BIO2305 Vascular Physiology Physiology of Systemic Circulation Determined by Dynamics of blood flow Anatomy of circulatory system Regulatory mechanisms that control heart and blood vessels Blood volume Most in the veins (2/3rd) Smaller volumes in arteries and capillaries Dynamics of Blood Circulation Interrelationships between: Pressure Flow Resistance Control mechanisms that regulate blood pressure Blood flow through vessels Blood Flow Recall: Cardiac output - the total volume of blood pumped by the ventricle per minute The actual volume of blood flowing through a vessel, an organ, or the entire circulation in a given period: Is measured in ml per min. Is equivalent to cardiac output (CO), considering the entire vascular system Is relatively constant when at rest Varies widely through individual organs, according to immediate needs Circulatory Changes During Exercise 1 Blood Pressure (BP) Blood Pressure – The measure of force exerted by blood against the vessel walls. Force per unit area exerted on the wall of a blood vessel by its contained blood Expressed in millimeters of mercury (mm Hg) Measured in reference to systemic arterial BP in large arteries near the heart Blood moves through vessels because of blood pressure, gravity, and skeletal pump The differences in BP within the vascular system provide the driving force that keeps blood moving from higher to lower pressure areas Blood Flow & Blood Pressure Blood flow (F) is directly proportional to the difference in blood pressure (P) between two points in the circulation F = Flow α = directly proportional to Δ = change in P = Pressure F α ΔP (“Flow is directly proportional to change in pressure”) If ΔP ↑, then F ↑ If ΔP ↓, then F ↓ Blood Flow: Pressure Changes Flows down a pressure gradient Varies with force of ventricular contraction Highest at the left ventricle (driving P), decreases over distance Capillary beds virtually diminish pressure Compliance (distensibility) on venous side maintains low pressure Greatest drop in pressure occurs in arterioles Decreases 90% from aorta to vena cava 2 Blood Flow Flow rate (F) through a vessel (volume of blood passing through per unit of time) is directly proportional to the pressure gradient (ΔP) and inversely proportional to vascular resistance (R) F = flow rate of blood through a vessel ΔP = pressure gradient R = resistance of blood vessels (“Flow is directly proportional to Change in Pressure and inversely proportional to Resistance.”) Meaning: If ΔP↑ and/or R↓, then F↑ if ΔP↓ and/or R↑, then F↓ Blood Flow Pressure gradient is pressure difference between beginning and end of a vessel Blood flows from area of higher pressure to area of lower pressure Resistance (R) – opposition to flow Measure of the amount of friction blood encounters as it passes through vessels Referred to as peripheral resistance (PR) Blood flow is inversely proportional to resistance (R) As one goes up, the other goes down R is more important than P in influencing local blood pressure (“Flow is inversely proportional to Resistance”) Resistance Factors Resistance factors: Viscosity of blood– thickness or “stickiness” of the blood Hematocrit [Plasma Proteins] Length of blood vessel– the longer the vessel, the greater the resistance encountered Radius of blood vessel – the wider the vessel, the lower the resistance Slight change in radius (vasoconstriction or vasodilation) produces significant change in blood flow Resistance is inversely proportional to radius4 As one goes up, the other goes down (“Resistance is inversely proportional to the radius of the vessel to the 4th power”) 3 Blood Vessel Diameter Changes in vessel radius significantly alter peripheral resistance Resistance varies inversely with the fourth power of vessel radius (one-half the diameter) Poiseuille’s Law: R= L r4 L = length of the vessel = viscosity of blood (Greek letter “eta”) r = radius of the vessel Vessel length and blood viscosity do not vary significantly and are considered CONSTANT = 1 Therefore: R = 1 r4 If the radius is doubled, the new resistance is 1/16th the original resistance If the radius is halved, the new resistance is 16 times the original resistance Note: α means “proportional to” Blood Flow, Vessel Diameter and Velocity As diameter of vessels increases, the total cross-sectional area increases and velocity of blood flow decreases 4 Blood Flow & Cross-Sectional Area At the capillary bed: Vessel diameter decreases, but number of vessels increase Therefore, total cross-sectional area increases Therefore, velocity slows, giving capillaries time to unload O2 and nutrients Vascular Tree Closed system of vessels consists of: Arteries carry blood away from heart to tissues Arterioles smaller branches of arteries Capillaries smaller branches of arterioles smallest of vessels across which all exchanges are made with surrounding cells Venules formed when capillaries rejoin return blood to veins Veins formed when venules merge return blood to heart 5 Structure of Blood Vessels Arteries have thicker walls and narrower lumens than those that of veins Arterial walls must withstand high pressures Thick layer of smooth muscle in tunica media controls flow and pressure Arteries and arterioles have more elastic and collagen fibers Remain open and can spring back in shape Pressure in the arteries fluctuates due to cardiac systole and diastole Veins have larger lumens. Vein walls are thinner than arteries and have valves Thin walls provide compliance - blood volume reservoir Blood pressure is much lower in veins than in arteries Valves prevent backflow of blood Capillaries have very small diameters (many are only large enough for only one RBC to pass through at a time) Composed only of basal lamina and endothelium Thin walls allow for gas, nutrient, waste exchange between blood and tissue cells. 6 Role of Arteries Elastic or conducting arteries Largest diameters, pressure high and fluctuates Pressure Reservoir Elastic recoil propels blood after systole Muscular or medium arteries Smooth muscle allows vessels to regulate blood supply by constricting or dilating 7 Role of Arterioles Transport blood from small arteries to capillaries Controls the amount of resistance Greatest drop in pressure occurs in arterioles, which regulate blood flow through tissues No large fluctuations in capillaries and veins Blood Pressure Force exerted by blood against a vessel wall Depends on: Volume of blood forced into the vessel Compliance (distensibility) of vessel walls Systolic pressure Peak pressure exerted by ejected blood against vessel walls during cardiac systole Averages 120 mm Hg Diastolic pressure Minimum pressure in arteries when blood is draining off into vessels downstream Averages 80 mm Hg Blood Pressure Measurement Critical closing pressure: Pressure at which a blood vessel collapses and blood flow stops Laplace’s Law: Force acting on blood vessel wall is proportional to diameter of the vessel times blood pressure 8 Measurement of BP Blood pressure cuff is inflated above systolic pressure, occluding the artery As cuff pressure is lowered, the blood will flow only when systolic pressure is above cuff pressure, producing the sounds of Korotkoff Named after Dr. Nikolai Korotkoff, a Russian physician who described them in 1905 Korotkoff sounds will be heard until cuff pressure equals diastolic pressure, causing the sounds to disappear Measurement of Blood Pressure Different phases in measurement of blood pressure are identified on the basis of the quality of the Korotkoff sounds Average arterial BP is 120/80 mm Hg Average pulmonary BP is 22/8 mm Hg 9 Pulse Pressure Pulse Pressure - Difference between systolic and diastolic pressures Increases when stroke volume increases or vascular compliance decreases Pulse pressure can be used to take a pulse to determine heart rate and rhythmicity Example: 120 mmHg (SP) – 80 mmHg (DP) = 40 mmHg (PP) Arterial Blood Pressure Blood pressure in elastic arteries near the heart is pulsatile (BP rises and falls) Pulse pressure – the difference between systolic and diastolic pressure Mean arterial pressure (MAP) – pressure that propels the blood to the tissues MAP = diastolic pressure + 1/3 pulse pressure Effect of Gravity on Blood Pressure Effect of Gravity: In a standing position, hydrostatic pressure caused by gravity increases blood pressure below the heart and decreases pressure above the heart 10 Role of Veins Veins have much lower blood pressure and thinner walls than arteries To return blood to the heart, veins have special adaptations Large-diameter lumens, which offer little resistance to flow Valves (resembling semilunar heart valves), which prevent backflow of blood Venous Blood Pressure Venous BP is steady and changes little during the cardiac cycle The pressure gradient in the venous system is only about 20 mm Hg Veins have thinner walls, thus higher compliance. Vascular compliance: Tendency for blood vessel volume to increase as blood pressure increases More easily the vessel wall stretches, the greater its compliance Venous system has a large compliance and acts as a blood reservoir Capacitance vessels – 2/3 blood volume is in veins Venous Return Venous pressure is driving force for return of blood to the heart. EDV, SV, and CO are controlled by factors which affect venous return Factors Aiding Venous Return Venous BP alone is too low to promote adequate blood return and is aided by the: Respiratory “pump” – pressure changes created during breathing squeeze local veins Muscular “pump” – contraction of skeletal muscles push blood toward the heart Valves prevent backflow during venous return 11 Capillary Network Blood flows from arterioles through metarterioles, then through capillary network Venules drain network Smooth muscle in arterioles, metarterioles, precapillary sphincters regulates blood flow Organization of a Capillary Bed True capillaries – exchange vessels Oxygen and nutrients cross to cells Carbon dioxide and metabolic waste products cross into blood Atriovenous anastomosis – vascular shunt, directly connects an arteriole to a venule 12 Capillaries Capillary wall consists mostly of endothelial cells Types classified by diameter/permeability Continuous capillary – Least permeable Do not have pores Only small molecules (water, ions) diffuse through tight junctions Seen in skin, muscle where small ions and molecules must enter/exit vessels Fenestrated capillary – Large fenestrations (pores) Small molecules and limited proteins diffuse Seen in kidney, small intestine where large molecules must enter/exit vessels Sinusoidal capillary – Most permeable Discontinuous basement Allow proteins and cells as necessary Seen in liver, bone marrow, spleen, where whole cells, proteins must enter/exit vessels Capillary Exchange and Interstitial Fluid Volume Regulation Blood pressure, capillary permeability, and osmosis affect movement of fluid from capillaries A net movement of fluid occurs from blood plasma into tissues – bulk flow Fluid gained by tissues is removed by lymphatic system 13 Diffusion at Capillary Beds Distribution of ECF between plasma and interstitial compartments Is in state of dynamic equilibrium Balance between tissue fluid and blood plasma Hydrostatic pressure: Exerted against the inner capillary wall Generated primarily by gravity and blood pressure Promotes formation of tissue fluid Source of Net Filtration Pressure (NFP) Colloid osmotic pressure: Exerted against the outer capillary wall Generated by [plasma proteins] Promotes fluid reabsorption into circulatory system Lymphatic System Extensive network of one-way vessels Provides accessory route by which fluid can be returned from interstitial spaces to the blood Initial lymphatics Small, blind-ended terminal lymph vessels Permeate almost every tissue of the body Lymph vessels Formed from convergence of initial lymphatics Eventually empty into venous system near where blood enters right atrium One way valves spaced at intervals direct flow of lymph toward venous outlet in chest Lymph Interstitial fluid that enters a lymphatic vessel 14 Lymphatic System 7,200 L blood pumped per day (5 L/min x 60 min x 24 hrs) 20 L of plasma leave arteries 17 L of plasma return to veins 3 L carried away as lymph Lymphatic System Functions: Return of excess filtered fluid (3 L/day) back to heart Defense against disease Lymph nodes contain phagocytes which destroy bacteria filtered from interstitial fluid Transport of absorbed fat from GI tract to liver (chylomicrons) Return of filtered protein Regulation of Blood Flow Intrinsic – local autoregulation (‘”self-regulation”) Autoregulation – In most tissues, blood flow is proportional to metabolic needs of tissues. If tissue metabolic processes increase, blood flow to tissue increases. Extrinsic – nervous and endocrine (non-local forces) Nervous System – CNS sends (or ceases) action potentials to smooth muscle in walls of blood vessels, stimulating vasoconstriction, or allowing vasodilation. Sympathetic neuron axon terminals at smooth muscle in blood vessels release NE, which stimulates vasoconstriction, decreasing blood flow. If release of NE from axon terminal decreases, blood vessels dilate, increasing blood flow. Sympathetic neuron axon terminals at cardiac muscle in the heart release NE, which increases cardiac output, increasing BP. Nervous system is immediately responsible for routing blood flow and maintaining blood pressure. Hormonal Control – Sympathetic action potentials to medulla of adrenal gland stimulate release of epinephrine and norepinephrine which reinforce systemic vasoconstriction, but cause vasodilation at skeletal muscle. Norepinephrine is primarily released from sympathetic neuron axon terminals directly onto end target organs. Epinephrine is primarily released from the adrenal medulla (80% Epi, 20% NE). Epi from the adrenal medulla travels through the blood and is able to bind with α1receptors on blood vessels, reinforcing vasoconstriction. However, α1-receptors have a lower affinity for Epi and do not respond as strongly to it as they do to NE. Epinephrine also binds to β2-receptors, found on vascular smooth muscle of heart, liver, and skeletal muscle arterioles. These receptors are not innervated and therefore respond primarily to circulating epinephrine. Activation of vascular β2-receptors in the heart, liver, and skeletal muscle by epinephrine causes vasodilation, increasing blood flow to these tissues [p. 524]. 15 Intrinsic Regulation of Blood Flow (Autoregulation) Blood flow can increase 7-8 times as a result of vasodilation of metarterioles and precapillary sphincters Vasodilator substances are produced as metabolism increases Intrinsic receptors sense chemical changes in environment Decreased O2 Increased CO2 Decreased pH (Lactic acid) Increased adenosine Increased K+ Intrinsic Regulation of Blood Flow (Autoregulation) Myogenic Control Mechanism: Contraction that originates within the vascular smooth muscle fiber as a result of stretch An increase in systemic arterial pressure causes vessels to contract A decrease in systemic arterial pressure causes vessels to dilate If ↑ Pressure, then ↑ Stretch. Response: Vasoconstriction If ↓ Pressure, then ↓ Stretch. Response: Vasodilation Intrinsic Regulation of Blood Flow (Autoregulation) 16 Extrinsic Regulation of Blood Flow Sympathoadrenal Increase cardiac output Increase TPR: α-adrenergic stimulation - vasoconstriction of arteries in skin and viscera Parasympathetic Parasympathetic innervation limited, less important than sympathetic nervous system in control of TPR Parasympathetic endings in arterioles promote vasodilation to the digestive tract, external genitalia, and salivary glands Blood Pressure (BP) Regulation Pressure of arterial blood is regulated by blood volume, TPR, and cardiac rate. MAP = CO TPR Arteriole resistance is greatest because they have the smallest diameter Capillary BP is reduced because of the total cross-sectional area 3 most important variables are HR, SV, and TPR Increase in each of these will result in an increase in BP BP can be regulated by: Kidney and sympathoadrenal system Short-Term Regulation of Blood Pressure Baroreceptor reflexes Change peripheral resistance, heart rate, and stroke volume in response to changes in blood pressure Chemoreceptor reflexes Sensory receptors sensitive to O2, CO2, and pH levels of blood Central nervous system ischemic response Results from high CO2 or low pH levels in medulla and increases peripheral resistance 17 Baroreceptor Reflex Control 18 Chemoreceptor Reflex Control 19 Baroreceptor Effects Long-Term Regulation of Blood Pressure Renin-angiotensin-aldosterone mechanism Vasopressin (ADH) mechanism Atrial natriuretic mechanism Fluid shift mechanism Stress-relaxation response Renin-Angiotensin-Aldosterone System (RAAS) 20 Vasopressin (ADH) Mechanism Atrial Natriuretic Peptide (ANP) Produced by the atria of the heart Stretch of atria stimulates production of ANP Antagonistic to Aldosterone and Angiotensin II Promotes Na+ and H2O excretion in the urine by the kidney Promotes vasodilation, lowering TPR “Atrial” = atria of the heart “natri-” = sodium “-uretic” = urination “Peptide” = small protein 21 Atrial Natriuretic Peptide (ANP) Cerebral Circulation Cerebral blood flow (CBF) is not normally influenced by sympathetic nerve activity Cerebral blood flow regulated almost exclusively by intrinsic mechanisms: Myogenic Mechanism: Dilate in response to decreased pressure Cerebral Perfusion Pressure (CPP) is the blood pressure within the brain. CPP is maintained within very narrow limits Too low = cerebral ischemia Too high = intracranial hematoma, cerebral edema Metabolic Mechanism: Areas of brain with high metabolic activity receive most blood Cerebral arteries dilate due to increased [K+] [CO2] [H+] and [Adenosine] in CSF 22