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Lecture 7

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Biological Sciences
Stephen Reid

1    Lecture 7: Heart Failure and Blood Flow Heart Failure: See the notes at the end of Lecture 6 A. Blood Flow 1. Measuring and Calculating Blood Flow There are several modern methods of measuring blood flow. Ultrasonic probes are one method, involving sensors placed upon the surface of the skin just above blood vessels, which use ultrasound to measure the flow of blood beneath them. Another method involves the use of blood flow probes actually placed around arteries, implanted during surgery. These give a direct measurement of blood flow, and are used during carotid artery surgery to give the most accurate possible measurement. Finally, MRIs can be used to measure blood flow, and they are generally used for studying blood flow to sensitive organs such as the brain. We can calculate blood flow (BF) by taking changes in pressure, or the pressure gradient, and dividing this by resistance to flow (BF = change in P/R). The pressure gradient is the difference between the high and low pressures at opposite end of a system (in this case, the blood vessels), and it is thus the driving force for blood flow. 2. Different Types of Blood Vessels The amount of resistance (to flow) in a blood vessel is dependent upon that type of vessel. Starting out of the muscular aorta, arteries are large, muscular, and highly elastic. Arterioles, which branch off arteries, are smaller, but still muscular, and well innervated. Capillaries, the smallest of blood vessels, are thin walled and highly permeable. Arterioles and capillaries are the primary sites of resistance to flow in the systemic circulation. Capillaries connect to venules, which are thin-walled with some smooth muscle. Finally, venules connect to veins, which are thin-walled (compared to arteries), fairly muscular, and highly distensible, and veins connect to the vena cava and back into the heart. Arteries are what we call pressure reservoirs, because they are much higher in pressure than the venous system. Veins are volume reservoirs, because most of the volume of blood is contained within them (the difference is about 60%-15% in the venous system's favour) 2    3. Vascular Compliance We can define compliance as the capacity to distend. If we look at a blood vessel as just being a tube, what we are interested in is the pressure inside the tube, and the pressure just outside it. The difference between these two values is the pressure gradient (distending pressure). If the pressure on the outside is greater than the pressure on the inside, the blood vessel will contract; if the opposite is true, it will expand. The relationship between volume and distending pressure is not linear. At higher pressures, vessels become less and less compliant. At low pressures, veins have far greater compliance than arteries - however, at higher pressure their ability to distend is quite similar. Since at higher pressures venous compliance is similar to arterial compliance, it makes veins suitable to serve as arterial bypass grafts in heart bypass surgery. 3    4. Distribution of Blood in the Circulation Under healthy conditions, approximately 61% of the five litres of blood in the body is found in the systemic veins and venules, with 9% in the heart, 7% in the arterioles and capillaries, 11% in the systemic arteries and 12% in the pulmonary circulation. However, the vast majority of the (blood) pressure in the circulatory system is found on the arterial side. 5. Pressure Drops within the Circulation The greatest pressure differential (or pressure decrease) in the systemic circulation is between the arteries and the arterioles and to some extent the capillaries. This occurs because the arterioles and capillaries are the two greatest sites of resistance to blood flow in the systemic circulation. In the pulmonary circuit the same is true the greatest pressure drops are in the arterioles and the capillaries. However, the pressure is far less in the pulmonary circuit than it is in the systemic circuit. This is due to the need to protect delicate lung tissue from high pressures. High blood pressure in the lungs would force fluid from blood vessels into the alveoli and cause pulmonary edema. However, blood flow between these two circuits is equal - and this means that resistance to flow in the pulmonary circuit must be lower than it is in systemic circuit (see below). 4    6. The Driving Forces for Blood Flow Mean arterial pressure (MAP) is the driving force for blood flow in the systemic circulation. Systemic blood flow is driven by the difference between mean arterial pressure (i.e., pressure in the aorta) and central venous pressure (pressure in the vessels emptying into the right atria). However, given that central venous pressure is very close to zero (and we approximate it to be zero for these purposes), we only really need to consider mean arterial pressure when calculating blood flow in the systemic circuit. In other words, MAP is the driving force for blood in the systemic circulation. The driving force for blood flow in the pulmonary circulation follows the same principle although the pressure in this circuit is far lower. The pressure gradient driving blood flow here is the pressure in the pulmonary artery (leaving the right ventricle and heading to the lungs) minus pressure in the pulmonary vein (emptying into the left ventricle). Pulmonary artery pressure is approximately 15 mmHg while pulmonary venous pressure (in the pulmonary vein) can be approximated to be zero. 5    7. Resistance to Blood Flow Blood flow equals the pressure gradient divided by the resistance to blood flow. There are a number of factors that influence the resistance to flow. We look at resistance from two points of view: from that of a single blood vessel and from that if the circulatory system as a whole. Resistance to blood flow in the circulation as a whole is called total peripheral resistance. Resistance is the degree to which blood flow is hindered. The relationship between pressure and resistance is as follows: for any given change in the pressure gradient, if resistance increases, then the flow of blood will decrease, and vice versa. Thus blood flow follows the formula of BF = change in Pressure/Resistance, however, this is only true of a single blood vessel. From the point of view of the entire system, increasing blood pressure actually increases blood flow. When we come to blood pressure regulation, taking the entire circulatory system into account becomes more important. 6    8. Factors Affecting Resistance to Blood Flow In a single blood vessel, there are four main factors which can affect the amount of vascular resistance. The first is the radius of the vessel itself. Generally the narrower the vessel the greater the resistance to blood flow. For example, there is far more resistance in arterioles and capillaries than there is in veins and arteries since arterioles and capillaries are narrower than arteries and veins. The magnitude of resistance to flow can be altered by having the vascular smooth muscle which surrounds blood vessels either constrict or dialate. Constriction narrows the vessel and reduces flow. Dilation widens the vessel and increases flow. Constriction and dilation are regulated by adrenergic innervation and by circulating epinephrine and norepinephrine. As we will see later, the radius affects resistance to the fourth power, so it has a very large effect on flow. However, although the radius of the blood vessel is the primary regulator of resistance, there are other factors involved. The length of the blood vessel is another factor that determines resistance. The longer a vessel is the more resistance to flow it has. However, this is not something that is physiologically regulated; vessel length will change as the body grows but on a day-to-day basis it is an unchanging factor. The viscosity of the blood also affects resistance. Viscosity is a measure or index of the internal friction of adjacent fluid layers sliding past one another, as well as the friction generated between the fluid and the wall of its vessel. An important factor in determining blood viscosity is what is termed haematocrit, which refers to the percentage of blood volume occupied by blood cells, both red and white. 7    Normally it is about 45% - the rest is blood plasma. As haematocrit increases, so does viscosity. Another factor influencing blood viscosity is temperature - for every degree Celsius the temperature drops, blood viscosity increases by approximately 2%. As body temperature remains mostly constant, this is not a particularly strong influence on flow, except in those blood vessels very close to the surface of the skin. Finally, flow rate can influence viscosity: as flow rate decreases, viscosity increases. This is due to an increase in cell to cell and protein to cell interactions that cause red blood cells to adhere to one another. The final factor that affects vascular resistance is the ratio of laminar to turbulent blood flow. Laminar flow refers to blood flow that is smooth and even, and travelling in a single direction within the blood vessel. Laminar flow will create a “cone” of concentric layers of fluid, with the velocity of fluid fastest in the center. With turbulent flow, the opposite is true: blood flow is chaotic and disordered. There is backflow, and it almost resembles rapids in a river. Turbulent flow is not especially common, but in unhealthy vessels with large amounts of plaque or fatty deposits, it can occur. Turbulent flow can also come from the heart, if the valves are diseased or the aorta has stenosis. 9. Poiseuille’s Law We can calculate resistance using Poiseuille's Law: R = 8Lη / πr 4 In which R is resistance, L is vessel length, η is viscosity, and r is radius. By looking at this equation, we can see that if viscosity increases, resistance increases. If the pressure gradient remains constant then flow will decrease. If the radius of the vessel increases, then resistance decreases. If pressure remains constant then flow will increase. Given that radius is to the fourth power in this equation, it exerts large an effect on resistance. Doubling the radius reduces the resistance to 1/16th its original level, whilst flow is increased 16 times. This is true, at least, for a single blood vessel. However, when we look at the circulatory system as a whole, we no longer look at the resistance in the same way as if it were in a single vessel. Instead we look at total peripheral resistance, which is the combined resistance of all blood vessels within the systemic circulation. The vast majority of this total peripheral resistance, the 8    so -called resistance vessels, is within the small arteries, arterioles and capillaries. The resistance of these vessels can be changed by the contraction or relaxation of rings of smooth muscle wrapped around these vessels. These rings of smooth muscle are under nervous and hormonal control and are innervated by the sympathetic nervous system and affected by circulating epinephrine and norepinephrine. Interestingly, the same hormone can cause different effects on blood vessels depending on the situation (see lecture 8). 10.
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