur. Blood flow to the heart muscle itself also depends on the continued beating of the heart and if this flow is stopped for more than a few minutes, as in a heart attack, the heart muscle may be damaged to such a great extent that it may be irreversibly stopped. The heart is made up of two muscle masses. One of these forms the two atria (the upper chambers) of the heart, and the other forms the two ventricles (the lower chambers). Both atria contract or relax at the same time, as do both ventricles.

An electrical impulse called an action potential is generated at regular intervals in a specialized region of the right atrium called the sinoauricular (or sinoatrial, or SA) node. Since the two atria form a single muscular unit, the action potential will spread over the atria. A fraction of a second later, having been triggered by the action potential, the atrial muscle contracts. The ventricles form a single muscle mass separate from the atria. When the atrial action potential reaches the juncture of the atria and the ventricles, the atrioventricular or AV node (another specialized region for conduction) conducts the impulse. After a slight delay, the impulse is passed by way of yet another bundle of muscle fibers (the Bundle of His and the Purkinje system.) Contraction of the ventricle quickly follows the onset of its action potential. From this pattern it can be seen that both atria will contract simultaneously and that both ventricles will contract simultaneously, with a brief delay between the contractions of the two parts of the heart. The electrical stimulus that leads to contraction of the heart muscle thus originates in the heart itself, in the sinoatrial node (SA node), which is also known as the heart's pacemaker. This node, which lies just in front of the opening of the superior vena cava, measures no more than a few millimeters. It consists of heart cells that emit regular impulses. Because of this spontaneous discharge of the sinoatrial node, the heart muscle is automated. A completely isolated heart can contract on its own as long as its metabolic processes remain intact. The rate at which the cells of the SA node discharge is externally influenced through the autonomic nervous system, which sends nerve branches to the heart. Through their stimulatory and inhibitory influences they determine the resultant heart rate. In adults at rest this is between 60 and 74 beats a minute. In infants and young children it may be between 100 and 120 beats a minute. Tension, exertion, or fever may cause the rate of the heart to vary between 55 and 200 beats a minute. The Heart Sounds The closure of the heart valves and the contraction of the heart muscle produce sounds that can be heard through the thoracic wall by the unaided ear, although they can be heard better when amplified by a stethoscope. The sounds of the heart may be represented as lubb-dubb-pause-lubb-dubb-pause. The lubb sound indicates the closing of the valves between the atria and ventricles and the contracting ventricles; the dubb sound indicates the closing of the semilunar valves. In addition, there may also be cardiac murmurs, especially when the valves are abnormal. Some heart murmurs, however, may also occur in healthy persons, mainly during rapid or pronounced cardiac action. The study of heart sounds

and murmurs furnishes valuable information to physicians regarding the condition of the heart muscle and valves. Coronary Circulation The coronary arteries supply blood to the heart muscle. These vessels originate from the aorta immediately after the aortic valve and branch out through the heart muscle. The coronary veins transport the deoxygenated blood from the heart muscle to the right atrium. The heart's energy supply is almost completely dependent on these coronary vessels. When the coronary vessels become blocked, as in arteriosclerosis or hardening of the arteries, blood flow to the cardiac muscle is compromised. This is when the common "bypass surgery" is performed where the coronary arteries are "bypassed" by replacing them with, for example, a vein from the leg. A "double bypass" is when two coronary arteries are bypassed. A "triple bypass" is when three are bypassed, etc. The Heartbeat The heart muscle pumps the blood through the body by means of rhythmical contractions (systole) and relaxations or dilations (diastole). The heart's left and right halves work almost synchronously. When the ventricles contract (systole), the valves between the atria and the ventricles close as the result of increasing pressure, and the valves to the pulmonary artery and the aorta open. When the ventricles become flaccid during diastole, and the pressure decreases, the reverse process takes place. The Pulmonary Circulation From the right atrium the blood passes to the right ventricle through the tricuspid valve, which consists of three flaps (or cusps) of tissue. The tricuspid valve remains open during diastole, or ventricular filling. When the ventricle contracts, the valve closes, sealing the opening and preventing backflow into the right atrium. Five cords attached to small muscles, called papillary muscles, on the ventricles' inner surface prevent the valves' flaps from being forced backward. From the right ventricle blood is pumped through the pulmonary or semilunar valve, which has three half-moon-shaped flaps, into the pulmonary artery. This valve prevents backflow from the artery into the right ventricle. From the pulmonary artery blood is pumped to the lungs where it releases carbon dioxide and picks up oxygen.

The Systemic Circulation From the lungs, the blood is returned to the heart through pulmonary veins, two from each lung. From the pulmonary veins the blood enters the left atrium and then passes through the mitral valve to the left ventricle. As the ventricles contract, the mitral valve prevents backflow of blood into the left atrium, and blood is driven through the aortic valve into the aorta, the major artery that supplies blood to the entire body. The aortic valve, like the pulmonary valve, has a semilunar shape. The aorta has many branches, which carry the blood to various parts of the body. Each of these branches in turn has branches, and these branches divide, and so on until there are literally millions of small blood vessels. The smallest of these on the arterial side of the circulation are called arterioles. They contain a great deal of smooth muscle, and because of their ability to constrict or dilate, they play a major role in regulating blood flow through the tissues. The blood passing through the arterioles passes through a bed of minute vessels called capillaries, which are a single cell thick. These capillaries are so small that the red blood cells must line up single file to pass through. The exchange of nutrients and waste products takes place between the capillary blood and the tissue fluids. The arterialized blood that enters the capillaries thus becomes venous blood as it passes through them. The capillaries empty the venous blood into collecting tubes called venules, and these in turn empty into small veins, which empty into larger veins, and so on until finally all the blood returns to the heart through two large veins, the superior and inferior vena cavae. These terminate in the right atrium, and the systemic circulation is complete. A one-way flow of blood in this system is maintained by valves located, not only in the heart, but in the veins as well. Some veins also have semilunar valves and the pressure of contracting muscles against the veins works with the action of these valves to increase the venous return to the heart. This is the reason that exercise is so important for the circulation. The Lymphatic System An often overlooked part of the circulatory system is the lymphatic system. As blood passes through the capillaries, some of the fluid diffuses into the surrounding tissues. One function of the lymphatic system is to collect and recycle this fluid (called lymph). Lymph passes from capillaries to lymph vessels and flows through lymph nodes that are located along the course of these vessels. Cells of the lymph nodes

phagocytize, or ingest, impurities such as bacteria, old red blood cells, and toxic and cellular waste. Finally, lymph flows into the thoracic duct, a large vessel that runs parallel to the spinal column, or into the right lymphatic duct, both of which transport the lymph back into veins of the shoulder areas where is mixes with blood and is returned to the heart. All lymph vessels contain one-way valves, like the veins, to prevent backflow. The tissues of the lymphatic system include the spleen. The spleen serves as a reservoir for blood, releasing additional blood into the circulatory system as needed. It is also involved with destruction of old cells and other substances by phagocytosis. The lymphatic system is also responsible for collecting nutrients that the digestive system has extracted from our foods, and is a very important part of the immune system. We will cover the lymphatic system in detail in the lesson on the immune system. The Blood The blood transports life-supporting food and oxygen to every cell of the body and removes their waste products. It also helps to maintain body temperature, transports hormones, and fights infections. The brain cells in particular are very dependent on a constant supply of oxygen. If the circulation to the brain is stopped, death shortly follows. Blood has two main constituents. The cells, or corpuscles, comprise about 45 percent, and the liquid portion, or plasma, in which the cells are suspended comprises 55 percent. The blood cells comprise three main types: red blood cells, or erythrocytes; white blood cells, or leukocytes, which in turn are of many different types; and platelets, or thrombocytes. Each type of cell has its own individual functions in the body. The plasma is a complex colorless solution, about 90 percent water, that carries different ions and molecules including proteins, enzymes, hormones, nutrients, waste materials such as urea, and fibrinogen, the protein that aids in clotting.

Red Blood Cells The red blood cells are tiny, round, biconcave disks, averaging about 7.5 microns (0.003 in) in diameter. A normal-sized man has about 5 l (5.3 qt) of blood in his body, containing more than 25 trillion red cells. Because the normal life span of red cells in the circulation is only about 120 days, more than 200 billion cells are normally destroyed each day by the spleen and must be replaced. Red blood cells, as well as most white cells and platelets, are made by the bone marrow. The main function of the red blood cells is to transport oxygen from the lungs to the tissues and to transport carbon dioxide, one of the chief waste products, it to the lungs for release from the body. The substance in the red blood cells that is largely responsible for their ability to carry oxygen and carbon dioxide is hemoglobin, the material that gives the cells their red color. It is a protein complex comprising many linked amino acids, and occupies almost the entire volume of a red blood cell. Essential to its structure and function is the mineral iron. White Blood Cells The leukocytes, or white blood cells, are of three types; granulocytes, lymphocytes, and monocytes. All are involved in defending the body against foreign organisms. There are three types of granulocytes: neutrophils, eosinophils, and basophils, with neutrophils the most abundant. Neutrophils seek out bacteria and phagocytize, or engulf, them.

The lymphocytes' chief function is to migrate into the connective tissue and build antibodies against bacteria and viruses. Leukocytes are almost colorless, considerably larger than red cells, have a nucleus, and are much less numerous; only one or two exist for every 1,000 red cells. The number increases in the presence of infection. Monocytes, representing only 4 to 8 percent of white cells, attack organisms not destroyed by granulocytes and leukocytes. The granulocytes, accounting for about 70 percent of all white blood cells, are formed in the bone marrow. The lymphocytes on the other hand are produced primarily by the lymphoid tissues of the bodythe spleen and lymph nodes. They are usually smaller than the granulocytes. Monocytes are believed to originate from lymphocytes. Just as the oxygen-carrying function of red cells is necessary for our survival, so are normal numbers of leukocytes, which protect us against infection. Platelets Platelets, or thrombocytes, are much smaller than the red blood cells. They are round or biconcave disks and are normally about 30 to 40 times more numerous than the white blood cells. The platelets' primary function is to stop bleeding. When tissue is damaged, the platelets aggregate in clumps to obstruct blood flow. Plasma The plasma is more than 90 percent water and contains a large number of substances, many essential to life. Its major solute is a mixture of proteins. The most abundant plasma protein is albumin. The globulins are even larger protein molecules than albumin and are of many chemical structures and functions. The antibodies, produced by lymphocytes, are globulins and are carried throughout the body, where many of them fight bacteria and viruses. An important function of plasma is to transport nutrients to the tissues. Glucose, for example, absorbed from the intestines, constitutes a major source of body energy. Some of the plasma proteins and fats, or lipids, are also used by the tissues for cell growth and energy. Minerals essential to body function, although present only in trace amounts, are other important elements of the plasma. The calcium ion, for example, is essential to the building of bone, as is phosphorus. Calcium is also essential to the clotting of blood. Copper is another necessary component of the plasma.

Formation of Blood Cells Hematopoiesis, the process of formation and development of blood cells, begins early in the development of the human embryo and must persist unabated through out ones lifetime. Cells in the peripheral blood have a finite life span and must be continuously renewed at a rate probably greater than 10 billion cells per day. During childhood, all blood cells are primarily produced in marrow sites of flat bones of the skull, sternum, clavicle, ribs, vertebrae and pelvis. After puberty, hematopoiesis becomes localized within the flat bones of the sternum, ilium, ribs, and vertebrae, sometimes occurring in the proximal ends of long bones. Stem cells are poorly characterized, undifferentiated cells that exist within the red marrow. These totipotent, or pluripotent, stem cells are self replicating and maintain a small population throughout the lifetime of the individual. Following stimulation by one or more signals called poetins, the stem cells can undergo differentiation into erythrocytes, leukocytes and megakaryotes. Growth factors or cytokines control blood cell growth, proliferation and differentiation.

The formation of erythrocytes is termed erythropoiesis. Normally, more than 100 million RBCs are formed to replace an equal number of destroyed cells. Erythropoietin increases the rate of RBC production when oxygen level decreases or during pregnancy. Healthy bone marrow has the capacity to increase its production of erythrocytes six to eight times over the normal rate and is thus able to keep pace with the increased destruction or loss of RBC.

Erythrocytes are produced in the red bone marrow. Required for this process are precursor cells, a proper microenvironment, and adequate supplies of oxygen, vitamin B12, pyridoxine, and traces of copper. Erythrocytes arise from nucleated cells called hematopoietic stem cells. Immature erythrocytes leave the bone marrow via veins in the marrow and enter the general circulation as nucleated reticulocytes. After their release from the marrow sites, the reticulocytes travel to the spleen, where they undergo conditioning and evolve into mature erythrocytes before being released into the general circulation. Individual platelets are produced by a fragmentation process from giant multinucleated cells in the red bone marrow called megakaryocytes. The time required for the formation of human platelets is about 5 days. Cytoplasmic extensions from megakaryoblasts are extruded into sinusoids, and platelets are formed by fragmentation at the terminal ends of the filaments. Normal human marrow may have up to 6 million magakaryocytes per kilogram of body weight, with each megakaryocyte being able to produce 1000 or more individual platelets. Platelet production appears to be under tight control by the hepatic hormone thrombopoietin. Hemostasis There are 3 mechanisms that work together to stop the flow of blood. They are Vasoconstriction Platelet plug formation Clotting of blood Vasoconstriction Vasoconstriction of a damaged blood vessel slows the flow of blood and thus helps to limit blood loss. This process is mediated by: Local controls. Vasoconstrictors such as thromboxane are released at the site of the injury. Systemic control. Epinephrine released by the adrenal glands stimulates general vasoconstriction.

Formation of Platelet Plug Platelets, also called thrombocytes, are small cellular fragments that lack a nucleus and are derived from megakaryocytes. When a blood vessel is damaged, the blood is exposed to collagen fibers in the basement membrane of the vessel (shown in green below). Platelets stick to collagen and become activated. Activated platelets release chemicals such as ADP, and thromboxane, that cause the aggregation of more platelets to the site of injury. Platelet aggregation results in the formation of a platelet plug which acts to stem the flow of blood from the broken vessel. It is essential that platelets become activated only at the site of a broken vessel. Otherwise activated platelets would form plugs and induce clots in inapropriate places. Healthy vessels secrete an enzyme called prostacyclin that functions to inhibit platelet activation and aggregation.

Small tears of the capillaries and arterioles are happening all the time. Platelets are responsible for quickly sealing these tears before the slower process of clotting completes the job. In the absence of adequate numbers of platelets these micro-tears allow blood to seep into the tissues. This is evidenced by purple blotches (thrombocytopenia purpura) visible on the skin. Clotting of blood

The blood contains about a dozen clotting factors. These factors are proteins that exist in the blood in an inactive state, but can be called into action when tissues or blood vessels are damaged. The activation of clotting factors occurs in a sequential manner. The first factor in the sequence activates the second factor, which activates the third factor and so on. This series of reactions is called the clotting cascade. Blood clotting is the transformation of liquid blood into a semisolid gel. Clots are made from fibers (polymers) of a protein called fibrin (see the diagram below). Fibrin monomers come from an inactive precursor called fibrinogen. The body of the fibrinogen molecule has caps on its ends that mask fibrinto-fibrin binding sites. If the caps are removed then fibrin monomers polymerize to form fibrin polymers. This process requires thrombin, the enzyme that converts fibrinogen to fibrin. This process also requires calcium, which acts as a kind of glue to hold the fibrin monomers to each other to form the polymeric fiber. The fibrin fibers form a loose meshwork that is stabilized by clotting factor XIII. The stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood. Control of the Clotting Cascade Thrombin is derived from an inactive precursor called prothrombin. There are two pathways that lead to the conversion of prothrombin to thrombin; the intrinsic pathway and the extrinsic pathway.

Intrinsic Pathway The intrinsic pathway, which is triggered by elements that lie within the blood inself (intrinsic to the blood), occurs in the following way. Damage to the vessel wall stimulates the activation of a cascade of clotting factors (for the sake of simplicity we will not consider the individual factors). This cascade results in the activation of factor X. Activated factor X is an enzyme that converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin monomers, which then polymerize in fibrin fibers. Fibrin fibers form a loose meshwork that is stabilized by crosslinks created by factor XIII. The stabilzed meshwork of fibrin fibers is now a clot that traps red blood cells and platelets and thus stops the flow of blood. Extrinsic Pathway The extrinsic pathway is triggered by tissue damage outside of the blood vessel. This pathway acts to clot blood that has escaped from the vessel into the tissues. Damage to tissue stimulates the activation of tissue thromboplastin, an enzyme that catalyzes the activation of factor X. At this point the intrinsic and extrinsic pathways converge and the subsequent steps are the same as those described above. Sources: http://www.biosbcc.net/doohan/sample/htm/Hemostasis.htm Medical Surgical Nursing, 8th edition, Joyce Black