Week 6_ Cardiovascular_20210504.pdf

Cardiovascular Physiology-P3 Copyright Notice • All materials found on Geisinger Commonwealth School of Medicine’s course and project sites may be subjecttocopyright protection,andmayberestricted from further dissemination, retention orcopying. • Disclosure • I have no financial relationship with...

Cardiovascular Physiology-P3 Copyright Notice • All materials found on Geisinger Commonwealth School of Medicine’s course and project sites may be subjecttocopyright protection,andmayberestricted from further dissemination, retention orcopying. • Disclosure • I have no financial relationship with a commercial entity producing health-care related products and/orservices. • Class material and recording will be posted every Monday by 9.00 AM. House Keeping • Office hours are Tuesdays 8-9 PM. I will be meeting you individually by appointment to answer any questions you may have • I will be holding live case study sessions on Tuesdays and Thursdays 78 PM. Attendance is not mandatory, but highly recommended. These sessions will be recorded. Learning Objectives 1. Explain types and characteristics of blood vessels 2. Explain the relationship between pressure, flow, compliance and resistance in the vasculature. 3. Apply Poiseuille’s Law influences to determine how changes in viscosity, resistance, cross-sectional area affect blood flow. 4. Predict the effects of changes in a) stroke volume, b) heart rate, c) arterial compliance, and d) total peripheral resistance on mean arterial pressure and pulse pressure. 5. Explain the concept of autoregulation of blood flow in the microcirculation. 6. Explain adjustments that occur to cardiac functions during exercise, and hemorrhage READINGS: 1. Text Book: Chapter 4; Pages 119-131, 163-187. 2. Class Notes REVIEW Types and Characteristics of Blood Vessels • The aorta has a small area and holds a very small blood volume, yet all systemic blood flows through this vessel. As it bifurcates into arteries to the various organs, the relative area and blood volume increase. • The arterioles represent the largest cross-sectional area on the arteriole side of the circulation but hold only a very small volume of blood. The arterioles are considered the resistance vessels of the system (TPR) because they have the greatest ability to alter their diameter (tonically active). Arterioles have the thickest layer of vascular muscle and are extensively innervated by sympathetic adrenergic nerve fibers. • The capillaries, albeit smallest in diameter, represent the largest cross-sectional area of any portion of the vascular system, with a moderate blood volume. • The veins represent the next largest cross-sectional area coupled with the largest volume of blood. Veins are considered to be capacitance vessels, recognizing their blood storing capacity. Blood contained in the veins is called unstressed blood (blood is under low pressure). Hemodynamics • The relationship between blood pressure, blood flow and resistance is referred to as hemodynamics. • The velocity of blood flow is the rate of displacement of blood per unit time. • Vessels within the cardiovascular system vary in terms of diameter and cross-sectional area, leading to considerable effects on velocity of flow. • The relationship between velocity, flow and cross- sectional area is as follows: v = Q/A where: v = Velocity of blood flow (cm/sec) Q = Flow (ml/sec) A = Cross-sectional area (cm2) Velocity is the linear velocity and refers to the rate of blood displacement per unit time. Flow (Q) is the volume flow per unit time. Area (A) is the cross-sectional area of the blood vessel. Velocity of Blood Flow • Flow at any point along the continuum of the cardiovascular system is the sum of all vessels at that level. • This means that the smallest vessel represents the aorta, the mediumsized vessel represents all of the arteries, and the largest vessel represents all of the capillaries. • The total blood flow at each level within the vascular tree is the same and equal to the cardiac output. • Applying the inverse relationship between velocity and total cross-sectional area, the velocity of blood flow will be highest in the aorta and lowest in the capillaries. • From the standpoint of capillary function (i.e., exchange of nutrients, solutes, and water), the low velocity of blood flow is advantageous, as it maximizes the time for exchange across the capillary walls. Relationship Between Blood Flow, Pressure and Resistance - Blood flow through a vessel or a series of vessels is determined by 2 factors: (1) the hydrostatic pressure difference between the ends of the vessel (the driving force for blood to move from one point to another) (2) the resistance of the vessel as an impediment to flow. - The relationship between flow, pressure and resistance is analogous to the relationship of current (I), voltage (∆V) and resistance (R) found in electrical circuits and described by Ohm’s law. - Ohm’s law states that I = ∆V/R Where Blood flow (Q) is analogous to current flow, Pressure gradient (∆P) is analogous to the voltage difference, Vascular resistance (R) is analogous to electrical resistance. Relationship Between Blood Flow, Pressure and Resistance Q =∆P/R Where Q = Flow (ml/min) ∆P = Pressure difference at both ends of the blood vessel (mm Hg) R = blood vessel Resistance (mm Hg/ml/min) • The magnitude of blood flow (Q) is directly proportional to the size of the pressure difference or pressure gradient across the length of the blood vessel. • The direction of flow is determined by the direction of the pressure gradient; always from high to low (flow is always down the pressure gradient). • The magnitude of blood flow is inversely proportional to resistance; increasing resistance (vasoconstriction) decreases flow and the opposite is true. • The resistance of the entire systemic vasculature is called the total peripheral resistance (TPR) or the systemic vascular resistance (SVR). • The major mechanism for changing blood flow within the cardiovascular system is by changing the resistance (diameter) of blood vessels, particularly the arterioles. Resistance to Blood Flow (1) • The walls of the blood vessels and the blood itself represent resistance to flow. The relationship between resistance, blood vessel diameter (or radius) and blood viscosity is described by the Poiseuille equation. • The total resistance offered by a set of blood vessels also depends on whether the vessels are arranged in series, or arranged in parallel. Resistance to Blood Flow (2) The most important concepts expressed in the Poiseuille equation are: 1. Resistance to flow is directly proportional to viscosity (η) of the blood. 2. Resistance to flow is directly proportional to the length of the vessel. 3. Resistance to flow is inversely proportional to the fourth power of the radius of the blood vessel. • This is a very powerful relationship, as the radius of the vessel decreases, its resistance increases not in a linear fashion but magnified by the fourth power relationship. • For example, a two-fold increase in radius decreases resistance 16 times. Resistance to Blood Flow (3) - Series resistance is illustrated by the arrangement of blood vessels within a given organ. The total resistance of the system arranged in series is equal to the sum of the individual resistances. Generally the greatest resistance is found within the arterioles. - Parallel resistance is illustrated by the distribution of blood flowing among the various major arteries branching off of the aorta. The cardiac output that flows through the aorta is distributed on a percentage basis among the various organ systems. The total resistance in a parallel arrangement is less than any of the individual resistances. Resistance to Blood Flow (4) - The effect of parallel arrangement is that there is no loss of pressure in the major arteries and that mean pressure in each major artery will be approximately the same as mean pressure in the aorta. - In a parallel arrangement, adding a resistance to the circuit causes total resistance to decrease. - Conversely, if resistance is increased in any of the circuits, total resistance will increase. Laminar Flow and Reynolds Number Blood flow within the cardiovascular system is laminar or streamlined. In laminar flow there is a parabolic profile of velocity within the vessel. Velocity is slowest next to the vessel wall and fastest in the center of the lumen. Laminar flow is effective and efficient. When an irregularity in a blood vessel disrupts this laminar flow (like a valve or a blood clot), a turbulent flow will result → blood will move radially and axially → much more energy is required to move blood flowing in a turbulent pattern compared to a laminar flow. • Turbulent flow is audible: o Korotkoff sounds (heard during auscultatory measurement of blood pressure) o murmurs (heard over the heart in case of cardiac valve disease) • Conditions that cause turbulent blood flow: 1. 2. Anemia; red cells are reduced → blood viscosity is reduced, and increases CO → ↑ blood velocity → turbulent flow Blood vessel thrombi; thrombi cause vessel narrowing at site of thrombus and cause blood to be turbulent. Compliance • The compliance or capacitance of a blood vessel is equal to the amount of blood the vessel can hold at a given pressure. • Compliance is a measure of how easily a vessel wall will stretch or how much blood a vessel will hold at a given pressure (capacitance). • Compliance is related to distensibility of blood vessels. • The curve describes how a unit change in pressure of a vessel affects volume of blood contained in that vessel (ΔV/ΔP). • The slope of each curve is the compliance: ₋ Compliance is high for the veins → can hold large volumes of blood at low pressure “unstressed volume”. ₋ Compliance of arteries is considerably lower. Arteries hold less blood at a significantly higher pressure “stressed volume”. slope slope slope Compliance • Changes in the compliance of veins will cause a redistribution of blood between unstressed and stressed volumes. For example, venoconstriction will decrease venous compliance and will decrease the amount of blood the veins can hold. This causes a shift of blood from veins to arteries (i.e. a shift from the unstressed volume to the stressed volume) → ↑ VR and ↑ Pms • The characteristics of arterial walls change with increasing age. The walls become stiffer, less distensible and less compliant. ₋ For a less compliant artery, more pressure is required to hold the same amount of blood. Arterial pressures are increased in elderly patients due to decreased arterial compliance. slope Pressure Profile in the Vasculature Blood pressure is not equal throughout the cardiovascular system. Blood flow requires a driving force, a pressure gradient. A pressure differential must exist for blood to flow, therefore hydrostatic pressures change throughout the vascular tree. The smooth curve gives the mean pressure which is highest in the aorta and the large arteries and progressively decreases as blood moves away from the heart. The progressive decrease in pressure is a reflection of energy being used to overcome the resistance due to friction as the blood flows through the vascular tree. The most dramatic pressure drop is present in the arterioles leading into the capillary beds. The further reduction in pressure is in the capillaries and is caused by 1) frictional resistance to flow and 2) filtration of fluid out of the capillaries (Starling forces). Arterial Pressure in Systemic Circulation • Mean pressure within the vascular system is high and constant, yet there are oscillations or pulsations of arterial pressure. • These pulsations are a reflection of the pulsatile activity of the heart. Large arteries have two functions: 1) Form low resistance conduits (large diameter) 2) Act as pressure reservoirs (distribute ventricular pressure) to maintain flow during diastole. • Arteries are strong elastic vessels which carry blood under pressure away from heart. • Arterial pressure is dependent upon: 1) Volume of blood 2) Vascular distensibility of the vessel’s wall or compliance of the vessel Vascular Distensibility = Increase in volume/ (Increase in pressure) x (Original volume) • Vascular Distensibility is expressed as the fractional increase in volume for each mmHg rise in pressure. Arterial Pressure in Systemic Circulation Blood vessels are composed of three distinct layers or tunics. 1) Tunica interna - innermost layer a. Forms inner lining and is in direct contact with blood as it flows through the lamina b. Endothelium – simple squamous epithelium c. Basement membrane d. In arteries: internal elastic lamina 2) Tunica media – muscular and connective tissue layer that displays variation among different vessel types a. Smooth muscle b. In arteries: external elastic lamina 3) Tunica externa – outer covering of blood vessel a. Consists of elastic and collagen fibers b. Anchors vessels to surrounding tissues Arterial Blood Pressure (1) Diastolic pressure is the lowest arterial pressure during the cardiac cycle. This is the pressure within the arteries during ventricular relaxation when no blood is being ejected from the left ventricle. Systolic pressure is the highest arterial pressure measured during the cardiac cycle. This is the pressure in the arteries after the blood has been ejected from the ventricle. The “blip” in the arterial pressure curve is called the dicrotic notch (incisura); a manifestation of the brief retrograde flow of blood caused by the closing of the aortic valve. Arterial Blood Pressure (2) • Pulse Pressure is the difference between systolic and diastolic pressures. • The magnitude of pulse pressure depends on: 1) Stroke Volume 2) Speed of contraction 3) Arterial distensibility • Diastole lasts longer than systole. Thus Mean Arterial Pressure = diastolic pressure + (1/3 P.P.) MAP = (80 + 13) = 93 mmHg. • Changes in the MAP are a measure of changes in flow. Control mechanisms respond to MAP because this is directly related to blood flow through an organ. Arterial Blood Pressure (3) Pathologic conditions that alter the arterial pressure: 1) Arteriosclerosis describes plaque deposition within the arterial walls, decreasing the diameter of the vessel and decreasing compliance (stiffer). A much higher pressure is required to eject blood from the ventricle. Recall C = ∆V/∆P or ∆P = ∆V/C if compliance (C) decreases then ∆P increases. 2) Aortic stenosis is narrowing of the aortic valve. This reduces the size of the opening through which the blood flows → reduction of stroke volume causing less blood to enter the aorta. Pulmonary Circulation Pressure • The pattern of pressure gradient within the pulmonary circulation is similar to the systemic circulation. • The entire pulmonary vasculature is at much lower pressure than the systemic vasculature. • Since the total flow through the systemic and pulmonary circulations are equal (i.e., cardiac output of the left and right sides of the heart are equal), the resistance of pulmonary circulation is lower (Q = ΔP/R) Regulation of Arterial Pressure • The overall function of the cardiovascular system is to deliver blood to the tissues so that O2 and nutrients can be delivered, and waste products carried away. • Blood flow is driven by pressure differences. • The driving force for this flow is the Mean Arterial Pressure (Pa). • Pa must be maintained at a high level, near 100 mm Hg. Pa = CO x TPR Where Pa = Mean Arterial Pressure (mm Hg) CO = Cardiac Output (mL/min) TPR = Total Peripheral Resistance (mm Hg/mL/min) • Changes in cardiac output, total peripheral resistance or both can alter Pa. • Both CO and TPR are not independent variable → oftentimes changes in either CO or TPR can affect the other parameter. Baroreceptor Reflex The baroreceptor reflex includes fast, neural mechanisms. This reflex is a negative feedback system that is responsible for the minute to minute regulation of arterial blood pressure. Baroreceptors are stretch receptors (mechanoreceptors) located within the walls of the carotid sinus, where the common carotid artery bifurcates into the internal and external carotid arteries. Baroreceptors are also located in the aortic arch. Stretch causes these receptors to increase their discharge of action potentials to afferent neurons that synapse in the medulla and the pons of the brainstem. From there, sympathetic discharge is delivered to the SA node, cardiac muscle, arterioles and the veins, while parasympathetic discharge is delivered to the SA node. Renin - Angiotensin II – Aldosterone System The Renin - Angiotensin II - Aldosterone System (RAAS) is a hormonally mediated mechanism. The response time for the RAAS system is much slower than neural pathways in the baroreceptor reflex. RAAS is used for long-term blood pressure regulation through adjusting blood volume. Mechanoreceptors found in the afferent arterioles of the kidneys detect a decrease in Pa. This decreased pressure causes prorenin to be converted to renin in the juxtaglomerular cells. The renin (an enzyme) is released to the plasma. Renin will convert angiotensinogen (produced in the liver) to Angiotensin I in the plasma. Circulating Angiotensin I will encounter membrane bound Angiotensin-Converting Enzyme (ACE), mostly in the lungs and kidneys, which converts Angiotensin I to Angiotensin II. Angiotensin II activates type 1 G-protein coupled angiotensin II receptors (AT1) located in the adrenal cortex, vascular smooth muscle, kidneys and brain. Actions of Angiotensin II ADRENAL CORTEX – Angiotensin II stimulates the zona glomerulosa cells to secrete aldosterone. Aldosterone acts upon the principal cells of the distal renal tubule causing an increase in Na+ reabsorption which increases blood volume. PROXIMAL TUBULE OF NEPHRON – Angiotensin II has a direct effect upon the Na+-H+ exchanger in this area of the nephron causing an increase in reabsorption of Na+ and HCO3-. HYPOTHALAMUS – Angiotensin II causes an increased thirst and water intake. It also stimulates the secretion of antidiuretic hormone (ADH), which increases water reabsorption in the collecting ducts of the nephron. ARTERIOLES – Angiotensin II acts directly on G-protein coupled AT1 receptors on smooth vascular muscle activating an IP3/Ca+ second messenger system that stimulates vasoconstriction. Stimulation results in an increase of TPR. Other Regulatory Mechanisms of Arterial Blood Pressure I) Peripheral Chemoreceptors in the carotid and aortic bodies are located near the bifurcation of the common carotid arteries and along the aortic arch. a. They are very sensitive to changes in partial pressure of oxygen (PO2). b. A decrease in the partial pressure of PO2 activates vasomotor centers that produce vasoconstriction, an increase in TPR and an increase in arterial pressure. II) Vasopressin “antidiuretic hormone (ADH)” is involved in the regulation of blood pressure in response to hemorrhage, but not in the minute to minute regulation of normal blood pressure. a. Atrial receptors respond to a decrease in blood volume (or blood pressure) → release of ADH from the posterior pituitary. b. Vasopressin has 2 effects that tend to restore blood pressure towards normal: 1) It is a potent vasoconstrictor that increases TPR by activating V1 receptors on the arterioles. 2) It increases water reabsorption by the renal distal tubules and collecting ducts via activating V2 receptors. III) Atrial Natriuretic Peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure. a. ANP causes relaxation of vascular smooth muscle fibers → dilation of the arterioles, and decreased TPR. b. ANP causes excretion of Na+ and water by the kidneys → reduces blood volume and attempts to restore arterial pressure down to normal. ANP also inhibits renin secretion. Other Regulatory Mechanisms of Arterial Blood Pressure IV) Cerebral Ischemia: a. When the brain is ischemic, the partial pressure of carbon dioxide (PCO2) in brain tissues increases. b. Central chemoreceptors in the medullary vasomotor center respond by increasing sympathetic outflow to the heart and blood vessels. Constriction of arterioles causes intense peripheral vasoconstriction and increased TPR. Blood flow to other organs (like the kidneys) is significantly reduced in an attempt to preserve blood flow to the brain. Mean Arterial Pressure can increase to life-threatening levels. • The Cushing Reaction is an example of the response to cerebral ischemia. An increase in intracranial pressure causes compression of the cerebral blood vessels, leading to cerebral ischemia and increased PCO2. The vasomotor center directs an increase in sympathetic outflow to the heart and blood vessels, which causes a profound increase in arterial pressure. • Vasovagal syncope or fainting is mediated by the vagus nerve. When emotions inhibit sympathetic activity within the cardiovascular system and create a temporary suspension of circulation or respiration. This can cause a temporary cerebral ischemia. Cardiopulmonary Baroreceptors Cardiopulmonary receptors “low pressure baroreceptors" are located in the veins, atria and pulmonary arteries. They sense changes in blood volume. Responses to an increase in blood volume will lead to: 1. Increased secretion of ANP in response to increased atrial pressure causing ANP to bind to receptors on vascular smooth muscle fibers → relaxation, vasodilatation and ↓ TPR. 2. Decreased secretion of ADH is mediated by pressure receptors in the atria, which project to the hypothalamus. These neurons suppress the secretion of ADH → ↓ water reabsorption in the collecting ducts in the kidneys. 3. Renal vasodilation is promoted by the inhibition of sympathetic output to the renal arterioles. The increased flow → increased Na+ and water excretion → compliments the action of ANP. 4. Increased heart rate is generated from output from the medullary cardiovascular centers (the Bainbridge reflex). Low pressure baroreceptors sense that blood volume is high → command an increase in heart rate and cardiac output → ↑ renal perfusion and ↑ Na+ and water excretion. Microcirculation Microcirculation refers to the function of the capillaries. Blood delivery to these capillaries is critically important because all exchange of materials between the blood and the tissues occurs in the capillaries. Exchange of solutes and gases across the capillary wall occurs by diffusion: 1. Some solutes diffuse through the endothelial cells and some diffuse between the endothelial cells. 2. Gases such as O2 and CO2 are highly lipid soluble and diffuse readily through plasma membranes. 3. Water soluble substances like water itself, ions, glucose and amino acids are not lipid soluble, thus must pass through the aqueous clefts between endothelial cells. a. The surface area for diffusion of water soluble substances is much less than for lipid soluble gases. b. The most important mechanism for fluid transfer across the capillary wall is osmosis, driven by hydrostatic and osmotic forces. These pressures are referred to as Starling pressures or Starling forces. 4. Proteins are generally too large to cross the capillary wall via the endothelial clefts. They are generally retained within the vascular compartment. Starling Equation STARLING EQUATION: Fluid movement across a capillary wall is driven by the Starling forces across the wall and are described as: Fluid movement (JV) = Kf [(PC- Pi ) – (πc – πi )] Where: Jv = fluid movement (ml/min) Kf = hydraulic conductance (ml/min · mm Hg) = water permeability Pc = capillary hydrostatic pressure (mm Hg) πc = capillary oncotic pressure (mm Hg) Pi = interstitial hydrostatic pressure (mm Hg) πi = interstitial oncotic pressure (mm Hg) Starling Forces (1) The magnitude of fluid movement is determined by the hydraulic conductance (water permeability) of the capillary wall, for a given pressure difference. Hydraulic Conductance is the water permeability of the capillary wall. Hydraulic conductance of capillary wall varies among tissues. Capillary injury from toxins or burns can alter hydraulic conductivity. Capillary hydrostatic pressure is a force favoring filtration out of the capillary. The magnitude of Pc is determined by both arterial and venous pressures. In case of heart failure, there is increased blood volume in blood vessels (failure of heart to pump blood efficiently), and capillary hydrostatic pressure increases → more filtration → edema. Interstitial oncotic pressure is a force favoring filtration. There is a small amount of protein in the interstitial fluid, as protein loss through capillaries is minimal. The magnitude of this force is very small. Starling Forces (2) Capillary oncotic pressure is a force opposing filtration. πc is the effective osmotic pressure of the capillary blood due to the presence of plasma proteins. Any change in the concentration of plasma proteins will alter this force. In cases of liver failure (where most proteins are synthesized), or in cases of nephrotic syndrome (featuring significant protein loss in urine); capillary oncotic pressure decreases → more filtration → edema Interstitial hydrostatic pressure is a force opposing filtration. Normally having a value near 0, or slightly negative. Lymphatic System (1) • Under normal circumstances, there will be a net filtration of fluids from the capillaries to the interstitial spaces. This amounts to about 4 L/day. • Lymphatic system is responsible for returning interstitial fluid and large molecules and conglomerates (e.g. proteins and fat) to the systemic circulation. Lymphatic capillaries have larger openings than vascular capillaries. • The lymph system is a passive system (no heart) consisting of capillaries that originate as blind end sacs in the tissues and continue to coalesce into larger vessels that culminate into a large thoracic duct. Thoracic duct empties into the vena cava. Lymphatic System (2) • The fluid flows in a single direction (toward the circulatory system) aided by one-way flap valves within the lymph ducts. Skeletal muscular contractions as well as stretch induced stimulation of smooth muscle within the lymph ducts walls move the lymph fluid through the system. • Lymphatic vessels are innervated by sympathetic system. Sympathetic stimulation will increase return flow. • An increase in interstitial fluid volume is called edema (swelling). Edema forms when the volume of interstitial fluid exceeds the allowed spatial limit. This occurs either due to increased fluid filtration, beyond the ability of the lymphatics to return it to the circulation, or when lymphatic drainage is impaired (as in case of parasitic infection of lymph nodes or removal of lymph nodes in cases of surgical removal of a tumor and its draining lymph nodes) Intrinsic Control of Regional Blood Flow (1) 1) Myogenic autoregulation of blood flow by organs like kidneys, brain, heart and skeletal muscle mediate changes in arterial pressure to maintain constant blood flow. The myogenic hypothesis states that when vascular smooth muscle is stretched, it contracts. Vascular smooth muscle tone is altered by changes in Ca2+ flux into the muscle cell. • For example, if arterial pressure in a coronary artery suddenly decreases, there is less stretch on the arterioles, causing them to relax and arteriolar resistance will decrease → maintaining constant coronary flow. Intrinsic Control of Regional Blood Flow (2) 2) Metabolic autoregulation of blood flow is mediated by vasodilator metabolites generated from metabolic activity. CO2, H+, K+, lactate and adenosine are the most common vasodilator metabolites. • A greater level of metabolic activity will yield increased vasodilation of the arterioles, matching O2 consumption by the tissues to O2 delivery by the cardiovascular system. • Active Hyperemia provides for blood flow that is proportional to metabolic activity. • Reactive hyperemia is increased blood flow in response to a previous decreased blood flow (for example temporary occlusion by mechanical compression). Extrinsic Control of Blood Flow Neural and Hormonal Control: • Sympathetic innervation of vascular smooth muscle varies widely throughout the body. • Sympathetic innervation of blood vessel in the skin and skeletal muscle exhibits high density, whereas coronary, pulmonary and cerebral vessels have little sympathetic innervation. • α1 receptors are abundant in cutaneous circulation yielding a vasoconstriction via sympathetic input. • Histamine is released in response to trauma and has powerful vascular effects. Simultaneously, it causes dilation of arterioles and constriction of venules, with the net effect being a large increase in Pc, which increases filtration out of capillaries, and local edema. • Serotonin is released in response to blood vessel damage and causes local vasoconstriction (in an attempt to reduce blood flow and blood loss). • Angiotensin II and vasopressin are potent vasoconstrictors that increase TPR. Control of Blood Flow in Special Circulations Coronary Circulation • Blood flow through the coronary circulation is controlled almost entirely by local metabolites (active and reactive hyperemia), mainly through hypoxia and adenosine. • Active Hyperemia: With increase in myocardial contractility, there is increased O2 demand by the cardiac muscle and increased O2 consumption, causing local hypoxia → vasodilation of the coronary arterioles → compensatory increase in coronary blood flow and O2 delivery to meet the demands of the cardiac muscle. • Reactive Hyperemia: During systole, the coronary circulation is under mechanical compression, which causes a brief period of occlusion and reduction of blood flow. When systole is over, reactive hyperemia occurs to increase blood flow and O2 delivery and to repay the O2 debt that was incurred during the compression. • Sympathetic innervation to the coronaries plays a minor role. Control of Blood Flow of Special Circulations Cerebral Circulation • The cerebral circulation is controlled almost entirely by local metabolites and exhibits autoregulation and active and reactive hyperemia. • The most important local vasodilator in the cerebral circulation is CO2 (or H+). An increase in cerebral Pco2 → ↑ H+ concentration and ↓ pH) causes vasodilation of the cerebral arterioles, which results in an increase in blood flow to assist in removal of the excess CO2. • Many circulating vasoactive substances do not affect the cerebral circulation because their large molecular size prevents them from crossing the blood-brain barrier. Control of Blood Flow of Special Circulations Skeletal Muscle: • The vascular smooth muscle present in skeletal muscle has both α1 and β2 receptors. Vessels with a greater abundance of α1 receptors will exhibit vasoconstriction and vessels with a greater abundance of β2 receptors will exhibit vasodilation with sympathetic input. • α1 receptors are most responsive (have a higher affinity) to the neurotransmitter norepinephrine. At rest, skeletal muscle circulation is most responsive to sympathetic input. • β2 receptors respond more (have a higher affinity) to epinephrine released from the adrenal medulla during fight or flight response. • During exercise, active hyperemia and activation of β2 receptors account for vasodilation of blood vessels in skeletal muscle. Response to Exercise • The CNS response includes a central command from the cerebral motor cortex, which directs changes in the autonomic nervous system. • This reflex produces increased sympathetic outflow to the heart and blood vessels and decreased parasympathetic outflow to the heart. • Sympathetic stimulation will cause: • Increased CO through: 1. Sympathetic stimulation and the decrease in parasympathetic activity cooperate to produce an ↑ heart rate. 2. Sympathetic stimulation produces an ↑ contractility → ↑ stroke volume. • Increased CO ensures that more O2 and nutrients are delivered to the exercising skeletal muscle. What will happen to VR? WHY? Response to Exercise • Sympathetic stimulation will cause selective vasoconstriction in some vascular beds so that blood flow is redistributed to the exercising skeletal muscle, the heart, and the brain. • Cutaneous circulation features a biphasic response: 1. Initially, vasoconstriction occurs (due to increased sympathetic outflow), but later 2. As body temperature increases, there is selective inhibition of sympathetic cutaneous vasoconstriction, resulting in vasodilation and dissipation of heat through the skin. Local Response in Muscle: • Active hyperemia drives the local response, as the metabolic rate of the skeletal muscle increases → ↑ production of vasodilator metabolites such as lactate, K+, and adenosine. • Vasodilation in the exercising muscle produces an overall decrease in TPR, maintaining constant blood flow. Response to Hemorrhage (1) Hemorrhage Maintain Blood Flow to Tissues Restore Blood Volume Restore Arterial Blood Pressure Response to Hemorrhage (2) Response of Baroreceptor Reflex: • Baroreceptor Reflex leads to increased sympathetic outflow to the heart and blood vessels, and decreased parasympathetic outflow to the heart. • Four major consequences: 1. Increased heart rate 2. Increased contractility 3. Increased TPR (due to arteriolar vasoconstriction except in the coronary and cerebral circulations) 4. Constriction of the veins → ↓ unstressed volume, ↑ VR, ↑ stressed volume. Response of RAAS: • When Pa decreases, renal perfusion pressure decreases, which stimulates RAAS, leading to; 1. Arteriolar vasoconstriction, reinforcing the increase in TPR (by the increased sympathetic outflow to the blood vessels) 2. Stimulation of aldosterone secretion, which circulates to the kidney and causes increased Na+ reabsorption → ↑ ECF volume. Response to Hemorrhage (3) Response of ADH: • ADH is released in response to decreased blood volume: 1. It increases water reabsorption by the renal collecting ducts to help restore blood volume. 2. It causes arteriolar vasoconstriction, reinforcing the vasoconstricting effects of sympathetic activity and angiotensin II. Response in the capillaries: • Vasoconstriction → ↓ capillary hydrostatic pressure → ↑ water absorption. Response to Hemorrhage (4) Other Responses: • In case of hypoxia → chemoreceptors in the carotid and aortic bodies sense the decrease in Po2 → ↑ Sympathetic stimulation to the blood vessels → vasoconstriction, ↑ TPR, and ↑ Pa. • In case of cerebral ischemia, → chemoreceptors in the medullary vasomotor center sense an increase in Pco2 and a decrease in pH → ↑ Sympathetic stimulation to the blood vessels → vasoconstriction, ↑ TPR, and ↑ Pa.