Chapter 21 The Cardiovascular system: physiology of circulation blood vessel structure and function physiology of circulation: blood flow, blood pressure, and resistance blood flow the amount of blood flowing through an organ, tissue or blood vessel in a given time (normally ml/min) perfusion is the rate of blood flow per given mass of tissue (normally ml/min/gram) I use these interchangeably blood flow/perfusion determines the speed of nutrient delivery and waste removal this is very important so they are carefully regulated the blood flow through the entire systemic circulation is 5L/ml or the cardiac output of the left ventricle of this cardiac output each tissue gets a small but ever changing (regulated) percentage of CO that increases with need What determines blood flow two factors that determine blood flow 1) blood pressure differences 2) resistance (R) flow = P1-P2/R blood pressure (BP) - liquids like blood cannot be compressed. A force exerted against a liquid generates a hydrostatic pressure (HP) that is conducted in all directions 1
in a blood vessel this force will push blood against the blood vessel walls and push blood down the vessel towards an area of lower pressure differences in blood pressure (DP) between different areas of the circulation provide the driving force for blood flow in the circulation the greater the DP the greater the flow in the systemic circuit the pressure gradient (DP) is the pressure difference between the base of the aorta and the entrance of the right atrium (95mmHg 5-2mmHg) or about 90mmHg flow = DP /R thus increases in blood pressure increase flow characterization of blood pressure through the circulatory system 1) arterial pressure (typically called blood pressure): is not a steady pressure it is pulsatile peak pressure is the systolic pressure occurs during ventricular systole lowest pressure is the diastolic pressure occurs during ventricular diastole normally written 120/75 pulse pressure systolic - diastolic pressure 120-75=45 is felt as the pulse with our finger is a measurement of the stress exerted on the wall of the arteries by the pressure surges generated by the heart remember the farther from the heart the lower the systolic and diastolic pressures 2
mean arterial pressure (MAP) is used to convert the pulsatile pressure of the blood into a single pressure value MAP is used to determine the DP is the average pressure during an entire cardiac cycle heart spends more time in diastole then systole so is not the sum of the two divided by two MAP = diastolic pressure + (pulse pressure/3) for 120/75 MAP = 75 + (120-75)/3 = 90mmHg MAP at aorta = 90-95mmHg MAP at just before capillaries = 35mmHg 2) capillary blood pressure pressure is not pulsatile due to elastic recoil pressure at the start of the capillaries is 35mm Hg by the end of cap bed it is 18 mm Hg low pressure is important 1. capillaries are fragile 2. capillaries are permeable -- high pressures would force out too much filtrate capillaries are very numerous so have largest cross section thus rate of blood flow is very low helps with exchange 3) venous blood pressure pressure is not pulsatile but steady and changes very little during the cardiac cycle entering small venules 18mmHg right atrium is 2-5 mmhg 3
as blood travels toward heart veins converge so cross sec. area drops resistance remains low and velocity of flow increases systemic circulatory pressure gradient = the pressure difference between the aorta and the entrance of the right atrium this is the DP for the systemic circulation MAP of aorta = 90-95 mmhg Blood pressure of right atrium = 2-5 mmhg systemic circulatory pressure gradient (DP) averages 90 mmhg this is mainly need to force blood through the arterioles which are the source of most resistance resistance any force that opposes movement the amount of friction blood encounters as it passes through the vessels greater the resistance the slower the flow of blood remember F = DP/R thus increases in resistance decreases flow and an increase in pressure is required to maintain flow peripheral resistance (PR) is the resistance that the blood encounters in the vessels as it travels through the circulatory system the resistance of the arterial system is the site of most peripheral resistance (mostly the arterioles) (venous resistance is very low so not important) greater the PR the higher the pressure must be to maintain flow F = DP/R sources of resistance blood flow (F) = π P r 4 /8ηl (Poiseuille s law) 4
η = viscosity l = length r = radius 1. blood viscosity = η thickness or stickiness of blood greater the viscosity the greater the resistance thus lower the flow blood is 5X thicker then water mainly due to erythrocytes and albumin changed by living at altitude, polycythemia, anemia, dehydration, liver disease, ect. 2. vessel length longer the vessel length the greater the cumulative friction between blood and the wall so the greater the resistance change in vessel length occurs slowly so not changed minute to minute added fat adds resistance 3. blood vessel radius = r the smaller the radius the greater the friction so more resistance radius is the only one that is not fairly constant and is changed moment to moment to adjust blood flow blood and pressure vasoconstriction narrowing stimulating the contraction of smooth muscle of the vessels vasodilation widening relaxing the smooth muscle of the vessels 5
resistance varies inversely with the fourth power of the vessels radius R 1/r 4 thus F r 4 double the radius the resistance is 1/16 and flow is 16 times more thus small changes in resistances equals big changes in flow small arterioles with the lowest total cross sectional area account for most of the peripheral resistance the resistance of a maximally constricted arteriole is 80 times the maximally dilated arteriole 4. turbulence (pathological) normally blood flow is laminar smoothly flowing in layers fastest in the middle irregular surfaces upset the smooth flow of blood and create eddies and swirls this turbulence increases resistance and lowers flow rates abnormal turbulence occurs with damaged heart valves and damaged blood vessels (atherosclerosis) abnormal turbulence causes a sound called a bruit in vessels and a murmur in the heart Cardiovascular Regulation (regulation of blood flow) The main purpose of the cardiovascular system is ensure that tissues are provided with the appropriate amounts of oxygen and nutrients If demand is not met cellular function drops and tissues begin to die To meet tissue demands blood flow is carefully regulated 6
Tissue blood flow is regulated by three factors 1. cardiac output- covered in the previous chapter but done forget it now 2. peripheral resistance 3. blood pressure all three are closely interrelated The goal or cardiovascular regulation is to ensure that changes in blood flow occur 1. at an appropriate time 2. in the right area 3. without drastically changing blood pressure flow to vital organs all three conditions must be met simultaneously Blood flow is regulated by controlling blood pressure and peripheral resistance Remember blood flow P/R blood pressure = (cardiac output) X (peripheral resistance) Resistance 1/r 4 hl mechanisms involved in regulation of cardiovascular function 1. local control or autoregulation work by controlling peripheral resistance in response to chemical changes at the tissues 2. neural mechanisms ANS work by controlling both peripheral resistance and cardiac output in response to changes in autonomic activity, blood gases and arterial pressure 3. endocrine factors work by controlling both peripheral resistance and cardiac output 1. autoregulation of blood flow within tissues while cardiac output remains stable the peripheral resistance within a tissue is adjusted to control local blood flow work by changing peripheral resistance 7
important in short-term regulation local vasodilators produced by tissues that have inadequate blood flow 1. decreased tissue oxygen 2. increases CO2 levels 3. rising K 4. H levels (lactic acid) 5. nitric oxide (NO) 6. heat Work by relaxing the smooth muscle of the precapillary sphincters produced due to high pressure local vasoconstrictors 1. endothelin 2. prostaglandins 3. thromboxanes Released from platelets, WBC, and endothelial cells following injury Work by triggering constriction of precapillary sphincters High concentrations will affect arterioles further reducing flow to the tissue 2. Neural mechanisms (ANS) controlling flow operates to control cardiac output and regulate peripheral resistance (thus blood pressure) to maintain adequate blood flow to vital tissues and organs important in short-term regulation cardiovascular centers medulla oblongata contains a complex cardiovascular centers has a cardiac and a vasomotor center can act independently cardiac center regulates cardiac output thus regulates blood pressure 8
change pressure= change flow blood flow P/R vasomotor center regulates peripheral resistance thus regulates blood flow controls sympathetic activity to the arterioles and blood vessels in general have two populations of neurons: both populations are part or the sympathetic nervous system 1. vasoconstriction center largest group of vasomotor neurons that decrease blood flow sympathetic fibers that release norepinephrine that cause constriction of smooth muscle in the vessels of the skin urinary, reproductive and the GI tract 2. vasorelaxation center small group of neurons that cause vasorelaxation thus stimulates flow sympathetic fibers that release Ach that relax vessels of the skeletal muscle heart and brain When sympathetic nervous system is activated the vasomotor center is activated constriction is greater then relaxation so initially blood pressure increases somewhat later on local autoregulation my result in a drop in return or even a drop in BP reflex control of vasomotor center 1. baroreceptor reflex located in the aortic arch and carotid art. Also have a similar medullary ischemic receptors 9
located in the hypothalamus and medulla Important for short term changes like adjustments in posture A drop in blood pressure as two effects 1. stimulation of cardioacceleratory center and thus increase heart rate thus increases CO = rise in pressure 2. stimulation of vasoconstriction center and thus increase in blood pressure By increasing CO and peripheral resistance blood pressure goes up Active tissues can know get higher flow through autoregulation An increase in blood pressure as two effects 1. inhibition of cardioacceleratory center and if severe, stimulation of cardioinhibitroy center resulting in a drop of CO = drop in pressure 2. inhibitition of vasoconstriction center and stimulation of vasorelaxation center = drop in pressure 2. chemoreceptor reflexes involve receptors located aortic arch subclavian art and carotid art. that monitors the blood Also have a receptor in medulla oblongata the monitors CSF All are sensitive to CO2, acid and O2 mostly CO2 and acid Major role is adjusting respiration High CO2 and acid and low O2 has two effects 1. stimulates the cardioacceleratory center while inhibiting the cardioinhibitory center = increase CO = increase in? P = increase in flow 10
So more blood returns to the lungs 2. stimulates vasoconstriction center to increase blood pressure increases blood flow to lungs low CO2 and acid and high O2 has opposite effects 3. hormones endocrine system provides both long-term and short-term regulation of blood flow F =? P/R long-term is the result of regulating of blood volume which has an effect on blood pressure blood pressure = (cardiac output) X (peripheral resistance) remember that CO = (HR) X (stroke volume) increase in blood volume increases venous return which increases stroke volume thus increasing CO short-term regulation is the result of regulating peripheral resistance and cardiac output which has an effect on blood pressure epinephrine and norepinephrine from adrenal medulla effects 1. binds to α receptors and triggers vasoconstriction in most vessels thus increases blood pressure (? P) the vessels that not constricted receive more flow active tissue receive more flow due to autoregulation 11
also increases cardiac output thus increases blood pressure (? P) 2. binds to β receptors in the vessels of the heart, brian and muscle and triggers relaxation both effects are short-term antidiuretic hormone released from the posterior pituitary when 1. blood volume drops 2. when osmotic concentration of the plasma increases 3. in response to circulation angiotension II effects immediately effect stimulates peripheral vasoconstriction increases blood pressure (? P) long-term effect stimulates the kidneys to conserve water by reabsorption from the urine increasing water in blood increases blood volume thus increases pressure angiotensin II produced in response to falling renal blood pressure cascade 1. low pressure stimulates release of renin 2. renin convert circulation angiotensinogen to angiotensin I 3. in lungs angiotensin converting enzyme (ACE) converts AI to AII short-term effects of AII 1. powerful vasoconstriction increase blood pressure 2. positive inotropic effects on heart increase contractility increase CO 12
long-term effects 1. stimulates the release of ADH vasoconstriction (short-term) water retention increase blood volume increase pressure 2. stimulates the release of aldosterone from adrenal cortex aldosterone stimulates sodium reabsorption from kidney water will follow increase blood volume increase pressure 3. stimulates thirst intake water increase blood volume increase pressure Erythropoietin release from kidneys if blood pressure drops or low O2 long-term effects increase RBC elevating blood volume increase pressure atrial natriuretic peptide released form right atrium when stretch is high works to lower pressure long-term effects 1. increase sodium loss from kidneys water will follow lower blood volume lower pressure 2. reduces thirst 3. blocks release of ADH 4. stimulates peripheral vasodilation blood flow through capillaries and capillary dynamics 13
the movement of materials across the typical capillary wall is mediated by three mechanisms 1. diffusion 2. transcytosis 3. filtration and reabsorption diffusion must have a concentration gradient for diffusions and must be permeable clefts and fenestrations make most substances permeable lipid-soluble substances pass through plasma membrane can move small amounts short distances not adequate for all movement of nutrients movement of oxygen, carbon dioxide and most nutrients and metabolic wastes between blood and interstitial fluid is by diffusions constant uptake of nutrients by cells keeps the gradient in place small water-soluble solutes like amino acids and sugars pass through capillary clefts or fenestrations if present lipid-soluble substances pass through cell membrane of endothelial cells transcytosis movement by pinocytosis of a droplet of fluid from one side of the plasma membrane to the opposite side can occur in ether directions is minor mechanism used to move large molecules like fatty acids albumin and some hormones filtration and reabsorption allows the movement of a large amount of fluid and substances dissolved in the fluid fluid leaves the arterial end and reenters the venous end filtration and reabsorption is determined by the balance of hydrostatic pressure and colloid osmotic pressure at the capillary 1) hydrostatic pressure is the pressure the fluid is under 14
2) osmotic pressure deals with movement of water works to hold water in the vessel occurs as the result of osmosis water tends to diffuse across the membrane towards the solution containing the higher concentration of solute the force of water movement towards the solution with the higher concentration of solute is called osmotic pressure in the capillary the only thing that can not cross the membrane (endothelial cells) are proteins so call it blood colloid osmotic pressure (BCOP) Arteriole side hydrostatic pressure at the arteriole side 1) capillary blood pressure = 30 mmhg outward 2) interstitial hydrostatic pressure = -3 so also outward -3 means there is a slight suction) so have 33 mmhg of outward pressure pushing fluid out of cap. Colloid osmotic pressure at arteriole side 1) Blood COP = 28 inward 2) interstitial hydrostatic pressure COP = 8 outward (very little protein here) so have 20 mmhg of inward pressure holding fluid in cap. Net filtration at the arteriole side is the difference between the outward and inward pressures 33out - 20in = 13 mmhg out of cap. Venous side hydrostatic pressure at the venous side 1) capillary blood pressure = 10 mmhg outward 2) interstitial hydrostatic pressure= -3 outward (suction) so have 13 mmhg pushing fluid out of cap. Colloid osmotic pressure at venous side (same as arterial end) 15
1) Blood COP = 28 inward 2) interstitial fluid COP = 8 outward (very little protein here) so have 20 mmhg of inward pressure holding fluid in cap. Net reabsorption at the venous side is the difference between the inward and outward pressures 20in - 13out = 7 mmhg inward into the cap. Because more pressure into the capillary we will see reabsorption of fluid Final tally we have 13mmHg pushing fluid out of arterial end and 7 mmhg pushing fluid into venous end there is not a balance of outward and inward pressures over the capillary bed so not all fluid is returned to the cap 13mmHg outward vs 7mmHg inward = 6mmHg is left This translates into 3.6L/day This volume enters the lymph vessels and returns to heart this leak would empty almost the entire blood in 24 hours if volume of fluid lost at the capillary is larger then lymph vessels can remove edema or fluid retention occurs a rise in interstitial hydrostatic pressure caps the amount of edema factors aiding in venous return pressure is normally too low to promote adequate venous return espicially if standing 1. respiratory pump pressure changes occurring in the ventral body cavity during breathing create a pumping action that sucks blood upward toward the heart inhale = lower pressure in chest allowing thoracic veins to expand and pulls blood toward heart speeding blood entry into the right atrium 16
exhale = increase pressure in abdomen pushing blood from the vessels into the atrium Valsalva s maneuver 2. muscular pump skeletal muscle activity milk blood toward the heart valves keep it in one direction 3. cardiac suction during ventricular systole the chordae tendineae pull the valves downward expanding the atrial space creating a slight suction 17