Greetings. So today we want to continue our discussion of the circulatory system. In particular we want to talk about the plumbing. That is, the vessels by which the blood is flowing through the body to deliver oxygen to the tissues and remove waste materials from those tissues. So you all know that the heart is the pump for the circulatory system. These are the blood vessels. The vessels plus the heart form a closed system. Our learning objectives are to describe the function of the arteries, the arterioles, capillaries, venules and veins. These are the various vessels through which the blood will be flowing. And secondly, we want to describe the relationship between pressure, flow, and resistance in regulating the distribution of the blood throughout the body. Third, we want to define the systolic, diastolic, and mean arterial pressures. You've already heard about systolic pressure and diastolic pressure. Simply, systolic is the pressure generated by the heart when it's ejecting blood. Diastolic pressure is the pressure that's within the vessels when all of the valves are closed and no blood is leaving the heart to enter into the arterial system. Then fourth, we want to explain what's known as the myogenic response, active and reactive hyperemia, and then reflex control of the blood vessel's resistance. Then five, we will talk about the factors that affect the trans-capillary movement of fluids and solutes. This is the way we deliver these fluids and solutes into the tissues. It is by local diffusion. Then six, we wan to explain the differences between capacitance and distributing vessels and the relationship between the blood circulation and the lymphatic circulation. So we have a very large list of items to cover, so let's get started. So the first is to consider the actual circulatory system. As I said, we have a heart. The heart is, essentially, composed of two separate hearts that are in series. The first is the right side. The right ventricle delivers blood to the lungs for oxygenation. Then oxygenated blood is returned to the left ventricle. The left ventricle then distributes the blood to the rest of the body. As the blood is ejected from the left ventricle it enters into a series of vessels which are called arteries. Of the vessels at the very beginning, the largest is the aorta. The aorta is what's called an elastic artery. This is an artery that has a lot of elastic tissue within its walls. It's able to stretch and then contract readily. These elastic arteries drain into what are called muscular arteries. The muscular artery is simply an artery that has more muscle in its wall, then elastic. These muscular arteries are the arteries which deliver the blood to specific organs. The delivery of the blood to the specific organs is going to be in parallel. When we deliver blood to the kidney, it's independent of delivery of the blood for instance to the the GI tract or to the lung. Once the blood is delivered to the specific organ, then it enters into the organ. And within the organ the distribution within the organ will be governed by what are called arterioles. The arterioles are little spigots within the system. And they are the ones that determine which portions of the organ will be perfused. From the arterioles, the blood drains into the capillaries. This is the site where we have exchange of solutes and fluids, such as water, between the tissue and the bloodstream, itself. Then draining from the capillaries are the smallest of the veins, the venous system. Tese vessels are called venules. These venules drain into veins. The veins eventually return to the heart. finally, the return of the blood to the heart is through the vena cavas. The veins have the largest capacity within the system. Most of the blood is actually sitting in the veins at any one time. Something about 60 to 70% of the total blood is within the venous system. It is on the vein side. In addition to that, the veins are a low-pressure system. The veins have valves. The blood is able to move through this system in a unidirectional manner, but cannot move in the opposite direction. The valves prevent back flow through the system. So the veins have large capacity and low pressure. This is in contrast to the aorta and the elastic arteries and the muscular arteries are a high pressure system. In this particular side then the pressure that is being generated by the heart is delivered into the aorta and then from the aorta into the arteries. There is a high pressure system on that side. Okay, so what are the rules for the cardiovascular system? So the first rule is that the flow of blood, is going to be unidirectional through the system. That the flow is generated by a pressure gradient, which is generated by the heart. Flow will go from high to low pressure states. The second is that the resistance will oppose flow as the blood is moving through the vessels. There's a certain resistance to the blood flow due to the blood cells bumping up against the walls, the fluid bumping up against the walls, and the blood cells themselves bumping up against each other. So there's a resistance to flow within the system. The resistance is dependent on the length of the tubes which in the human, is essentially fixed once you reach the adult state. Secondly, it is depedent on the radius of the tube. This is the most important factor. This is the control site. If you change the radius of the tube, you can increase resistance within the tube. If you make the radius smaller, smaller diameter vessel, then has a higher resistance. [COUGHING] Excuse me. We'll come back to that point later. Resistance is dependent on the viscosity of the blood. As you know if you do blood doping you can increase the viscosity of the blood. If you have dehydration then the loss of volume from the vasculature can increase the viscosity of the blood. But these are unusual circumstances. Under normal circumstances, the viscosity of the blood is not a factor. The third thing that we have to think about is flow rate. That is simply the volume of the blood that passes through a given point per unit time. This is liters per minute. This will be determined by the pressure gradients and by the resistance within an area. And last, we have the velocity of the blood. This is how far the volume of blood travels per unit of time. This is in millimeters per second. This is determined predominantly by cross sectional area. The slowest flow, the slowest of velocity or speed of flow through the system will be found in the capillaries. The capillaries are very small diameter vessels, but there are many, many, many capillaries. The total cross sectional area of the capillaries is quite large. So the flow then will be very slow across the capillaries. This will be important because we need to have time for exchange of the solutes and fluids across the capillaries with the tissues. This, of course, is by diffusion. So we need some time for the diffusion to occur. There is slow flow then through the capillaries. Okay, so let's look at the pressure gradients through the entire system. We'll only consider the pressure gradients through the circulatory system that's delivering blood to the body. Initially when the blood is ejected, it has a systolic pressure. The systolic pressure is usually 120 mmHg. We'll consider it to be 120 millimeters of mercury. And the diastolic pressure will be 80 mmHg. When the blood is ejected, then we have a high pressure. But as blood is no longer ejected from the heart and is entering the aorta, the pressure will drop. It drops within the aorta. Note that there is a pulsatility of pressure within the blood entes the aorta. That's the difference between systolic pressure and diastolic pressure. That pulsatility is maintained through the aorta and through the elastic arteries and into the muscular arteries. This pulsatilty is actually quite important. What happens is that in the elastic arteries, as the blood is being delivered to them, we have a systole. We have a high pressure. This causes the walls of the arteries to stretch. There a lot of volume that's being delivered to the vessel. It is the stretched walls of the aorta that maintains the pressure gradient in diastole. Recall that in diastole there's no blood being leaving the heart. But there is blood within the elastic artery. The elastic artery recoil then, is presses against the fluid and maintains the pressure gradient. The elastic artery stretches with a change in volume. It changes volume with a change in pressure. This is called compliance. Compliance then, is equal to a change in volume over a change in pressure. The elastic arteries have a compliance, which allows them to maintain the pressure gradient. As the blood then flows from the elastic arteries into the muscular arteries, we begin to distribute it to the different organs. Now the resistance within the system starts to cause a drop in pressure. The dominant area where the pressure drop occurs, is within the arterioles. The pressure falls dramatically within the arterioles. At that time, the pulsatility is also diminished as blood moves through the arterioles. The arterioles are the spigots. The arterioles are the dominant way that the blood is distributed within the organs. This distribution causes an increase in resistance to flow. So we have a pressure drop, a dramatic pressure drop, across the arterioles. Then from the arterioles, the blood enters into the capillaries. Again, there's a pressure drop across the capillaries. But it is less than what occured through the arterioles. The pulsatility is lost. Blood flow is essentially smooth once it enters the veins and into the vena cava. This is the largest of the veins. It delivers the blood back to the heart. At this time, blood flow is smooth and there is a very low pressure within the system. There's two things to remember: one is pulsatility of blood flow on the arterial side and secondly blood pressure diminishes as blood runs through the entire circuit and returns to the heart itself. It's pretty easy to remember the idea about the pulsatility. Simply that if you cut your wrist and the blood is spurting out from your wrist, you know that you've cut the artery. But if you cut your wrist and the blood is just oozing out then you know that you have cut the vein. Okay, so what about these blood pressures? So, the blood pressure, then, we are refering to is the mean arterial pressure. The mean arterial pressure is not calculated by adding diastolic pressure to systolic and dividing by 2. Instead, it is diastolic pressure plus one-third times systolic pressure minus the diastolic pressure. The systolic pressure minus the diastolic pressure is referred to as the pulse pressure. Why is the mean arterial pressure is not simply taking the systolic pressure plus the diastolic pressure and dividing by two? The reason the equation is weighted for the diastolic pressure is because the heart stays in diastole longer than it is in systole, So the diastolic pressure then, adds a larger component to the calculation of the mean arterial pressure. Okay, so now, we need to distributed the blood to the various organs. I told you that the distribution will occur through a parallel system. I can distribute blood to the GI tract and not be distributing blood to the skeletal muscles. Why is it that? Why have this movement of blood from organ system to another organ system depending on demand? It is simply because there's not enough blood within the circulatory system to allow us to perfuse all of the capillary beds within the body at one time. If all of the capillary beds were dilated, so they were all open and you were able to perfuse every capillary in the body, then you would pass out. In order then to distribute the blood to specific organs that need the blood for that particular state, we have distributing vessels called arteries. The flow as it goes through this arteries will be dependent on the pressure gradient divided by the resistance. For the entire cardiovascular system, This is mean arterial pressure minus the pressure in the vena cava divided by the total peripheral resistance. This is what we will consider if we are talking about the entire vascular system. But within an organ itself, it would be the pressure that's within the mean arterial pressure minus the venous pressure of that organ divided by the resistance of that organ. And in both the case of the entire systemic circulation, as well as in the case of the organ, the venous pressure is very low compared to the mean arterial pressure. It's considered to be essentially zero. The vena-cava has a pressure of about 12 mmHg where the mean arterial pressure is something like a hundred mmHg. So, we really don't factor it in. We make the adjustment that the cardiac output is equal to mean arterial pressure divided by the total peripheral resistance. Or the perfusion pressure for the organ is equal to mean arterial pressure divided by the resistance in the organ. Once within the organs, then specific capillary beds will be perfused within that organ. Oh, one other point that I should make, and that is, that although the arteries are regulating which blood flow goes to particular organs/tissues at any one time, for instance, in the fed state, the GI tract receives a large amount of the blood flow, but the skeletal muscle may be only getting 20% of the cardiac output. The two organ systems that always get a 100% of their needs are the heart and the brain. So the heart and the brain, regardless of the state, whether it's a fed state and we're diverting blood to the GI tract. Or it's a state of exercise where we are diverting blood predominantly to the skeletal muscle and not so much to the GI tract. The heart and the brain get 100% profusion. Okay, so let's talk about arterioles. Arterioles regulate the blood flow within the organs. In the arterioles there is a complicated set of control systems. The first is that the arterioles are governed by local conditions. There are essentially three types of local conditions. The first is the Myogenic response. This is simply if there's more volume, more pressure being delivered to the arterioles, then the arteriole walls, the smooth muscle that's within their walls, stretch. When they stretch, it causes a contraction because you're opening stretch activated calcium channels. These smooth muscle cells will contract and restore the original diameter to the vessel, or perhaps even make it smaller. This change in wall tension is important. That change in wall tension maintains the flow rate or pressure within that vessel. This is a simple Myogenic response. The second is called Hyperemia. This is when there is a change in the interstitial space. The components within that interstitial space, outside of a given tissue, change. So for instance, if we're exercising. our skeletal muscle uses up a lot of oxygen. It's generating a lot of CO2. CO2 levels, within in the interstitial space, outside of the skeletal muscle, rise. In addition, you can have an increase in protons within that area or of potassium within that area. This increase in these metabolites cause an active Hyperemia, where the local arteriole will dilate. This causes the smooth muscle to relax in the walls of those arterioles. More blood is fed into those very active sites. This effectively washes away the by-products, those metabolites, that were generated by contraction, or by the activity of the skeletal muscle. This is called active Hyperemia, because the muscle is actively working. It is generating these metabolites. There is a second type of Hyperemia where again we will have an opening of the vessel. We have relaxation of the smooth muscle of the arteriole and an opening of those vessels. This allows more profusion of the capillary beds in that region. This response is due now not to an active exercise state, but in fact to a loss of profusion within that area. If for some reason there's ischemia within a specific region of the organ, then metabolites accumulate within that area. The metabolism of the cells continues. They're using up oxygen, but new oxygen is not being delivered to the cells. Local levels of CO2 rise. When you re-open profusion to that region after the ischemic event, then there is a greater flow of blood through the region. That's due to reactive Hyperemia. When does this occur? You all know, if If you go into the doctors office they take your blood pressure. The nurse puts a blood pressure cuff on your arm and then increases the pressure outside of the artery that is perfusing the lower arm. This is the brachial artery that perfuses the forearm. This will collapse the brachial artery. When that happens blood flow to the forearm is stopped. You now have an ischemic state in the forearm. Then, as the nurse slowly releases the pressure of the cuff, there is a release of the pressure in the cuff, blood flow resumes within the forearm. At that point, all of the arterioles and the arteries in this area dilate to allow more blood profusion to occur transiently. This washes out local metabolites that had increased during the ischemic state. The arteries and arterioles can also be regulated through reflex control. In particular we are talking about arterioles. Reflex control involves the sympathetic nervous innervation. In sympathetic innervation, norepinephrine is the neurotransmitter. It works on the alpha one adrenergic receptors which are present on the smooth muscle of the arterioles. Secondly, we can have hormones which will act in this area. The hormones can be either constrictors or dilators. The hormones can cause the smooth muscle to either relax if it's dilator or to contract if it's a constrictor. In the case of vasopressin and antidiuretic hormone, these this are constrictors. Epinephrine is again a constrictor. It acts on the alpha one adrenergic receptors. Now there are some cases where epinephrine can act on the beta 2 receptors. In that case, the beta 2 receptors, for instance, on the bronchi, the smooth muscle of the bronchi, epinephrine causes a dilation or a relaxation of those smooth muscles, Dilation of the bronchi, the tubes of the airways increases their diameter. So depending upon on the type of receptor that the epinephrine is acting upon, you can either have constriction, which would be an alpha-1-adrenergic receptor, present on blood vessels, or the beta-2-adrenergic receptors, which are found on the smooth muscle of the bronchi. [COUGH] Okay so these arterioles act as nozzles (spigots) within the vasculature. The dynamic change within their contracted state, that is going from their basal tonal state, to either contracted or relaxed, changes the diameter of the arteriole itself. The blood flow through that vessel will be affected. It not only affects the blood flow through the arteriole but it affects the blood flow in the capillary bed which is downstream, immediately downstream to that arteriole. That's what's diagrammed here. On the y axis we have pressure. Pressure's increasing in this direction. Along the x axis we've diagrammed a artery, arteriole, and capillary. What's shown is the change in the arteriole. We start looking here at this, at the blue, or the basal state. This is our basal tone for the smooth muscle in the walls of the arteriole. We see that there is a drop in pressure as the blood flows across the arteriole. This drop in pressure is due to resistance. It's a small, narrow tube, and so, it has high resistance to the blood flowing through the tube. If we cause a relaxation in the smooth muscle in the walls of the arteriole, then the blood flow within increases. That means the down-stream flow in the capillary increases; pressure is increased. There's more flow delivered to the capillary. There's more pressure, a higher pressure within the capillary. Conversely, if we constrict the arteriole, and close the lumen of the arteriole further, then the pressure falls within the capillary. There's less flow delivered to the capillary bed, and so less pressure. There is less pressure within the capillary bed immediately downstream to the arteriole. One of the ways that you can think about this system is that the arteriole is the nozzle on your garden hose. If you open the nozzle completely, or close the nozzle, it changes the flow rate to the tube, the actual hose attached to your nozzle. That hose attached to the nozzle would be the capillaries. If you think of the capillaries as a soaker hose, full of the little holes, then you'll understand that as the flow goes through the capillary, the flow rate slows. This is due to the interaction between the fluid within the capillary and the walls. There's essential no barrier between the movement of the fluid and the garden itself. All right. So the pressure gradients found within the capillaries are actually very important for delivery of solutes and fluids to the tissues. That capillary and its profusion are diagramed here. We have effectively two pressures that we need to consider. So the first pressure is simply the hydrostatic pressure. This is the main arterial pressure that's coming into the organ. It is the hydrostatic pressure entering the arteriole. The hydrostatic pressure, as it goes across capillary, falls. Such that the pressure that exits the capillary is less than the pressure that entered at the arteriole side. That's due to the resistance to flow within the capillary vessel itself. That's our hydrostatic pressure. The second pressure, oncotic pressure, is generated by the proteins within blood. They're attracting water. They keep water within the vascular system. The oncotic pressure as it moves through this region is here. The oncotic pressure is essentially stable. So we have hydrostatic pressure and oncotic pressure. On the arteriole side of the capillary, as you see, the hydrostatic pressure is greater than the oncotic pressure. When the hydrostatic pressure is greater than the oncotic pressure, then there is a net filtration. That is a net movement of fluid from the capillary itself across the capillary walls and into the interstitial space. This occurs in most regions of the body. There's a few exceptions where you have sealed capillaries, but under most conditions there's an easy movement of materials from the capillary, across the endothelial cells, and into the interstition. On the opposite side, on the side towards the venule. Now the hydrostatic pressure is less than the oncotic pressure. Under these conditions, fluid is attracted back into the capillary. That's due to the proteins which are present within the blood. This is predominantly albumin. So under these conditions we have reabsorption. So, reabsorption then occurs when the oncotic pressure is greater than the hydrostatic pressure. This is under normal conditions. So, what happens under a condition where we have very high pressures within the vascular system? Let's say we have hypertension within the system. Now, instead of having a blood pressure of 120 over 80, we may have a blood pressure that's 180 over 90. Under these conditions of hypertension, the hydrostatic pressure, as it's travels across the capillary, stays relatively high. The oncotic pressure Is the same as it was before. But if you notice now, all the way across the capillary, from the arteriole side to the venule side, we have a hydrostatic pressure is greater than the oncotic pressure. So under these conditions we will get filtration. Filtration occurs across the entire capillary, including on the venule side. There's no movement of fluid back into the capillary toward the venule side, There's a net movement of fluid out into the interstitium, out into the tissues. Under this condition, we then have a pooling of fluid outside of the vasculature. This is called edema. So the pressure gradients across the capillaries determine whether or not we have a net filtration and a net reabsorption, or whether we have only filtration across the entire capillary. We can also have a condition of hypotension. With hypotension then we'll get the opposite. In hypotension we can have a situation where all the way along the capillary. the tension that's generated, the hyperstatic pressure that's generated, is very low. If we have a very low hydrostatic pressure, then we have a hypotensive situation where the hydrostatic pressure starts very low and drops across the length of the capillary. Under these conditions, the ancotic pressure can be in fact, higher. When the oncotic pressure is greater than the hydrostatic pressure, then there's reabsorption of fluid back into the capillary all the way along the capillary bed. So the pressures that feed the capillary bed are important for the delivery of oxygen, nutrients, and so forth to the tissues. In addition, they are very important to the removal of fluids. Once we've delivered the materials to the tissues then the fluid needs to be reabsorbed and reenter into the circulatory system. What about this extra fluid? Sometimes there's a mismatch in this fluid. So the fluid leaves at the arteriole end but not all of it is taken back up into the venule end. There's a little bit of extra fluid that stays in the tissues. This fluid is picked up by another circulatory system called the lymphatic system. That is what's diagramed here. The lymphatic system is a system that starts as a blind ended capillary in the tissues themselves. It then drains the fluid from the tissues, this extra fluid, this lymph from the tissues, and returns it to the blood stream. It returns it on the venous side near the vena cava back into the circulatory system. On route, it will go through one filter or more. These filters are called lymph nodes. On a given day, you could have as much as three liters of lymph return to the blood. So this is actually a fairly significant amount of fluid that needs to be returned from the tissues, back into the circulatory system. The lymphatic drainage is found in almost all parts of the body including the CNS as was recently shown. Disruption to this lymphatic system can have profound effects on edema within the tissue. For instance, in individuals who have breast cancer, often these nodes are removed. When the draining lymph nodes are removed from underneath the armpit near the breast that was affected. These nodes are tested to see whether or not metastasis of cancer cells has occurred. That is whether or not there are cancer cells within these little filtering units or nodes. When they strip these nodes and also possibly nodes that are further within the system, and disrupt the lymphatic vessels, then fluid is no longer able to be drained away through the lymphatic system and back into the circulatory system. Fluid can build up within the lymphatic drainage. Then to get the fluid back into the circulatory system,, the individual has to massage the arms or exercise the arm to help move the fluid back through these vessels and back into the circulatory system. All right, what's our general concepts? The general concepts then, the first is that the heart consists of two pumps that drive the unidirectional flow of blood through the pulmonary and the systemic circulations. Secondly, this vascular system is a conduit for the blood flow. It's a dynamic system because it can control the distribution of the blood from one area of the body to another. That the distribution to the organs is in parallel so that if I shut off the distribution to one arm, it does not affect the flow into the other arm. This arm is not in series with this arm. These arms are perfused in parallel. So I can affect the distribution of blood here, and not alter the distribution of blood over here. Thirdly, the arteries are low resistance conduits that maintain the pressure, in particular the aorta and the elastic arteries. They maintain the pressure during diastole when there's no flow of blood coming from the heart. They allow this pressure gradient to be maintained and distributecblood to the organs. Fourth, the arterioles are dominant site of resistance within the system. They determine what region within the organ be perfused. Five, capillaries are the site of exchange. It's the balance between the hydrostatic and oncotic forces that determine the direction of fluid movement, either into or out of the capillaries. When we have a higher pressure, hydrostatic pressure greater than oncotic pressure, there's a filtration. This is a net movement of fluid from the lumen of the capillary into the tissue. But if the oncotic pressure is greater than the hydrostatic pressure present within the blood, then fluid will move from the tissue back into the blood stream. And six, veins are low resistance conduits for venous return. They are volume reservoirs. They have a very large capacity. About 60% to 70% of the blood within the system at any time resides on the venule side, or on the vein side, the venous side. Six, the sympathetic nervous system constricts the smooth muscle of the vein and can increase venous return and thereby increase stroke volume and cardiac output. This we know is called the preload. So we can increase preload by affecting venous return. Seven, the lymphatic system provides a one-way route for the return of interstitial fluid to the cardiovascular system. And this interstitial fluid is called lymph. It comes from a little mismatch between fluid that's being filtered across the capillary and what's being reabsorbed back in to the capillary. And eight, disease states that alter the hydrostatic or oncotic pressure can result in edema. If we have hypertension, then the individual can generate edema. Hydrostatic pressure remians high all the way across the capillary causing filtration all the way along the capillary. There are other states where the oncotic pressure can be reduced within the system. This may occur if you have a problem with the liver. Say you have cirrhosis of the liver. Under these conditions then the liver is not able to make sufficient quantities of albumin. Consquently the oncotic pressure within the blood is less. That means that the attraction of water back into the bloodstream is less on the venule side. In this case, we will have higher hydrostatic pressure than oncotic pressure all the way along the capillary. Again edema will form. You can have problems during heart failure where the hydrostatic pressure is changed. Liver disease, as I've just described, where the oncotic pressure is changed. Kidney diseases where we are holding too much water or we're not able to urinate and so there's a large volume within the system. This will elevate pressures within the system. We can have protein malnutrition. Again, the oncotic pressures can be diminished. This system then is a balance between the hydrostatic pressure and the oncotic pressure. Fluids will be distributed according to which pressure is the highest across the capillaries and within the tissues. Okay, so see you next time when we'll talk about how this entire system is a gigantic reflex loop and how the reflex loop is controlled. See you then.