Veins (Recorded) Physiology Lecture Notes PDF

Seema Nimer, Leith Nuseir Fares Alassaf, Ahmad Shawabkeh Cardiovascular Physiology Fatima Ryalat, MD, PhD Assistant Professor, Physiology and Biochemistry Department School of Medicine, University of Jordan Veins The structure of large veins is characterized by having a lar...

Seema Nimer, Leith Nuseir Fares Alassaf, Ahmad Shawabkeh Cardiovascular Physiology Fatima Ryalat, MD, PhD Assistant Professor, Physiology and Biochemistry Department School of Medicine, University of Jordan Veins The structure of large veins is characterized by having a large diameter, thin walls, a thin smooth muscle layer which is supplied by sympathetic stimulation but the contraction isn’t as robust as that in the arterioles. Another thing that characterizes them is compliance. They’re compliant, meaning that they can accommodate large volumes of blood without changing the pressure significantly. However, unlike the elastic arteries, they don’t have elastic recoil/elasticity in their walls. They are capacitors (store blood within their walls until needed by the circulation). This is very important characteristic that allows veins to be considered as blood reservoirs. If you lose 20% of your blood volume, you won’t experience great hemodynamic changes because of those capacitors. When these veins are stimulated sympathetically, veno-constriction happens, decreasing the diameter and so capacitance of these veins. This Venous return (VR) is the volume of blood increases venous return, so blood moves brought back to the RA by the veins per unit from the veins to the heart so we time. achieve an effective circulation.  Veins as blood reservoir more than 60% of all the blood in the circulatory system is usually in the veins. For this reason, and also because the veins are so compliant, the venous system serves as a blood reservoir for the circulation. Even after as much as 20% of the total blood volume has been lost, the circulatory system often functions almost normally because of this variable reservoir function of the veins.  Venous capacity Venous capacity (the volume of blood that the veins can accommodate) depends on the distensibility of the vein walls (how much they can stretch to hold blood) and the influence of any externally applied pressure squeezing inwardly on the veins. At a constant blood volume, as venous capacity increases, more blood remains in the veins instead of being returned to the heart. Such venous storage decreases the effective circulating blood volume, the volume of blood being returned to and pumped out of the heart. Conversely, when venous capacity decreases, more blood is returned to the heart and is subsequently pumped out. Thus, changes in venous capacity directly influence the magnitude of venous return, which in turn is an important determinant of effective circulating blood volume. VR is a flow and it depends on the pressure gradient and it depends on the resistance. Remember that after capillaries, venules will have a pressure of about 17 mm Hg, but the pressure in the RA is about 0 mm Hg. This is a very low pressure gradient as compared to the one that was in the aorta (100) compared to the arteriolar side (about 37)! So the pressure gradient is low, and veins are known to have low resistance due to their large diameter. We need something to help increase VR to the RA, and one of the ways is sympathetic stimulation. Remember that veno-constriction is less than arteriolar one that happens due to sympathetic stimulation of the SMCs, and if you think of the effect on the VR, keep in mind that when we sympathetically stimulate the venous system, we reduce the capacity and increase pumping of blood to the heart, increasing the effective volume in the circulation. But arteriolar vasoconstriction decreases blood flow to the tissues and veins, decreasing the venous return.  Sympathetic stimulation of the veins Veins are not very muscular and have little inherent tone, but venous smooth muscle is abundantly supplied with sympathetic nerve fibers. Sympathetic stimulation produces venous vasoconstriction, which modestly elevates venous pressure; this, in turn, (decreases the capacity of veins) and increases the pressure gradient to drive more of the stored blood from the veins into the right atrium, thus enhancing venous return. Veins normally have such a large radius that the moderate vasoconstriction from sympathetic stimulation has little effect on resistance to flow. Even when constricted, veins still have a relatively large radius and are still low-resistance vessels.  Arteriolar vs venous vasoconstriction Arteriolar vasoconstriction immediately reduces flow through these vessels because of their increased resistance (less blood can enter and flow through a narrowed arteriole), whereas venous vasoconstriction immediately increases flow through these vessels because of their decreased capacity (narrowing of veins squeezes out more of the blood already in the veins, increasing blood flow through these vessels). In addition to mobilizing the stored blood, venous vasoconstriction sustains increased venous return. With the filling capacity of the veins reduced, less blood draining from the capillaries remains in the veins but continues to flow instead toward the heart.  Venous valves the valves in the veins are arranged so that the direction of venous blood flow can only be toward the heart. Consequently, every time a person moves the legs or even tenses the leg muscles, a certain amount of venous blood is propelled toward the heart. This pumping system is known as the venous pump or muscle pump, and it is efficient enough that under ordinary circumstances, the venous pressure in the feet of a walking adult remains less than +20 mm Hg. If you're standing for a very long time, you keep distending the walls of the veins and this pulls the valves, leaving them incompetent! Blood will move backwards, increasing pressure in the lower extremities, and this high venous pressure will go to capillaries, and capillaries increase ultrafiltration and fluid in interstitial spaces, causing edema. This is common in patients with varicose veins. These patients may have a genetic predisposition for this case. This edema will cause impairment in substance exchange, and so they suffer from pain in the legs, skin ulceration, and stagnation of blood may put the patient at a risk of thrombosis. The solution is to keep moving the legs to keep contracting skeletal muscles and use compression stockings for long periods of time. Refer to slide 17 as you read this slide. Venous valves If a person stands perfectly still (for a long time), the venous pump does not work, and the venous pressures in the lower legs increase to the full gravitational value of 90 mm Hg in about 30 seconds. The pressures in the capillaries also increase greatly, causing fluid to leak from the circulatory system into the tissue spaces leading to edema. As a result, the legs swell, and the blood volume diminishes; 10% to 20% of the blood volume can be lost from the circulatory system within the 15 to 30 minutes of standing absolutely still. The solution here is to make sure you walk and stretch/move/contract the skeletal muscles and especially those of the lower limbs because they squeeze the veins at different parts of the vein. Recall that valves prevent blood backflow.  Varicose veins Stretching the veins increases their cross-sectional areas, but the leaflets of the valves do not increase in size. Therefore, the leaflets of the valves no longer close completely. With this lack of complete closure, the pressure in the veins of the legs increases greatly because of failure of the venous pump, which further increases the sizes of the veins and finally destroys the function of the valves entirely. Thus, the person develops what are called varicose veins, which are characterized by large bulbous protrusions of the veins beneath the skin of the entire leg, particularly the lower leg.  Varicose veins Whenever people with varicose veins stand for more than a few minutes, the venous and capillary pressures become very high, and leakage of fluid from the capillaries causes constant edema in the legs. The edema, in turn, prevents adequate diffusion of nutritional materials from the capillaries to the muscle and skin cells, so the muscles become painful and weak, and the skin may even become gangrenous and ulcerate. The best treatment for such a condition is continual elevation of the legs to a level at least as high as the heart. Tight binders or long compression stockings on the legs also can be of considerable assistance in preventing the edema and its sequelae.  Factors enhancing venous return In addition to the driving pressure imparted by cardiac contraction, five other factors enhance venous return: sympathetically induced venous vasoconstriction, skeletal muscle pump, venous valves, respiratory pump, and cardiac suction  Skeletal muscle pump When a person stands up, however, gravitational effects are not uniform. In addition to the usual pressure from cardiac contraction, vessels below heart level are subject to pressure from the weight of the column of blood extending from the heart to the level of the vessel. This increased pressure has two major consequences. First, the distensible veins yield under the increased hydrostatic pressure, further expanding so that their capacity is increased. Even though the arteries are subject to the same gravitational effects, they are not nearly as distensible and do not expand like the veins. Much of the blood entering from the capillaries tends to pool in the expanded lower-leg veins instead of returning to the heart. Because venous return is reduced, CO decreases and the effective circulating volume shrinks. Second, the marked increase in PC resulting from the effect of gravity causes excessive fluid to filter out of capillary beds in the lower extremities, producing localized edema. Because most of the veins are below the level of the heart, they have to overcome the effect of gravity to bring the venous blood back to the heart, and this will be hard especially for the lower parts of the body since hydrostatic pressure depends on the weight of the blood in that column; the greater the weight, the more the pressure. For example, in the foot it's about 90 mmHg, less in the calf, and as you go up it becomes lesser. The increase in pressure increases the capacitance of the veins, distending the wall more, and there should be something to help with pumping upwards, against gravity. While walking, skeletal muscles squeeze on the veins and decrease the column of the blood that will be considered for the hydrostatic pressure, decreasing the pressure in the veins. When you squeeze a tube in the middle, the blood flows in both directions. This doesn’t happen in the veins due to valves in the venous walls.  Skeletal muscle pump Two compensatory measures normally counteract these gravitational effects. First, the resultant fall in MAP that occurs when a person moves from a lying- down to an upright position triggers sympathetically induced venous vasoconstriction, which drives some of the pooled blood forward. Second, when a person moves around, the skeletal muscle pump “interrupts” the column of blood by completely emptying given vein segments intermittently so that a particular portion of a vein is not subjected to the weight of the entire venous column from the heart to that portion’s level So far, we discussed 3 mechanisms of increasing VR. 1. Increasing sympathetic stimulation 2. Skeletal muscle pump contraction 3. Venous valves We will discuss 2 more mechanisms that act as suction pumps in the next slides.  Respiratory pump As a result of respiratory activity, the pressure within the chest cavity averages 5 mm Hg less than atmospheric pressure (sub-atmospheric). As the venous system returns blood to the heart from the lower regions of the body, it travels through the chest cavity, where it is exposed to this subatmospheric pressure. Because the venous system in the limbs and abdomen is subject to normal atmospheric pressure, an externally applied pressure gradient exists between the lower veins (at atmospheric pressure) and the chest veins (at less than atmospheric pressure). This pressure difference pushes blood from the lower veins to the chest veins, promoting increased venous return. This mechanism of facilitating venous return is called the respiratory pump because it results from respiratory activity. Increased respiratory activity, the skeletal muscle pump, and venous vasoconstriction, all enhance venous return during exercise. This works as a suction pump.  Cardiac suction effect The extent of cardiac filling does not depend entirely on factors affecting the veins. The heart plays a role in its filling. During ventricular contraction, the AV valves are drawn downward, enlarging the atrial cavities (increasing intra-atrial volume, reducing its pressure). As a result, atrial pressure transiently drops below 0 mm Hg, thus increasing the vein-to-atria pressure gradient so that venous return is enhanced. In addition, rapid expansion of the ventricular chambers during ventricular relaxation creates a transient negative pressure in the ventricles so that blood is “sucked in” from the atria and veins—that is, the negative ventricular pressure increases the vein-to-atria-to-ventricle pressure gradient, further enhancing venous return. Thus, the heart functions as a “suction pump” to facilitate cardiac filling.  Right atrial pressure Veins are capable of constricting and enlarging and thereby storing small or large quantities of blood and making this blood available when required by the remainder of the circulation. Blood from all the systemic veins flows into the right atrium of the heart. Therefore, the pressure in the right atrium is called the central venous pressure. The normal right atrial pressure is about 0 mm Hg, which is equal to the atmospheric pressure around the body. Right atrial pressure is regulated by a balance between (1) the ability of the heart to pump blood out of the right atrium and ventricle into the lungs and (2) the tendency for blood to flow from the peripheral veins into the right atrium.  Venous return factors that can increase this venous return and thereby increase the right atrial pressure are as follows: (1) increased blood volume increases VR; (2) increased large vessel tone throughout the body with resultant increased peripheral venous pressures.; and (3) dilation of the arterioles, which decreases the peripheral resistance and allows rapid flow of blood from the arteries into the veins increasing venous return. Their constriction decreases BF to veins and decreases VR. Decreasing diameter of veins lowers capacitance, increasing venous pressure and leading to more VR Take a look at this formula for venous return before continuing to the next slides: VR = Delta P/R = (MSFP – RAP)/RVR VR: Venous return Delta P = Mean systemic filling pressure – right atrial pressure (RAP is also known as the central venous pressure) R = Resistance to venous return Further explanation regarding the previous slide: The venous function curve is similar to the curve of the cardiac output against The graph in the previous slide, a venous function curve, shows how the the end diastolic volume: venous return changes in response to changes in the right atrial pressure. Let’s start from 0 mmHg, which is the normal RAP. At 0 mmHg, the venous return is 5 L/min. If the RAP increases from 0 mmHg, it would be a backward force against the venous return, meaning the venous return would decrease as the RAP The EDV represents the RAP, so instead increases. of the EDV on the curve we can write RAP instead. Because of the link between the The venous return would decrease until there is no more venous return and two curves, the venous function curve and the CO-EDV curve, we can combine the thus, no blood flow. This point is called the mean systemic filling pressure. two of them into one curve: On the other hand, if the right atrial pressure decreases from zero (negative pressure), then you might assume that the venous return increases. However, this is not the case, there’s a transitional phase followed by a plateau. An increase in the negativity of the RAP causes a collapse in the veins, and if we combine both the increase in delta P caused by the decrease in RAP as The point of intersection between the well as the collapse in the veins, a plateau as seen in the graph in the two curves is called the equilibrium point previous slide is caused. or the steady state point. At this point, the CO and VR are equal.  Right atrial pressure is also called central venous pressure since all Venous return curve the veins will bring back blood to the RA so it's a central collection point. three principal factors that affect venous return to the heart from the systemic circulation: 1. The more VR, the higher the Right atrial pressure/Central Venous Pressure, which exerts a backward force on the veins to impede flow of blood from the veins into the right atrium. Normally the pressure is about 0 mmHg. 2. Degree of filling of the systemic circulation (measured by the mean systemic filling pressure), which forces the systemic blood toward the heart (this is the pressure measured everywhere in the systemic circulation when all flow of blood is stopped, discussed in detail later). 3. Resistance to blood flow between the peripheral vessels and the right atrium. These factors can all be expressed quantitatively by the venous return curve  Vascular function curve or venous return curve The inverse relationship between venous return and right atrial pressure is explained as follows: Venous return back to the heart, like all blood flow, is driven by a pressure gradient. The lower the pressure in the right atrium, the higher the pressure gradient between the systemic arteries and the right atrium and the greater the venous return. Thus as right atrial pressure increases, this pressure gradient decreases and venous return also decreases.  Vascular function curve The knee (flat portion) of the vascular function curve occurs at negative values of right atrial pressure. At such negative values, the veins collapse, impeding blood flow back to the heart. Although the pressure gradient has increased (i.e., as right atrial pressure becomes negative), venous return levels off because the veins have collapsed, creating a resistance to blood flow. The slope of the vascular function curve is determined by total peripheral resistance (TPR).  Mean systemic filling pressure Two factors influence the value for mean systemic pressure: (1) the blood volume and (2) the distribution of blood between the unstressed volume and the stressed volume. In turn, the value for mean systemic pressure determines the intersection point (zero flow) of the vascular function curve with the X-axis. Imagine that the heart stopped pumping for a few moments. This would mean that there is no flow, which in turn would mean that there is no pressure gradient. This results in equal pressure everywhere in the circulation. This pressure of the blood volume filling the circulation is called the mean systemic filling pressure, which is normally about 7 mmHg. In other words, the mean systemic filling pressure is the overall intravascular pressure under zero flow conditions. Furthermore, the MSFP reflects venous pressure more than arterial pressure since 2/3 of the volume in the blood circulation is within the venous side. The mean systemic filling pressure is different than the mean circulatory filling pressure since the MCFP also includes the pulmonary circulation. increased blood volume and decreased compliance of the veins produce an increase in mean systemic pressure and shift the vascular function curve to the right. Decreased blood volume and increased compliance of the veins produce a decrease in mean systemic pressure and shift the vascular function curve to the left.  Combining cardiac and vascular function curves In the steady state, cardiac output and venous return are, by definition, equal at the point of intersection. Combining these curves provides a useful tool for predicting the changes in cardiac output that will occur when various cardiovascular parameters are altered. the system will move to a new steady state.  Inotropic effect Positive inotropic agents produce an increase in contractility, an increase in stroke volume, and an increase in cardiac output for any level of right atrial pressure. Thus the cardiac function curve shifts upward, but the vascular function curve is unaffected. The point of intersection (the steady state point) of the two curves now has shifted upward and to the left. In the new steady state, cardiac output is increased and right atrial pressure is decreased. The decrease in right atrial pressure reflects the fact that more blood is ejected from the heart on each beat as a result of the increased contractility and increased stroke volume. (The stronger the contractility in the heart, the more the emptying of the right atrium into the right ventricle then into the arteries. This emptying will decrease the right atrial pressure, increasing the pressure gradient)  e.g. digitalis Cardiac output increases with lower RAP Cardiac output decreases with higher RAP  Blood volume effect Increases in blood volume increase the amount of blood in the stressed volume and therefore increase the mean systemic pressure. Mean systemic pressure is the point on the vascular function curve where venous return is zero. Increases in blood volume shift this intersection point to the right and therefore shift the curve to the right in a parallel manner. (The shift is parallel because there is no accompanying change in TPR, which determines the slope of the vascular function curve.) In the new steady state, the cardiac and vascular function curves intersect at a new point at which cardiac output is increased and right atrial pressure is increased.  e.g. blood transfusion e.g. hemorrhage MSFP increases -> new curve MSFP decreases; lower CO with lower RAP shows higher CO with higher RAP  TPR effect Increases in TPR cause an increase in arterial pressure by “holding” blood in the arteries. This increase in arterial pressure produces an increase in afterload on the heart, which decreases cardiac output. The cardiac function curve shifts downward as a result of the increased afterload. This means that less blood returns to the heart for a given right atrial pressure—venous return is decreased. The curves intersect at a new steady state point at which both cardiac output and venous return are decreased. Decrease in TPR causes the exact opposite of an increase in TPR.