Blood Pressure - Blood Pressure Arterial Blood Pressure...

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Unformatted text preview: Blood Pressure Arterial Blood Pressure When the left ventricle ejects blood into the aorta, the aortic pressure rises. The maximal aortic pressure following ejection is termed the systolic pressure (Psystolic). As the left ventricle is relaxing and refilling, the pressure in the aorta falls. The lowest pressure in the aorta, which occurs just before the ventricle ejects blood into the aorta, is termed the diastolic pressure (Pdiastolic). When blood pressure is measured using a sphygmomanometer, the upper value is the systolic pressure and the lower value is the diastolic pressure. Normal systolic pressure is 120 mmHg or less, and normal diastolic pressure is 80 mmHg or less. The difference between the systolic and diastolic pressures is the aortic pulse pressure, which typically ranges between 40 and 50 mmHg. The mean aortic pressure (Pmean) is the average pressure (geometric mean) during the aortic pulse cycle. When arterial pressure is measured using a sphygmomanometer (i.e., blood pressure cuff) on the upper arm, the systolic and diastolic pressures that are measured represent the pressure within the brachial artery, which is slightly different than the pressure found in the aorta or the pressure found in other distributing arteries. As the aortic pressure pulse travels down the aorta and into distributing arteries, there are characteristic changes in the systolic and diastolic pressures, as well as in the mean pressure. The systolic pressure rises and the diastolic pressure falls, therefore the pulse pressure increases, as the pressure pulse travels away from the aorta. This occurs because of reflective waves from vessel branching, and from decreased arterial compliance (increased vessel stiffness) as the pressure pulse travels from the aorta into systemic arteries. There is only a small decline in mean arterial pressure as the pressure pulse travels down distributing arteries due to the relatively low resistance of large distributing arteries. 1 Blood Pressure Arterial Pulse Pressure As the left ventricle ejects blood into the aorta, the aortic pressure increases. The greater the stroke volume, the greater the change in aortic pressure during ejection. The maximal change in aortic pressure during systole (from the time the aortic valve opens until the peak aortic pressure is attained (see Cardiac Cycle) represents the aortic pulse pressure, which is defined as the systolic pressure minus the diastolic pressure. For example, if the systolic pressure is 130 mmHg and the diastolic pressure is 85 mmHg, then the pulse pressure is 45 mmHg. Pulse Pressure = Systolic Pressure Diastolic Pressure The rise in aortic pressure from its diastolic to systolic value is determined by the compliance of the aorta as well as the ventricular stroke volume. In the arterial system, the aorta has the highest compliance, due in part to a relatively greater proportion of elastin fibers versus smooth muscle and collagen. This serves the important function of dampening the pulsatile output of the left ventricle, thereby reducing the pulse pressure (systolic minus diastolic arterial pressure). If the aorta were a rigid tube, the pulse pressure would be very high. Because the aorta is compliant, as blood is ejected into the aorta, the walls of the aorta expand to accommodate the increase in blood volume. As the aorta expands, the increase in pressure is determined by the compliance of the aorta at that particular range of volumes. The more compliant the aorta, the smaller the pressure change during ventricular ejection (i.e., smaller pulse pressure) (see figure). Therefore, aortic compliance is a major determinant, along with stroke volume, of the pulse pressure. 2 Blood Pressure Summary: A highly compliant aorta (i.e., less stiff) has a smaller pulse pressure for a given stroke volume into the aorta. A larger stroke volume (not shown in the figure) produces a larger pulse pressure at any given compliance. Aortic compliance decreases with age due to structural changes, thereby producing age-dependent increases in pulse pressure. For a given stroke volume, compliance determines pulse pressure and not mean aortic pressure. However, because vessels display dynamic compliance, increasing the rate of ventricular ejection (as occurs with increased ventricular inotropy) will increase the pulse pressure compared to the same volume ejected at a lower rate. 3 Blood Pressure Vascular Compliance The ability of a blood vessel wall to expand and contract passively with changes in pressure is an important function of large arteries and veins. This ability of a vessel to distend and increase volume with increasing transmural pressure (inside minus outside pressure) is quantified as vessel compliance (C), which is the change in volume (DV) divided by the change in pressure (DP). The volume-pressure relationship (i.e., compliance) for an artery and vein are depicted in Figure 1. Two important characteristics stand out. First, the slope is not linear because the blood vessel wall is a heterogeneous tissue. Therefore, compliance decreases at higher pressures and volumes (i.e., vessels become "stiffer" at higher pressures and volumes). Second, 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. This makes veins suitable for use as arterial by-pass grafts. There is no single compliance curve for a blood vessel. For example, vascular smooth muscle contraction, which increases vascular tone, reduces vascular compliance (Figure 2); conversely, smooth muscle relaxation increases compliance. This is particularly important in the venous vasculature for the regulation of venous pressure and cardiac preload. Contraction of smooth muscle in arteries reduces their 4 Blood Pressure compliance, thereby decreasing arterial blood volume and increasing arterial blood pressure. Another example of changing compliance is reduced aortic compliance with age or disease (e.g., arteriosclerosis). When this occurs, there is a qualitatively similar downward shift in the compliance curves as shown in Figure 2 for vein. Such compliance changes in the aorta are responsible in large part for the increase in aortic pulse pressure with advanced age or arterial disease. Compliance, as depicted in Figure 1, represents static compliance that is generated by expanding a vessel by a known volume and measuring the change in pressure at steady-state. However, prior to achieving a steady-state pressure, the pressure will actually be initially higher than the steady-state pressure when the volume of fluid is first added. The transient fall in pressure at a constant volume is called stress relaxation and is related to the viscous properties of biological tissues. If the initial pressure increase is used instead of the steady-state pressure when the vessel volume is suddenly increased, the compliance will be lower (i.e., the vessel will appear more stiff). Therefore, the compliance of the vessel is also dependent upon the rate by which the change in volume occurs i.e., there is a dynamic component to compliance. 5 Blood Pressure Mean Arterial Pressure As blood is pumped out of the left ventricle into the arteries, pressure is generated. The mean arterial pressure (MAP) is determined by the cardiac output (CO), systemic vascular resistance (SVR), and central venous pressure (CVP) according to the following relationship, which is based upon the relationship between flow, pressure and resistance: MAP = (CO SVR) + CVP (eq. 1) Because CVP is usually at or near 0 mmHg, this relationship is often simplified to: MAP approx = CO SVR (eq. 2) Therefore, changes in either CO or SVR will affect MAP. If CO and SVR change reciprocally and proportionately, then MAP will not change. For example, if CO doubles and SVR decreases by onehalf, MAP does not change (if CVP = 0). It is important to note that variables found in equation 1 are all interdependent. This means that changing one variable changes all of the others. In practice, MAP is not determined by knowing the CO and SVR, but rather by direct or indirect measurements of arterial pressure. From the aortic pressure trace over time, the shape of the pressure trace yields a mean pressure value (geometric mean) that is less than the arithmetic average of the systolic and diastolic pressures as shown to the right. At normal resting heart rates, MAP can be approximated by the following equation: For example, if systolic pressure is 120 mmHg and diastolic pressure is 80 mmHg, then the mean arterial pressure is approximately 93 mmHg using this calculation. At high heart rates, however, MAP is closer to the arithmetic average of systolic and diastolic pressure (therefore, almost 100 mmHg in this example) because of the change in shape of the arterial pressure pulse (it becomes narrower). To determine mean arterial 6 Blood Pressure pressure with absolute accuracy, analog electronic circuitry or digital techniques are used. In normal clinical practice, however, systolic and diastolic pressures are measured, not MAP. That measurement is only measured when SVR needs to be calculated. To learn what factors alter cardiac output and systemic vascular resistance, and therefore alter arterial pressure, CLICK HERE 7 Blood Pressure Neurohumoral Mechanisms The heart and vasculature are regulated, in part, by neural (autonomic) and humoral (circulating or hormonal) factors. Neural mechanisms primarily involve sympathetic adrenergic and parasympathetic cholinergic branches of the autonomic nervous system. In general, the sympathetic system stimulates the heart and constricts blood vessels resulting in a rise in arterial pressure. The parasympathetic system depresses cardiac function and dilates selected vascular bed. There are several very important humoral mechanisms including circulating catecholamines, the renin-angiotensin system, vasopressin (antidiuretic hormone), atrial natriuretic peptide, and endothelin. Each of these humoral systems directly or indirectly alter cardiac function, vascular function, and arterial pressure. Adrenergic and Cholinergic Receptors in the Heart Adrenergic and Cholinergic Receptors in Cardiac Muscle Sympathetic adrenergic nerves innervate the SA and AV nodes, conduction pathways, and myocytes in the heart. These adrenergic nerves release the neurotransmitter norepinephrine (NE), which binds to specific receptors in the target tissue to produce their physiological responses. Neurotransmitter binding to receptors activates signal transduction pathways that cause the observed changes in cardiac function. Adrenergic receptors (adrenoceptors) are receptors that bind adrenergic agonists such as the sympathetic neurotransmitter NE and the circulating hormone epinephrine (EPI). The most important adrenoceptor in the heart (not including coronary vascular adrenoceptors) is the b1-adrenoceptor. When activated by a b1-agonist such as NE or EPI, heart rate is increased (positive chronotropy), conduction velocity is increased (positive dromotropy), contractility is increased (positive inotropy), and the rate of myocyte relaxation is increased (positive lusitropy). There are also b2-adrenoceptors in the heart and stimulation by b2-agonists has similar cardiac effects as b1-adrenoceptor stimulation. The b2-adrenoceptors become 8 Blood Pressure functionally more important in heart failure because b1-adrenoceptors become down regulated. NE can also bind to a1-adrenoceptors found on myocytes to produce small increases in inotropy. Circulating catecholamines (epinephrine) released by the adrenal medulla also binds to these same alpha and beta adrenoceptors on the heart on myocytes. In addition to sympathetic adrenergic nerves, the heart is innervated by parasympathetic cholinergic nerves derived from the vagus nerves. Acetylcholine (ACh) released by these fibers binds to muscarinic receptors in the cardiac muscle, especially at the SA and AV nodes that have a large amount of vagal innervation. ACh released by vagus nerve binds to M2 muscarinic receptors, a subclass of cholinergic receptors. This produces negative chronotropy and dromotropy in the heart, as well as negative inotropy and lusitropy in the atria (the negative inotropic and lusitropic effects of vagal stimulation are relatively weak in the ventricles). The autonomic nerve terminals also possess adrenergic and cholinergic receptors (prejunctional receptors) that function to regulate the release of NE (not shown in figure). Prejunctional a2-adrenoceptors inhibit NE release, whereas prejunctional b2adrenoceptors facilitate NE release. Prejunctional M2 receptors inhibit NE release, which is one mechanism by which vagal stimulation overrides sympathetic stimulation in the heart. Drugs are available for blocking adrenergic and cholinergic receptors. For example, beta-blockers are used in the treatment of angina, hypertension, arrhythmias, and heart failure. Muscarinic receptor blockers such as atropine are used to treat electrical disturbances (e.g., bradycardia and conduction blocks) associated with excessive vagal stimulation of the heart. Many of these adrenergic and cholinergic blockers are relatively selective for a specific receptor subtype. Adrenergic and Cholinergic Receptors in Blood Vessels Most arteries and veins in the body are innervated by sympathetic adrenergic nerves, which release norepinephrine (NE) as a neurotransmitter. Some blood vessels are innervated by parasympathetic cholinergic or sympathetic cholinergic nerves, both of which release acetylcholine (ACh) as their primary neurotransmitter. Neurotransmitter binding to the adrenergic and cholinergic receptors activates signal transduction pathways that cause the observed changes in vascular function. NE preferentially binds a1-adrenoceptors to cause smooth muscle contraction and vasoconstriction. Similar responses occur when NE binds to postjunctional a2adrenoceptors located on some blood vessels. NE also binds weakly to postjunctional b2-adrenoceptors, which causes vasodilation (this can be observed during alpha 9 Blood Pressure adrenoceptor blockade), although this vasodilator effect of NE is relatively minor and overwhelmed by alpha adrenoceptor-mediated vasoconstriction. Circulating epinephrine (EPI) binds with high affinity to smooth muscle b2-adrenoceptors to cause vasodilation in some organs; however, the effect EPI is very concentration dependent. While EPI has a higher affinity for b2 than postjunctional a1 or a2-adrenoceptors, at high concentrations it does bind to the postjunctional a1 and a2adrenoceptors, which can override the vasodilatory effects of b2-adrenoceptor stimulation and produce vasoconstriction. Some blood vessels in the body are innervated by parasympathetic cholinergic fibers (e.g., coronary vessels). These nerves release ACh, which binds to muscarinic receptors on the smooth muscle and/or endothelium. M2 receptors on the vascular endothelium are coupled to the formation of nitric oxide (NO), which causes vasodilation; however, ACh causes smooth muscle contraction through a smooth muscle M3 receptor when formation of NO is blocked. This latter finding has been used to assess coronary vascular dysfunction in humans in which NO production is diminished in diseased coronary arteries. Some arterial blood vessels, for example in skeletal muscle, are innervated by sympathetic cholinergic nerves that release ACh and cause vasodilation. This may contribute to active hyperemia in skeletal muscle, particularly at the onset of exercise. Drugs are available for blocking vascular adrenergic receptors. Alpha-blockers, for example, are used in treating hypertension. Some of the alpha-blockers are relatively selective for a specific receptor subtype, whereas other as non-selective. 10 Blood Pressure Arterial Baroreceptors Arterial blood pressure is normally regulated within a narrow range, with a mean arterial pressure typically ranging from 85 to 100 mmHg in adults. It is important to tightly control this pressure to ensure adequate blood flow to organs throughout the body. This is accomplished by negative feedback systems incorporating pressure sensors (i.e., baroreceptors) that sense the arterial pressure. The most important arterial baroreceptors are located in the carotid sinus (at the bifurcation of external and internal carotids) and in the aortic arch (Figure 1). These receptors respond to stretching of the arterial wall so that if arterial pressure suddenly rises, the walls of these vessels passively expand, which stimulates the firing these receptors. If arterial blood pressure suddenly falls, decreased stretch of the arterial walls lead to a decrease in receptor firing. The carotid sinus baroreceptors are innervated by the sinus nerve of Hering, which is a branch of the glossopharyngeal nerve (IX cranial nerve). The glossopharyngeal nerve synapses in the nucleus tractus solitarius (NTS) located in the medulla of the brainstem. The aortic arch baroreceptors are innervated by the aortic nerve, which then combines with the vagus nerve (X cranial nerve) traveling to the NTS. The NTS modulates the activity of sympathetic and parasympathetic (vagal) neurons in the medulla, which in turn regulate the autonomic control of the heart and blood vessels. Of these two sites for arterial baroreceptors, the carotid sinus is quantitatively the most important for regulating arterial pressure. The carotid sinus receptors respond to pressures ranging from 60-180 mmHg (Figure 2). Receptors within the aortic arch have a higher threshold pressure and are less sensitive than the carotid sinus receptors. 11 Blood Pressure Maximal carotid sinus sensitivity occurs near the normal mean arterial pressure; therefore, very small changes in arterial pressure around this "set point" dramatically alters receptor firing so that autonomic control can be reset in such a way that the arterial pressure remains very near to the set point. This set point changes during exercise, hypertension, and heart failure. The changing set point explains how arterial pressure can remain elevated during exercise or chronic hypertension. Baroreceptors are sensitive to the rate of pressure change as well as to the steady or mean pressure. Therefore, at a given mean arterial pressure, decreasing the pulse pressure (systolic minus diastolic pressure) decreases the baroreceptor firing rate. This is important during conditions such as hemorrhagic shock in which pulse pressure as well as mean pressure decreases. The combination of reduced mean pressure and reduced pulse pressure reinforces the baroreceptor reflex. How do the baroreceptors respond to a sudden decrease in arterial pressure and how is cardiovascular function altered? A decrease in arterial pressure (mean, pulse or both) results in decreased baroreceptor firing. The "cardiovascular center" within the medulla responds by increasing sympathetic outflow and decreasing parasympathetic (vagal) outflow. Under normal physiological conditions, baroreceptor firing exerts a tonic inhibitory influence on sympathetic outflow from the medulla. Therefore, acute hypotension results in a disinhibition of sympathetic activity within the medulla, so that sympathetic activity increases. These autonomic changes cause vasoconstriction (increased systemic vascular resistance, SVR), tachycardia and positive inotropy. The latter two changes increase cardiac output. The increases in cardiac output and SVR lead to a partial restoration of arterial pressure. It is important to note that baroreceptors adapt to chronic changes in arterial pressure. For example, if arterial pressure suddenly falls when a person stands, the baroreceptor firing rate will decrease; however, after a period of time, the firing returns to near normal levels as the receptors adapt to the lower pressure. Therefore, the long-term regulation of arterial pressure requires activation of other mechanisms (primarily hormonal and renal) to maintain normal blood pressure. 12 Blood Pressure Circulating Catecholamines Circulating catecholamines, epinephrine and norepinephrine, originate from two sources. Epinephrine is released by the adrenal medulla upon activation of preganglionic sympathetic nerves innervating this tissue. This activation occurs during times of stress (e.g., exercise, heart failure, hemorrhage, emotional stress or excitement, pain). Norepinephrine is also released by the adrenal medulla (about 20% of its total catecholamine release is norepinephrine). The primary source of circulating norepinephrine is spillover from sympathetic nerves innervating blood vessels. Normally, most of the norepinephrine released by sympathetic nerves is taken back up by the nerves (some is also taken up by extra-neuronal tissues) where it is metabolized. A small amount of norepinephrine, however, diffuses into the blood and circulates throughout the body. At times of high sympathetic nerve activation, the amount of norepinephrine entering the blood increases dramatically. There is also a specific adrenal medullary disorder (chromaffin cell tumor) that causes very high circulating levels of catecholamine pheochromocytoma. This can lead to a hypertensive crisis. Circulating epinephrine causes: Increased heart rate and inotropy (1-adrenoceptor mediated) Vasoconstriction in most systemic arteries and veins (postjunctional a 1 and a 2 adrenoceptors) Vasodilation in muscle and liver vasculatures at low concentrations (b2-adrenoceptor); vasoconstriction at high concentrations (a1-adrenoceptor mediated) The overall cardiovascular response to low-to-moderate circulating concentrations of epinephrine is increased cardiac output and a redistribution of the cardiac output to muscular and hepatic circulations with only a small change in mean arterial pressure. Although cardiac output is increased, arterial pressure does not change much because the systemic vascular resistance falls due to b2-adrenoceptor activation. At high plasma concentrations, epinephrine increases arterial pressure because of binding to a-adrenoceptors on blood vessels, which offsets the b2adrenoceptor mediated vasodilation. 13 Blood Pressure Circulating norepinephrine causes: Increased heart rate (although only transiently) and increased inotropy (1adrenoceptor mediated) are the direct effects norepinephrine on the heart. Vasoconstriction occurs in most systemic arteries and veins (postjunctional a 1 and a 2 adrenoceptors) The overall cardiovascular response is increased cardiac output and systemic vascular resistance, which results in an elevation in arterial blood pressure. Heart rate, although initially stimulated by norepinephrine, decreases due to activation of baroreceptors and vagal-mediated slowing of the heart rate. Pharmacologic blocking of the actions of circulating catecholamines Because catecholamines act on the heart and blood vessels through alpha and beta adrenoceptors, the cardiovascular actions of catecholamines can be blocked by treatment with alpha-blockers and beta-blockers. Blocking either the alpha or beta adrenoceptor alone alters the response of the catecholamine because the other adrenoceptor will still bind to the catecholamine. For example, if a low dose of epinephrine is administered in the presence of alpha-adrenoceptor blockade, the unopposed b2-adrenoceptor activation will cause a large hypotensive response due to systemic vasodilation despite the cardiac stimulation that occurs due to b1-adrenoceptor activation. 14 Blood Pressure Systemic Circulation Vascular Network The left ventricle ejects blood into the aorta, which then distributes the blood flow throughout the body using a network of blood vessels. These are illustrated in the following figure: The relative sizes and functions of different blood vessels are summarized in the following table: The aorta, besides being the main vessel to distribute blood to the arterial system, dampens the pulsatile pressure that results from the intermittent outflow from the left ventricle. The actual dampening is a function of the aortic compliance. Large arteries branching off the aorta (e.g., carotid, mesenteric, renal arteries) distribute the blood flow to specific organs. These large arteries, although capable of constricting and dilating, serve virtually no role in the regulation of pressure and blood flow under normal physiological conditions. Once the distributing artery reaches the organ to which it 15 Blood Pressure supplies blood, it branches into smaller arteries that distribute blood flow within the organ. These vessels continue to branch and become arterioles. Together, the small arteries and arterioles represent the primary vessels that are involved in the regulation of arterial blood pressure as well as blood flow within the organ. These vessels are highly innervated by autonomic nerves (particularly sympathetic adrenergic), and respond to changes in nerve activity and circulating hormones by constricting or dilating. Therefore, these vessels are referred to as resistance vessels. As arterioles become smaller in diameter, they lose their smooth muscle. Vessels that have no smooth muscle, but are composed of endothelial cells and a basement membrane, are termed capillaries, and represent the smallest vessels within the microcirculation. Capillaries are the primary exchange vessels within the body. Across the capillary endothelium, oxygen, carbon dioxide, water, electrolytes, proteins, metabolic substrates and by-products (e.g., glucose, amino acids, lactic acid), and circulating hormones are exchanged between the plasma and the tissue interstitium surrounding the capillary. When capillaries join together, they form postcapillary venules, which also serve as exchange vessels, particularly for large macromolecules as well as fluid. As postcapillary venules join together and form larger venules, smooth muscle once again appears. These venous vessels, like the resistance vessels, are capable of dilating and constricting, and serve an important function in regulating capillary pressure. Venules form larger veins that serve as the primary capacitance vessels of the body - i.e., the site where most of the blood volume is found and where regional blood volume is regulated. For example, constriction of the veins decreases venous volume and increases venous pressure, which alters cardiac output. The final venous vessels are the inferior and superior vena cava, which carry the blood back to the right atrium of the heart. Distribution of Pressures and Volumes As shown in the figure to the right, the aorta and arteries have the highest pressure. The mean aortic pressure is about 95 mmHg in a normal individual. The mean blood pressure does not fall very much as the blood flows down the aorta and through large distributing arteries. It is not until the small arteries and arterioles that there is a large fall in mean blood pressure. 16 Blood Pressure Approximately 50-70% of the pressure drop along the vasculature occurs within the small arteries and arterioles. By the time blood reaches the capillaries the mean pressure may be 25-30 mmHg, depending upon the organ. The pressure falls further as blood travels into the veins and back to the heart. Pressure within the thoracic vena cava near the right atrium is very close to zero, and fluctuates from a few mmHg negative to positive with respiration. Regarding the distribution of blood volume within the circulation, the greatest volume resides in the venous vasculature, where 70-80% of the blood volume is found. For this reason, veins are referred to as capacitance vessels. The relative volume of blood between the arterial and venous sides of the circulation can vary considerably depending upon total blood volume, intravascular pressures, and vascular compliance. 17 Blood Pressure Central Venous Pressure Venous pressure is a term that represents the average blood pressure within the venous compartment. The term "central venous pressure" (CVP) describes the pressure in the thoracic vena cava near the right atrium (therefore CVP and right atrial pressure are essentially the same). CVP is an important concept in clinical cardiology because it is a major determinant of the filling pressure and therefore the preload of the right ventricle, which regulates stroke volume through the Frank-Starling mechanism. A change in CVP (DCVP) is determined by the change in volume (DV) of blood within the thoracic veins divided by the compliance (Cv) of the these veins according to the following equation: DCVP = DV / Cv Therefore, CVP is increased by either an increase in venous blood volume or by a decrease in venous compliance. The latter change can be caused by contraction of the smooth muscle within the veins, which increases the venous vascular tone and decreases compliance. The effects of increased venous blood volume and decreased venous compliance on CVP are illustrated in the figure to the right. In this figure, point A represents a control operating point for the venous vasculature. The curve that point A is on is the compliance curve for the thoracic veins. If the volume of blood within these veins is increased, then the operating point will shift up and to the right (from A to B) along the same compliance curve. This will lead to an increase in pressure that is determined by the change in volume and the venous compliance (slope of the curve). CVP will also be increased if venous smooth muscle contraction is enhanced (e.g., by sympathetic nerve stimulation). When this occurs, the venous compliance decreases (dashed red line), and the new operating point C will reflect a smaller venous volume but at a greater venous pressure. It is important to note for a proper conceptual understanding that the compliance of the large thoracic veins (especially the vena cava) does not undergo large changes. Instead, the major site for venous compliance changes is smaller veins located outside of the thorax. These smaller veins are can undergo significant compliance changes. When the compliance of these veins decreases (e.g., by sympathetic nerve stimulation), constriction of these veins and the resulting increased pressure is transmitted up to the thoracic veins, which increases their volume and therefore pressure. 18 Blood Pressure In the body, venous compliance and venous volume are not static, but dynamic, with many factors influences these two variables, such as cardiac output, respiratory activity, contraction of skeletal muscles (particularly legs and abdomen), sympathetic vasoconstrictor tone, and hydrostatic forces (i.e., gravity). Venodilator drugs, which are often used in the treatment of acute heart failure and angina, relax venous vessels (increase their compliance) and thereby lower central venous pressure. All of the above factors influence central venous pressure by either changing thoracic venous blood volume or venous compliance. These factors or mechanisms are summarized in the following table: Factors Increasing Central Venous Pressure Primarily a change in compliance (C) or vol (V) Decreased cardiac output Increased blood volume Venous constriction Changing from standing to supine body posture Arterial dilation Forced expiration (e.g., Valsalva) Muscle contraction (abdominal and limb) V V C V V C V, C A decrease in cardiac output either due to decreased heart rate or loss of inotropy (e.g., in ventricular failure) results in blood backing up into the venous circulation (increased venous volume) as less blood is pumped into the arterial circulation. The resultant increase in thoracic blood volume increases CVP. An increase in total blood volume as occurs in renal failure or with activation of the renin-angiotensin-aldosterone system increases venous pressure. Venous constriction caused by sympathetic activation of veins, or by circulating vasoconstrictor substances (e.g., catecholamines, angiotensin II) decreases venous compliance, which increases CVP. A shift in blood volume into the thoracic venous compartment that occurs when a person changes from standing to supine position increases CVP. Arterial dilation as occurs during withdrawal of sympathetic tone or with arterial vasodilator drugs causes increased blood flow from the arterial into the venous compartments. This increases venous blood volume and CVP. This is what occurs when the heart is functioning normally. It is important to note, however, that arterial dilation in ventricular failure leads to a decrease in CVP instead of an increase. This occurs because the arterial dilation decreases afterload on the ventricle leading to an increase in stroke volume. Ventricular stroke volume is more strongly influenced by afterload when the ventricular is in failure than when it has normal function. CVP is also increased during a force expiration, particularly against a high resistance (as occurs with a Valsalva maneuver) due to external compression of the thoracic vena cava as intrapleural pressure rises. Muscle contraction, particularly of the limbs and abdomen, compresses the veins (i.e., decreases compliance) and also forces blood into the thoracic compartment. 19 Blood Pressure Systemic Vascular Resistance Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. This is sometimes referred as total peripheral resistance (TPR). SVR is therefore determined by factors that influence vascular resistance in individual vascular beds. Mechanisms that cause vasoconstriction increase SVR, and those mechanisms that cause vasodilation decrease SVR. Although SVR is primarily determined by changes in blood vessel diameters, changes in blood viscosity also affect SVR. SVR can be calculated if cardiac output (CO), mean arterial pressure (MAP), and central venous pressure (CVP) are known. SVR = (MAP - CVP) CO Because CVP is normally near 0 mmHg, the calculation is sometimes simplified to: SVR = MAP CO It is very important to note that SVR can be calculated from MAP and CO, but it is not determined by either of these variables. A more accurate way to view this relationship is that at a given CO, if the MAP is very high, it is because SVR is high. Mathematically, SVR is the dependent variable in the above equations; however, physiologically, SVR and CO are normally the independent variables and MAP is the dependent variable (see Mean Arterial Pressure). 20 Blood Pressure Factors Regulating Arterial Blood Pressure Mean arterial pressure is regulated by changes in cardiac output and systemic vascular resistance. The following scheme summarizes the factors that regulate cardiac output and systemic vascular resistance. Cardiac output is determined by the product of stroke volume and heart rate. Stroke volume is determined by inotropy and ventricular preload. (The effects of afterload on stroke volume are not shown in this figure.) Ventricular preload is altered by changes in venous compliance and blood volume. A decrease in venous compliance, as occurs when the veins constrict, increases ventricular preload by increasing central venous pressure. Total blood volume is regulated by renal function, particularly renal handling of sodium and water. Blood volume shifts within the body (not shown in figure) as occurs when changing body posture, also change central venous pressure and preload. Heart rate, inotropy, venous compliance, and renal function are all strongly influenced by neurohumoral mechanisms. Systemic vascular resistance is determined by the anatomy of the vascular network (series versus parallel resistance elements). Generally, vascular structure remains relatively unchanged; however, pathological conditions (e.g., vascular thrombosis) can affect the number of perfused blood vessels. Furthermore, changes can occur in the relative number of parallel and series resistance elements. In hypertension, there is evidence that rarefaction occurs - that is, a decrease in the anatomical number arterioles and capillaries. 21 Blood Pressure The most important mechanism for changing systemic vascular resistance involves changes in vessel lumen diameter. The Poiseuille relationship shows that resistance is inversely related to the fourth power of the vessel radius. In chronic hypertension, vessel radius is often reduced due to a thickening of the vessel wall - this leads to a reduction in lumen size. Vascular factors such as nitric oxide, endothelin, and prostacyclin have important influences on vessel diameter. Furthermore, myogenic mechanisms intrinsic to the vascular smooth muscle also can alter vessel diameter. Tissue factors (e.g., adenosine, potassium ion, hydrogen ion, histamine) are chemicals released by parenchymal cells surrounding blood vessels and can significantly alter vessel diameter. In general, tissue factors are more concerned with regulating organ blood flow than systemic arterial pressure; however, any change in vessel tone will affect both organ blood flow and systemic arterial pressure. Finally, neurohumoral mechanisms play a very important role in regulating systemic vascular resistance and arterial pressure, particularly in certain forms of secondary hypertension. Neurohumoral mechanisms are regulated principally by arterial baroreceptors and to a lesser extent by chemoreceptors. Many of the therapies used for reducing arterial pressure involve inhibiting the action of neurohumoral mechanisms. 22 Blood Pressure Blood Volume Blood volume is determined by the amount of water and sodium ingested, excreted by the kidneys into the urine, and lost through the gastrointestinal tract, lungs and skin. The amounts of water and sodium ingested and lost are highly variable. To maintain blood volume within a normal range, the kidneys regulate the amount of water and sodium lost into the urine. For example, if excessive water and sodium are ingested, the kidneys normally respond by excreting more water and sodium into the urine. The details of how the kidneys handle water and sodium are beyond the scope of this cardiovascular web site; therefore, the reader is encouraged to consult general medical physiology textbooks to learn more about this topic. The following paragraphs briefly describe how renal excretion of water and sodium are regulated and how blood volume affects cardiovascular function. Regulation of Blood Volume by Renal Excretion of Water and Sodium The primary mechanism by which the kidneys regulate blood volume is by adjusting the excretion of water and sodium into the urine. There are several mechanisms by which this regulation occurs. For example, increased blood volume increases arterial pressure, renal perfusion, and glomerular filtration rate. This leads to an increase in renal excretion of water and sodium that is termed pressure natriuresis. In certain types of renal disease, the pressure natriuresis relationship is altered so that the kidneys retain more sodium and water at a given pressure, thereby increasing blood volume. Activation of the renin-angiotensin-aldosterone system causes increased sodium retention which also leads to reduced water loss into the urine. Both angiotensin and aldosterone, although by different mechanisms, stimulate distal tubular sodium reabsorption and decreases sodium and water loss by the kidney. Activation of the renin-angiotensin-aldosterone system occurs in renal artery stenosis, which is one cause of secondary hypertension. Drugs that block the formation of angiotensin II (i.e., angiotensin converting enzyme inhibitors), or block aldosterone receptors (e.g., spironolactone) enhance sodium and water loss, and thereby reduce blood volume. Therefore, any mechanism or drug that alters the activity of the reninangiotensin-aldosterone system will affect blood volume. Another important hormone in regulating water balance is vasopressin (antidiuretic hormone; ADH). This hormone is released by the posterior pituitary. One of its actions is to stimulate water reabsorption in the collecting duct of the kidney, thereby decreasing water loss and increasing blood volume. How Blood Volume Affects Blood Pressure Changes in blood volume affect arterial pressure by changing cardiac output. An increase in blood volume increases central venous pressure. This increases right atrial pressure, right ventricular end-diastolic pressure and volume. This increase in ventricular preload increases ventricular stroke volume by the Frank-Starling mechanism. An increase in right ventricular stroke volume increases pulmonary venous blood flow to the left ventricular, thereby increasing left ventricular preload and stroke volume. An increase in stroke volume then increases cardiac output and arterial blood pressure. 23 ...
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This note was uploaded on 04/18/2008 for the course PHYS 1010 taught by Professor Thompson during the Fall '07 term at New York Medical College.

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