NROSCI/BIOSC 1070 and MSNBIO Cardiovascular 1&2. August 28 & 30, 2017

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1 NROSCI/BIOSC 1070 and MSNBIO 2070 Cardiovascular 1-2 August 28 & 30, 2017 We, as multicellular organisms, cannot depend on diffusion alone to bring critical substances to our cells and to eliminate wastes. It is for this reason that we have a cardiovascular system to facilitate these processes. Role of the Cardiovascular System Move oxygen from the lungs to all body cells Move nutrients and water from the gastrointestinal system to all body cells Move metabolic wastes from all body cells to kidney for excretion Move heat from cells to skin for dissipation Move carbon dioxide from body cells to lungs for elimination Move particular toxic substances from some cells to liver for processing Move hormones from endocrine cells to their targets Move stored nutrients from liver and adipose tissue to all cells Carries immune cells, antibodies, and clotting proteins to wherever they are needed Anatomy of the Cardiovascular System The diagrams above illustrate the anatomy of the cardiovascular system. In essence, the cardiovascular system is comprised of two fused pumps (the left and right heart), a set of pipes (arteries) that carry the blood to the periphery, that branch into capillaries which permit diffusion between the fluid in the cardiovascular system (blood) and the cells of the body. Fluid from the capillaries is dumped into much larger pipes (veins) for return to the heart. 8/28/17 & 8/30/17 Page 1 Cardiovascular 1&2

2 The two pumps that form the heart circulate blood in different circuits. The right heart pumps blood into the pulmonary circulation of the lungs, which functions to permit gas exchange (oxygenation of the blood and removal of carbon dioxide). In contrast, the left heart pumps blood into the systemic circulation, which perfuses all the cells of the body (except those of the inner lung). Each of the two pumps of the heart has 2 chambers: an atrium and a ventricle. Upon return from the body, blood flows from the superior and inferior vena cavae into the right atrium, and then into the right ventricle. The blood moves through the tricuspid valve on its way between the two chambers. The tricuspid valve assures that the flow of blood is unidirectional, so that ventricular contraction does not cause blood flow back to the atrium. Contraction of the right ventricle forces blood through the pulmonary semilunar valve into the pulmonary arteries, which carry the blood to the lungs. Note that the blood in the vena cavae, right heart, and pulmonary arteries is usually bluish in color, as it carries less oxygen than blood in the systemic circulation. Blood is oxygenated within the lungs, and returned to the heart via the pulmonary veins. The blood enters the left atrium, and is transferred from there through the bicuspid (mitral) valve into the left ventricle. Contraction of the left ventricle forces blood through the aortic semilunar valve into the aorta, which branches to distribute the oxygenated blood throughout the body. The heart itself is enclosed in a tough membranous sac, the pericardium. The heart is mainly comprised of cardiac muscle, or myocardium. Matching of Pulmonary and Systemic Blood Flow The volume of blood leaving the left and right heart per unit time must be precisely matched. Otherwise, fluid would accumulate in one system, resulting in serious clinical disease. For example, if the myocardium of the left ventricle is severely damaged by a myocardial infarction, the amount of blood leaving the left heart could be less than that leaving the right heart. As a result, blood would accumulate in the vessels of the pulmonary circulation, leading to an impairment of gas exchange in the lungs. The Fluid Circulated by the Cardiovascular System: BLOOD Blood is essentially a two-phase fluid consisting of formed cellular elements suspended in a liquid medium, plasma. The formed elements are red cells (erythrocytes), white cells (leukocytes), and platelets. If a blood sample is centrifuged in a tube, the cellular elements will settle to the bottom. The red cells will lye on the bottom of the tube, and will occupy 40-45% of the total volume of blood. The white cells, being less dense, will settle on top of the red cells, and will occupy about 5% of blood volume. The remaining 50-55% of blood volume is contributed by the plasma. The volume of red blood cells present in blood is referred to as the hematocrit. Red blood cells contain hemoglobin, which has a remarkable capacity to bind with and transport oxygen. The white cells are mainly involved with immune processes and with bodily defense. The platelets are vital elements in blood coagulation. Blood plasma contains a variety of plasma proteins (e.g., albumin, globulin), electrolytes, hormones, enzymes, and blood gases. 8/28/17 & 8/30/17 Page 2 Cardiovascular 1&2

3 The physical properties governing circulation The main principal governing the operation of the cardiovascular system is quite simple: fluid moves from regions of higher pressure to regions of lower pressure. Pressure is continually changing as it moves through the cardiovascular system, and pressure in every blood vessel is different. Pressure (P) is a measure of force applied perpendicular to the surface of an object per unit area over which that force is distributed. In terms of the cardiovascular system, we normally think of pressure as the force exerted by the push of blood against the vessel wall. Pressure is generated by the contraction of the ventricles, and is necessary to propel blood against the force of gravity, as we will discuss later. The pressure in a particular vessel is influenced by a number of factors that will be discussed later, including the actions of gravity, the vessel characteristics, the amount of fluid (blood) circulating, and resistance to blood flow. Resistance (R) is a measure of the opposition to fluid movement in the cardiovascular system. A major factor in determining resistance is vessel diameter: resistance increases as diameter decreases. This is because the forces resisting blood flow are much higher in a small vessel. A major force generating resistance is friction. In the cardiovascular system, most of the resistance is provided by the arterioles. There are many parallel pathways for blood to flow, and thus if resistance is high in one pathway, there are alternate pathways through which blood can circulate. Since the pathways are arranged in parallel, the total resistance must be calculated by adding reciprocals: 1/R total = 1/R 1 + 1/R 2 + 1/R 3 + 1/R 4 +1/R 5 In this example, if: R 1 =5 R 2 =10 R 3 =25 R 4 =50 R 5 =100 1/R total = 1/5 + 1/10 + 1/25 + 1/50 + 1/100 = 0.37 R total = 2.70 RU (resistance units) Paradoxically, the total resistance is lower than the resistance in any one vascular bed. Often the term total peripheral resistance is used to describe the total resistance across the vascular beds. Flow (Q) is the volume flow rate of blood, and is expressed as volume per time (e.g., ml/min). Note that in terms of the tissues, flow is the most important physical parameter, as it is dictates the delivery of materials such as oxygen and glucose. As flow increases, more materials are delivered to the cells. 8/28/17 & 8/30/17 Page 3 Cardiovascular 1&2

4 Ohm s law is satisfactory to explain many of the dynamics within the cardiovascular system, particularly the relationships between pressure, resistance, and flow. Ohm s law does not perfectly explain cardiovascular hemodynamics, as blood vessels are not rigid tubes and blood is not a perfect Newtonian fluid. However, Ohm s law certainly works to approximate many dynamic properties in the cardiovascular system. As you may recall, Ohm s law can be formulated as follows: ( Q = P/R ) or ( P = Q * R ) or ( R = P/Q ) In these equations, P indicates the change in pressure on two ends of a vessel, and not the pressure within the vessel itself. In other words, P in the following two cases is the same: Note that Ohm s law indicates that flow through a vessel will be INVERSELY proportional to its resistance. Poiseuille s Law further explains the flow of fluid through tubes of different sizes. Although this law can be derived mathematically, we will simply be concerned with its implication. Poiseuille s Law can be expressed as follows: Q = π Pr 4 / 8ηl Q = flow π/8 is a constant P = the pressure driving force r = radius of the vessel η = viscosity of the fluid l = length of the vessel As you can imagine, because there is a relationship between flow, pressure gradient and resistance (Ohm s law), Poiseuille s Law can also be expressed as follows: R = 8ηl / πr 4 8/28/17 & 8/30/17 Page 4 Cardiovascular 1&2

5 What are the implications of Poiseuille s Law? Altering the radius of a vessel greatly affects both its resistance and the flow of fluid through it. In other words, if you half the diameter of the vessel, its resistance will increase by 16 times, and the flow through the vessel will decrease by 16 times. Why is the basis of Poiseuille s Law? Poiseuille s Law occurs because of the properties of laminar flow. If you induce fluid in a vessel to flow, the fluid on the inside moves faster than the fluid on the outside, creating a parabolic profile of flow. The fluid molecules touching the wall will hardly move because of adherence to the vessel wall. The next level of molecules slips over these, the third level second, etc. As you move towards the center of the tube and away from the walls, molecules slip past each other very easily. In a small vessel, essentially all the blood is near the wall, and thus essentially all the blood flows slowly because it adheres to the wall. The Poiseuille law is valid only under conditions of laminar flow. As the blood flow velocity increases, eventually a critical velocity is reached at which the concentric layers break down, giving rise to side-toside motion of fluid, or turbulence. With turbulent flow, not only is the frictional resistance increased, but vibrations are set up which are in the audible frequency range. Sounds which emanate from the circulatory system (murmurs) are the result of localized turbulence, often a consequence of some structural defect. Normal blood flow is laminar and therefore silent. Flow under any circumstances can be characterized by a dimensionless number known as Reynolds number (Re): Re = dvd/η d = density of fluid; v = velocity; D = tube diameter; η = viscosity For blood, the critical Re is about If conditions are such that Re < 1000 flow will be laminar; if Re > 1000 flow will be turbulent. Note that turbulent blood flow is more likely in large vessels when blood flow velocity is high. 8/28/17 & 8/30/17 Page 5 Cardiovascular 1&2

6 What is the real world significance of Poiseuille s Law? By affecting the size of blood vessels through vasoconstriction (or vasodilation), it is possibly to massively affect blood flow through particular vascular beds (by altering vessel radius and thus resistance). Most of the resistance occurs in small arterioles, which can alter their radius by up to fourfold. Thus, by producing maximal vasoconstriction, it is possible to reduce flow through a vascular bed by up to 4 4 or 256 times. Other implications of Poiseuille s Law. One term in Poiseuille s Law relates to the viscosity of the fluid moving through the vessel. As viscosity increases, resistance increases and flow decreases in proportion. If the hematocrit of blood increases substantially, then its viscosity will also increase. As a result, its flow through vessels will decrease. Patients with anemia (low hematocrit) will tend to have a higher velocity blood flow than patients with polycythemia (high hematocrit). Blood pressure The time during which the cardiac muscle relaxes is called diastole, and the time during which it contracts is called systole. Obviously, there is both atrial and ventricular diastole and systole, but the terms are frequently reserved to describe the actions of the ventricles. Typically, diastole lasts about twice as long as systole. Thus if the heart rate is 67 beats per min (cardiac cycle=900 msec), then diastole lasts for about 600 msec and systole lasts for about 300 msec. When the left ventricle contracts, a pressure wave or pulse is transmitted through the circulation. The amplitude of this pressure wave is defined as the pulse pressure, which is the difference in systolic and diastolic pressure measured from a large artery. 8/28/17 & 8/30/17 Page 6 Cardiovascular 1&2

7 Arteries contain substantial amounts of both fibrous and elastic connective tissue. When high-pressure blood comes in contact with the arterial wall, significant energy ( potential energy ) is absorbed when the artery becomes stretched. More than 95% of the work done by the contracting ventricle appears as potential energy stored, during systole, in the stretched arterial wall. This energy is released as kinetic energy through elastic recoil. This process limits the drop in arterial blood pressure during diastole. Moreover, since the arterial tree can function as an elastic reservoir the flow of blood from arteries to capillaries is continuous even though the flow from ventricle to aorta is pulsatile. What might affect pulse pressure? 1) Compliance of arteries. 2) Stroke volume. The ability of the arterial tree to store potential energy depends on its compliance (C), which can be defined as the tendency of a hollow organ to resist recoil toward its original dimensions. If the vessels were completely rigid (compliance = zero) all of the energy of contraction would appear as kinetic energy. The arterial compliance can be approximated by the relation: C = V/ P or P = V/C In this instance, V=stroke volume and P=pulse pressure, so pulse pressure ~ stroke volume/c Thus, the magnitude of the pulse pressure will depend on the volume of blood ejected and the compliance of the arteries. In contrast, the driving force for fluid entering the arterial circulation is mean arterial pressure (MAP). MAP can be determined by measuring blood pressure continuously and determining the mean level. As you may know, a continuous measurement of blood pressure is difficult in humans. Thus, it is convenient to estimate MAP from measurements of systolic and diastolic blood pressure. The formula typically used to estimate MAP from recordings of diastolic and systolic blood pressure is: MAP = diastolic P + 1/3(systolic P diastolic P) or MAP = 2/3(diastolic P) + 1/3 (systolic P) This formula is based on the observation that typically diastole lasts for twice as long as systole. If heart rate becomes very high, then the relative amount of time spent in diastole decreases, and the formula becomes inaccurate. 8/28/17 & 8/30/17 Page 7 Cardiovascular 1&2

8 Measurement of blood pressure In the laboratory, the simplest way of measuring blood pressure is simply by placing a pressure transducer into an artery. Alternately, a fluid-filled line can be led from an animal, and attached either to a pressure transducer (strain gauge) or mercury manometer. In the later case, the pressure of the blood displaces the mercury column by a certain height, which can be read from a scale. This is the time-honored way of measuring blood pressure, and this method gave rise to the standard units used to express blood pressure: mm Hg. However, placing arterial lines in humans is dangerous. Ohm s Law Returns to Haunt US!! Ohm s law states that: P = Q * R If pressure in the vena cava is assumed to be 0, then P is the same as MAP. The conventional manner of measuring blood pressure is still sphygmomanometry. A cuff is used to eliminate blood flow through a limb (usually the arm). The pressure in the cuff is reduced until a sound can be heard during each heart beat using a stethoscope placed above a large artery just distal to the cuff. The sound, called a Kortokoff sound, is due to turbulent flow through the artery which is partially constricted. The highest cuff pressure at which the sound can be heard is systolic blood pressure. Subsequently, the pressure in the cuff is reduced until no sound is heard. This is the diastolic blood pressure, since when cuff pressure is below diastolic pressure there is no obstruction to flow. Furthermore, Q and CO (cardiac output) must be the same, as flow through the cardiovascular system is clearly equal to cardiac output. Thus, Ohm s law can be stated as: MAP = CO * R In this case, R refers to the total resistance in the cardiovascular system (or TPR, total peripheral resistance ). This is the sum of resistances provided by every arterial bed in the body. Thus, mean arterial pressure is increased when either CO or TPR increases. Clinical Manifestations of Alterations in Vessel Properties Imagine the situation where a rubber tube is attached to a sink faucet, and water is flowing through the tube at a constant rate. If a clamp is placed on the tube, then pressure in front of the clamp increases tremendously. However, behind the clamp pressure and flow both drop. 8/28/17 & 8/30/17 Page 8 Cardiovascular 1&2

9 Raising central blood pressure through constriction of smooth muscle in arterioles profoundly diminishes blood flow to capillaries downstream from the constricted vessels. Thus, raising blood pressure by increasing vasoconstriction comes at the cost of depriving the tissues downstream from the constricted arterioles of oxygen and nutrients. This is illustrated further in the following examples: In example 1 to the right, all vascular beds have a resistance of 2 RU. In example 2, vasoconstriction has resulted in the diameter of vessels in beds 2 and 4 being half the previous diameter. Thus, resistance increases 16 times in both beds 2 and 4, and becomes (16 * 2)=32 RU. Thus, for example 1: 1/R total = 1/2 + 1/2 + 1/2 + 1/2 + 1/2 = 2.5; R total =0.4 For example 2: 1/R total = 1/2 + 1/32 + 1/2 + 1/32 + 1/2 = 1.56; R total =0.64 Thus, if cardiac output remained the same and the cardiovascular system acted in a pure Newtonian fashion, then the 60% increase in total peripheral resistance would result in a 60% increase in aortic pressure. This would mean an increase in P across the vascular beds, and increased flow through beds 1, 3, and 5. Blood flow through beds 2 and 4 is sharply curtailed by the reduced diameter of perfusing vessels. Tissues perfused by beds 2 and 4 would receive far less oxygen and other nutrients than before the vasoconstriction was initiated. Although Poiseuille s Law indicates that changes in blood pressure should increase blood flow through dilated vasculature, the relationship between pressure and flow is not so simple. As we will see later in the course, myogenic autoregulation tends to normalize blood flow through a vascular bed as pressure changes, such that only large changes in pressure result in a change in tissue perfusion. So, what is the advantage of increasing blood pressure? Pressure serves to push blood against the force of gravity (see below) and also pushes fluid out of capillaries into the interstitial space (see Capillary lecture notes). Raising blood pressure assures that blood can reach the head when an individual is upright, and that there is adequate pressure in brain arterioles to push fluid into the interstitial space. During aging, compliance in the large arteries decreases. From the equation listed two pages back (pulse pressure = stroke volume/c), it is evident that a 20% decrease in arterial compliance would result in a 20% increase in pulse pressure. The larger transients in blood pressure in the elderly have been shown to be an important cardiovascular risk factor. The pulse pressure amplification with aging is due to large artery stiffening. Different factors may contribute to this stiffening; for example, a decreased connective tissue elasticity, atherosclerosis and a decrease in smooth muscle relaxation. 8/28/17 & 8/30/17 Page 9 Cardiovascular 1&2

10 The Issue of Gravity in Cardiovascular Control Normal mean arterial pressure is approximately 100 mm Hg, which is equivalent to a column of blood about 4.5 feet high. Thus, when standing erect, if the brain were > 4.5 feet above the heart, it could not be perfused. Fortunately, the placement of the heart in the upper part of the body assures that the brain will always receive a constant blood supply. In general, overcoming the force of gravity is the greatest challenge that the cardiovascular system faces. If an individual is exposed to hypergravity 3 times that which normally occurs (as in high performance aircraft during sharp turns), the brain will not be perfused and syncope (fainting) will occur. Just as blood pressure drops as blood is propelled upwards against the force of gravity, it also increases as it moves downward with the force of gravity. When standing, arterial pressure at the level of the head is ~70 mm Hg, whereas that in the feet is near 170 mm Hg. This pressure differential affects hemodynamics in capillaries, as we will see later in the course. Pressure Waves in Arteries The ejection of blood from the left ventricle establishes a pressure wave that moves forward at a rate of 3-5 m/sec; this pressure wave can be felt via palpitation as the peripheral pulse. The speed of propagation of the pressure wave is a function of stroke volume and arterial compliance (lower compliance and higher stroke volume favor faster wave propagation). When the arterial pressure wave reaches the small peripheral bifurcations, it is reflected back in the reverse direction. On average, the reflected waves are in phase with the oncoming waves, thus leading to a distortion of the arterial wave form. This distortion is seen as a greater systolic and pulse pressure in the peripheral arteries than in the larger proximal arteries. Mean arterial blood pressure decreases as the pressure pulse moves down the arterial tree, as resistance is overcome. However, it is important to note that for any given mean arterial pressure, the values for the systolic and diastolic pressures will depend on where the measurement is made. 8/28/17 & 8/30/17 Page 10 Cardiovascular 1&2

11 The opening and closing of the heart valves is governed by the pressure differences on the two sides. Because of the properties of arteries such as the aorta, pressure does not drop as rapidly as in the left ventricle. As such, there is a brief period at the end of systole when blood flows backwards from the aorta into the ventricle, as shown in the figure to the left. This reverse blood flow triggers the closure of the aortic valve. It also establishes a discontinuity in the pressure tracing (called the dicrotic notch or incisura), which serves as a marker for aortic valve closing. Valve closure terminates retrograde flow. We will learn about the heart and its actions in great detail in subsequent lectures. As arteries divide into smaller and smaller branches, the amount of connective tissue in the walls diminishes but muscularity increases. This is why the smallest arteries, the arterioles, are the major resistance vessels. Because of the large resistance imposed by the arterioles, blood pressure drops substantially when blood flows through these vessels. Also note that as the pressure pulse progresses through the high-resistance arterioles, the pulse is almost completely damped out. 8/28/17 & 8/30/17 Page 11 Cardiovascular 1&2

12 Why do Large Arteries Contain More Connective Tissue than Small Arteries? Poiseuille s Law (Q =π Pr 4 / 8ηl) shows that in order to maintain rapid flow through an artery without losing pressure, the artery size has to be relatively large. However, this raises another problem: surface tension, which is described by the Law of Laplace. In relation to a thin-walled cylinder, the Law of Laplace can be expressed as: T=Pr where T= wall surface tension, P=transmural pressure, and r=radius. Hence, a small vessel (low r) can sustain a high pressure without having a high surface tension and breaking. Large vessels need a tremendous amount of connective tissue reinforcement to sustain pressure, as the surface tension is high. The diagram to the left illustrates how blood flows from arterioles to capillaries to venules. Note that the circulation contains specialized blood vessels, called metarterioles. Small bands of vascular smooth muscle, called precapillary sphincters are found at the junction between a metarteriole and a capillary. If these precapillary sphincters contract, then blood flow into the capillaries diminishes. In addition to the constriction of arterioles, this mechanism provides an additional means to shunt blood away from capillary beds. The metarterioles, as well as other arteriovenous bypasses, permit large white cells to flow from the arterial to the venous side of the circulation. Capillaries are composed of a single layer of endothelial cells and a basement membrane; the thickness of the wall is only about 0.5 micrometers. We will discuss exchange of materials between capillaries and cells in much greater detail in a subsequent lecture. Flow Rate of Materials through Capillaries The flow rate of materials through blood vessels is expressed by the following equation: V=Q/A where V=Velocity of Blood Flow Q=Flow Rate A=Cross Sectional Area Thus, the flow rate of materials through capillaries is much lower than arteries or veins, as the total surface area of the capillaries is enormous. 8/28/17 & 8/30/17 Page 12 Cardiovascular 1&2

13 Portal Circulations In specialized circulations, called portal circulations, two capillary beds occur in series with each other. One portal circulation occurs between the hypothalamus and the pituitary gland. Two other large portal circulations also exist in the body, as illustrated in the diagram to the left. One portal circulation exists between the digestive tract and the liver, and a second within the kidney. We will discuss the importance of these two specialized circulations when we study the digestive system and the renal system. Venous Return to the Heart Most of the blood volume in the circulatory system is present in the veins. In addition, venous pressure is one of the most important determinants of cardiac output, as discussed later in the course. When we are lying down, the pressure left in blood after it has moved through the capillary bed is sufficient to produce a return of blood to the heart. When standing, however, the force of gravity greatly increases the pressure needed to push blood back to the heart. In a person of average 8/28/17 & 8/30/17 Page 13 Cardiovascular 1&2

14 height, venous pressure would have to equal 90 mm Hg if this were the only mechanism involved in venous return. Fortunately, a number of specializations exist in veins to aid in the process (see below). Veins have thinner walls than arteries, typically have a larger diameter, and are more numerous. Furthermore, they are extremely compliant. As such, they expand easily when filled with blood (see below). Because of their high compliance, blood pools in the dependent veins (those subjected to the force of gravity) as the intravenous pressure increases during standing. Thus, upon standing blood is translocated from the thorax to the abdomen and legs. Blood flow in the dependent veins also decreases appreciably during postural changes, which was only recently documented (in the lecturer s laboratory). Below are averaged data from 6 conscious animals showing the effects of head-up tilts of different amplitudes on blood flow through the femoral vein. Note that femoral venous blood flow drops precipitously at the onset of large-amplitude head-up tilts, but then increases towards baseline levels. The mechanisms responsible for recovery of venous blood flow during postural alterations are discussed below. There are three major mechanisms at work that assist in returning blood to the heart when standing: 1) Venous valves 2) Skeletal muscle pumping 3) Venomotor tone Venous valves permit unidirectional flow of blood towards the heart. They are located every 2-4 cm in most peripheral veins. When veins are exposed to extreme venous pressures over a long time period (this sometimes happens in people who stand for many hours per day), the veins become stretched. However, the valves do not expand to fill the vessel, and they do not adequately close. This condition, called varicose veins, can be quite problematic. Venous return to the heart diminishes, and pressure in the leg veins becomes very high, during standing. The compression of veins by skeletal muscle is one of the most important mechanisms involved in return of blood to the heart. For example, during movement, leg muscle contractions force blood from intramuscular veins and towards the heart. As you might imagine, this skeletal muscle pumping only works efficiently because valves are present in the veins, permitting unidirectional flow of blood. Veins also contain smooth muscle, which is innervated by the sympathetic nervous system. Venoconstriction also is important in translocating blood from the periphery to the heart. 8/28/17 & 8/30/17 Page 14 Cardiovascular 1&2

15 In terms of physics, venoconstriction and skeletal muscle pumping increase venous return by decreasing the compliance of the vein. Since P = V/C, a reduction in compliance means that more pressure is generated when a particular volume of blood enters a vein. This pressure is the force that moves the blood forward in the vein. As discussed previously, >60% of the blood in the circulatory system is in the veins. This blood distribution is purposeful: the veins act to store blood that can be liberated if more cardiac output is required. Venoconstriction in some beds can have a particularly large effect in enhancing cardiac return of blood. Four venous beds in particular serve as blood reservoirs: the spleen, the liver, the large abdominal (splanchnic) veins, and the venous plexus beneath the skin. In particular, the spleen acts as a huge reservoir for red blood cells. Venous sinuses in the spleen store whole blood, and the pulp of the spleen stores highly-concentrated red blood cells. The capillaries in this region are highly permeable, but special structures (called trabeculae) serve to trap the red blood cells so they cannot return to the circulation. Constriction of the spleen serves to return large amounts of red cells to the blood, and can raise the hematocrit by 1-2%. In some mammals, however, the spleen is even more efficient in storing blood cells. We should also not forget that the heart is located in a cavity whose pressure changes every few sec in conjunction with breathing. During inspiration, descent of the diaphragm produces negative pressure in the thorax, which sucks air into the lungs. The same effect also tends to suck blood into the chest from the abdomen. However, because pressure changes in the chest during breathing are not extreme, this mechanism has limited capacity to aid in venous return to the heart. Although fluid filling of the heart is largely passive, it is noteworthy that ventricular contraction results in a change in shape of the atria, slightly increasing their size and producing a small suction effect that pulls blood into the atria. For all practical purposes, however, this effect is negligible. Venous Compliance and Its Changes with Aging As noted above: P = V/C Veins ordinarily have a very high compliance, so a large change in blood volume generates only a small change in pressure. Since pressure is the force that moves blood forward in the cardiovascular system, the high compliance of veins makes it difficult to generate enough pressure to translocate blood back to the heart. Hence, the mechanisms described above play an important role in moving blood forward ion the veins. However, the relationship is complex, as indicated in the graph below: 8/28/17 & 8/30/17 Page 15 Cardiovascular 1&2

16 The slope is not linear because the vein vessel wall is a heterogeneous tissue. Vein compliance decreases at higher pressures and volumes (i.e., vessels become stiffer at higher pressures and volumes). At lower pressures, the compliance of a vein is about 10 to 20-times greater than an artery. Therefore, veins can accommodate a large changes in blood volume with only a small change in pressure. However, at higher pressures and volumes, venous compliance (slope of compliance curve) becomes similar to arterial compliance. Vascular smooth muscle contraction, which increases vascular tone, reduces vascular compliance, as shown by the arrow in the graph to the left. Conversely, smooth muscle relaxation increases compliance. As noted above, this is particularly important in the venous vasculature for the regulation of venous pressure and venous return to the heart. Cardiac output is extremely dependent on venous return, as we will discuss later. Because venous return drops during postural alterations, cardiac output and blood pressure also tend to decrease (remember Ohm s Law: MAP = CO * R). This drop in blood pressure can result in insufficient perfusion of the brain, during a condition called orthostatic hypotension (a drop in blood pressure due to a change in posture). Orthostatic hypotension can occur if the mechanisms discussed above that are involved in venous return (e.g., skeletal muscle pumping) are impaired, blood volume is low, extensive vasodilation is present, cardiac output is impaired by heart disease, etc. Aging alters the structure of the vein wall, leading to an increase in compliance. This increase in compliance increases the tendency for blood to pool in the veins, thereby reducing venous return. As a result, the tendency for orthostatic hypotension to occur increases during aging. Our Path Forward During this lecture, we have seen that control of the cardiovascular system is related to muscle contraction. Contraction of cardiac muscle in the heart provides the force that moves blood forward in the cardiovascular system. Contraction of smooth muscle in arterioles determines which capillary beds are perfused with blood. Contraction of skeletal muscles, in addition to producing movement causes blood to move forward in veins. We must understand muscle contraction in order to understand the operation of the cardiovascular system. Over the next few lectures, we will discuss the process of muscle contraction and how it is regulated, and then will return to the cardiovascular system. 8/28/17 & 8/30/17 Page 16 Cardiovascular 1&2