Physiology - Regulation of Blood Pressure and Blood Volume PDF

Donal S. O'Leary, Ph.D. Cardiovascular Physiology REGULATION OF BLOOD PRESSURE AND BLOOD VOLUME Learning Objectives: 1. Describe a feedback control system 2. Discuss the factors affecting baroreceptor nerve activity 3. Discuss the compensatory responses to hemorrhage. 4. Disc...

Donal S. O'Leary, Ph.D. Cardiovascular Physiology REGULATION OF BLOOD PRESSURE AND BLOOD VOLUME Learning Objectives: 1. Describe a feedback control system 2. Discuss the factors affecting baroreceptor nerve activity 3. Discuss the compensatory responses to hemorrhage. 4. Discuss the "vicious cycle" 5. Describe long term control of blood pressure 6. Describe orthostasis Lecture Outline: 1. Negative feedback control systems 2. Arterial baroreceptors 3. Compensatory responses to hemorrhage a. Short term responses b. Long term responses 4. Ventricular C fibers and the vicious cycle of hemorrhagic shock. 5. Long term control of blood pressure 6. Orthostasis SYSTEMS CONTROL: The control of arterial pressure can be viewed like any other feedback control system (i.e. temperature regulation system, cruise control, etc.). Every control system contains three major elements Sensor, Integrator and Effector: SENSOR(S) - Some mechanism to detect the level of the parameter being controlled. This information is relayed to the: INTEGRATOR(S) - the area which analyzes the information relayed from the sensor and then decides if adjustments are necessary. The integrator attempts to regulate the level of the variable under control by controlling the activity of the: EFFECTOR(S) - able to affect the variable under control. 1 Donal S. O'Leary, Ph.D. Cardiovascular Physiology The major control system regulating arterial blood pressure on a moment-to-moment basis is the Baroreflex. The sensors for the baroreflex are basically stretch receptors and can be divided into two classes Arterial Baroreceptors - located in the walls of the carotid sinus and aortic arch. Cardiopulmonary baroreceptors - located in the atria, ventricles, and pulmonary vessels. Baroreceptors are basically stretch receptors. As blood pressure increases, the baroreceptors are stimulated. Each baroreceptor displays three characteristics. THRESHOLD As blood pressure increases from very low levels, baroreceptors remain silent until the threshold is reached. MAXIMAL SENSITIVITY A range of blood pressures above threshold wherein the receptors are highly responsive to changes in pressure. The slope of the relationship between baroreceptor nerve activity is high. SATURATION As blood pressure rises, baroreceptor nerve activity ceases to increase further. Other factors affecting baroreceptor nerve activity include pulse pressure and the rate of rise in pressure. Different individual baroreceptor afferents have different thresholds, sensitivities (slopes) and different points of saturation. The relationship between baroreceptor whole nerve activity and arterial blood pressure is sigmoidal. As pressure increases from low levels, the threshold for more and more afferents is surpassed and whole nerve activity increases. In the midrange of pressure around the normal level the slope of the whole nerve activity is the highest. In this area the baroreceptors 2 Donal S. O'Leary, Ph.D. Cardiovascular Physiology are able to relay information regarding small changes in blood pressure and is termed the area of maximal sensitivity. As pressure increases, the slope decreases as more and more afferents reach saturation. The carotid sinus baroreceptor afferents travel in the glossopharyngeal nerve to the CNS. Baroreceptors in the aortic arch and the cardiopulmonary baroreceptors travel in the vagus nerve to the CNS. The integrator is generally termed the Vasomotor Center located in the medulla. Here the information from the various afferents is integrated. The vasomotor center controls the activity of the effectors - autonomic nervous system in order to maintain arterial pressure at the desired level (setpoint). At normal levels of arterial pressure, there is tonic activity of the arterial baroreceptors, tonic activity of the parasympathetic and sympathetic nerves. When pressure falls, baroreceptor afferent activity decreases causing a reflex inhibition of parasympathetic activity and excitation of sympathetic activity to the heart and vasculature. When pressure rises above normal, baroreceptor afferent nerve activity rises causing a reflex increase in parasympathetic activity and inhibition of sympathetic activity. The magnitude of the changes in afferent activity and resultant change in autonomic activity is dependent of the extent of change in arterial pressure. 3 Donal S. O'Leary, Ph.D. Cardiovascular Physiology Hemorrhage Rapid blood loss causes a decrease in venous return to the heart therefore decreases cardiac preload. A decrease in preload will decrease stroke volume. A decrease in stroke volume will decrease cardiac output (remember CO = SV x HR). A decrease in CO will decrease mean arterial pressure (remember MAP = CO x TPR). A decrease in MAP will decrease baroreceptor nerve activity. With a decrease in baroreceptor nerve activity the extent of inhibition to the vasomotor center will decrease and thus parasympathetic activity will decreases and sympathetic activity will increases. Combined these will increases heart rate and inotropic state which will tend to increases cardiac output back towards normal levels. However, the most important component in the responses is the increase in sympathetic activity to the peripheral blood vessels increasing total peripheral resistance. The vasoconstriction and venoconstriction will act to decrease venous volume through passive and active changes in venous compliance, respectively. Decreases in peripheral venous volume will force blood centrally increasing cardiac preload. 4 Donal S. O'Leary, Ph.D. Cardiovascular Physiology Hormonal and long-term responses to hemorrhage. Increases in sympathetic activity to the kidney will increases release of renin with the subsequent formation of angiotensin II. AII is a potent vasoconstrictor and also stimulates release of aldosterone which acts on the kidney to increases Na+ and H2O retention which will increase blood volume and thus cardiac preload and cardiac output. Decreasing inhibition to the vasomotor center will also induce the release of vasopressin. Vasopressin also is a potent vasoconstrictor. Vasopressin also acts on the kidney to reduce H2O loss in the urine thus also increasing blood volume. The vasoconstriction will decrease pressure in the capillaries thus favoring reabsorption of fluid from the interstitium also increasing blood volume. The time course of the responses varies. Renin and vasopressin are released fairly quickly (minutes) and their actions on blood vessels occur rapidly after release. However, the effects on the kidney take longer to have significant impacts on blood volume (hours). The fluid reabsorption from the interstitium is also a long-term response. 5 Donal S. O'Leary, Ph.D. Cardiovascular Physiology CAROTID AND AORTIC CHEMORECEPTORS: Highly vascularized carotid and aortic bodies (located near the carotid sinuses and aortic arch, respectively) contain afferents which respond to changes in blood pO2 and pCO2. With decreases in pO2, changes in vascular resistance do not occur until large decreases in pO2 occur, however, note that large changes in resistance do occur with small changes in pCO2. CENTRAL CHEMORECEPTORS: During severe hemorrhage, if O2 delivery to the brain becomes markedly compromised, then a marked increase in sympathetic activity occurs - cerebral ischemic pressor responses – also known as the Cushing Reflex. Severe vasoconstriction will occur shunting blood towards the brain. Once perfusion pressure is reduced below a threshold level, very large increases in systemic arterial pressure occur with further reductions in brain perfusion. This reflex is thought to be responsible for the hypertension often seen in patients with head injuries. The swelling inside the skull increases pressure within the brain thereby reducing the effective perfusion pressure to the brain. The reflex increases in systemic pressure occurs in order to overcome the reduced perfusion pressure to the brain. 6 Donal S. O'Leary, Ph.D. Cardiovascular Physiology CARDIOPULMONARY BARORECEPTORS: Atrial and venous receptors: In general these cardiopulmonary baroreceptors act in the same fashion as arterial baroreceptors, except that they are much more sensitive to small changes in pressure - as is appropriate for their location. Thus, during hemorrhage reductions in atrial and central venous pressure would reinforce the enhanced sympathetic drive generated by the arterial baroreflex. In addition, located in the atrial walls are cells which contain Atrial Natriuretic Peptide (ANP). Within the walls of the ventricles are cells which store and release Brain Natriuretic Peptide (BNP, so termed because first discovered in the brain). With stretch of the atrial and ventricular walls ANP and BNP are released. The physiological role of these are unclear, however infusion into an animal results is loss of Na+ and H2O in the urine. Thus, these may act to maintain blood volume. With an increased blood volume, central venous and atrial and ventricular pressures, this in turn stretches the atria and ventricles which releases ANP and BNP which in turn acts on the kidney to increase Na+ and H2O in the urine thus decreasing blood volume. During hemorrhage, ANP and BNP release would be lessened and thus help maintain blood volume. Ventricular receptors: Response pattern is in general similar to that of arterial baroreceptors and they tend to reinforce the arterial baroreflex. However, in severe circumstances they may induce a "vicious cycle". VICIOUS CYCLE OF HEMMORHAGIC SHOCK: With severe blood loss, often blood pressure will initially recover only to fall drastically and often lead to death. What occurs during this time is not well understood. Factors thought to be important in this responses include cardiac failure, acidosis, inadequate cerebral blood flow, aberrations of blood clotting, depression of the gut - blood barrier and the reticuloendothelial system. During severe hemorrhage, high circulating catecholamines (especially epinephrine) and high sympathetic activity to the left ventricle combined with very low preload activates ventricular receptors (C fibers) whose afferents travel in the vagus nerve (vagal afferents). Activation of these afferents causes bradycardia and peripheral vasodilation due to activation of the parasympathetic nervous system and inhibition of the sympathetic nervous system. These afferents may also be activated during cardiac ischemia (myocardial infarction). These changes in autonomic outflow can also occur during severe reductions in cerebral perfusion. Acidosis often occurs during severe hemorrhage due to the anoxia and subsequent increased production of lactic acid. Acidosis depresses cardiac function and decreases the reactivity of resistance vessels to norepinephrine released from the sympathetic nerves. Depression of the 7 Donal S. O'Leary, Ph.D. Cardiovascular Physiology gut - brain barrier and the reticuloendothelial system leads to invasion of the circulation by bacteria normally present in the intestinal flora leading to accumulation of endotoxins which may further depress cardiac function and circulatory homeostasis. LONG TERM CONTROL OF BLOOD PRESSURE The mechanisms mediating long term control of blood pressure remain unclear. One hypothesis is that long term regulation of blood pressure occurs via changes in blood volume (via changes in the rate of urine formation) induced by changes in blood pressure. With an increase in arterial pressure, baroreflex reductions in total peripheral resistance (TPR) and cardiac output (CO) occur (short term responses). Over time, the increase in arterial pressure increases glomerular filtration rate and thus urine formation (pressure diuresis). The increased urine flow decreases blood volume which helps restore blood pressure back to normal levels. Pressure Diuresis  Arterial pressure (disturbance) SHORT-TERM LONG-TERM Fluid  Urine output rate barorecpetor reflex fluid balance intake rate blood volume  Fluid volume - - + TPR CO + + +  Blood volume Arterial pressure -  Cardiac output kidney + Urine output rate  Arterial pressure (compensation) 8 Donal S. O'Leary, Ph.D. Cardiovascular Physiology ORTHOSTATIC INTOLERANCE Orthostatic intolerance refers to the inability to assume an upright posture without fainting. With many respects the initial responses to upright posture are similar to a modest hemorrhage. Note that simply contracting the muscles of the legs can nearly normalize cardiovascular parameters by "pumping" blood back to the heart. (? how might these responses be different in cardiac transplant patients? hint - no innervation of the heart (both afferent and efferent)). However, with prolonged orthostasis, cardiac afferents (c fibers) may become activated by the abnormal ventricular contraction patterns which occur when contractility is high but preload is low. Activation of these afferents causes reflex bradycardia (via increased parasympathetic tone) and inhibition of peripheral sympathetic vasoconstrictor activity. The result is a decrease in cardiac output and peripheral vasodilation. Arterial pressure falls therefore perfusion to the brain decreases and fainting often results. Orthostatic intolerance can develop after prolonged bed rest and prolonged space flight. In both instances it is believed that blood volume progressively decreases thus making the subjects more susceptible to the large blood volume shifts accompanying upright posture. In addition, highly trained athletes are often more susceptible to orthostatic intolerance. The reasons are not clear but may be associated with the larger hearts and increased number or activation of ventricular afferents. Arterial baroreflex function may also be decreased in these subjects. Orthostatic intolerance is often observed in patients with defects in the control of autonomic function. In this setting peripheral vasoconstriction is markedly less. 9