Peripheral Circulation and Regulation Functions of Peripheral Circulation 1. Contain the blood 2. Exchange nutrients, waste products, and gases with tissues 3. Transport 4. Regulate blood pressure, along with cardiac output 5. Control direction of blood flow 6. Participate in thermoregulation Blood Vessel Structure and Function Blood vessels closed system delivery system of dynamic structures that begins and ends at heart Work with lymphatic system to circulate fluids Arteries - delivery carry blood away from ventricles oxygenated except for pulmonary circulation and umbilical arteries of fetus closer to the heart, greater the pressure artery must tolerate Capillaries - exchange Numerous small vessels = high surface area direct contact with tissue cells; directly serve cellular needs endothelium only one layer of squamous cells Veins - return carry blood toward atria deoxygenated except for pulmonary circulation and umbilical veins of fetus Built to tolerate lower blood pressures and prevent backflow 60,000 miles of vessels in average body Large veins (capacitance vessels) Venous pathways are more interconnected Venous system Heart Large lymphatic vessels Lymph node Lymphatic system Arterial system Elastic arteries (conducting arteries) Muscular arteries (distributing arteries) Note subdivisions and by-pass vessels Small veins (capacitance vessels) Arteriovenous anastomosis Lymphatic capillaries Arteries run deep, whereas veins are both deep and superficial Sinusoid Arterioles (resistance vessels) Postcapillary venule Thoroughfare channel Capillaries (exchange vessels) Precapillary sphincter Terminal arteriole Metarteriole 1
Photomicrograph of Artery and Vein lumen Or externa Structure of Blood Vessel Wall Tunica intima Smooth, friction-reducing, innermost layer in contact with blood Endothelium: simple squamous epithelium lines lumen of all vessels is continuous with endocardium Tunica media Middle layer composed mostly of smooth muscle and sheets of elastin Sympathetic vasomotor nerve fibers innervate this layer Thickest in arteries - responsible for maintaining blood flow and blood pressure Tunica externa Outermost layer of wall mostly loose collagen fibers that protect and reinforce wall and anchor it to surrounding structures Infiltrated with nerve fibers, lymphatic vessels, and Vasa vasorum Capillaries Endothelium with sparse basal lamina Artery Tunica intima Endothelium Subendothelial layer Internal elastic membrane Tunica media (smooth muscle and elastic fibers) External elastic membrane Tunica externa (collagen fibers) Vasa vasorum Valve Vein Lumen Capillary network Lumen Capillary Basement membrane Endothelial cells Vasomotor tone: what s up with that? 2
conducting arteries -maintain pressure between contractions distributing arteries -deliver to organs resistance arteries -control perfusion locally capacitance vessels - Serve as blood reservoir Capillaries Functions: exchange between blood and interstitial fluid Small diameter vessels force RBCs to pass in single file Slows flow and promotes exchange Thin tunica intima; in smallest vessels, one cell forms entire circumference Supply almost every cell, except for cartilage, epithelia, cornea, and lens of eye Continuous capillary Continuous capillaries are the least permeable and most common. Pericyte Red blood cell in lumen Basement membrane Tight junction Endothelial nucleus Intercellular cleft Endothelial cell Pinocytotic vesicles Continuous Capillaries: Abundant in skin, muscles, lungs, and CNS. Often have associated pericytes. Pinocytotic vesicles ferry fluid across the endothelial cell. Brain capillary endothelial cells lack intercellular clefts and have tight junctions around their entire perimeter. Fenestrated Capillary: Occur in areas of active filtration (e.g., kidney) or absorption (e.g., small intestine), and areas of endocrine hormone secretion. Fenestrated capillary Fenestrated capillaries have large fenestrations (pores) that increase permeability. Pinocytotic vesicles Red blood cell in lumen Fenestrations (pores) Endothelial nucleus Basement membrane Intercellular cleft Endothelial cell Tight junction Fenestrations are Swiss cheese like holes that tunnel through endothelial cells. usually covered by a very thin diaphragm Readily allows solute and fluid movement. In some digestive tract organs, the number of fenestrations in capillaries increases during active absorption of nutrients. 3
Sinusoidal Capillaries: Occur in liver, bone marrow, spleen, and adrenal medulla. Have large intercellular clefts as well as fenestrations; few tight junctions; incomplete basement membranes. Are irregularly shaped and have larger lumens than other capillaries. Sinusoid capillary Sinusoid capillaries are the most permeable and occur in limited locations. Endothelial cell Red blood cell in lumen Large intercellular cleft Tight junction Incomplete basement membrane Nucleus of endothelial cell Allow large molecules and even cells to pass across their walls. Blood flows slowly through their channels. Macrophages may extend processes through the clefts to catch prey or, in liver, form part of the sinusoid wall. Anatomy of a capillary bed. Capillary bed: interwoven network of capillaries between arterioles and venules Microcirculation: flow of blood through bed Precapillary sphincters Terminal arteriole Metarteriole Vascular shunt Thoroughfare channel True capillaries Postcapillary venule Sphincters open blood flows through true capillaries. Capillary beds vessels 1. Vascular shunt: channel that connects arteriole directly with venule (metarteriole thoroughfare channel) 2. True capillaries: actual vessels involved in exchange Terminal arteriole Postcapillary venule Sphincters closed blood flows through metarteriole thoroughfare channel and bypasses true capillaries. Relative crosssectional area of different vessels of the vascular bed Total area (cm 2 ) of the vascular bed Velocity of blood flow (cm/s) 5000 4000 3000 2000 1000 0 50 40 30 20 10 0 4
Capillary transport mechanisms Venules postcapillary venules consist of endothelium and a few pericytes Very porous; allow fluids and WBCs into tissues Larger venules have one or two layers of smooth muscle cells Veins Have all tunics Large lumen and thin walls make veins good storage vessels Blood pressure lower than in arteries, so adaptations ensure return of blood to heart Large-diameter lumens offer little resistance Venous valves Prevent backflow of blood Most abundant in veins of limbs filling effect Relative proportion of blood volume throughout the cardiovascular system. Pulmonary blood Systemic arteries and arterioles 15% vessels 12% Heart 8% Capillaries 5% Systemic veins and venules 60% Venous reservoir provides a source of blood to fill dilating arteries upon initiation of exercise compensation to maintain blood pressure Lumen Caveolae Pinocytotic vesicles Intercellular cleft Endothelial fenestration (pore) 4 Transport via vesicles or caveolae (large substances) 1 Diffusion through membrane (lipid-soluble substances) Basement membrane 2 Movement through intercellular clefts (water-soluble substances) 3 Movement through fenestrations (water-soluble substances) 5
Fluid Movements Out of Capillaries Capillary pressures 35 mm Hg at beginning of capillary bed 17 mm Hg at the end of the bed Low capillary pressure is desirable Fluid is forced out clefts of capillaries at arterial end, and most returns to blood at venous end Bulk fluid flow across capillary walls causes continuous mixing of fluid between plasma and interstitial fluid; maintains interstitial environment. Direction and amount of fluid flow depend on two opposing forces Hydrostatic pressures Colloid osmotic pressures Hydrostatic pressure (HP) Capillary hydrostatic pressure (HP c ) Interstitial fluid hydrostatic pressure (HP if ): assumed to be zero because lymphatic vessels drain interstitial fluid Capillary colloid osmotic pressure (oncotic pressure, OP c ) Remember the presence of plasma proteins Interstitial fluid colloid osmotic pressure (OP if ) inconsequential Hydrostatic-osmotic pressure interactions Net filtration pressure (NFP): NFP = (HP c + OP if) (HP if + OP c) Net fluid flow out at arterial end (filtration) Net fluid flow in at venous end (reabsorption) More fluid leaves at arterial end than is returned at venous end Excess interstitial fluid is returned to blood via lymphatic system How do the pressures drive fluid flow across a capillary? Net filtration occurs at the arteriolar end of a capillary. Capillary lumen Boundary (capillary wall) Interstitial fluid Hydrostatic pressure in capillary (HP c) pushes fluid out of capillary. HPc = 35 mm Hg Osmotic pressure in capillary (OPc) pulls fluid into capillary. OP c = 26 mm Hg Hydrostatic pressure HPif = 0 mm Hg (HP if) in interstitial fluid pushes fluid into capillary. Let s use w hat w e know about pressures to determine the net filtration pressure (NFP) at any point. (NFP is the pressure driving fluid out of the capillary.) To do this w e calculate the outw ard pressures (HP c and OP if) minus the inw ard pressures (HP if and OP c). So, OP if = 1 mm Hg Osmotic pressure (OPif) in interstitial fluid pulls fluid out of capillary. NFP = (HP c + OP if) (HP if + OP c) = (35 + 1) (0 + 26) = 10 mm Hg (net outward pressure) NFP = 10 mm Hg As a result, fluid moves from the capillary into the interstitial space. 6
Venule Arteriole Fluid moves through the interstitial space. Lymphatic capillary Net reabsorption occurs at the venous end of a capillary. Capillary lumen Hydrostatic pressure in capillary pushes fluid out of capillary. The pressure has dropped because of resistance encountered along the capillaries. HP c = 17 mm Hg Boundary (capillary wall) Interstitial fluid Osmotic pressure in capillary pulls fluid into capillary. OP c = 26 mm Hg HP if = 0 mm Hg OP if = 1 mm Hg NFP= 8 mm Hg Hydrostatic pressure in interstitial fluid pushes fluid into capillary. Osmotic pressure in interstitial fluid pulls fluid out of capillary. Again, w e calculate the NFP: NFP = (HP c + OP if) (HP if + OP c) = (17 + 1) (0 + 26) = 8 mm Hg (net inw ard pressure) Notice that the NFP at the venous end is a negative number. This means that reabsorption, not filtration, is occurring and so fluid moves from the interstitial space into the capillary. Arterial side NFP = 10; venous side NFP = -8 Capillary bed NFP is therefore 10 8 = 2 mm Hg 2 mm Hg pressure causes a net fluid loss from bed to tissues The big picture Each day, 20 L of fluid filters from capillaries at their arteriolar end and flows through the interstitial space. Most (17 L) is reabsorbed at the venous end. For all capillary beds, 20 L of fluid is filtered out per day almost 7 times the total plasma volume! 17 L of fluid per day is reabsorbed into the capillaries at the v enous end. About 3 L per day of fluid (and any leaked proteins) are removed by the lymphatic system Control Over Blood Pressure and Flow Blood pressure (BP) Expressed in mm Hg, systolic over diastolic Measured as systemic arterial BP in large arteries at same level as heart Pressure gradient provides driving force that keeps blood moving from higher- to lower-pressure areas Blood flow Measured in ml/min Overall is relatively constant when at rest, varies at individual organ level, based on needs Resistance (peripheral resistance) Measurement of amount of friction blood encounters with vessel walls, generally in peripheral (systemic) circulation Three important sources of resistance Blood viscosity Total blood vessel length Blood vessel diameter Turbulent flow constrictions in vessel interrupt laminar flow, eddys result Laminar flow frictional forces slow blood in direct contact with endothelium 7
Blood pressure (mm Hg) Blood viscosity The thickness or stickiness of blood due to formed elements and plasma proteins Increased viscosity equals increased resistance Increasing hematocrit increases viscosity Total blood vessel length The longer the vessel, the greater the resistance encountered Essentially remains constant once adulthood is reached Goal of blood pressure regulation is to keep blood pressure high enough to provide adequate tissue perfusion, but not so high that blood vessels are damaged Example: If BP to brain is too low, perfusion is inadequate, and person loses consciousness If BP to brain is too high, person could have stroke Pulse Pressure = 120-80 mmhg Systolic pressure 120 100 80 60 40 20 0 Diastolic pressure Mean pressure Pumping action of heart generates blood flow Pressure results when flow is opposed by resistance Systemic pressure is highest in aorta and declines throughout pathway Steepest drop occurs in arterioles Arterial Blood Pressure Pulse pressure and MAP both decline with increasing distance from heart With increasing distance, flow is nonpulsatile with a steady MAP pressure 8
Measuring Arterial Blood Pressure using auscultatory methods and a sphygmomanometer 1. Wrap cuff around arm superior to elbow 2. Increase pressure in cuff until it exceeds systolic pressure in brachial artery 3. Pressure is released slowly, and examiner listens for sounds of Korotkoff with a stethoscope Venous Blood Pressure Small pressure gradient, only about 15 mm Hg Factors aiding venous return 1. Backflow prevention 2. Muscular pump 3. Respiratory pump 4. Sympathetic venoconstriction The muscular pump. Venous valve (open) Contracted skeletal muscle Venous valve (closed) Vein Direction of blood flow 9
Regulation of Blood Pressure Maintaining blood pressure requires cooperation of heart, blood vessels, and kidneys All supervised by brain Three main factors regulating blood pressure Cardiac output (CO) Peripheral resistance (PR or just R) Blood volume Blood pressure varies directly with CO, PR, and blood volume Poiseuille s Law Simplifying: Flow = π ( P) r 4 ---------------- 8 v l P = P 1 P 2 or the change in pressure over the length of the vessel v is the viscosity of the blood l is the length of the blood vessel from P 1 to P 2 r is the radius of the blood vessel (diameter = 2r) π is a constant 1. Resistance to flow is caused by viscosity, vessel length, and vessel radius 1. Once mature, length of vessel fairly constant no impact 2. Viscosity and flow are inversely proportional Homeostatic mechanisms control viscosity 3. Small changes in radius or diameter (vasoconstriction/dilation) significantly impact flow 2. Minimum pressure differential required - no difference, no flow a) Must maintain pressure above critical closing pressure b) Heart as the generator of pressure can compensate Regulation of Blood Pressure MAP = SV HR R Anything that increases SV, HR, or R will also increase MAP SV is affected by venous return (EDV) HR is maintained by medullary centers R is affected mostly by vessel diameter 10
Regulation of Blood Pressure Factors can be affected by: Short-term regulation: neural controls Neural controls operate via reflex arcs that involve: Cardiovascular center of medulla Baroreceptors Chemoreceptors Higher brain centers Short-term regulation: hormonal controls Long-term regulation: renal controls Baroreceptor reflex 2 Baroreceptors in carotid sinuses and aortic arch are stimulated. 1 Stimulus: Blood pressure (arterial blood pressure rises above normal range). 5 CO and R return blood pressure to homeostatic range. 3 Impulses from baroreceptors stimulate cardioinhibitorycenter (and inhibit cardioacceleratory center) and inhibit vasomotor center. 4b Rate of vasomotor impulses allows vasodilation, causing R. Homeostasis: Blood pressure in normal range 4b Vasomotor fibers stimulate vasoconstriction, causing R. 4a Sympathetic impulses to heart cause HR, contractility, and CO. 5 CO and R return blood pressure to homeostatic range. 1 Stimulus: Blood pressure (arterial blood pressure falls below normal range). 4a Sympathetic impulses to heart Cause HR, contractility, and CO. 3 Impulses from baroreceptors activate cardioacceleratorycenter (and inhibit cardioinhibitorycenter) and stimulate vasomotor center. 2 Baroreceptors in carotid sinuses and aortic arch are inhibited Short-Term Regulation: Neural Controls (cont.) Chemoreceptor reflexes Aortic arch and large arteries of neck detect increase in CO 2, or drop in ph or O 2 Cause increased blood pressure by: Signaling cardioacceleratory center to increase CO Signaling vasomotor center to increase vasoconstriction Influence of higher brain centers Reflexes that regulate BP are found in medulla Hypothalamus and cerebral cortex can modify arterial pressure via relays to medulla increases blood pressure during stress mediates redistribution of blood flow during exercise and changes in body temperature 11
Long-Term Mechanisms: Renal Regulation Short-Term Mechanisms: Hormonal Controls Hormones regulate BP in short term via changes in peripheral resistance or long term via changes in blood volume Adrenal medulla hormones Epinephrine and norepinephrine from adrenal gland increase CO and vasoconstriction Angiotensin II stimulates vasoconstriction ADH (or vasopressin): high levels can cause vasoconstriction Atrial natriuretic peptide decreases BP by antagonizing aldosterone, causing decreased blood volume Direct renal mechanism Indirect renal mechanism (renin-angiotensin-aldosterone) Arterial pressure Arterial pressure Initial stimulus Physiological response Result Inhibits baroreceptors Sympathetic nervous system activ ity Filtration by kidneys Angiotensinogen Renin release from kidneys Angiotensin I Angiotensin conv erting enzyme (ACE) Angiotensin II Urine formation Adrenal cortex ADH release by posterior pituitary Thirst v ia hypothalamus Vasoconstriction; peripheral resistance Secretes Aldosterone Blood v olume Sodium reabsorption by kidneys Water reabsorption by kidneys Water intake Blood v olume Mean arterial pressure Mean arterial pressure Summary of Factors that Increase MAP Activity of muscular pump and respiratory pump Release of ANP Fluid loss from hemorrhage, excessive sweating Crisis stressors: exercise, trauma, body temperature Vasomotor tone; bloodborne chemicals (epinephrine, NE, ADH, angiotensin II) Dehydration, high hematocrit Body size Conservation of Na + and water by kidneys Blood volume Blood pressure Blood ph O 2 CO 2 Blood volume Baroreceptors Chemoreceptors Venous return Activation of vasomotor and cardioacceleratory centers in brain stem Stroke volume Heart rate Diameter of blood vessels Blood viscosity Blood vessel length Cardiac output Peripheral resistance Initial stimulus Physiological response Result Mean arterial pressure (MAP) 12
Control of Blood Flow Tissue perfusion: blood flow through body tissues; involved in: 1. Delivery of O 2 and nutrients to, and removal of wastes from, tissue cells 2. Gas exchange (lungs) 3. Absorption of nutrients (digestive tract) 4. Urine formation (kidneys) Rate of blood flow is controlled by extrinsic and intrinsic factors Extrinsic control: sympathetic nervous system and hormones control blood flow through whole body Intrinsic control: Autoregulation (local) control of blood flow: blood flow is adjusted locally to meet specific tissue s requirements Local arterioles that feed capillaries can undergo modification of their diameters Organs regulate own blood flow by varying resistance of own arterioles Metabolic controls smooth muscle response to metabolic wastes Myogenic controls smooth muscle response to increasing and decreasing MAP Long-term autoregulation angiogenesis and vessel enlargement Intrinsic and extrinsic control of arteriolar smooth muscle in the systemic circulation Intrinsic controls (autoregulation) Metabolic or myogenic controls Distribute blood flow to individual organs and tissues as needed Vasodilators Metabolic Neural O2 Sympathetic tone CO2 H + Hormonal K + Atrial natriuretic Prostaglandins peptide Adenosine Nitric oxide Vasoconstrictors Extrinsic controls Neural or hormonal controls Maintain mean arterial pressure (MAP) Redistribute blood during exercise and thermoregulation Myogenic Stretch Metabolic Endothelins Neural Sympathetic tone Hormonal Angiotensin II Antidiuretic hormone Epinephrine Norepinephrine 750 Brain Heart Skeletal muscles Skin 750 250 1200 500 750 12,500 Kidneys 1100 Abdomen Other 1400 600 1900 Total blood flow at rest 5800 ml/min 600 600 400 Total blood flow during strenuous exercise 17,500 ml/min 13