pecchiari lesson 1 transcript - 5:3:2015

Pecchiari Lesson 1 05 March 2015

TRANSCRIPTFrederico Gonçalves Pereira

Introduction to the cardiovascular system.

This lesson is particular. Usually during lessons i try to consider systematically, but during this lesson I won’t because this is an introduction to the c.v. system. I want to show you the landscape in which you will work during the second part of the semester. We will deal with many topics, but details will be given later.

Here (silde 1) i want to show an analogy. in the past two lessons we have studied the skeletal muscle (an organ meant to produce forces and displacements, a mechanical system). Now we turn to an hydraulic system, the c.v. system. If for the skeletal muscle the relevant parameters were force velocity and length, now the relevant parameters are pressure (instead of force), flow (instead of velocity) and (volume instead of length)

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We won’t start with Physics, because you’ve already done this with Cerbino.We already know the Pascal law and the definition of Pressure.

You know the pressure units:

We use Pa N/m^2

We use mmH20 and mmHg for the respiratory and cardiovascular system, respectively. While it is worth studying these units, because much of the literature is written using these units of measurements, in the more recent literature they are being replaced by Pa, or multiples of it. However, the conversion is rather easy, because 1 cm of H20 is ~1 hectoPa.

The use of these units (mmH20 and mmHg) are due to a matter of magnitude. In the sense that often the pressures in the cardiovascular system are much bugger than in the respiratory system. When talking about the pulmonary circulation, the pressures are very low, of the same order of magnitude as the pressures inside of alveoli and inside of the pleural space, and here we will use a common unit, that can cause some confusion. But we will deal with it later.

The relation between atmospheric pressure and altitude. Imagine you are at sea level and you travel to the Dead Sea, so that barometric pressure increases if you measure your mean arterial pressure at sea level. When you are at the Dead Sea your Mean arterial pressure at sea level and is always 100 or less mmHg larger than atm pressure. What is kept constant is not the absolute pressure of the arterial compartment, but the relative relative to the ambient pressure.

I will always use gauge pressure (i.e. the pressure in a given compartment related to the ambient pressure).

Now, we can start doing some important definitionImagine your brachial arterial Imagine we measure a pressure of 100 mmHg. Here, the difference btwn inside the compartment and the the pressure in the ambient is 100mmHg. A different concept is the Transmural pressure at the level of this artery (or at the level at an hollow organ), given by the difference in the pressures inside and outside. In this particular case, the pressure inside the artery minus the pressure in the interstitial compartment, pressure acting on the outer wall of the artery.

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Let’s consider the distinction i did for this particular artery? Is this important? Is it important to differentiate between the transmural and the gauge pressure in the brachial artery? In this case no, simply because the pressure in the interstitial case is just a a few mmHg less than the ambient pressure. The arterial pressure at the brachial artery is 100, the transmural is 98. However, this distinction is very important in other places. Eg. in the intra-thoracic compartment, it is very important to think about the transmural pressure, at the level of the big vessels, instead of the pressure that simply references to the ambient. Arterial pressure refers ONLY to the pressure with reference to the ambient. Transmural pressure refers to the difference between the pressure inside and the pressure outside.

Why is transmural pressure o important? Because most of the cardiovascular system is made by structures which have elastic properties, so that they can increase/decrease in volume, and pressure (which is proportional to the volume) is the transmural pressure at the level of the compartment.

FIGURE 1

Now, we’ll take a look at the cardiovascular system. This is a classic picture of a man in supine and in a standing position. On the left we see values of arterial and venous pressures in different compartments. In the lower panel we have the same. Please disregard the values (-35 and -19 (on the top)). They were not recorded, but calculated, and they are wrong. We will say something about them later.

1.In both the standing and supine position, the pressure inside of the c.v. system is different to the pressure outside of the c.v. system.

2. The pressure in the arterial compartments is different to the pressure in the venous compartment.

3.In a given compartment (both arterial and venous), when we change position, pressure changes. Eg. compare the values at the foot in supine and standing position (95 to 181).

We need to answer to these 3 questions above.

With out knowledge of Physics we have the answer to some of these.

Let’s take the second question.

We have flow on the arterial to the venous compartment, and between the two compartments we have resistances, and therefore between the two compartments there should be a pressure drop. There should be a pressure drop between the arterial and venous compartment. All we have to do is study the details of this pressure distribution.

The answer to the third question, is not entirely to do with the relative position of the compartment being studied relative to the heart (as Cerbino said the day before). This will mostly be dealt with during the second part of the lessons.

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I want to first answer to the first question: Why is the pressure inside of the c.v. system is different to the pressure outside of the c.v. system. One can say is the heart that creates that pressure different. This is both true and false, because if the subject we study dies, we will discover that the pressure in the different compartments becomes equal, but this pressure (which is the same in all compartment) is NOT equal to the ambient pressure. And so? What is a simple explanation of this finding? The volume of blood is higher than the volume of the c.v. system at rest (resting volume of the c.v. system. Pressure, even in the absence of flow and gravity, is greater than the ambient pressure!

FIGURE 2.

This is a simple representation of the cardiovascular system. This is the systemic arterial and systemic venous system. When the heart beats, the pressure in the arterial compartment is about 120mmHg, and in the venous compartment is much lower, 4mmHg. If we stop the heart, and if there is continuous communication between the different compartments, we will see that the arterial compartment decreases, and increases in the venous, until the value of the pressures in both compartments meet, each at about 7mmHg. This pressure , which we would measure in the absence of blood flow, and if communication between the compartments is maintain, is called (by Gaiton) mean systemic filling pressure. Note that this is note the mean between the arterial and the venous compartments’ pressure, it’s much closer to the pressure in the venous. Why??

Figure 3

In order to understand this, we have to warp our imagination here. Imagine to measure the relation btwn the transmural pressure and volume at the level of the c.v. system. This relation has been recorded for a particular vein, just to make you understand what we have. In order to characterise this relationship, we can imagine to take a piece of a vein, we can imagine to isolate this piece, and connect the inside of this vein with a pressure transducer (or a manometer), and recording the value of pressure when you change the volume of your vein by injecting or removing blood form inside of the vein.

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Interpreting the graph:

NOTE: It’s very hard to understand the explanation of the graphs. In most occasions, Pecchiari speak abouts ‘here’ and ‘there’, which in the transcript make no sense. I try to make it a little bit simpler, will without changing the meaning of his words. These sections should be studied along with your notes.

The transmural pressure is 0, but the volume of the vein(although low) is not 0. This is the resting volume of this vein. As you inject blood inside the vein, pressure increases. First, pressure increases slowly with an increase in volume, but then the situation changes and small increases of volume causes big changes in pressure. How can we characterise this relation?

One parameter is the resting volume. The other is compliance (DRAWING ON BOARD) - defined as ∂V/∂P (∂ is the change in…) (the slope of this graph). What can we say about compliance in this case? It continuously changes! At first is slow, then increases in the mid portion of the volume range. But for greater volumes, compliance decreases and the veins become STIFFER and stiffer. By the way, Gaiton points out an important distinction between compliance and distensibility (∂V/(∂P*Vo) (Vo is resting volume), the compliance divided by the resting volume. So why is this important?

Let’s say that we want to compare the characteristics of the systemic and pulmonary circulation. If we take a venue of these locations and compare the stiffness of the two venules, we will see that the in pulmonary circulation a venule is less stiff that similar venules in systemic circulation. So we say that the distensibility of a venule is greater in the pulmonary circulation. But considering the stiffness of the pulmonary circulation and that of the systemic circulation as a wall, the systemic circulation is more compliant, though, due to the fact that, even though individually the vessels of the pulmonary are more distensible, but they are fewer than the number in the systemic circulation. Therefore, at the wall, adding 100ml in the systemic circulation, the change in pressure is much smaller than the same 100ml injected in the pulmonary circulation.

(He then illustrates this with a diagram, answering to a question by a student, with the example of an increase of 5mmHg and a volume change of x, showing that distensibility in the systemic circulation is smaller

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Ds < DpCs > Cp

This was at the level of an individual vein. Now let’s consider this Pressure-Volume relation at the level a whole compartment (the arterial and the venous). In the venous we also include the capillary compartment. the situation is shown here

FIGURE

Note that pressure is now on the y axis. Looking at the arterial system, we see that big changes in transmural pressure cause only small changes of the volume of the arterial system. The opposite is seen for the venous system. We see that a given change in pressure causes a greater change in volume. Now the slope of these two curves is no longer compliance, but “1/Compliance”, also called Elastance.

We note: 1. the p-V relation of an individual vein was markedly not linear, while the relation between the whole arterial and whole venous compartments are rather straight. This is fortunate for us, because we need less effort to draw the system (line instead of parabola).

2. The resting volume of the venous system is much bigger than that of the arterial.

3. the venous system is much compliant than the arterial system.

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How could we calculate graphically the relationship of the arterial and the venous compartment?

(There is some discussion between the students and the professor at this point, not important)

Re-stating the Question: The resting volume of the venous compartment is 2000ml, and the resting arterial is 500ml. What is the total? The total is the SUM: we can just sum the volumes at a given pressure in the two compartments, and what we obtain is a line which starts at 2500ml, and with a rate of change that will be lower. In terms of compliance, the whole system has a greater compliance. I was talking about this because I was talking about mean systemic pressure. Because when we want to stop circulation, this mean systemic pressure is much closer to the venous pressure curve than to the arterial one. Venous circulation is much more compliant than the arterial circulation. When we stop the circulation, a volume of blood is transferred from the arterial to the venous compartment, but as the compliance of the arterial compartment is much less than the compliance of the venous compartment, the pressure decrease in the arterial compartment is much greater than the pressure decrease in the venous compartment. What we have is that from a value of 4 mmHg it increases to 7 when we stop the pump.

REVIEW THE WHOLE SLIDE!

We can now express the same using mathematics

Va - volume of arterial compartment Vo,a - resting volume of arterial compartment

same for Vv and Vo,v

Pms - Mean systemic felling pressure . Given by the equation in the bottom.

Now, we imagine to stop the pump, and we see that the pressure inside of venous compartment increases it becomes equal to the arterial compartment. At this point, considering that the total volume of blood is the sum of the arterial+venous, we can substitute and find an expression for the Pms. (Reads the equation)

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This is important for a doctor. We need the Pms is an independent determinant of the cardiac output. In a physiological range, if Pms is low, cardiac output will tend to be low, and vice-versa. Using this, we can discuss a clinical entity such as Shock (the traditional physio-pathological definition: a situation in which cardiac output is so low that the vital organs are under hypo-profusion). This happens because if the heart is not working, then cardiac output is low. so we have a big category of shock called Cardiac/Central shock - a problem of a pump. But if the mean systemic pressure in low and the problem is not at the level the heart, instead of Central shock we talk about Peripheral shock. (revised)

Looking at the equation. Pms can be low if the total blood volume is low - the subject could have lost an amount of blood (making the numerator of the equation is small). A subcategory of peripheral shock is hemorrhagic shock.

But, later in our course, we will understand how even in the absence of blood, we can have a reduction of the vascular volume simply because we have movement of fluid from intravascular to extravascular wall (Retraction of the intravascular volume, as it moves to extravascular) Some water leaves the inter vascular to the the interstitial compartment, and we have increase of permeability. this happens during Shock. Eg. Septic shock, lots of bacterial that produce substance such as Lipopolysaccharide that has direct impact on the permeability. Also, endogenous stuff produced by humans can have the same effect on permeability. Another situation can be that the numerator of the equation is low not because the blood volume is low, but because the resting volume is high. In order to understand this situation we have to recall the vascular tone, which is the degree of contraction of the smooth muscle inside of our vessels, determined by the degree of orthosympathetic stimulation.

Consider a patient with spinal trauma, and orthosympathetic stimulation stops. Immediately, the tone of the vessel decreases, and the resting volume of the systemic circulation increases. Therefore, the numerator decreases, Pms decreases — and the patient undergoes Neurogenic shock. The same substance that are produced in response to bacteria, in septic shock, can have a relaxant effect on our vessels, causing also increase of the resting volume, contributing to an increase of the numerator. The same substance act directly on the cardiac muscle, decreasing its contractility.

Question: When we have neurogenic shock, and we have increased extravasation, do we only increase the resting volume, or also the compliance?

Answer: only the resting body.

INTERVAL

We have said something about why the pressures are different inside and outside. We’ll do a lesson explaining how resistances causes differences between each compartment.

Now: Effects of gravity on the c.v. system. I have pointed that the pressures in a given compartment change with a change in posture.

Back to FIGURE 1

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I don’t like in an exam answer the implicit assumption that the pressure at the level of the heart does not change during a postural change. Here, we see a line of the level of hydrostatic indifference, where the pressure doesn’t change during postural changes. This level is a big below the heart, so that during a postural change the pressure acting on the heart actually changes. Why is it important to understand the physical meaning of level of hydrostatic indifference. Because what Stevin’s Law predicts the pressure difference between two levels in the vertical direction. To make you understand I have prepared two slides

SLIDE OF EQUATIONS

We can see in the image the pressure difference between the thoracic aorta and an artery of the foot should be around 100 mmHg during a postural change. At the same time the pressure difference between the thoracic aorta and the temporal artery should be -40. This is what Stevin’s Law can predict.

NEXT SLIDE (man standing with 3 tubes).

We have a man in standing position, with the pressure being measured at the level of the foot, the heart and the the head.

The actual pressure that we measure in this situation are important in the first column of numbers (60, 100, 200) At the same time I have also reported wrong values (40, 80, 180 and 20, 60, 160)All three columns obey to Stevino’s principle (the same pressures differences). But the columns 2 and 3 are wrong, and column 1 is right. How can we predict which column is right and which is right? Knowing the hydrostatic indifference level - The level in the vertical plane in which the pressure doesn’t change from supine to standing. Which are the determinants of the level of hydrostatic indifference?

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To do this, we imagine that we have a cylinder. We close the cylinder on the top and on the bottom, using compliant membranes. Let’s imagine that we fill this cylinder with fluid, when we are on the space station (no gravity), up to its resting volume, so that there is no tension in the membranes. (We can also do this example with a volume of fluid greater than the resting volume, this is just for this particular example). Where is the level at which the pressure inside the cylinder is equal to the pressure outside? In a sense, this is like asking which is the hydrostatic indifference level for the system. I will try to explain a little better

(Draws two cylinders, one standing and one supine)

The assumption of all this discussion is that when you are in the supine position, the vertical gradient that we have is negligible (very small), because the vertical distance is small. We can do this as for the systemic circulation it’s true, but not for the pulmonary circulation. We will study this later So, in the very same way, we can imagine that if our cylinder is put in the supine position, this gradient is small because the cylinder it longer than thicker, and therefore we measure the pressure, which is the ambient pressure (in this particular example) because we said we fill it to its resting volume.When you turn it in the vertical position, where is the level where the pressure inside of the cylinder is equal to the other position, i.e. where is the level of hydrostatic indifference?

SLIDE : Again, this is very hard to understand from the transcript. Use notes.

This is my cylinder and its compliant membrane. When we exposed the cylinder to the gravity, we will have that the membrane will go a bit downwards, and also the other one. So that the volume displaced by the upper and lower membrane is exactly the same, because the fluid is imcompressible.

First empirical result. If we measure a different level the pressure inside of a cylinder, we find that if the two membrane are exactly equal for what regards their elastic properties, the hydrostatic indifference level, the 0 level in this particular case (Pin=Pout) is exactly midway between the two membranes.

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In order to understand the determinant of the position of level of hydrostatic indifference, we can imagine to repeat the experiment using membranes of different thicknesses - of different elastances. We can try to use a membrane which is stiffer than the other - elastance at top is less than at the bottom Et>Eb. Again, we measure the pressure in the vertical direction to see where the pressure inside is the same as outside. We find that, in contrast to what we have seen before, the level of hydrostatic indifference has moved upwards. By the way, we can consider a glass of water (a cylinder where the lower membrane is infinitely stiffer, and the upper membrane (non existant) is more infinitely compliant) Here the zero level is at the upper surface. As we increase the stiffness of the lower part compared to the upper part, we increase the 0 level. The extreme case is a rigid container in which we have a membrane in the other part.

We can say that the position of the level of hydrostatic indifference is determined by the elastic characteristic of the container. If the lower part is stiffer than the upper part, the level of hydrostatic indifference (LHI) will move upwards relatively to the mid position. Clearly, we can take a pencil, some paper, do some algebra, and find out the equation for the LHI. But there is an easier way. To understand how it works, you only need general principles. Reason in this way: let’s look at our container - the volume by the upper membrane should be equal to the volume displaced by the lower membrane, simply because the liquid is not compressible. At the very same time, the displacement of a membrane should depend of the pressure difference between the two sides of the membranes. If the membrane is bending downwards, this means that the pressure is greater on the top is greater than the pressure ‘here’ (sorry…). and if the pressure on the top is atmospheric, then on the bottom it should be less/sub-atmospheric. In the very same way, if the pressure in the membrane moves downwards, then this means that the pressure ‘here is greater than the pressure ‘here’ is greater than the pressure ‘here’. The displacement of the two membranes should be equal, but if this membrane is stiffer than the other, in order to have the same displacement as in the previous, we need a greater pressure difference. Therefore, if we increase the stiffness of one of the membranes, the pressure will become greater and greater (than atmospheric), and the other will become more and more sub-atmospheric. As Stevin’s principle should be respected inside this contained, the zero LHI should go up.

Supine and standing heart

Above the heart is represented the upper body circulation, and below the lower body circulation.Changing the position of the body, fluid is transferred form the upper part to the lower part, and because of the elastic characteristic of this system, the level of hydrostatic indifferent is a bit lower (5-10cm) than the level of the heart.

Important: When you change the posture, the pressure acting on the heart changes! If we think that the pressure at the heart is constant, then a postural change would not change it. This is not true for humans.

Remember that the compliance and the resting volume of the venous system are larger than the equivalents for the arterial system.

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So we can predict that we change the pressure inside the vessel because we are changing position, a greater volume change takes place at the level of the base.

SLIDE Here we have a subject in upright position, with its blood distribution inside of the c.v. system.

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Normally, in the arteries, we have about 10% of the total blood volume (total blood ~5L for 70kg man).

61% of blood is in veins and venules.

Blood inside the capillaries and arterioles is much smaller than the amount of blood in the veins and in the arteries (7%) in the systemic circulation. In the heart, we find around 10% and in the pulmonary circulation 12%.

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SLIDE postural change

This is not a normal postural change. This was produced by a tilting table, in which the subject is bound, and the table is rotated so that a change in position does not need any change of the subject’s skeletal muscle activity. We are thus looking at an extreme condition.

Subject is initially supine. when he moves to upright immediately there is a decrease in central venous pressure of -3mmHg (measured in vena cava), is simply due to the fact that the level of hydrostatic indifference is below the heart. If we change the posture, we should have a decrease of the pressure inside the central veins. Now we need an act of faith: the central venous pressure is an index of pre-load (precise definition will come later) - the degree of of filling of the heart at the end of the relaxation phase of the filling phase of diastole.

Pre-load can be indexed by various parameters, one of them the central venous pressure. What is important is that if central venous pressure decreases (and preload) the stroke volume (the volume of blood ejected during each systole of the aorta) decreases. Here the stroke volume decreases by a considerable amount (40%). Clearly, stroke volume is a determinant of the cardiac volume, which is stroke volume*heart rate. If we have a decrease of the stroke volume, then the same should happen for cardiac output.

Most of the decrease of the cardiac output results from a decrease of profusion of the splanchnic, renal and upper part of the body. As we change the position volume of blood should be displaced between the central and the peripheral part of the body. The central blood volume is displaced substantially (-400m), and the volume of the legs increases substantially (+600ml). This happens immediately when tilting the subject from supine to upright!

decrease in pre-load —> decrease in stroke volume —> decrease in cardiac output

Our body is not happy with this, and it tries to compensate for the decrease of the cardiac output, limiting it. Where the common carotid bifurcates into int and ext, we have the carotid sinuses in which we have sensors which send to the Central Nervous System information regarding the arterial pressure at this location. When we change posture, and the LHI due to Stevin’s Law, the pressure at the level of the baroreceptors decreases, and this is transduced into a decrease of the rate of firing of the sensor, the CNS responds with an increase of the orthosympathetic tone, and with an increase of the heart rate, which partially compensates the change in stroke rate. So instead of being 40%, the decrease in cardiac output it is only 25% (look at the graph). But we have also another problem. Because of gravitational effects, we have a huge increase of the pressure inside the circulation of the legs, a pressure increase in the capillaries of the foot. We will study later that an increase of intramuscular pressure increases the filtration, and this will results in edema of the upper part of the body.

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This is counter-balanced by some mechanisms. The first mechanism can be related to the increase of the orthosympathetic activation - the main capillary resistances increase, so the pressure drop between the arterial and capillaries increases, and at the end the pressure of the capillary pressure decreases. At therefore we have a decrease of capillary pressure, a decrease in filtration, and this increase of the resistances is shown here as the Total Peripheral Resistances (see graph) increases (due to orthosympathetic tone. In the legs we have also an intrinsic mechanism to limit the dilation of the vessel at that level. The arterial side we have an intrinsic regulation of the diameter of the arterioles, in the sense that there is a local compensation of increased contraction of smooth muscle and therefore vasoconstriction (also orthosympathetic)

Measuring the urine output of the subject in the supine position and during postural change, immediately after the postural change there is a transient decrease of the urine output. this means the organism is sending fluids in order to expand the intravascular compartments.

Question: Imagine a subject that goes from supine to standing in two situations: In ambient and in a swimming pool. What is the difference in the urine output?

It will be higher in the swimming pool! Because the pressure increase inside of the vessel is counterbalanced by the increase of the pressure outside of the vessel so that the transmural pressure (the determinant vessel dimension) does not change much.

Remember that the tilting table is an extreme change! In ordinary life, during standing, we activate our muscles. Our leg muscle operate as an auxiliary pump that help return the blood to the heart.

SLIDE. A new kind of representation

Time vs pressure at the level of the leg.

First the subject is standing still (39º). then at 33ºC and finally at 25ºC. We measure the pressure continuously.

When the subject starts walking, pressure inside of the vein decreases and increases at each step. The degree of increase/decrease is temperature dependent, in a sense. We can see that while the rise and fall of the pressure is complete at 39º, is is not so for the there two temperatures. This is because of the arrangement of the veins in the lower limbs, and the presence of the valves we studied in Anatomy, that create an auxiliary pump able to void the legs of blood.

Question: Why do have temperature have an effect on the pressure?

This is a superficial vein, and the cutaneous circulation is controlled mainly by the action of the orthosympathetic system, whose discharge is dependent on temperature. If temperature is very high (39º), we have very low resistances at the level of superficial circulation, and therefore the time for filling, when you have this things, is very short and you can Page � of �14 15


have these neat oscillations, which are absent below, where the lower temperature causes vasoconstriction and resistance is higher.

A final point. Why is this point of postural change important for us? We have seen the effects of postural change are limited by baroreceptor reflexes. Note that these reflexes are efficient if you exercise them. If not, they lose efficiency. Space travellers know this very well. After landing on Earth, they look like something like a dead corpse that is put on a bed.

This kind of patient is not your main interest but it is analogous to having a patient in bed rest or immobilisation. Expect problems of orthostatic hypotension. Clearly, the proper activation of the orthosympathetic system is very important in order to avoid the consequences of postural change.

Consider that if you are not able to the fall of the cardiac output when you go from supine to standing, you can have syncope (?), meaning the pressure decreases too much and you faint.

This happen during diabetes, there is peripheral neuropathy, which can decrease the efficiency of postural reflexes.

Another condition even more common - when diagnosing and treating essential hypertension, we’ll give the patient a number of drugs, which will decrease the intervascular volume, or have the effect to block some action of the orthosympathetic system: the ß-blockers. If a subject is unable to have ß-receptor stimulation, he cannot increase the heart rate in this way! Therefore, a subject who is treated with ß-blockers has some pre-disposition to orthostatic hypotension.

Another important cause which can induce orthostatic hypotension is the state of filling of the c.v. system, that is intravascular volume. If you are volume depleted, your control systems are activated to compensate for the lack of volume inside the systemic circulation. So we have already a big activation of the the orthosympathetic system. Changing position, there should theoretically be a further increase of the activation of orthosympathetic system to compensate for the further reduction of the preload. But this is impossible if the subject already experienced nearly full orthosympathetic activation. And therefore, if you have a volume depleted patient he can experience a orthostatic hypotension. This is particularly nasty when the subject is treated with ß-blockers if for example, you decide the doses given to the patient during the winter. Then, the temperature outside increases, and the same dose can be excessive during the summer, because of thermal dissipation.

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pecchiari lesson 1 transcript - 5:3:2015

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