11. Blood Pressure Regulation Handout

Objectives have been taken from The American Physiological Society Medical Curriculum Objectives Project http//:www.the-aps.org/education/MedPhysObj/medcor.htm In some case, the order of the topics and the objectives have been modify

Objectives: 1. List the anatomical components of the baroreceptor reflex. 2. Explain the sequence of events in the baroreceptor that occur after an acute increase or decrease in arterial blood pressure. Include receptor response, afferent nerve activity, CNS integration, efferent nerve activity to SA node, ventricles, arterioles, venules , and hypothalamus. 3. Contrast the sympathetic and parasympathetic nervous system control of the heart rate, contractility, TPR, and venous capacitance. Predict the cardiovascular consequence of altering sympathetic nerve activity and parasympathetic nerve activity 4. Outline the cardiovascular reflexes initiated by decreases in blood O2 and increases in blood CO2. 5. CNS ischemic response. Explain the importance and sequence of events of the CNS ischemic response and the Cushing reaction. 6. Cardiopulmonary receptors. Explain the sequence of events mediated by cardiopulmonary (volume) receptors that occur after an acute increase or decrease in arterial blood pressure. Include receptor response, afferent nerve activity, CNS integration efferent nerve activity to the heart, kidney, hypothalamus, and vasculature. 7. Describe the release, cardiovascular target organs, and mechanisms of cardiovascular effects for Angiotensin, ANF, EDRF. 8. Kidney in long term regulation of BP. Explain the role of the kidney in the long term regulation of arterial pressure. 9. Contrast the relative contribution of short-and long term mechanisms in blood pressure and blood volume regulation

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CENTRAL REGULATORY RESPONSE OF THE HEART AND THE VASCULATURE Introduction The cardiovascular system is organized to respond to multiple demands simultaneously, and specially to meet crises. Intrinsic mechanism within tissue stabilize tissue flow and capillary pressure within organs. At the same time, extrinsic mechanism operating via nerves and hormones coordinate functional needs of the organism as a whole. For example, fear causes neurally mediated constriction of most vascular beds. Generalized vasoconstriction mobilizes blood from fight-or-flight, while is the heart and striated muscle, intrinsic mechanism can override the vasoconstrictor signals to allow the muscles to do the work of escaping. In time of crisis the vascular function of all organs will be sacrificed to maintain the cerebral blood flow and to permit the animal or person to escape. I.

REGULATORY CENTERS

A.

Vasomotor or vasoconstrictor center - the pressor area-

• • • • • • B. • • C. • • • •

Is the major integrative area for all central nervous system control Regulates cardiac function with both the sympathetic and parasympathetic nervous outflow. Located in the dorsal medulla Stimulation causes: cardioacceleration, vasoconstriction, increased myocardial contractility Generates continuous low level of neural ctivity in the sympathetic fibers which causes vasoconstriction (sympathetic tone) Tonic activity is modulated by a wide variety of inputs from chemoreceptor and baroreceptors throughout the body Vasomotor center –the depressor area-Located in the ventromedial and caudal region of the medulla Caused dilation mediated by the action through vasomotor center and through spinal pathways Hypothalamus Integrative center for various regulatory processes such a s temperature control Stimulation of the anterior hypothalamus causes decreased blood pressure, vasodilation, and bradycardia Stimulation of the posterolateral hypothalamus causes tachycardia and vasocostriction Cutaneous thermal receptors induce vasodilation or vasoconstriction in response to heat and cold respectively

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II.

Blood pressure control system

Overall aim of the system is to keep aortic pressure constant and let the organs regulate their own flow through autoregulation. A.

Blood pressure control is based on negative feedback that requires: • • • • •

B.

A detector (sensor receptor) Afferent neural pathway An integrator or coordinating center An efferent neural pathway and An effector

Integrator or coordinating center •

Pressure information from the peripheral baroreceptors is integrated in the medulla of the brainstem. The first synapse for all afferent signals is in the Nucleus tractus solitarius (NTS)

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• • •

III. 1. 2. 3. 4. 5.

1.

Activity in the NTS activates neurons in the dorsal motor nucleus of the vagus (DMV). That in turn Activates parasympathetic vagal efferent fibers to the heart. Activity in the NTS also activates neurons in the nucleus ambiguous. That also activates vagal efferent fibers to the heart. Activity in the NTS also inhibits neurons in the C1 region of the vasomotor area. The outflow from this area is sympathetic innervation to the peripheral blood vessels, the heart and the adrenal medulla. The short term control mechanism of blood pressure (neural) are: Baroreceptor reflexes Chemoreceptor reflexes CNS ischemic response (reflex) Cushing reaction Atrial and pulmonary artery reflexes (low pressure receptors) Atrial reflex to kidney Bain-bridge reflex

Baroreceptor reflexes

Peripheral baroreceptors (stretch receptors) detect a change in the blood pressure. They send their signals to the medulla which compares the actual pressure to an internal set point. The medulla then sends information over the autonomic nerves to stimulate or inhibit the blood vessels and heart as is required. That in turn returns the blood pressure to the set point.

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A. Sensor: Arterial baroreceptors Location: carotid sinus and arch of aorta Stimulus: stretch of the vessel B. Afferent pathway 1. Stretch receptors in the walls of the carotid sinuses. These receptors are innervated by the Herring’s nerve (branch of the glossopharyngeal. a. Increased blood pressure stretches the walls and increases their frequency of action potentials. A fall in pressure decreases the frequency. b. Are rate-sensitive and respond to pulsatile pressures better than a steady pressure particularly at low mean pressures 2. The aortic arch has similar receptors that are innervated by the aortic nerve, a branch of the vagus. 3. The Aortic baroreceptors stop firing at pressures below 100 mmHg while carotid sinus receptors continue firing all the way down to 50 mmHg. Both saturate at about 200 mmHg Then carotid baroreceptors are more sensitive than aortic

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4. The baroreceptors are sensitive to both mean (MAP) and pulse pressure (PP) The figure to the right shows the nerve discharge along the glossopharyngeal nerve to the medulla. The baroreflex acts primarily to control minute-to-minute blood Pressure (pressure changes). The baroreceptors quickly adapt to long-term changes in pressure.

C. Effectors 1. Heart 2. Blood vessels D. Efferent Pathway 1. Sympathetic nervous system acts to increase pressure by increasing heart rate, contractility and constricting the arteries and veins 2. Parasympathetic nervous system acts to decrease pressure by slowing heart rate. Acetylcholine acts to inhibit cAMP in the heart and lowers contractility. The human ventricle receive very few vagal fibers as a result the parasympathetic causes only a very light decrease in contractility. In order to decrease contractility the CNS can do it only by a decrease sympathetic tone. PS do not have effect on the vasculature. A reduction in MAP or PP causes constriction of both arterioles and venules. Measurements are made while manipulating the MAP and PP. The nerve fires with each rise in the arterial pressure. Also the number of spikes with each pulse increases as the MAP increases. E. Function of baroreceptors in body posture changes. When a person stand up after having been lying down, the arterial pressure in the upper parts of the body tends to drop and sometimes the patient has loss of consciousness. This because of gravity effect that pulls down blood This drop in pressure immediately causes a decrease in baroreceptors activity and an

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then a strong sympathetic activity to vessels and heart to return to normal the blood pressure in the upper part of the body. F. Clamping of both carotid arteries In a dog, the clamping of both common carotid arteries (after cutting the two vagus nerves), causes a drop in sinus pressure, then baroreceptors are inactivated and the VMC increase its activity causing the sympathetic stimulation to the heart and vessels and blood pressure will remain elevated during the time the carotid occlusion is maintained. When the occlusion is release the aortic pressure falls below the normal as overcompensation and then return to normal. G. Blood pressure increases with exercise. With exercise the working muscles increases the blood flow by active hyperemia, the peripheral resistances drop and thus the blood pressure. Baroreceptors detect the drop in BP and initiate a reflex to return pressure back toward the set point pressure but not pass it. In heavy exercise, however, pressure will actually be higher than before the start of the exercise. That is because the CNS actually increases the set point during heavy exercise.

2. Peripheral chemoreceptors (carotid and aortic bodies). This is an important mechanism for maintaining arterial blood pO2, pCO2, and pH within appropriate physiological ranges. Carotid and aortic bodies are stimulated by: 1. Low PO2 (hypoxemia) 2. High PCO2 (hypercapnia) 3. Low pH A. Stimulation of the chemoreceptors directly decreases heart rate and constricts the peripheral blood vessels.

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Generally systemic hypoxia causes a tachycardia due to the increased respiratory activity . The overall effect is to raise the blood pressure. B. Circulatory shock and respiratory failure (conditions that decrease arterial pO2 and pH, and increase PaCO2) dramatically increase chemoreceptor activity leading to enhanced sympathetic outflow to the heart and vessels via activation of the vasomotor center. C. The threshold pO2 for activation is about 80 mmHg (normal arterial pO2 is about 95 mmHg). Any elevation of pCO2 above a normal value of 40 mmHg, or a decrease in pH below 7.4 causes receptor firing. If respiratory activity is not allowed to change during chemoreceptor stimulation (thus removing the influence of lung mechanoreceptors), then chemoreceptor activation causes bradycardia and coronary vasodilation (both via vagal activation) and systemic vasoconstriction (via sympathetic activation). If respiratory activity increases, then sympathetic activity stimulates both the heart and vasculature to increase arterial pressure. 3. Ischemic response of the CNS. A. Is an emergency control system. Cerebral ischemia at the level of the VMC causes the neurons of the VMC strongly become activated, this produces a drastic increase in MAP to maximal possible level (sometimes 250 mmHg). The extreme excitation of the VMC neurons is caused probably by increased local concentration of CO2 as consequence of the low blood flow what elicit a strong and powerful sympathetic stimulation to the vasomotor nervous control areas in the brain. B. The ischemic response of the CNS becomes activated when the MAP falls down 60 mmHg. Reaching the greatest stimulation with MAP of 15 to 20 mmHg. 4. Cushing reaction A. Special type of CNS ischemic response is activated by an increase in intra cranial pressure that can occur from increase in CSF pressure, edema of the brain or an intercranial bleed. The increased pressure collapses the blood vessels within the vault . The ischemia in the CNS causes intense stimulation of both the sympathetic and parasympathetic outflow. Because the sympathetic system has the more profound effect on blood pressure, blood pressure becomes quite high in an attempt to restore the blood flow into the brain. Because theacetylcholine can inhibit norepinephrine’s effect at the SA node the heart rate will tends to decrease. Thus the patient will present with a bradycardia and a hypertension. 5. Cardiopulmonary mechanoreceptors Low pressure receptors (A and B type) are located in the left atrium. A fibers are stimulated by atrial systole while B fibers are stimulated by atrial distention (increase in volume). Atrial stretch activates B fibers which: 1. Increases the heart rate (Bainbridge reflex) through a neural reflex. Atrial stretch also increases the rate by a direct mechanical effect on the SA node. The Bainbridge reflex is about 50% direct and 50% neural effect. The overall effect is to detect buildup of blood behind the heart and move it forward. 2. Decreases sympathetic tone to the kidney causing increased filtration and urine formation. 3. Decreased production of vasopressin (anti-diuretic hormone) to promote fluid loss at the kidney. 4. Atrial stretch directly causes production of atrial naturetic peptide (ANP) by the atrial cells. This causes dilation of blood vessels and loss of sodium and water by the kidney. The overall effect (2-4 above) is to cause reduced blood volume when the atria are distended and to decrease MAP.

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IV.

Long term regulation of arterial blood pressure. –The kidneyA. The kidney is the primary controller of long term arterial blood pressure. Arterial pressure directly determines fluid loss at the kidney and thus the kidney controls blood pressure by a negative feedback system. Salt (and therefore fluid volume) loss at the kidney is highly dependent on blood pressure and relatively independent of salt intake. B. Renin-Angiotensin system While some of the kidney’s control is direct through the effect of arterial pressure on glomerular filtration, the majority is indirect through the Rennin-Angiotensin system. Low blood flow to the kidney causes secretion of Renin. Renin causes the conversion of Angiotensinogen in the blood to Angiotensin I. This is quickly cleaved by ACE in the lungs to the powerful vasoconstrictor Angiotensin II (AII). Besides the action of AII as powerful constrictor of the peripheral vessels it also causes the kidney to retain fluid and thus

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Guyton Hall. Medical Physiology 11 Ed.

increase blood volume. People with essential hypertension have an elevated set point for fluid loss. Those that are salt-sensitive also have a decreased slope in the renal function curve. The baroreceptor reflex will quickly adapt (within 3 days) if the kidney’s set point is raised

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