Blood vessels 3 types (arteries capillaries and veins) All of them are lined by endothelial cells The cells the blood is in contact with A type of epithelial cell lining on a basement membrane In capillaries the endothelial cells are the only cells present In arteries and veins on top of the endothelial layer there are layers of connective tissue and smooth muscle Connective tissue has elastic elements for flexibility and collagen so there is too much flexibility Blood leaves the hear through the aorta which then splits into arteries and then arteriole and the arteriole leading to the capillaries The capillaries are the smallest vessels but they are the most numerous and a result the surface area is highest in this place Capillaries coalesce into venoules and veins and eventually lead back to a single vessel that returns blood to the heart7 Capillaries are the site of exchange between the blood and the tissues A large surface area facilities effective exchange This also means that the velocity of blood flow in the capillaries is very low Flow from human heart= 5L/min This means that there is 5 L/min throughout the whole circ system When blood is flowing in single vessels it flows at a high velocity When blood flows through capillaries which count as a broad channel when all capillaries are taken into account, the velocity of flow is very slow Think in terms of a river Water passing down the grand canyon is channeled through a narrow river and so the speed of the water is very high; As it approaches the ocean it opens up into a delta which is a very large area with very low flow As area gets larger in the capillaries the velocity of movement falls This is important because it is a point of exchange Low speed of blood through the capillaries allows time for exchange to occur Pressure generated by the heart is what drives the blood through the circ system and this pressure drives blood flow through resistance The smaller vessels(arterioles, capillaries and venoules) provide the most resistance As blood passes the aorta and blood comes back through the veins Bp falls. The relationship between pressure, resistance and flow are important in figuring out the circ system works Resistance is proportional to the length It is inversely proportional to radius4 As the radius gets smaller the resistance increases to the fourth power Meaning small changes in radii results in large impacts in resistance Viscosity also affects resistance Thicker it is, higher the resistance Poiseuilles equation describes flow as a function of the driving force and the resistance(length, viscosity and radius4) There are a number of assumptions linked with poiseuilles equation Laminar flow Straight rigid tubes Assumes laminar flow Laminar flow is one that shows the parabolic profile found in slide 31 All the layers are sliding past each other in an organized fashion giving parabolic velocity profile where blood in the center is moving the fastest Most places in the circ system flow is laminar and so this assumption is needed Viscosity The internal friction to try and get these layers of blood sliding past each other Resistance to sliding The circ system gives high resistance in that plasma has 2x the viscosity of water and when the blood cells are added resistance become 3-4x more than water We tend to assume that viscosity is constant in the entire circ system One exception to this is present in vessels that are quite small Vessels that are around 0.3mm in diameter In these bv, the blood cells line up in the middle of the vessel- so not scattered So what is left on the edges is plasma and the viscosity of plasma is less than blood. This is a good thing because it lowers the amount the work the heart has to do since resistance has been lowered Making It easier to get blood through the small blood vessels This is known as the Fahraeus Lindgvist effect Turbulent flow In a clinical setting turbulent flow is used to measure Bp Bp pump is used based on turbulent flow Also assume that the lengths of the blood vessels dont change and so the main determinant of resistance in the circulatory system is the radius of the vessels Another Straight rigid tubes BV are rarely straight and they are not rigid This assumption has consequences for the productions that are made based on Ps equation In slide 32 the two tubes have the same P however the low pressure vessel will have lower flow than the high pressure vessel In a vessel that can change sizes high pressure will expand the vessel and so a higher starting pressure, this tends to stretch the vessel and increases the radius and lowers resistance. This fact can screw up the assumptions one makes when using Ps equation This fact is taken into consideration by calculating compliance Compliance is the change in volume for a given change in pressure In highly compliant vessels one can see high changes in volume for only small changes in pressure. This is the bases of giving blood The venous system is compliant Large changes in blood volume with very little pressure Meaning you can take a litre of blood out of the venous system with affecting overall blood pressure. Because of this high compliance the venous system tends to act like a reservoir And the arterial end acts as a pressure reservoir Important in maintaining function of the circ systemBlood vessels by function Windkessesl vessels These dampen pressure oscillations These are the aorta and the largest arteries They function to dampen pressure oscillation therefore maintaining blood flow Ventricle pushes blood into the aorta The aorta though elastic has low compliance This mean that when the heart ejects blood into the aorta the aorta stretches a little bit to accommodate that volume When the heart relaxes and starts to fill again, the stretch rebounds There is elastic recoil, and this maintains blood pressure and blood flow while the heart is relaxed and not contraction It is this recoil that maintains blood in ones body while the heart is in diastolic. If blood flow relied solely on the ventricles it would flow when the heart is contracting and stop flowing when the heart relaxes. The elastic recoil from the aorta prevent pressure from dropping and therefore maintains blood flow The ability to dampen pressure oscillations are due to the elastic element in the wall of the aorta and large arteries(the Windkessesl vessels) If these vessels disappear or harden heart functions is affected These vessels also have very thick walls b/c they are high pressure vessels and they have a large radius The large radius is another important function on its own These vessels distribute blood to the heart out to the periphery The most effective way to do that is to be low resistance vessels The large radius=low radius Large radius+ low pressure= thick walls As blood leaves the aorta and large arteries it passes into progressively smaller arteries and then the arterioles Pre-capillary resistance vessels These are the smallest arteries and arterioles Their small size provide a high amount of resistance Small radius=high resistance Pressure drops abruptly as it goes through the precapillary vessels These vessels set and regulate blood pressure and in turn regulate blood flow In a fight or flight system blood is redirected away from your intestines and towards the exercising muscles and this redirection of blood is accomplished by the pre-cap resistance vessels Alternatively when one has just had lunch and the gut is busy digesting, blood is being directed to the blood and away from skeletal muscles This too is done by the pre-cap resistance vessels Structural feature involving their ability to set blood pressure and blood flow is the smooth muscle that lines the walls of these vessels allows the radius to be adjusted The smooth muscles in walls regulated by both the nervous system and the endocrine system (sympathetic system or hormones) They are also regulated by environmental condition When one is working out and the muscles are metabolically active and produce more CO2 and waste products local metabolic conditions will regulate blood flow so increased blood flow will get to the exercising muscles Pre-capillary sphincters These are just little bands of smooth muscle leading into the capillary bed They set blood flow at a local level They are not innervated and respond to local condition Help to determine where blood goes within the capillary bed This takes blood to the capillaries Capillaries Thin walled vessels Very numerous Form an extensive network so that any cell is predicted to be 3 or 4 cells Site of exchange Thin walls and high surface area help with the exchange High surface area results in low velocity of flow are also important for exchange More is coming later Post-capillary resistance vessels Blood exists the capillaries and flow into the post-cap resistance vessels These are the venoules and the smallest veins The walls of these vessels contain smooth muscle and so the radius can be adjusted to help control pressure within the capillary bed If constricted there is higher pressure in the capillaries Capacitance These are the large veins Highly distensible the walls are relatively thin Their walls contain smooth muscles and so the radius can be adjusted to the amount of blood that is present Allows them to function as capacitance vessels Large changes in volume but little change in pressure This is important they act as a volume reservoir When giving blood, blood is taken from the venous reservoir When one exercises and an increase in blood flow is needed, volume is immobilized from the venous reservoir to increase blood flow to exercising muscles If volume of the system is not adjusted to the volume of blood that is there Standing still/perfectly for two long and the skeletal muscle pumps cannot return blood to the heart Blood will pool in the lower extremities and the consequence of that is fainting This happens because Blood pools in the venous system which is very complaint and due to gravity blood will be pulled down Typically the muscles pump the blood pooled into the venous system back to the heart But in the case of standing perfectly still the muscles are not moving and so cannot do this This results in a decrease of venous flow to the heart and when this falls it results in a decrease in cardiac output This decrease in cardiac output reduces blood flow to the brain and the consequence of this is fainting. If there is no constant flow to the brain the circ system rearranges the position in order to redistribute the blood back to the brain The brain is very sensitive to lack of oxygen and requires constant flow Loss of blood also results ^^Capillary function These are the key to the circ system b/c its in the capillaries that exchange between tissues and blood occur Capillaries are important in the exchange of nutrients, gasses, waste products This occurs by diffusion The Fick equation basically tells you how much is diffusing and this is dependent on: The amount that is being transferred the amount that is transferred by diffusion depends on the gradient and the gradient is set by partial pressure or concentration if the cells are using oxygen you are given a partial pressure gradient for oxygen movement from the blood to the tissues using up glucose will give a concentration gradient Permeability Lipid soluble (O2 +CO2) vs lipid insoluble substances(or water soluble like glucose or urea/ ions/amino acids) Lipid soluble molecules can simple move through the walls of the capillaries through the cell membrane Water soluble compounds can only move through the walls of the capillaries either by being transported or by moving though water channels Capillaries vary in permeability and water channels that are present Depends on surface area Larger surface area the more diffusion Inversely proportional to the thickness of the walls Diffusion is harder to accomplish in a thick wall vs a thin wall

Types of capillaries Continuous capillaries Capillaries where there are no major gaps Just narrow intercellular clefts between the cells about 4nm in width Will allow water and ions to pass through But no proteins can enter through these clefts b/c the clefts are small In some areas there are no intracellular cleft ex the blood brain barrier This occurs b/c the capillaries in the brain have tight junctions instead of intracellular clefts Fenestrated capillaries These have holes/pores 80nm in diameter Increases the ease in which water soluble molecules can cross the walls These holes are still too small for proteins to go through Sinusoidal capillaries Has gaping holes between the cells And these holes are large enough for a blood cell to get through s well as an incomplete basement membrane

Lec 5 Capillaries manage fluid balance In a closed system animal has blood an interstitial fluid and these two fluids differ in compositon Blood contains blood cells and plasma proteins; intertsital fluid does not Interstitial fluid is 3x more in volume than blood Losing blod causes the interstitial fluid to become a sourceof fluid that brings the blood volume back to normal Capillaries allow fluid to move into the interstitial fluid or out of the interstitial fluid to maintain volume Fluid balance in capillaries is driven by two sets of pressrues There is a filtration pressure that tends to meove fluid out of the capillaries This is created by the hydrostatic pressure for blood that blood pressure There is also fluid pressure in the interstial tissues which is the ineetrstial fluid hydrostatic pressure Normally blood pressrure is greater than hydrostatic fluid pressure This difference tends to drive fluid out of the capillaires Filtration persure: blood pressure- intersitical pressure There is a difference in osmotic pressure between he interstitial flid and the blood his is beciase the blood has protesin and the interstitial fluid does not Osmotic ressure of blood is greater than that of the intestinal fluid and that tend to draw fluid into the capillairs Absorption pressure= osmotic pressure of blood- osmotic c pressure of IF If filtration pressure is greater than abosprtive pressure water moves out tf the capillaires and if the aborptive pressure is greater than filtration pressure water will move into the capillaries. Under normal odntions at the artieal end of the capillary there is a tendency to lose water b/c blood pressure is high and the osmotic pressure stays constant throughout the length of the capillary At the venous end bp is lower therefore there is a tendency for water to move back nto the capillaries. So essentially there isa circulation water exited at the arterial end and taken up at the venous end If these two things do not match fluid loss or fluid gain into the circ system will occur Starling Landis hypotheis There is a circulation within the capillaries with no net loss of fluid However this is not true The lost fluid is collected by the lymphatic system Carries the fluid and proteins that leak out and puts it back into the circ system

Lecture 6Lymohatic system There is overall a net loss of fluid from the capillaris this lost fluid or proteins needs to go back to the cirualatory system This retuen is the function of the lymphatic system The lymphatic system parallels the venous system; It has leaky lynoh capillariescollect fluid and protein that are lost from the cicurlatory syste and they return it to the circ system The lymph vessels are very thin walled and non musclr but they are compressed by surrounding muscles They have valves that direct fluid flow Fluid that accumulates in the lymoh capillarie are gradually moved into the circularoty system The lymh vesels empty into the lareg veisn in the neck This is where the lowerst pressures of the circulatory system are found Although lymph flow is not a large as carisct output Cariac out put=5l/min Lymphatic flo= 2ml/min Without the lymph flow to collectthe fluid and proteins you end up with odema Oedema occurs when the tissue swells The importnac eof the lymphatic system becomes mre porminant when its function is blocked Filariasis A diseases in which larval nematdes invade te lymphtic systm by blocking the lymph vessels resulting in extremely severe oedema Under normal condtions sometimes the lymphatic system cannot keep up with fluid lossKwashiorkers syndrome In K syndrome the individual is getting enough calories to maintain life but is protein deficient The consequence of this causes tissue oedema in the lower legs, feet and esp in the abdomen In K syndrome the lymphatic system is working normally The physiological basis of K syndrome Lloss of fluid into surrounding tissues is cause dbby insuffienct protein in the blood to balance the absorptive force and filtration force The filtration becomes greater than absorbption and so there is net loss of fluid As the fluid leaves the circ system and accumaltes in the tissues the hydrostatic pressure of the ISF increases As a result the filtration rate becomes smaller and balance is re-established where filtration=absorption except for the fact that tissue oedema persists If the lymphatic did clear away all the fluid; the cyle would just repeat itself Low osmotic pressure in the blood lowers th absorptive force and so there is net loss of fluid. Thisnet loss of fluid into the tissues increases the hydorsttic pressure of the fluid making the filtration force smaller and bringing things bck into balance But with significant tissue oedema

Control of regional circulation Circulatory system works on a propity system so the tissues that are least resistance to oxygen lack have the highest priority for blood flow Ex the brain-very susceptible to lack of O2 top of priority system; next in line are the Heart+ gas exchange organ. Everything else happens to be expendable If there isa problem with lack of blood the blood will be cut off from non essential tissies like the viscera in oder to maintain blood flow to the essential tissues Important definitions Ischemia Lakc of blood flow Hyperemia Higher blood flow than normal Active hyperemia Occurs when tissues are metaboliccaly active During exercise Reactive hyperemia The higher than usually blood flow that follows ischemia Reynauds syndrome People that sufer from this have an unsually strong response to cold Hands become white because blood flow is comletelt shut off It can be so strong that the tissues can become ischemic In odrde to reestibish blood flow one must apply an external heating source(running hands under warm water) Control mechanisms of different blood flow patterns Local mechanism Act at the level of the tissue; and neural and hormornal mechnsisms; higher level of control going donw to the tissues these mechs operate at the arteriole and pre-capillary sphincters control at arterioles allows blood to be directed to some tissues but not other in a flight-fight response conttrole of the arterioles seds blood tot heexercisin mucsles bu notto the digestive muscles or kidney control at precapillary spincters is within a tissue; regilatinfg blood flow within a capillary bed Neural and hromaonal mechanism Under control of the sympatheic nervous system Sympathetyi neurons release noradrenaline which then acts on 1 adrenergic receptors that are present in the smooth muscle of the arteriole walls When the 1 adrenorecepotrs are activated they increase cytosoclic calcium levels in the muscles cells;;the muscles contract and vasoconstriction occurs Blood vessels become smaller Vasomotor tone The background level of activity in the sympatheic nerve going to the smooth muscles of blood vessels An increase in symathic activity cause the vessels to constrict further but it can also decrease sympathetic acivity to decrease level of constirtcion/dilate No paarsympatheitc comonnent. It is all being run by the sympatheic system Tha 1 adrenorecprots proveds the mechanism to cause vasoconstriction These receptors are found in most arterioles but not in arterioles founf in the brain, heart, or lungs/gills The activiation of the sympathic nervous system will result in the shut down of blood flow to the viscera(abdomical organs) by causes vasoconsticiton but this will not affect bllod flow to the brain, heart or gas exchange organ helps maintain priority second level on control at the level or arteiroles based on the smypaththix nervous system but this time the adrenal medulla rekeases a curuclatin catecholamine this acts on the 2 receptor the 2 receptor are acatteered thoughout blood vessels and are found in the arteriole smooth muscle these cause the muscle to relax when they are activated the blood vessles dilate both the 1 and 2 recepotrs can be found in the same tissuehoweeer you will typically find slightl different distibutions between tissues the viscera is well endowned with -1 receptors skeletal muscles contin 1 receptors(how cold indiced lessesned blood flow to the hands work however they also contain a lot of 2 receptors which allow you to override the vasoconstrictory response in emergency situations when it is a teu fight orflight situation one gets a kick ofadrenealine adrenal gland suddenly releases adrenaline into circulation; when this happens adronergeic resceptors are activated and you get vasodilation in a true full out sympathetic panicblood flowis shut down to thhe viscera through the 1 receprots while at the sametime casuign vasodilation in the skeletal muscles allowing to escape from the predator all this is at the level of the smoot muscle of the arteriole wallLocal Control Meahcnissm ofbloodflow this controls arteriles and pre-capillarysphincters heat promotes vasodilation compounds produced and released from endothelial cells promotes vasodilation and ncreases blood flow ex nitricoxide inflammatory mediators promotes vasodilation and ncreases blood flow ex histamine metabolic control when tissues are metabolical active they automatically experience vasodilation and this does not require nerves or hormones this is ecause metabolic activity decreases O2 levels and increases CO2, proton, adenosine, K+ (collecviely known as metabolites) this combination f low O2 and high metabolites casues vasodilation this acts on the arterioles and the pre-capillaru sphincters it is also very highly developed in skeletal muscles skeletal muscles that are metabolic active experiences increase in blood flow and this is the basis of reactive huporemia pulmonary capillaries respond in the opposite fashion to oxygen low oxygen levels casues pulomary capillaries to constrict rather than dilate low O2 in the lung means that, thatpart of the lung is not getting good air flow th purpose of the lung is to take up oxygen theres no point sending blood to where there is no oxygen so this mechanism redirectsblood to where there is more oxygen on the other hadn in skeletal muscles, low O2 results in increased blood flow to dieliver O2 to exercising tissue

Physiological basis of: cold induced ischemia when exposed to cold the sympathetic system is activated shutig down blood flow to the hands this is caused by the response of 1 receptors lackof heat resultsin vasoconstriction In the case of reynauds syndrome blod would be comolelt shut off from the hands. Individual runs hands under warm water usinf heat to get the vessles to dilate reactive hyperemia when there is no blood flow to the tissues during ischemia, metabolism still contiains but oxygen is just not being supplied and those levels fall the metabolites are not being removed and so their levels increase CO2, adenosine, proton, K+ etc levels increase Thisis the basis of vasodialton in reactive hyperemia There is accumaltion of metabolite and loss of oxygen and so when blood flow is reestblished there is a higher than normal blood flow to bring ocnditions back normal.Control of blood pressure The maintence of blood flow is blood pressure Mainatning blood pressure mainatince blood flow to the brain, herat and lungs/gills The other value lies in the maintanence of fluid balance between the blood and the tissue Regukation of blood flow is accomplished by two mechanism Chronic emhanism Requires hours to days to come into effect and are based on the kidneys If bp is too high then one urinates more in order to reduce blood volume and this brings b back to normal Urine flow rate is being matched to either the increase or decrese in volime to bring it back to normal This is mechanism is great for lng term control of blood volume and blood pressure But does not help withmoment to moment processes Acute mechanism Based on neural reflex arc They specifically regukate hert rate and the raidus of the arterioles in order to control blood pressure They are based on P=QR See slide 50 Regulation of blood pressure= rgulaiton of P In order to regulate P; Q and R must be regulated as well Q= SV x HR Im mammals geart rate is adjusted more thn stroke volume R(Total periphery resisyance) Focus is mostly on arterioles Construction of arterioles resistance increase; if the arterioles are dilated resistance will go down Vsasoconstrcitio or vasodilation of arterioles tend to set pressure But do not foget the venous system Conriction of the venous system is important because it moves blood back to the heart Increasesvenous ceiling pressure and filles the ehart fuller to help increase crdiac output Regulating blood pressrure is mosly dependent on the regulation of heart rate and the radius of the arteriole In an acute sense Acute mechanism of bood pressure control is depende on neural reflex arcs One of the most important reflex arcsinvolved in regulation bp is the baroreceptor reflex arc Baroreceprors Sensory receptors that detect pressure as stretch in a blood vessel wall Found in the walls of blood vessles Thye are the sensory component of the neureal reflex arc Under normal conditions he barorecptors fire at an intermediate rate (pridce APs at a background rate) If pressure goes up the vessles expand a little bit and this casues the barorrecptorss to become mor e active telling the brain that bp has gone up. If bp falls blood vessles reduce in steetch and the baroreptor firing decreases and it tells the brain that blood pressure has fallen To allow for the maintencneof blod flowto the brain baroreptors are found in theaortic arch b/cthat monitors bp in the systemic circ as a whole The barorepors are alos found in the carotid sinus The arteirs taking blood from the heat to the veins are carotid arteries in the neck these arteries spilt and just at the end where they split there is a little widendin g called the crotid sinus The baroreports found here are perfectly placed to montor blood pressureto the brain. In this neural arc the information of blood pressureentring th beian goes to the cardiovasucla centre of the brain in the brainstem Takes int information coming from the barorepots Proceses the information and then ends out approtoare response These reposnes regulate heart rateand the smooth vessles of the blood vessel walls- the arterioles in particular