Unformatted text preview: COPYRIGHT Mammalian Physiology BIOAP 4580 2011 Prof. Beyenbach The Cardiovascular System
1. Functional role: serving homeostasis a) Bulk transport of respiratory gases, nutrients, vitamins, and metabolic „wastes‟, b) Selective distribution of fuels to active sites, c) Transport system for endocrine primary messengers (hormones), d) Regulation of body temperature, e) Mediating the functions of the immune system. 2. Components of circuitry a) The heart. Inter alia, the heart is a mechanical device that incorporates two pumps in series, each in series with a major circulatory bed (Fig.1). The right heart receives venous blood from the body and sends it on to the lungs for oxygenation and CO2 removal (Fig. 1). The left heart receives oxygenated blood from the lungs and sends it on to the rest of the body. Pulmonary and systemic circulations are in series as are the right and the left hearts. Flow is the same at any one point in the circuit. Yet pressures generated by the right heart are substantially lower than those generated by the left heart. Since flow is the same in both pulmonary and systemic vascular beds, it follows that the pulmonary circulation offers much less resistance to flow than the systemic circulation. This is indicated by the relative size of the „resistors‟ in Fig. 1. Fig. 1. Circuit diagram of the cardiovascular system. Flow from the right heart goes to the lungs, and flow from the left heart goes to the rest of the body. The size of the batteries reflects pressure-generating capacity. b) The systemic circulation. In Fig. 1 the systemic circulation is shown as a single resistor that represents the sum total of vascular beds arranged mostly in parallel (Fig. 2). The advantages of the parallel arrangement of vascular beds are: 1) the input perfusion pressure (arterial pressure) is the same for all tissues, 2) the selective increase in the perfusion of one vascular bed does not affect flow in other vascular beds (within limits), 3) the parallel arrangement of vascular beds reduces the workload on the heart (review parallel vs. series resistances in electrical circuits), 4) each circulatory bed can „tap‟ what it needs from a well oxygenated, nutrient-rich source, namely, arterial blood in the high pressure reservoir (aorta and major arteries). 1/12 Some systemic circulatory beds are in series, one behind the other, in so-called portal circulations. Portal circulations serve specific functions. For example, in the liver the hepatic portal circulation serves to detoxify nutrient-rich blood returning from the intestine (Fig. 2). Here, the capillary bed in the intestine is in series with the capillary bed in the liver. In the kidney, the afferent arteriole gives rise to glomerular capillaries that serve filtration. Merging glomerular capillaries combine to yield the efferent arteriole that gives rise to the peritubular capillary network. Thus, glomerular capillaries and peritubular capillaries are two capillary beds in series. Peritubular capillaries serve to return to the body life essential materials: Na+, Cl-, K+, glucose, amino acids that have been reabsorbed by the renal tubules. Fig. 2. Parallel and series arrangement of vascular beds in the systemic circulation. The battery represents the left heart only. The resistors are equivalent to resistances of small arterioles and pre-capillary sphincters. Two capillary beds in series define a “portal circulation” as in the hepatic and renal portal circulation. In the portal circulation, capillaries in the intestine merge to give rise to a hepatic portal vein leading to the liver where the vein gives rise to a capillary network for the detoxification of blood coming from the intestine. In the kidney, the afferent arteriole (a.a.) gives rise to glomerular capillaries and the efferent arteriole (e.a.) gives rise to peritubular capillaries. b) The transported medium, blood, is a “flowing tissue”. Blood consists of aqueous and cellular portions, plasma and cells respectively. Plasma is a solution of approximately 300 mOsm/kg H2O containing Na+, Cl-, K+, HCO-3, Mg2+, Ca2+, albumin, etc. Cells floating (suspended) in the plasma include erythrocytes, leukocytes, monocytes, lymphocytes, etc. 3. The systemic circulation: geometry, volumes, flows, velocities (Figs, 3, 4). In general, arteries are thick-walled and built to withstand pressure. Arteries tend to be more internal than external. Buried in the tissue, arteries are protected against injury. In contrast, veins are thin-walled and built to accommodate volume. Veins tend to be located near the surface of the body (and accessible for IV infusions). 2/12 a) Aorta, arteries, arterioles, pre-capillary sphincters. Only 20% of the blood volume resides on the arterial side. The arterial system serves as pressure reservoir for the systemic circulation. In particular, the heart is a compressor pump that pressurizes a tank (the arterial side) with each cardiac contraction. The heart is not a constant flow pump. The ejection of blood into the small space of the aorta and arterial system pressurizes the arterial side. The pressure on the arterial side is maintained because blood cannot run freely into the tissues because arterioles and precapillary sphincters are largely constricted, allowing only some flow into the tissues. The tonic partial vasoconstriction of arterioles and pre-capillary sphincters stems from a heavy layer of smooth perivascular muscle (Fig. 3). It is that vasoconstriction that maintains a high pressure on the arterial side. If many arterioles and pre-capillary sphincters were to vasodilate at the same time, as might occur during a swim1 after a meal2 on a hot day3, the „run off‟ of blood from the pressure tank (arterial system) to skeletal muscles, the intestine and the skin (for thermoregulation) could reduce arterial pressure to levels insufficient for the perfusion of the brain. The result would be fainting in water. 1 vasodilation of arterial vessels in all skeletal muscles, 2 vasodilation of arterial vessels in the GI-tract, 3 vasodilation of arterial vessels in the skin. Fig. 3. Size and composition of blood vessels. Every blood vessel has an endothelial lining. Tight junctions between endothelial cells hold endothelial cells together and also account in part for the blood-brain-barrier in cerebral capillaries. Note that capillaries and small venules have no smooth muscle. Though capillaries and small venules (not shown above) lack elastic tissue, they certainly have an intrinsic elasticity (from Berne & Levy, 1987). b) Capillaries. While all other vessels of the circulatory system serve primarily the axial flow of blood, the capillaries serve radial1 transport, namely the vital nutrient supply of the tissues and the removal of wastes. Concentration differences drive this radial transport from capillary to cell and vice versa. 1radial, in the direction of the radius. c) Venules, small veins, large veins, vena cava. The venous system serves as volume reservoir. At any one time, most of the blood (80%) is located on the venous side (Fig. 4). Blood stored on the venous side provides 1) a functional volume reserve for physiological needs in the case of exercise and increased cardiac output, and 2) safety reserve in the case of hemorrhage. The walls of veins are far more elastic than those of 3/12 arteries. As a result, veins can accommodate volume in volume expansions. An unneeded blood transfusion is unlikely to increase arterial blood pressure since most of the infused blood volume will reside on the venous side of the circulation (which may increase the venous pressure at the distal end of the capillary). Venules, small veins, and veins can constrict, thereby shifting blood to the arterial side of the circulation in case of need. Fig. 4. Structural and functional profiles down the vascular circuit. The pressure near the heart is pulsatile on the arterial side, oscillating between diastolic and systolic values. Pulsatile pressures diminish with distance from the heart in view of increasing numbers of arterial blood vessels that 1) increase the arterial capacitance (C) for blood, and 2) decrease the total resistance (R) to arterial flow. Accordingly, the arterial side behaves like an (electrical) RC filter that dampens oscillations of pressure. With length down the arterial tree the pressure oscillations (systolic/diastolic) eventually disappear altogether at the level of capillaries. Mean pressure is the “average” of diastolic and systolic pressures. It is approximated as Pd + 1/3(Ps - Pd), where Ps and Pd are systolic and diastolic pressures respectively. Ps Pd is also known as pulse pressure. (from Berne and Levy, 1987). Veins and large veins are endowed with one way valves that direct the flow of venous blood towards the heart. What moves venous blood from the legs upward to the heart is the so-called „skeletal muscle pump‟, where the contraction of skeletal muscle in the legs (as during walking) rhythmically squeezes (compresses) veins. Since thin-walled veins transmit this external pressure to an uncompressible medium (blood), venous blood is pressurized to flow upward. Downward flow is prevented by one way valves. Soldiers standing at attention for long periods of time often pass out for lack of skeletal muscle pumping in their legs. As much blood pools on the venous side in their legs, venous return to the heart diminishes to such an extent that cardiac output decreases. The decrease in cardiac output decreases the „tank pressure‟ on the arterial side with the effect of reducing blood flow to the brain. Passing out, the soldier assumes a supine position, with the beneficial effect of increasing venous return, especially from the legs. 4. Forces and flows, resistance and capacitance. a) The heart is an intermittent rather than a constant pump. Contracting periodically, the 4/12 heart pressurizes the arterial compartment with a compressor-like function that expels blood from the left ventricle in spurts, leading to a pulsatile pressure peak at systole (ventricular contraction). As blood runs off into the tissue at the distal end of the arterial tree, the systolic pressure falls, reaching the diastolic pressure. b) The pressure reservoir. The pressure reservoir extends from the aortic valve of the left ventricle (100 mmHg mean pressure) to the proximal end of the capillary (30 mmHg) (Fig. 4). c) The volume reservoir. The volume reservoir extends from the distal end of the capillary to the right atrium (Fig. 4). d) Resistance and capacitance vessels (Fig.5). Resistance vessels mediate blood flow on the arterial side and capacitance vessels mediate flow on the venous side. Resistance vessels have low capacitance and strong vasoconstrictor tonus. Capacitance vessels have high capacitance and weak vasoconstrictor tonus. Fig. 5. Pressure profile down the vascular tree. Mean pressure is shown (see legend to Fig. 4). For a systolic pressure of 120 mmHg and a diastolic pressure of 80 mmHg, the mean pressure is 92 mmHg (from Berne & Levy, 1987). e) Laminar and turbulent flow: Roles in the measurement of blood pressure. The blood pressure cuff is inflated to a pressure such that arterial blood flow through the brachial artery stops completely (the tourniquet effect). Cuff pressure is then slowly released with careful listening to the first rush of turbulent flow through the compressed artery. This first sound coincides with the pulse and marks the highest pressure, i.e. the systolic pressure. Turbulent flow through the brachial constriction will continue with each heart beat until it changes to laminar flow at little cuff constriction. The change from turbulent to laminar flow can be detected by a change in pitch of sound as blood now passes smoothly through the artery with each cardiac contraction. Normal systolic and diastolic pressures in an adult are 120/80 mmHg at rest. But systolic pressure may rise to 180 mmHg and more during exertion. During exercise, systolic pressure rises as the result of the increased cardiac output (the epinephrine effect) and diastolic pressure falls as the result of arterioles dilating in working muscles. Working muscles produce heat and CO2; both dilate blood vessels. 5. Operation of the closed circulatory system: coupling heart and circulation. a) Cardiac output. Cardiac output in a human at rest is 5 liter/min. If the heart beats 70 times per minute, the stroke volume is therefore 71.4 ml. The cardiac output is influenced by the heart itself, by the so-called cardiac factors, and by the functional states 5/12 of veins and arteries, the so-called coupling factors (Fig. 6). The cardiac factors include the heart rate and myocardial contractility. When epinephrine increases cardiac output it does so by increasing the heart rate (the chronotropic effect) and by increasing the strength of each single cardiac contraction (the myotropic effect). Outside the heart, the venous return determines the cardiac output by presenting variable volumes of blood to the heart. For example a hand-stand will suddenly increase venous return from the legs, thereby increasing cardiac output. Dehydration, volume loss, hemorrhages all tend to decrease venous return and cardiac output. For these reasons, changes in venous return are called changes in preload as they affect the loading of ventricles. Changes on the arterial side will also affect the cardiac output. Suppose that the mean arterial pressure has increased because terminal arterioles are too vasoconstricted (essential hypertension). The increased pressure residing on the arterial side works against the left ventricle trying to eject blood into the aorta. The increased arterial vasoconstriction (aka arterial pressure) constitutes a rise in the afterload. As a result, cardiac output decreases and left ventricular residual volume increases. Thus, as afterload increases, cardiac output decreases. Fig. 6. Determinants of the cardiac output. Heart rate is determined by neural input (Vagus nerve, acetylcholine), circulating catecholamines (epinephrine), and other endocrine and paracrine agents. Myocardial contractility is determined by circulating catecholamines, and other endocrine and paracrine agents. Preload is largely determined by the venous return that in turn is dependent on physical activity, posture (standing or lying), and ambient temperature. Cold is a peripheral vasoconstrictor in the skin that shifts blood to the center, increasing the preload. Heat is a dilator1. Afterload is largely determined by vascular smooth muscle tone of small arteries and pre-capillary sphincters. Vascular smooth muscle tone in turn is dependent on emotional state, circulating catecholamines, personality type, calcium and magnesium, and general level of fitness. 1 Peripheral vasoconstriction shifts blood to the center, giving rise to a pale looking skin and an „apparent‟ central volume expansion to which the kidney responds by reabsorbing less fluid, bringing about the so-called cold-diuresis. 6/12 b) A push-pull system with different compliances. Preload and afterload are considered coupling factors because they couple the heart to the vasculature. Not much is gained by this definition, since heart rate and contractility also couple the heart to the vasculature. Actions of the heart affect the vasculature, just as actions of the vasculature affect the heart. For example a decrease in the heart rate will leave more blood on the venous side, increasing volume there while decreasing pressure on the arterial side. On the other hand, receiving bad news may cause so much vasodilation on the arterial side that arterial volume and pressure drops to levels inadequate for the perfusion of the brain. One passes out and spontaneously assumes a supine position that increases venous return from the legs that brings about consciousness again. Is this design or coincidence? The point is that the heart cannot be imagined without a circulatory system (one hand washes the other, also a form of coupling). The interplay between the heart and the vasculature is best illustrated in an example of cardiac arrest and resuscitation (Fig. 7). Suppose cardiac arrest is produced by intense stimulation of the Vagus nerve or by a high dose of Ca2+ channel blocker. Cardiac output would fall immediately from 5 L/min to 0 L/min (Fig. 7b). The arterial side is still pressurized at this time, providing run-off to the venous side. Accordingly, venous volume and pressure rises, and arterial volume and pressure fall. At equilibrium, when there is no flow from the heart and no flow through the capillaries, the pressure is the same at any one point in the system. The equilibrium pressure turns out to be 7 mmHg, the static pressure on the venous and arterial side of the circulation when flow has come to a complete stop (Fig. 7c). Fig. 7. Sending the cardiovascular system to equilibrium by induced cardiac arrest. Pa, arterial pressure, Pv, venous pressure. Equilibrium = no flow any place = equal pressure every place = 7 mmHg (from Berne & Levy, 1987). 7/12 Suppose now we resurrect the heart. As the heart begins to beat, it takes volume from the venous side and transfers it to the arterial side, let us say at a pump rate of 1 L/min. What the venous side loses, the arterial side gains, but with variable pressure changes. Removing 1 liter from the venous side lowers the venous pressure from 7 mmHg to only 6 mmHg, but it increases pressure on the arterial side from 7 mmHg to 26 mmHg (Figs. 7d, 8). The reason for this enormous difference in pressure lies in venous vascular compliance (capacitance) that is much greater than arterial vascular compliance. Like expandable lungs that can take up large volumes of air at little pressure changes, veins can take up or give up large volumes with little pressure change. In contrast, thickwalled arteries with little powers of distension experience a large change in pressure for a given volume addition or deletion. Compliance (C) is defined as eq. 1 where V is volume and P is pressure. On average, the venous compliance is about 19 times greater than the arterial compliance. The transfer of 1 liter of blood from the venous to the arterial side is eq. 2 where a and v are arterial and venous respectively. The compliance of the arterial system (Ca) and the venous system (Cv) are respectively eqs. 3,4 Rearranging equations 3 and 4 and substitution in equation 2 yields eq. 5 Since Cv is 19 times greater than Ca, it follows that eq. 6 Thus, for a 1 mmHg decrease in venous pressure (- 1 mmHg), the arterial pressure will rise 19 mmHg (-1(-19)). Accordingly, as Pv goes from 7 mmHg to 6 mmHg, Pa goes from 7 mmHg to 26 mmHg (Figs. 7,8). By the time cardiac output has returned in the resuscitated heart to 5 L/min, venous pressure has dropped to 2 mmHg from 7 mmHg. The change, 5 mmHg multiplied by 19 yields the arterial pressure change, 95 mmHg, which added to 7 mmHg brings the arterial pressure 102 mmHg (Figs. 7, 8). 8/12 Fig. 8. Resuscitating the heart. At arrow 1, one liter of blood has been transferred from the venous to the arterial side, at arrow 2 cardiac output is again 5 L/min. At this time pressure has build up sufficiently in the arteries to overcome the resistance residing in the small arterioles and precapillary sphincters: i.e. the system is now in steady state again where -on balance- cardiac output equals peripheral runoff. CO, cardiac output; P, pressure; a, artery; v, vein (from Berne & Levy, 1987). 6. Vascular and cardiac function curves. The two function curves illustrate how vascular and cardiac systems interact. In particular, the combination of vascular function curves and cardiac function curves illustrates how the activity of the heart affects the vasculature and vice and versa. The two curves are first discussed separately and then together. a) Vascular function curves. In Fig. 9 the effect of cardiac output on venous pressure is shown in a way you are not accustomed to examining graphs. Normally, one plots the independent variable on the x-axis, namely that parameter endowed with high confidence or under good control in the experiment. One plots the dependent variable on the y-axis, to examine how y changes as a function of x. This convention is violated in Fig. 9 for reasons that will become clear later.
CARDIAC OUTPUT (L/MIN) 7 6 5 4 3 2 1 normal transfusion blood loss Fig. 9. The vascular function curve. As cardiac output increases, venous pressure decreases because the heart sucks blood from the venous compartment. Cardiac output cannot increase further after the venous pressure has dropped to 0 mm Hg (from Berne & Levy, 1987). Note the effect of extracellular fluid volume on the vascular function curve.
6 7 8 9 -2 -1 0 1 2 3 4 5 CENTRAL VENOUS PRESSURE (mm Hg) Here we allow cardiac output (y-axis) to increase on the y axis, so as to have an effect on the venous pressure. Looking backward into the veins, the heart functions like a suction pump, decreasing the venous pressure with the increase in cardiac output. Alternatively, as cardiac output decreases, venous pressure increases because volume is 9/12 not removed. When cardiac output is zero, venous pressure is at the static pressure of 7 mmHg (Figs. 7, 8). It stands the reason that volume expansion increases static pressure and dynamic pressure at any level of cardiac output (Fig. 9). Likewise, volume contraction mediated by dehydration or hemorrhage, decreases static pressure and dynamic pressure. b) Cardiac function curves. In Fig. 10 normal convention has returned to the diagram where the independent variable is plotted on the x-axis to explore the effects of venous pressure (i.e. venous return) on cardiac output. Here we see the effect of increasing venous return on increasing cardiac output: what goes in must come out in steady states. Frank and Starling are credited with making these observations first, noting that cardiac output increases as venous return rises, even in the isolated heart. Passive stretch of any muscle will increase the force of contraction (up to a limit) because it takes the slack out of the muscle before contraction begins. In the un-stretched muscle, the initial work of the contracting muscle is spent on stretching the elastic elements of the muscle. In the heart, the increase in venous return (pressure) increases the filling volume thereby stretching cardiac muscle fibers. As a result, the force of the subsequent muscular contraction is not wasted on tacking out slack in muscle. Instead, it immediately shortens the muscle thereby moving blood.
9 8 7 6 5 4 3 2 1 heart failure normal epinephrine Fig. 10. The cardiac function curve. Effect of myocardial state on cardiac function curves. At any venous pressure cardiac output is less in the weak heart than in the normal or stimulated heart (from Berne & Levy, 1987). Note the effects of epinephrine and a weak heart on cardiac output.
8 9 CARDIAC OUTPUT (L/MIN) -2 -1 0 1 2 3 4 5 6 7 CENTRAL VENOUS PRESSURE (mm Hg) A weak heart (hypodynamic heart, a heart in failure) falls short of the normal cardiac output at any venous pressure (Fig.10). The right heart will not pump out what it receives. As a result, the right heart will leave volume on the venous side, raising venous pressure, and causing general edema. A weak left heart will not pump out what it receives from the lungs, raise the venous pressure in the pulmonary circulation, and cause pulmonary edema. Coronary occlusion (cardiac ischemia) will render the heart weak on both right and left sides. Epinephrine increases cardiac output at any given venous pressure (Fig. 10) for two reasons: 1) the chronotropic effect, i.e. the increase in heart rate, and 2) the myotropic effect, i.e. the increase in the force of contraction. c) Combined vascular and cardiac function curves. In Figure 11, normal vascular and cardiac function curves are shown together to illustrate the normal setpoint where cardiac and vascular function curves are intersecting. At this setpoint the total “pull-push” 10/12 system has found its steady state position: 5 L/min at a venous pressure of 2 mmHg. Fig. 11. Combined vascular and cardiac function curves. The setpoint indicates the value of venous pressure and cardiac output at which the system tends to operate in a stable (steady state) manner (from Berne & Levy, 1987). In the event of a failing heart, cardiac output decreases along the vascular function curve from A to B in Fig. 12. As a result venous pressure increases from 2 mmHg to 2.6 mmHg because volume remains on the venous side. Fig. 12. Acute changes in the cardiovascular system. A weak heart decreases cardiac output displacing the setpoint of the total system from A to B. A blood transfusion increases venous volume, moving the function of the whole system from point A to C (from Berne & Levy, 1987). In a blood transfusion the vascular function curve increases along the cardiac function curve to point C. Venous pressure increases because most of the transfused volume goes to the venous side of the circulation. Cardiac output increases because of the increased venous pressure which increases venous return by the Frank-Starling mechanism. 6. The cardiac/renal axis. General edema is usually the sign of a weak heart. How edema comes about in cardiac insufficiency is illustrated in Fig. 13. Point A is the normal setpoint of cardiac and vascular functions in normal health. A weak heart shifts the cardiac function curve to point B along the vascular function curve. Note the increase in venous pressure to 2.6 mmHg. Since the kidneys now receive less blood than under normal health, they activate the renin-angiotensin system (RAS) to restore „blood volume‟. Activation of RAS cause the kidneys to reabsorb more NaCl and water from the tubular fluid, thereby increaseing extracellular fluid volume and with it venous volume and venous pressure. As a result, the setpoint moves from B to C. Although the renal fluid retention has returned the cardiac 11/12 output to nearly control values, it did so at the expense of increasing venous pressure which now is at 3.5 mmHg, increasing the edema that already was observed at setpoint B. Increased edema in the body may be the „price‟ for restoring good cardiac output, which is so important in supporting all tissues. Fig. 13. Renal compensation of a weak heart. A weak heart decreases the cardiac function curve from setpoint A to B. The kidneys, receiving less blood, interpret the decrease as a volume loss. They respond by conserving volume which increases extracellular volume, and hence plasma volume, and blood volume. Although the kidneys have restored their own blood supply, they have increased the edema. Note a correction would be the restoration of cardiac contractility (which can be attempted with nitroglycerine and other agents that increase cytosolic Ca2+ levels in cardiomyocytes). RECOMMENDED READING: Boron & Boulpaep. Medical Physiology. Saunders, Philadelphia, 2003. Chapter 17: Organization of the Cardiovascular System, p. 423 - 435. Chapter 18: Arteries and Veins, p 447- 453, Berne, R.M and M.N. Levy. Cardiovascular Physiology. 7th edition, Mosby Year Book, 1997. Guyton, A.C. Textbook of Medical Physiology. A recent edition, W.B. Saunders Co. Brobeck, J.R. Best & Taylor‟s Physiological Basis of Medical Practice. A recent edition, Williams & Wilkins Co. Baltimore. 12/12 ...
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This note was uploaded on 04/09/2011 for the course BIOAP 4580 taught by Professor Beyenbach,k. during the Spring '11 term at Cornell.
- Spring '11