Bio 3302 Lec 2 Mechanisms of oxygen delivery and co2 removal is based upon 2 systems circulatory system and respiratory system Oxygen moves around in cells by the use of diffusion The time for diffusion depends on how far the oxygen has to travel Time required= distance2 As distance gets larger time required to increases fairly quickly Larger animals need a system to enhance the rate of delivery of oxygen Metabolic rate also come into play in terms of oxygen delivery The higher the metabolic rate the more oxygen needed Ex large animals with very low metabolic rates may not really need a circulatory system Ex 2 small animals with very high met rates may need a circ system in order for faster O2 delivery Once animal that is an exception to this rule of having a high met rate= having a circ system These are insects. They have the highest known met rates but dont use their circ system for oxygen delivery This is b/c they have a tracheal system which circulates gas until it is very close to the tissues and then oxygen diffuses from the end of the tracheal system into the mitochondria Circ system can also be used for Waste excretion Nutrient delivery Cell to cell communication Hormone transport Thermoregulation Circ syst will transport anything that can move in a fluid but it can also transport heat Generates force Animals with hydrostatic skeletons rely on fluid force generated by the circ system Animals that need to enlarge or extend an organ also uses the circ system to do so. Ex monarch butterfly Monarch caterpillars and they use the circ system to move Once they are done feeding off milkweed they will form into a crystal And they emerge from the crystals with their wings folded up the force that unfurls their wings is hydrostatic force provided by a circ system Circ system has 3 key elements A pump Usually a heart but not always The pumps work by generating force and pushing the fluid a head of them(+pressure) 3 basic types of pumps Peristaltic pump Ex type of heart found in insects and crustaceans Its a tube with muscular walls and a wave of contractions passes along the tube pushing the blood in front of it This heart has force generation and direction built into one Direction in which contraction moves determines the direction in which the blood moves Chamber pump with contractile walls Ex Human heart muscle chamber and when muscle contracts it squeezes the blood pushing it out in order for blood to move in the right direction a series of valves are needed to direct the flow chambered pump with non-muscular walls; but is surrounded by external factor(muscle) that compresses this also needs valves to direct flow the external muscle will contract squeezing the chamber and then the valves determines where the fluid flows ex of this type of pump in humans The large veins in the leg act as chambers to collect blood and when one moves their legs muscle contraction squeeze those veins to return blood to the heart. Network of vessels(vascular system) 3 types of tubes Arteries Take blood from heart to the periphery of the animal Capillaries Specialized for exchange of material Veins Collect blood from periphery and take it back to the heart Not all 3 are present in all animals Collectively known as vascular system or peripheral system Circulating fluid This can be blood or haemolymph Open vs closed system shows where you see the presence or absence of the diff types of blood vessels(bvs) Open Circulatory System Animals with open circ system do not have capillaries Blood will be pump by the heart into a set of arteries form there it goes to the tissues directly The blood bathes the tissues directly; there is only exchange between the circulating fluid and the tissues themselves Circulating fluid is then collected up and returned back to the heart and this may/may not involve some type of venous system It is quite difficult to direct flow with an open system Tend to be low flow, low pressure, low resistance systems If the system of vessels is open one cannot distinguish between the circulating fluid and the fluid that is bathing the tissues directly Animals with open circ systems have haemolymph instead of blood Makes up 30% of animals body mass Closed Circulatory system The blood is in vessels the entire way; from leaving the heart to returning to the heart Animals with higher met rates tend to have closed circ systems This is a evolutionary trend Reason for this trend is the ability to better control the rate of blood flow and hence the rate of O2 delivery with a closed separated system As met rate increases you tend to see the trend of closed circ system Within these animals a second trend can be seen As met rate goes up there tends to be more separating of blood flow to the gas exchange organs(resp circ) and blood flow to the rest of the tissues(systemic circ) As met rate goes up there is an increased separation between the respiratory and systemic circulatory systems The animals with higher metabolic rates are air breathers and along with this there is a shift to separating out the respiratory and systemic circulation Basic fish plan; Closed implies that there is a complete set of vessels Blood leaves the heart and arteries exchange between the tissue and blood occurs in the capillaries and blood returns to the heart in veins It is a continuous circuit of vessels with an exchange between the circulating fluid and the tissues happening at the capillaries These circulatory systems are found in all vertebrates(fish, amphibians, reptiles, mammals, birds) and in a number of invertebrates particularly ones that have a high metabolic rate(cephalopods-squid and octopus; or in animals that use the circ system for a hydrostatic skeleton-earth worm) b/c blood is circulating in vessels all the time the circ system provides quite a bit of resistance to flow and so higher pressures must be generated in order to move the blood through the closed systems of vessels these are often considered to be high pressure/high resistance systems more force must be generated to move the fluid around but they are able to direct and control the speed of the flow In this case one can distinguished between the circulating fluid(blood) and the fluid that bathes the tissues (interstitial fluid ISF) Blood contains red blood cells and proteins in the palms ISF lacks both rbcs and proteins Keeping blood and ISF separate is quite important Plasma proteins that escape from the blood and into the ISF have to be collected up and returned to the blood The is a function of the lymphatic system Together the blood and ISF make up the ECF(in both closed and open systems) ECF accounts for about 30% of body mass But in this case blood is only about 5% of that total with the remaining amount being the ISF Fish The circulatory plan in the fish is fairly simple Blood is pumped by the heart, goes to the gills and is oxygenated, the oxygenated blood is carried to the systemic tissues where it gives up its oxygen and the blood returns to the heart The problem with this circ sys is that the heart has to pump blood to the gills and the systemic circulation both of which are sites of resistance Heart must generate relatively high pressures The gills as the first point of the system are going to see relatively high points of pressure They are able to withstand this because there is water on the other side of the gill to counter balance this pressure Pressure of the system as a whole is limited to the pressure that the gills can withstand Fish heart has 4 chambers in a series Blood enters the sinus venoses the atrium ventriclebulbous or conus arteriosis The ventricle is where the main force generation occurs Bulbous and conus arteriosis are structurally different but share the same purpose functionally which is to maintain blood flow when the heart relaxes Same function as the aorta in a mammal Sinus venosus is only found in fish; it disappears it land living organisms Mammals and birth Essential there are 2 two chambered hearts They are physically together in the same organ however when broken down you have 2, 2 chambered hearts The left side of the heart and a right side. Left side Always on the right when looking at a diagram and right side is the left in the diagram The left side of the hear takes blood returning from the lungs and pumps it out to the systemic circulation The right side of the heart takes blood returning from systemic circulation(deoxygenated) and it pumps it to the lungs to be oxygenated Each side of the heart both have an atrium and a ventricle Left for systemic; right for pulmonary Low pressure is needed in the pulmonary circuit and high pressure in the systemic circulation This is possible because in effect they have 2 hearts The left/right sides are operating independently So the left ventricle can generate high pressure to send blood to the systemic circulation The right ventricle generates lower pressure to send blood to the pulmonary circuit The only problem with this circulatory design is that blood flow always has to go to both parts As it comes back from the systemic circulation it has to go back to the pulmonary circuit There is no way to stop blood flow to the lungs (like when you hold your breath...doesnt happen bud) Intermittent air breathers- amphibians; reptiles+ air breathing fish Typically have lower metabolic rate Heart has 2 atria; one for blood collection from the lungs and one that is collecting blood from the systemic circulation Typically has one ventricle- that directs the flow of blood to the tissues In reptiles its partially separated into a left and right ventricle In amphibians there is only one ventricle So deoxygenated blood from the tissues and oxygenated blood from the lungs come into the same ventricle and are pumped out to the lungs and tissue Even though there is a single ventricle the oxygenated and deoxygenated blood is relatively separated The mechs for this are not well understood Blood pressure in this animal as a whole is fairly low Having a high bp will destroy its lung Bp is limited by what the lungs can withstand Low bp and low met rate animals The advantage of this is that when the animal is under water/ holding its breath the lungs become useless So the system reduces blood flow to the lungs and redistributes it to the skin where it can still take up oxygen When it resurfaces it redistributes the blood back to the blood It has the capacity to shunt blood to diff organs depending on its require The presence of a single ventricle makes this possible Same idea is seen in reptiles though there is as light separation in ventricles Same plan in air breathing fish lung fish These fish can drown Obligate air breathing fish without any access to air they will drown They have a set out gills, a lung and a heart They have low met rates Tend to breath once every five minutes During the rime spent underwater the animal is depleting the oxygen in its lung There is a single 4 chambered heart (like a standard fish heart) As the blood leaves the heart it is directed to the gills The gills are separated into anterior gills which are not used for O2 uptake and posterior gills which are used for O2 uptake From the posterior gills the blood moves up either to the lung-if there is usable oxygen here- or if there is no useable O2 in the lung the ductus opens up and directs the blood from the gills to the systemic tissues Oxygenated blood is directed by anterior gills to the tissues Deoxygenate blood is directed to posterior gills which direct to lungs if there is air there or it its directed to the tissues The state of the ductus determines whether the blood goes to the tissues or to the lungs The ventricle generates pressure for the lungs, gills, systemic tissues. Systemic circuit as a whole Must be a low pressure pump so the lungs are blown These are low met rate animalsLecture 3Mammalian heart Systemic half on the left has much thicker walls which allows for higher levels of pressure Blood returning from lung enters the left atrium and from there goes into the left ventricle and is pumped out to the systemic tissue where it is deoxygenated The deoxygenated blood is pumped into the right atrium and then into the right ventricle and is pumped out to the lung This heart is a chambered heart with contractile walls and based on this there are valves that direct blood flow In the mammalian heart there are vales between the atria and the ventricles to control blood flow Heart is made of cardiac muscle It is similar to skeletal muscle These are considered to be striated because they contain sarcomeres They are quite short and are connected end to end by intercalated discs In these discs one will find gap junctions Which are communicating junctions that allow electrical communication between the different cells of the heart so they can contract as a unit The heart is innervated by the ANS Within the ANS; there are 2 divisions Sympathetic Responsible for fight/flight alarm type situations Neurotransmitter of choice is noradrenaline Interact with receptor in the tissues that are adrenergic receptors B-1 receptors are more important for the heart Parasympathetic Responsible for housekeeping or vegetative functions the rest and digest system Responsible for functions outside of alarm situations Neurotransmitter of choice is acetylcholine Interacts with muscular genic receptors in the effector organ Main one for the heart is the m2 receptor Both sympathetic and parasympathetic divisions are active and in most tissues you can find innervation from both Heart is innervated by both but they have opposite affects Sympathetic will increase heart rate to allow for response in emergency situation Parasympathetic will slow it down They have antagonistic effects ANS allows good control of internal functions without any conscious control Most of the heart is made of cardiac muscle cells and these come in two types 99% is made up of strongly contractile muscle cells Packed full of sarcomeres; responsible for generating force Other 1% are the cells of the conducting system Pacemaker cells They do not have a lot of contractile apparatus They are specialized for controlling and coordinating heart beat Include the cells of the sinoatrial node, the atrial ventricular node and the other cells forming the conducting system that direct electrical activity over the heart as a whole The pacemaker cells have a resting potential that is quite unstable They have arresting potential that changes over time-pacemaker potential and the presence of this changing resting potential is the key characteristic of a pacemaker cell The pacemaker cells slowly depolarize because of the changing membrane potential and when they reach a certain threshold they trigger an action potential which the trigger a heartbeat/ contraction of heart Initiate heart beat+ control it The pacemaker potential reflects the presence of the funny channel It is considered to be funny because it is open and then slowly closes and it functions as a Na+ leak channel Allows Na+ to leak into the cell causing a gradual depolarization Also present in the cell are voltage gated Ca2+ channels(t-types) when the membrane potential depolarizes to the threshold these channels open and it creates an action potential this is what initiates the heart beat in a vertebrate heart and because it is a muscle cell for the initiation of this heart beat; vertebrates hearts are considered to be myogenic neurogenic: nervous activity activate heart beat gap junctions allow electrical communication between cells once an action potential is fired within a cell that is then spread to the other cells in their heart spreads from one heart cell to another by the gap junctions the heart rate is then set by the cells that depolarize most quickly and these happen to be the cell of the sinuses venoses in fish or sinoatrial node in mammals pacemaker cells set the heart rate the pacemaker cells in human sinoatrial node fire at rate of 100 time per minute 100 depolarizations a minute This means the heart rate should be 100beats/min Heart beat is controlled by other mechanisms There is input from the parasympathetic nervous system that regulates heart rate Sinoatrial node is in the atrium of the mammalian heart and it fires its action potential first and this spreads across the atria real quick It slows down when it gets to the atrial ventricular node There is a layer of connective tissue between the two atria and the two ventricle The cells of the atria re connected by gap junctions and the cells of the ventricle are connected by gap junctions But the atria and the ventricles do not communicate This layer of connective tissue means there is no electrical communication between the atria and ventricles except through the atrial ventricular node Conduction though this part of the system is quite slow Once it gets through this system it speeds up tremendously and shoots up through the ventricles at a rate of 4or 5 m/s ECG Measures the consequence of all the action potentials in the bod fluid as a whole It is the sum effect of all the action potentials happening together Measured by placing electrodes upon the bodys surface not by trying to impale a single heart cell to measure membrane potential of that cell In the standard mammalian EKG there is a small wave called the p wave This shows the atria depolarizing There is a larger wave(QRS): this is the ventricles depolarizing Small t wave- this is the ventricular repolarization The repolarizing of the atrium is not seen because it occurs at the same time that the ventricles depolarize and so it is masked by this Value of the EKG tries to figure out what is going on in the heart The heart as a pump Electrical activity in the conducting system has to be converted into muscle contractions in 99% contractile part of the heart To get these cells to contract the heart first has to be depolarized A strong action potential is needed in the muscle contractile cells (an ex can be found in slide 22/23) There is stable resting potential; there is a strong depolarization, then there is a plateau phase Slide 22 Action potential f contractile cells Stable resting potential and when it is triggered it undergoes depolarization and a voltage gated Na+ channel opens allowing Na+ to pour into the cell and this gives you a strong depolarization There is also a voltage gated Ca2+ channel that opens a little bit later and this calcium channel stays open for a while and that is how one gets the plateau region This is an L-type gates calcium channel; in pacemaker there is a t-type calcium channel The flow of calcium into the cell triggers calcium release from stores within the cell Not only have calcium moving into the cell through the voltage gated channels you also have calcium being released from stores inside the cell The release of these stored calcium the triggers the contraction of the cell Calcium inflow + calcium released=occurrence of muscle contraction The cell then repolarizes and this represents a K+ channel that is opened which allows K+ ions to flow out. Note in the diagram there is a prolonged plateau phase and a refractory period This is long refractory period is important because the heart has to relax and refill with blood before it can contract again So the refractory period allows for the cells to rest and reset as well as gives time for the heart to relax and be refilled with blood The long plateau in the action potential is necessary because it allows all the muscle cells to contract at the same time This also makes sure that the heart cannot go into a tetanic contraction-no muscle cramp in the heart Refractory period: period where the cell is resting before another AP can occurSlide 23 Systolic When heart is contracting Diastolic When the heart is relaxing Stroke volume Volume of blood pumped b the heart When heart contracts it ejects a volume of blood called the SV and this is the difference in volume of the heart when it is full(end diastolic volume) and after it contracts(end systolic volume) Most of the filling of the ventricles is due to venous pressure The valves between the atria and ventricle sis open and so the blood flow through the valves to the ventricle from the atria This is driven by venous pressure; the atrial contraction helps but it is only responsible for 1/3 of the volume in the ventricle Venous pressure does all the work For the heart to function properly output from the heart must match the need for oxygen delivery This can be achieved by increasing heart rate or stroke volume Regulation of stroke volume is referred to as inotropic control and its caused by both a mechanical relationship and neural and hormonal control The mechanical relationship is the frank-starling relationship See in slide 23 It shows that as end diastolic volume increases(as heart if filled) SV also increases The fuller the heart the more forceful the contraction and this ejects more blood It is ;mechanical b/c as you fill the heart fuller it stretches out muscle and this result in a more forceful contraction Very important because you always want to empty the heart to the same point so by filling the heart fuller you need more blood out of it to get back to the same empty point As heart rate goes higher there is less time needed to fill it with blood and so the SV gets smaller there hormonal and neural; mechanisms to accompany the mechanical relationship and these mechs work to stoop stroke volume from falling Neural/hormonal control of the heart The sympathetic nerves innervate the ventricles and strongly contractile muscle cells they release noradrenaline which acts on 1 androgenic receptors and this increases the force of contraction As you increase sympathetic activity at any given volume more blood is released from the heart; vice versa for decreased sympathetic activity Frank Starling relationship describes the change in SV for a change in filling For any given level of sympathetic stimulation there is a spec frank starling curve (only sympathetic control over SV) Circulating catecholamines Sympathetic cells release noradrenaline The cell that you find in the centre of the adrenal gland are sympathetic neurons but instead of releasing neurotransmitter onto the nerve it releases the NTM into the blood and it circulates as a hormone Which is responsible for the fight or flight response This too can regulate strong volume by acting on the 1 adrenergic receptors heart rate controlling heart rate is the chonotropic effect the pacemaker is innervated by both the sympathetic and parasympathetic systems contains 1andrenrgic receptors activated by sympathetic system or by circulating catecholamines also contains m2 muscarinic receptors activate by ACh which are activated by the parasympathetic system sympathetic leads to an increase; parasympathetic causes it to decrease Sympathetic nervous system When the 1 receptor is activated by adrenaline or noradrenaline it acts to open the sodium channels more to get a faster depolarization(faster pacemaker potential) parasympathetic When ACh acts on the m2 receptors it has the effect of opening up potassium channels which allows positively charged ions escape from the cell and there for it depolarizes more slowly The consequence of this is as low heart rate At rest both the sympathetic and parasympathetic systems are active Sympathetic tone which helps set the resting heart rate Parasympathetic tone Parasympathetic nerve that goes to heart is the vagus nerve(can also be called vagal tone) This also helps set the resting heart rate. Chonotropic effects only affects the pacemaker potentialBIO3302

Lec 4

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 composition Blood contains blood cells and plasma proteins; interstitial fluid does not Interstitial fluid is 3x more in volume than blood Losing blood causes the interstitial fluid to become a source of 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 pressures There is a filtration pressure that tends to move fluid out of the capillaries This is created by the hydrostatic pressure for blood that blood pressure There is also fluid pressure in the interstitial tissues which is the interstitial fluid hydrostatic pressure Normally blood pressure is greater than hydrostatic fluid pressure This difference tends to drive fluid out of the capillaries Filtration pressure: blood pressure- interstitial pressure There is a difference in osmotic pressure between he interstitial fluid and the blood his is because the blood has proteins and the interstitial fluid does not Osmotic pressure of blood is greater than that of the intestinal fluid and that tend to draw fluid into the capillaries Absorption pressure= osmotic pressure of blood- osmotic c pressure of IF If filtration pressure is greater than absorptive pressure water moves out of the capillaries and if the absorptive pressure is greater than filtration pressure water will move into the capillaries. Under normal donations at the arterial 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 into the capillaries. So essentially there is a 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 hypothesis 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 6Lymphatic system There is overall a net loss of fluid from the capillaries this lost fluid or proteins needs to go back to the circulatory system This return is the function of the lymphatic system The lymphatic system parallels the venous system; It has leaky lymph capillaries collect fluid and protein that are lost from the circulatory system and they return it to the circ system The lymph vessels are very thin walled and non-muscular but they are compressed by surrounding muscles They have valves that direct fluid flow Fluid that accumulates in the lymph capillaries are gradually moved into the circulatory system The lymph vessels empty into the large veins in the neck This is where the lowest pressures of the circulatory system are found Although lymph flow is not a large as cardiac output Cardiac output=5l/min Lymphatic flow= 2ml/min Without the lymph flow to collect the fluid and proteins you end up with oedema Oedema occurs when the tissue swells The importance of the lymphatic system becomes more prominent when its function is blocked Filariasis A diseases in which larval nematodes invade the lymphatic system by blocking the lymph vessels resulting in extremely severe oedema Under normal conditions sometimes the lymphatic system cannot keep up with fluid lossKwashiorkors 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 Loss of fluid into surrounding tissues is caused by insufficient protein in the blood to balance the absorptive force and filtration force The filtration becomes greater than absorption and so there is net loss of fluid As the fluid leaves the circ system and accumulates 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 cycle would just repeat itself Low osmotic pressure in the blood lowers the absorptive force and so there is net loss of fluid. This net loss of fluid into the tissues increases the hydrostatic pressure of the fluid making the filtration force smaller and bringing things back into balance But with significant tissue oedema

Control of regional circulation Circulatory system works on a priority 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 is a problem with lack of blood the blood will be cut off from non-essential tissues like the viscera in order to maintain blood flow to the essential tissues Important definitions Ischemia Lack of blood flow Hyperemia Higher blood flow than normal Active hyperemia Occurs when tissues are metabolically active During exercise Reactive hyperemia The higher than usually blood flow that follows ischemia Reynauds syndrome People that suffer from this have an unusually strong response to cold Hands become white because blood flow is completely shut off It can be so strong that the tissues can become ischemic In order to re-establish 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 hormonal mechanisms; higher level of control going down 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 others in a flight-fight response control of the arterioles seeds blood to the exercising muscles but not to the digestive muscles or kidney control at precapillary sphincters is within a tissue; regulating blood flow within a capillary bed Neural and hormonal mechanism Under control of the sympathetic nervous system Sympathetic 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 cytosolic 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 sympathetic nerve going to the smooth muscles of blood vessels An increase in sympathetic activity cause the vessels to constrict further but it can also decrease sympathetic activity to decrease level of constriction/dilate No parasympathetic component. It is all being run by the sympathetic system The 1 adrenorecepotrs provides the mechanism to cause vasoconstriction These receptors are found in most arterioles but not in arterioles found in the brain, heart, or lungs/gills The activation of the sympathetic nervous system will result in the shutdown of blood flow to the viscera(abdominal organs) by causes vasoconstriction but this will not affect blood flow to the brain, heart or gas exchange organ helps maintain priority second level on control at the level or arterioles based on the sympathetic nervous system but this time the adrenal medulla releases a circulating catecholamine this acts on the 2 receptor the 2 receptor are scattered throughout blood vessels and are found in the arteriole smooth muscle these cause the muscle to relax when they are activated the blood vessels dilate both the 1 and 2 receptors can be found in the same tissues however you will typically find slightly different distributions between tissues the viscera is well endowed with -1 receptors skeletal muscles contain 1 receptors(how cold induces lessened blood flow to the hands work however they also contain a lot of 2 receptors which allow you to override the vasoconstrictor response in emergency situations when it is a true fight or flight situation one gets a kick of adrenaline adrenal gland suddenly releases adrenaline into circulation; when this happens adrenergic receptors are activated and you get vasodilation in a true full out sympathetic panic blood flow is shut down to the viscera through the 1 receptors while at the sometimes causing vasodilation in the skeletal muscles allowing to escape from the predator all this is at the level of the smooth muscle of the arteriole wallLocal Control Mechanism of blood flow this controls arterioles and pre-capillary sphincters heat promotes vasodilation compounds produced and released from endothelial cells promotes vasodilation and increases blood flow ex nitric oxide inflammatory mediators promotes vasodilation and increases blood flow ex histamine metabolic control when tissues are metabolically active they automatically experience vasodilation and this does not require nerves or hormones this is because metabolic activity decreases O2 levels and increases CO2, proton, adenosine, K+ (collectively known as metabolites) this combination of low O2 and high metabolites causes vasodilation this acts on the arterioles and the pre-capillary 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 hyperemia pulmonary capillaries respond in the opposite fashion to oxygen low oxygen levels causes pulmonary capillaries to constrict rather than dilate low O2 in the lung means that, that part of the lung is not getting good air flow the purpose of the lung is to take up oxygen theres no point sending blood to where there is no oxygen so this mechanism redirects blood to where there is more oxygen on the other hand in skeletal muscles, low O2 results in increased blood flow to deliver O2 to exercising tissue

Physiological basis of: cold induced ischemia when exposed to cold the sympathetic system is activated shutting down blood flow to the hands this is caused by the response of 1 receptors lack of heat results in vasoconstriction In the case of Reynauds syndrome blood would be completely shut off from the hands. Individual runs hands under warm water using heat to get the vessels to dilate reactive hyperemia when there is no blood flow to the tissues during ischemia, metabolism still contains 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 This is the basis of vasodilation in reactive hyperemia There is accumulation of metabolite and loss of oxygen and so when blood flow is re-established there is a higher than normal blood flow to bring conditions back normal.Control of blood pressure The maintenance of blood flow is blood pressure Maintaining blood pressure maintains blood flow to the brain, heart and lungs/gills The other value lies in the maintenance of fluid balance between the blood and the tissue Regulation of blood flow is accomplished by two mechanism Chronic mechanism 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 decrease in volume to bring it back to normal This is mechanism is great for long term control of blood volume and blood pressure But does not help with moment to moment processes Acute mechanism Based on neural reflex arc They specifically regulate heart rate and the radius of the arterioles in order to control blood pressure They are based on P=QR See slide 50 Regulation of blood pressure= regulation of P In order to regulate P; Q and R must be regulated as well Q= SV x HR In mammals heart rate is adjusted more than stroke volume R(Total periphery resistance) Focus is mostly on arterioles Construction of arterioles resistance increase; if the arterioles are dilated resistance will go down Vasoconstriction or vasodilation of arterioles tend to set pressure But do not forget the venous system Constriction of the venous system is important because it moves blood back to the heart Increases venous ceiling pressure and fills the heart fuller to help increase cardiac output Regulating blood pressure is mostly dependent on the regulation of heart rate and the radius of the arteriole In an acute sense Acute mechanism of blood pressure control is depends on neural reflex arcs One of the most important reflex arcs involved in regulation bp is the baroreceptor reflex arc Baroreceptors Sensory receptors that detect pressure as stretch in a blood vessel wall Found in the walls of blood vessels They are the sensory component of the neural reflex arc Under normal conditions he baroreceptors fire at an intermediate rate (produce APs at a background rate) If pressure goes up the vessels expand a little bit and this cause the baroreceptors to become more active telling the brain that bp has gone up. If bp falls blood vessels reduce in stretch and the baroreceptor firing decreases and it tells the brain that blood pressure has fallen To allow for the maintenance of blood flow to the brain baroreceptors are found in the aortic arch b/c that monitors bp in the systemic circ as a whole The baroreceptors are also found in the carotid sinus The arteries 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 widening g called the carotid sinus The baroreceptors found here are perfectly placed to monitor blood pressure to the brain. In this neural arc the information of blood pressure entering the brain goes to the cardiovascular centre of the brain in the brainstem Takes int information coming from the baroreceptors Processes the information and then ends out appropriate response These responses regulate heart rate and the smooth vessels of the blood vessel walls- the arterioles in particularBIO3302 Lec 7

Lec 6 recap Baroreceptor reflex is one of the really important neural pathways for the acute regulation of blood pressure But its not the only neural pathway There are chemoreceptors that detect blood and CO2 levels that help regulate blood pressure Baroreceptors are still the key mechanism for the adjustment of blood pressure on a moment to moment basis Going from lying down to standing up They are sensory receptors in the all of the aorta and carotid sinuses and are activated by stretch Have a resting firing rate and as pressure goes up they fire more, as pressure falls they fires less This degree of firing is integrated by the cardiovascular center in the medulla and appropriate output is sent to the effector organs(heart and smooth muscle in blood vessel walls) and they adjust pressure To adjust pressure heart rate and vasoconstriction of the arterioles are adjusted and this occurs in a negative feedback fashion Slide 52 Arterial blood pressure has increased Could happen if one quickly drink a large volume of water Or going from standing up to lying down Increase in bp and want to bring down to the normal value This increase is detected by the baroreceptors Causes the firing to increase Firing is detected and integrated by the cardiovascular center in the brain stem It adjust the sympathetic and parasympathetic activity in the heart and blood vessels Heart If blood pressure increased, decrease cardiac output must occur to bring heart rate down Parasympathetic control So heart rate has to slow down by increasing the parasympathetic activity through the vagus nerve and m2 receptors Need to increase vagal tone The increase in parasympathetic activity will in turn decrease heart rate and decrease cardiac output Sympathetic control Decrease in sympathetic activity will lower heart rate and stroke volume 1 receptor activation allows for this all of these process will lower heart rate and in turn lower blood pressure the vasomotor center in order to reduce bp vasodilation is needed in this center vasodilation is achieved by decreasing sympathetic activity which decreases tonic activity in the arteries and veins and this will cause them to dilate which lowers resistance and reduces bp 1 receptors are involved when baroreceptors are at the normal resting value, then everything is in the tonic/background level of activity and there is no need to change activity as soon as activity changes and any minor changes in bp are immediately corrected through this pathway problem with baroreceptors is that they adapt to the change of pressure over time if one has consistently high bp(hypertension) the baroreceptors reset so that the high bp becomes the new norm same thing for hypotension the adjustment of vasodilation/constriction arterials cause an immediate effect on pressure b/c such activity affects resistance on the other hand the adjustment of vasomotor tone to the venous system, venous return is affected which affects cardiac output which affects blood pressureExercise increases met rate an in turn increase O2 consumption by 5-10x this mean that increased oxygen delivery to the exercising tissues in part this oxygen delivery is the responsibility of the circ system to meet the high O2demand caused by exercise an increased cardiac output is needed so more o2 can get to the tissues there is also a redistribution of cardiac output some tissues are not used very much where other are heavily used the blood is redistributed to meet the needs of the tissues slide 54 the blood flow priorities during rest+ exercise Large increase in cardiac out put Significant changes where the blood is going to But these changes occur with only small consequences on blood pressure P=QR P remains the same Increase in Q R would decreaseCirculatory responses to exercise Hyperemia Exercising muscles need increased blood flow Active hyperemia is one method of achieving such It is a local metabolic effect Even before you start exercising there is an increase in sympathetic activity in anticipation of exercise This causes dilation of some of the blood vessels in skeletal muscles b/c some of the sympathetic neurons can release ACh As the sympathetic system is activated there is some vasodilation to the skeletal muscle As soon as the muscle starts exercising active hyperemia takes over and massive blood flow to exercising muscle can occur Increases Cardiac Output This increase in blood flow has to be met with increasing cardiac output The increased sympathetic activity increases heart rate and the force of contraction of the heart Peripheral Vasoconstriction This will be achieved through the1 receptors Blood flow going to abdominal organs will be reduced It could cause vasoconstriction in muscle fibers but active hyperemia takes over Does cause constriction of the veins; this is a benefit because it increases venous return and this helps to increase cardiac output As you exercise the skeletal muscle pumps in the legs also promote venous return and this helps cardiac output An increase in cardiac output tends to increase bp, however at the same time there is an increase in cardiac output there is an overall fall in peripheral resistance The fall in peripheral resistance is driven primarily by vasodilation in skeletal muscles There is vasoconstriction to abdominal muscles but this constriction is offset by the vasodilation in the skeletal muscle So over all resistance falls and cardiac out increases and pressure stays the same