Blood Pressure Homeostasis: Learning Objectives: Explain how and why blood pressure varies throughout the circulation

n Describe the factors that determine arterial blood pressure Explain how arterial blood pressure is regulated acutely by the baroreflex Explain how the kidneys regulate arterial blood pressure, with reference to the reninangiotensin system Explain how salt intake influences blood pressure Blood Pressures throughout circulation: The heart pumps blood continually into the aorta. The wall of the aorta is compliant it accommodates the blood forced into it from the contracting left ventricle by stretching outwards and because the wall is also highly elastic it readily springs back into place. In this way the elasticity of the aorta allows it to store energy that is then imparted to the blood so forcing it further along the vessel. Pulse pressure is the difference between peak (systolic) and minimum (diastolic) pressures in the arterial circulation. As the arteries are distensible, they buffer the pressure wave from the left ventricle. Thus pulse pressure is a function of stroke volume and arterial distensibility. The arterial pressure alternates between a systolic pressure (peak arterial pressure) level of 120 mm Hg and a diastolic pressure (minimum arterial pressure) level of 80 mm Hg. Mean arterial pressure is the average arterial pressure throughout a cardiac cycle and it is approximately 90mm Hg as the heart spend more time in diastolic.

At any level of the circulatory system blood flow will be the same (i.e. approx 5L/min at rest). As diameter of vessels decreases, the total cross-sectional area increases and velocity of blood flow decreases. There is only one aorta with a cross-sectional area of 5 cm2 but the total cross-sectional area of the millions of capillaries is 2500 cm2. This situation is much like a river that flows rapidly through a narrow gorge but flows slowly through a broad plane. (Circulation time approx. 1 minute.) Blood pressure averages 100 mm Hg in aorta and drops to ~0 mm Hg by the time the blood gets to the right atrium. Greatest drop in pressure occurs in arterioles which regulate blood flow through tissues. This is because as cross-sectional area of vessels increases the pressure decreases (P = Force/Area).There are no large fluctuations in capillaries and veins. Muscular arteries and arterioles are capable of constricting or dilating in response to autonomic and hormonal stimulation. Muscular arteries regulate flow into a region of the body; arterioles regulate flow into a specific tissue.

The arterioles are the last small branches of the arterial system; they act as control conduits through which blood is released into the capillaries. The arteriole has a strong muscular wall that can close the arteriole completely or can, by relaxing, dilate it several fold, thus having the capability of vastly altering blood flow in each tissue bed in response to the need of the tissue.

Measuring Blood Pressure (Auscultatory Method): 1. Cuff applies pressure to antecubital artery 2. When applied pressure exceeds systolic (peak) pressure, the artery is closed off 3. As cuff pressure is released, blood spurts through compressed artery as arterial pressure transiently exceeds applied pressure. This causes the Korotkoff sounds. 4. Cuff pressure continues to fall. As long as applied pressure is greater than diastolic pressure there will be Korotkoff sounds. 5. Cuff pressure drops below diastolic pressure. The artery is now always open, but still compressed. Korotkoff sounds become muffled 6. Applied pressure drops to the point where the artery is practically unaffected. Korotkoff sounds disappear. ***It is important to note that this is just a good estimation of blood pressure but for accurate measure need to sample pressure from a vessel. Sounds are emitted due to turbulence created in blood as it passes through the lumen of blood vessels (or through the heart). Factors that determine Arterial Blood Pressure: 1. BLOOD VOLUME: via increased cardiac output 2. CARDIAC OUTPUT: back to Ohms law, P = F (CO) R. It depends on: a. Stroke Volume: is the volume of blood ejected at each beat of the heart. Stroke volume is directly related to the force of ventricular contraction. Thus, when cardiac

output is increased exclusively through an increase in stroke volume, SP rises more than DP, thus causing an increase in PP. b. Heart Rate: A large increase in heart rate (HR) is associated with a decrease in filling time for the ventricle and a decreased run off time for the arterial circulation. Thus, if cardiac output is raised exclusively through increased HR, DP rises more than SP and PP falls. 3. PERIPHERAL RESISTANCE: Ohms law again. It is the sum of the resistances offered by the rest of the vascular system. When resistance in the circulation downstream from the major arteries increases, this is reflected more in the DP than in the SP, thus DP increases more than SP and PP falls accordingly. 4. VENOUS CAPACITANCE: A reduction in venous capacitance frees up venous blood, increasing venous return boosting cardiac output via the Frank Starling mechanism 5. GRAVITY: Hydrostatic pressure The effect of gravity means that blood pressure in the feet should be approximately 90 mmHg grater than at the heart. This is HYDROSTATIC PRESSURE. The full effect of hydrostatic pressure is not normally exerted because of the VENOUS VALVES. The contraction of the leg muscles expels blood from the microvasculature; combined with the venous valves this system is called the MUSCLE PUMP. Because of the muscle pump, hydrostatic pressure only increases venous pressure by ~20 mm Hg in a walking adult. The central venous pressure (CVP) is the venous pressure measured at the entrance to the right atrium. In health CVP is 0-2 mmHg (i.e. very close to atmospheric pressure). When standing upright CVP remains unchanged although the venous pressure in the brain should fall to -10 mmHg (or 10 mmHg below atmospheric). This is due to the fact that the brain is above RA. In actual fact, because veins have thin, pliable walls, veins above the heart simply collapse so that lumen pressures remain essentially atmospheric. Any increase in venous return will cause an increase in cardiac output via the Frank Starling mechanism (to be covered later). Thus in accordance with Ohms law, an acute increase in venous blood volume (via infusion) or in venous return (due to a selective vasoconstriction) will secondarily increase ABP due to an increase in FLOW. Short Term Control of ABP: Baroreflex: Short term control of ABP relies on the presence of baroreceptors that monitor the degree of stretch (hence pressure) applied to artery walls. Baroreceptors are spray-type nerve endings that lie in the walls of the arteries; they are stimulated when stretched. Locations rich in baroreceptors include the aortic arch and the carotid sinus. Afferents from the aortic baroreceptors run in the vagus nerve (X), while afferents from the carotid sinus run in the glossopharyngeal nerve (IX). Afferent pathways from the carotid sinus and aortic arch pass via cranial n. IX and X. These inputs are integrated within the nucleus solitarius located in the medulla. Output from the CVC is relayed to sympathetic motor neurons via inhibitory inter neurones. The efferent pathways involve thoracic sympathetic nerves that innervate the heart (SA node and muscle) and the smooth muscle of blood vessels. Note, especially that in the normal operating range of arterial pressure, even a slight change in pressure causes a strong change in the baroreflex signal to re-adjust arterial pressure back toward normal. Thus, the baroreceptor feedback mechanism functions most effectively in the pressure range where it is most needed.

After the baroreceptor signals have entered the nucleus solitarius (CVC) of the medulla, secondary signals inhibit the vasoconstrictor centre of the medulla and excite the vagal parasympathetic centre. The net effects are (1) vasodilation of the veins and arterioles throughout the peripheral circulatory system and (2) decreased heart rate and strength of heart contraction. Therefore, excitation of the baroreceptors by high pressure in the arteries reflex causes the arterial pressure to decrease because of both a decrease in peripheral resistance and a decrease in cardiac output. Conversely, low pressure has opposite effects, reflex causing the pressure to rise back toward normal.

CNS ischemic response: when blood flow to the vasomotor centre in the lower brain stem becomes decreased severely enough to cause nutritional deficiencythat is, to cause cerebral ischemiathe vasoconstrictor and cardioaccelerator neurons in the vasomotor centre respond directly to the ischemia and become strongly excited. The CNS ischemic response is one of the most powerful of all the activators of the sympathetic vasoconstrictor system. Chemoreceptor reflex: a drop in arterial PO2 sensed by the carotid and aortic bodies and leads to the activation of the SNS. Long Term control of ABP: Long-term control of arterial blood pressure is achieved by regulation of blood volume. Control of blood volume is carried out by the kidneys. An additional layer of control occurs via the hormonal pathway known as the Renin-Angiotensin System (RAS).

Increasing arterial pressure causes a corresponding rise in renal urinary output (pressure diuresis). It also causes an increase in sodium output (pressure natiuresis). When the body contains too much extracellular fluid, the blood volume and arterial pressure rise. The rising pressure in turn has a direct effect to cause the kidneys to excrete the excess extracellular fluid, thus returning the pressure back toward normal. Long-term ABP is at the balance point between fluid intake and renal output. Thus two factors account for the long-term ABP: 1. Chronic intake of water and salt 2. The left-right shift of the renal function curve Changes in peripheral resistance will only change arterial blood pressure acutely. Long-term arterial blood pressure is SOLELY DETERMINED BY FLUID BALANCE. However, changes in vascular function may impact the renal circulation and thus indirectly alter blood volume (and thus long-term ABP) by shifting the renal function curve.

The overall mechanism by which increased extracellular fluid volume elevates arterial pressure follows the sequential events: (1) increased extracellular fluid volume (2) increases the blood volume, which (3) increases the mean circulatory filling pressure, which (4) increases venous return of blood to the heart, which (5) increases cardiac output, which (6) increases arterial pressure. There are two ways in which an increase in cardiac output can increase the arterial pressure. One of these is the direct effect of increased cardiac output to increase the pressure, and the other is an indirect effect to raise total peripheral vascular resistance through autoregulation of blood flow. When increased blood volume increases the cardiac output, the blood flow increases in all tissues of the body, so that this autoregulation mechanism constricts blood vessels all over the body. This in turn increases the total peripheral resistance. Finally, because arterial pressure is equal to cardiac output times total peripheral resistance, the secondary increase in total peripheral resistance that results from the autoregulation mechanism helps greatly in increasing the arterial pressure.

The Renin-Angiotensin System (RAS):

(from the liver) to form angiotensin I. Angiotensin I has a mild vasoconstrictor properties but not enough to cause significant changes in circulatory function. Ang I is then converted to ang II in the pulmonary circulation by angiotensin converting enzyme (ACE) present in the endothelium of the lung vessels. Angiotensin II is an extremely powerful vasoconstrictor. Angiotensin II has two principal effects that can elevate arterial pressure. The first of these, vasoconstriction in many areas of the body, occurs rapidly. Vasoconstriction occurs intensely in the arterioles and much less so in the veins. Constriction of the arterioles increases the total peripheral resistance, thereby raising the arterial pressure. Also, the mild constriction of the veins promotes increased venous return of blood to the heart, thereby helping the heart pump against the increasing pressure. The second principal means by which angiotensin II increases the arterial pressure is to decrease excretion of both salt and water by the kidneys. This slowly increases the extracellular fluid volume, which then increases the arterial pressure. This long-term effect, acting through the extracellular fluid volume mechanism, is even more powerful than the acute vasoconstrictor mechanism in eventually raising the arterial pressure.

Angiotensin causes the kidneys to retain both salt and water in two major ways: 1. Angiotensin acts directly on the kidneys to cause salt and water retention. 2. Angiotensin causes the adrenal glands to secrete aldosterone, and the aldosterone in turn increases salt and water reabsorption by the kidney tubules. Thus, whenever excess amounts of angiotensin circulate in the blood, the entire long-term renal body fluid mechanism for arterial pressure control automatically becomes set to a higher arterial pressure level than normal. Aldosterone, salt and ADH: Aldosterone (secreted by the adrenal glands) acts on the kidneys to increase Na+ reabsorption. Na+ stimulates thirst centres and causes increased fluid ingestion; it also stimulates release of ADH from the pituitary. ADH strongly stimulates water reabsorption by the kidneys. Remember: Where sodium goes, water follows.

Salt Intake and ABP: Experimental studies have shown that an increase in salt intake is far more likely to elevate the arterial pressure than is an increase in water intake. The reason for this is that pure water is normally excreted by the kidneys almost as rapidly as it is ingested, but salt is not excreted so easily. As salt accumulates in the body, it also indirectly increases the extracellular fluid volume for two basic reasons: 1. When there is excess salt in the extracellular fluid, the osmolality of the fluid increases, and this in turn stimulates the thirst centre in the brain, making the person drink extra amounts of water to return the extracellular salt concentration to normal. This increases the extracellular fluid volume. 2. The increase in osmolality caused by the excess salt in the extracellular fluid also stimulates the hypothalamic-posterior pituitary gland secretory mechanism to secrete increased quantities of antidiuretic hormone. The antidiuretic hormone then causes the kidneys to reabsorb greatly increased quantities of water from the renal tubular fluid, thereby diminishing the excreted volume of urine but increasing the extracellular fluid volume. Thus, for these important reasons, the amount of salt that accumulates in the body is the main determinant of the extracellular fluid volume. Because only small increases in extracellular fluid and blood volume can often increase the arterial pressure greatly, accumulation of even a small amount of extra salt in the body can lead to considerable elevation of arterial pressure. Role of atrial natriuretic hormone (ANH) in the control of blood pressure: Stretching of the wall of the right atrium, as occurs with an increase in ECF volume, causes the release of ANH from atrial cells. ANH acts on the adrenal cortex to inhibit the release of aldosterone, leading to loss of Na+ from the kidney. The Na+ is accompanied by water. This leads to reduction in ECF volume and hence also blood pressure.