The circulatory system of animals enables dissolved materials--oxygen, carbon dioxide, nutrients, and waste--to be transported throughout the body. The simpler the animal, the simpler the circulatory system. Conversely, the evolution of this system has made possible the development of complex organisms. This system is vital to the continuation of the \Tmetabolism\t of all animal life. The function of the system is to enable the dissolved materials to pass from one area to another by means of \Tdiffusion\t. Even in a single-celled animal, however, such diffusion may not meet the metabolic requirements of the body. Diffusion processes, therefore, may be aided by active transport of materials across the \Tcell\t membrane. In animals that are several cell thicknesses in size, the central cavity, or \Tcoelom\t, is often adapted to continually move the water in which the animal lives into, through, and out of the body. Larger and more complex animals have developed a specialized system of tubes through which a fluid circulates. This fluid is adapted, even in many invertebrates, to transport oxygen and other materials. In more advanced animals this fluid is known as \Tblood\t and contains hemoglobin cells. In primitive animals the motion of the fluid may be produced by the peristaltic action of the vessels containing the fluid; in more advanced animals muscular \Lheart\ls pump the fluid throughout the system. In the higher vertebrates the circulatory system is quite complex, having two twin-chambered pumps that are combined into a single heart of four chambers. One side of the heart serves to pump blood through the pulmonary arteries and veins of the \Trespiratory system\t, where blood is exposed to gaseous exchange with the environment. The other side pumps blood through the rest of the body to provide oxygen and nutrients to tissues. The control of heart action and blood flow is complex, and the capabilities of the circulatory system allow animals to survive under a wide variety of stressful conditions. CIRCULATORY SYSTEMS IN INVERTEBRATES The circulation in more primitive animals is characterized by that in the sponges and some coelenterates. In these animals the water in which they live is drawn into a central cavity through pores in the body wall. The water is kept flowing by the beating action of cilia, which are tiny hairs, and it circulates upward through an opening called the osculum. This type of circulation serves to replenish continually the fluid in which the body cells are bathed so that the oxygen and nutrients are not depleted. In the more highly developed animals--for example, the bryozoans, nematodes, and \Lrotifer\ls--fluids are moved through a primitive body cavity (the pseudocoelom) largely by body movements. In some primitive \Lmollusk\ls, the coelom is specialized to function as a pericardial cavity, the forerunner of a true heart. This pericardial cavity is connected by channels to the gonads and kidneys. Most \Larthropod\ls, ascidians, and many mollusks have a defined heart that pumps hemolymph (a primitive blood) through actual vessels and through a hemocoel, which is a specialized circulatory organ. In these animals, the hemolymph passes into the tissue spaces and then returns through sinuses to the heart. The final stage in this type of development is a closed circulatory system, which is seen in some \Lechinoderm\ls, \Lleech\les, oligochaetes, some polychaetes, and some mollusks. In closed circulatory systems, the transport medium, such as hemolymph in the \Linvertebrate\ls, is confined to specialized vessels, which constitute a complete circuit. The hearts of invertebrates vary from simple vessels, which act by peristaltic contractions, to true hearts, which have muscle that contracts, creating pressure in their cavities. Even the invertebrates have considerable control over their circulatory systems, and measurements of pressure and fluid flow in those systems reveal considerable adaptation to movement, environmental temperature, and other influences. CIRCULATORY SYSTEMS IN VERTEBRATES Vertebrates are characterized by having closed circulatory systems, and the most highly developed of these are in the higher primates, typified by humans. These closed systems vary considerably; some are arranged with the respiratory organs and the general body tissues combined in a single circuit. In other, more advanced vertebrates, the blood makes a double transit through the heart; one system carries the blood through the respiratory organs (gills or lungs), and the other takes the blood to the other body tissues. Most invertebrates have circulatory fluid that contains chlorocruorins (an iron-based pigment in combination with a porphyrin), hemerythrins (iron-based, but not with porphyrin), or hemocyanin (a copper-based respiratory pigment). All these pigments increase the ability of the circulating fluid to carry oxygen. Vertebrates, with rare exceptions, have blood that contains \Themoglobin\t, a highly efficient oxygen transport medium that consists of an iron-porphyrin (heme) in combination with a protein (globin). Some invertebrates also have hemoglobin, but this is usually dissolved in the circulating, or coelomic, fluid. In higher invertebrates (echinoderms and higher) the hemoglobin is confined to special blood cells. Vertebrates characteristically have the hemoglobin confined to such cells. In \Lcyclostom\les and \TFish\t, the heart drives blood through the gills, then distributes it by means of the dorsal aorta to the rest of the body tissues. Even in these primitive animals, there is relatively advanced control of the major blood vessels, and blood pressure and heart output are regulated to the needs imposed by exercise. In some primitive vertebrates (elasmobranchs and cyclostomes) a negative pressure is developed in the heart, which helps it to fill; \Lteleost\ls do not possess such a filling aid. Some cyclostomes have accessory hearts that serve important functions in moving fluid through low-pressure areas with semiopen sinuses. \Tamphibians\t and \Lreptile\ls characteristically have three-chambered hearts (two atria and one ventricle), but the flow pattern in such hearts permits effective function of the heart as two separate heart pumps. In Amphiuma, alligators, iguanas, and other animals, left-to-right shunting of blood in the heart serves a useful function in adapting the animal to diving, excessive heat, and so on. THE HUMAN CIRCULATORY SYSTEM The human heart begins beating early in fetal life and continues regular beating after birth and throughout the life span of the individual, stopping only at the time of death. 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, the heart muscle is damaged to such a great extent that it may be irreversibly stopped. The human circulatory system is organized into two major circulations. Each has its own pump, both pumps being incorporated into a single organ, the heart. The right side of the heart pumps blood through the pulmonary circulation; the left side of the heart pumps the blood through the systemic circulation. Blood returning from the body tissues enters the right atrium, which is the upper chamber of the right side of the heart. When the muscles of this chamber contract, they force the blood into the right ventricle, which is the major pump chamber of the right side of the heart. When the ventricle muscle contracts, it forces blood out through the pulmonary artery and through the small blood vessels of the lungs. In these small lung vessels, the blood is separated from air by very thin membranes, and oxygen enters the blood and carbon dioxide leaves the blood by simple diffusion. This cleaned and refreshed (arterialized) blood then passes into the left atrium. From the left atrium, the blood passes into the left ventricle. The muscular wall of the left ventricle is powerful, and when it contracts, it pushes the blood, under considerable pressure, into the systemic circulation by means of a large artery called the \Taorta\t. The pressure developed in the aorta by the contractile forces of the left ventricle is great enough to drive the blood to all the tissues of the body in sufficient quantity to supply their needs. 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; so the exchange of nutrients and waste products takes place easily between the capillary blood and the tissue fluids. Thus, the arterialized blood that enters the capillaries 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 in the heart and veins. Between the right atrium and the right ventricle is the tricuspid valve, which prevents blood from flowing from the ventricle back into the atrium. At the opening of the pulmonary valve is a set of semilunar valves, which prevent blood from flowing back into the right ventricle. Similarly, on the left side of the heart, the bicuspid valves prevent backward flow between the left ventricle and the left atrium, and another set of semilunar valves, the aortic valves, prevent blood from flowing from the aorta back into the left ventricle. 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. All the energy required to produce the flow of blood is imparted to the blood by the contraction of the heart muscle. The movement of blood follows the physical principles of fluid flow. Hence, blood always flows from a region of higher pressure to a region of lower pressure. The Heart 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). These muscles are peculiar in that their cells are interconnected by protoplasmic bridges. As a result, each muscle mass acts as a single contractile unit, and activity beginning in one part of either cardiac muscle mass spreads automatically to the rest of that muscle mass. Thus, both atria contract or relax at the same time, as do both ventricles. The two sides of the heart are separated by septa; in the adult human heart the interatrial septum and the interventricular septum are complete, so that the two sides are anatomically and functionally separate pumping units. Normally, 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) node. Since the two atria effectively form a single muscular unit, the action potential will spread over the atria; a short time later, the atrial muscle contracts, having been triggered by the action potential. The ventricles also form a single muscle mass--separate, however, from the atria. When the atrial action potential reaches the juncture of the atria and the ventricles, the atrioventricular 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) specialized for conduction to the muscle of the ventricle. Again, contraction of the ventricle quickly follows the onset of its action potential. From this pattern, it is apparent that both atria will contract simultaneously and that both ventricles will contract simultaneously, with a brief delay between the contraction of the two parts of the heart. Before the contraction of the atria occurs, blood fills the ventricle, mostly by passive means. Thus, atrial contraction plays a minor role in the pumping action of the heart; it merely completes the filling of the ventricle, and the heart can continue to function quite well even when the atria are not contracting. A property of the heart muscle is its automaticity. This means that any part of the heart can generate an action potential that can trigger the beat of the heart. Normally, the sinoauricular node is the site of origin of the heartbeat. This is because its inherent frequency of discharge is greater than that of other parts of the heart. The amount of blood ejected by the left ventricle in each beat is called the stroke volume (SV), which is determined by a number of factors, the most important being the amount of blood in the ventricle before contraction. Thus, the rapid filling of the heart results in a larger stroke volume, as does a longer filling time (slow heart rate). The heart rate (HR) is the number of times the heart beats a minute. A normal resting heart rate is about 72 beats a minute. The cardiac output (CO) is the amount of blood pumped by the heart each minute. This is equal to the stroke volume (SV) times the heart rate (HR). Therefore, if the SV is 70 ml a minute and the HR is normal, the cardiac output would be 5,040 ml a minute. Since the total volume of blood for the average adult is about 5,000 ml, this equation (CO = HR X SV) would indicate that the total volume of the blood in the body is circulated every minute. The cardiac output can be adjusted by altering both the stroke volume and the heart rate. The heart rate of a trained athlete may be increased during \Texercise\t to as much as 150 beats a minute, and the venous return of blood to the heart is increased so that the stroke volume may be as much as 170 ml. Thus, the cardiac output under such conditions is 25,500 ml, an increase over the resting value of more than 400 percent. Strenuous activity is made possible by the adaptability of the pumping action. The pressure in the aorta averages about 100 torr (0.14 kg/sq cm, or 2 lb/sq in). The pressure of ejected blood must be greater than this in order to move the blood into the aorta. The pressure energy (equal to pressure times the volume) imparted to the blood by the contraction of the left ventricle is the primary source of energy for the work done by the heart. The right ventricle does about one-sixth as much work as the left ventricle, because the pressure in the pulmonary artery is only about one-sixth that in the aorta. Last, the heart must use energy in imparting motion to the blood. Thus, the total work of the heart is given by the equation W = 7/6 PV + mvv in which W is the work per minute, P is the aortic pressure, V is the cardiac output, m is the mass of blood pumped per minute (nearly equal to the cardiac output), and v is the mean velocity of the blood as it passes through the valve openings. At rest, the work of the heart amounts to about 5 percent of the total energy expenditure of the body. The cardiac reserve represents the amount of work the heart can do over and above the requirements at rest. In a diseased heart, the cardiac reserve may be considerably reduced. Exercise and excitement, for example, may call for a cardiac output greater than the cardiac reserve can supply. The result may be \Theart failure\t. One complete heartbeat is called a cardiac cycle. The events just outlined represent most of the attributes of the cycle. Heart sounds are characteristic of the cardiac cycle and are important in assessing the functioning of the heart. These sounds are associated with the closing of the valves of the heart. There are two major sounds, the first generated by the closing of the atrioventricular valves, and the second by the closing of the semilunar valves of the pulmonary artery and aorta. The sound vibrations are caused by the stretching of the elastic parts of these valves. The physician, listening to these sounds with a \Tstethoscope\t, can tell a great deal about the condition of the heart, and especially the valves, from these sounds. Blood Vessels The largest blood vessel in the body is the aorta. Its walls are thick and made of a strong elastic material. Its primary functions are to act as a reservoir for the temporary storage of blood and the distribution of the blood to the systemic circulation. The aorta curves up and back, then down along the spinal column into the abdominal cavity, ending in the lower extremities. All along its course, the aorta branches into the major vessels called arteries. Each branching produces smaller arteries, but the total cross-sectional area of the arterial bed grows larger as the branching continues. Smaller arteries, the arterioles, contain less elastic tissue and more muscle tissue. In fact, they are almost all smooth muscle. This is important for the control of blood flow. The arterioles supply a bed of \Lcapillari\les, which are in intimate contact with the tissues. Many of these capillaries are so small that a red blood cell (diameter about 7 microns/0.0003 in) can barely squeeze through. Pores in the capillary wall are large enough to allow the water, sugar, dissolved gases, and other small molecules to pass through them, but small enough to hold back the larger protein molecules. Thus, they act as an ultrafilter, contributing to the formation of tissue fluids. Veins are quite thin-walled and are subject to low pressures. Some large veins have valves that serve, with the aid of outside pressure from contracting muscles, to increase the venous return of blood to the heart. The ability of the aorta and large arteries to act as an elastic reservoir for blood serves to reduce the amount of pressure produced by the ejection of blood into them by the heart. The pressure swing, or pulse pressure, is about 40 torr (0.056 kg/sq cm; 0.8 lb/sq in) at rest. The maximum pressure (systolic pressure) is about 120 torr (0.168 kg/sq cm; 2.4 lb/sq in). The minimum pressure (diastolic pressure), reached as blood drains out of the central reservoir before the next cardiac ejection, is about 80 torr (0.112 kg/sq cm; 1.6 lb/sq in). The mean arterial pressure, as stated, is about 100 torr. For practical purposes, this is the effective pressure producing blood flow. The mean pressure is reduced gradually in the large arteries and more rapidly in the small arteries. There is a marked drop in pressure across the arterioles, and a modest decrease in the capillaries. The difference in pressures at the arterial and venous ends of the capillaries results in the movement of fluid into the tissue spaces at the arterial end, and from the tissue spaces into the capillaries at the venous end. This phenomenon is important in the control of body tissue fluids. Blood Flow in the System In general, the flow of blood follows the laws of fluid flow. The basic law is expressed by the following equation: flow equals pressure divided by resistance. In cardiovascular physiology, the flow considered is usually cardiac output; the pressure is the mean arterial pressure; and the resistance is the resistance to flow of the small blood vessels, especially in the arterioles. Taken in greater detail, this law, as applied to the flow of viscous fluids through rigid tubes, is known as Poiseuille's equation, by which the flow of blood can be roughly described. However, that equation assumes that the fluid is truly Newtonian, and blood is not; it also assumes that the tubes are rigid, and the blood vessels are not; and it assumes that the fluid is of constant viscosity, and the viscosity of blood is not. As an approximation and for some understanding about the control of blood flow, however, Poiseuille's equation is useful. The flow of blood in the large and medium arteries is marked by pulsation, which is damped and barely discernible at the arterial end of the capillaries. Physiologists have developed detailed theories describing the flow and pressure-pulse transmission in blood vessels, and the action of the resistive elements, especially the arterioles, is well understood. Control of Circulation The pressure-flow relationships are basic to the control of circulation. All circulatory control is by the action of the heart muscle or arteriolar smooth muscle. Cardiac output is controlled primarily by the heart rate; arterial pressure by cardiac output and peripheral resistance; and the flow of blood through local tissue beds by arteriolar constriction or dilation. The heart muscle and smooth muscle of the circulatory system are controlled by nerves that originate in cardiovascular centers found in the medulla oblongata of the brain. These in turn are influenced by nerve impulses from receptors located in many parts of the body. The circulatory function can be adapted to a wide variety of environmental conditions and extremes of muscular activity. The control of the circulation is complex and is, without question, one of the most advanced evolutionary developments in animals. Ralph W. Stacy Bibliography: Avraham, Regina, The Circulatory System (1989); Berne, R. M., and Levy, M. N., Cardiovascular Physiology, 5th ed. (1986); Guyton, A. C., Circulatory Physiology, 3 vols. (1973-80); Mountcastle, V. B., Medical Physiology, 14th ed. (1979); Rushmer, Robert, Structure and Function of the Cardiovascular System, 2d ed. (1976); Shepherd, J. T., and Vanhoutte, P. M., The Cardiovascular System (1979).