Circulation

Circulation 13: physiology of circulation – anatomy

Unicellular organism: it is the simplest organism composed by one cell. Waste and nutrient diffuse over the plasm membrane. There is a metabolism where nutrients come in the internal milieu and the waste produced by the metabolism are expelled out into the external milieus. Unicellular doesn't need circulation because the diffusion keeps the cells alive.

Multicellular: it functions with invagination and central cell has access to the external milieu, but it means that the central part is exposed to high concentration of waste and low concentration of nutrients which is a vulnerable conditions respect to the peripherical cells. This organism required:

• Single circulation with one pump: is in contact with the internal milieu and exchange waste and nutrients, transport nutrients to the various part of the cell in the circulation and the waste are take away.
• Two circulation with two pumps: one is done specializing in exchange non-volatile substance with the external milieu and the other part of circulation is specialized in exchanging gases.

The human circulation

It has a various number of variations which includes:

• Blood takes many parallel pathways from left to right heart. In most cases, the blood flows through two capillaries in series, for instance upper limbs.
• For functional reasons, the blood flows through an arrangement of parallel and serial pathways, in the liver case.
• Blood takes many parallel pathways from left to right heart.
• In most cases, the blood flows through two capillaries in series, for instance upper limbs.
• For functional reasons, the blood flows through an arrangement of parallel and serial pathways, in the liver case.
• In contrast, the blood flowing from the right to the left heart can only take a single pathway, across a single capillary bed in the lungs.

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• Finally, some deoxygenated blood mixes with oxygenated blood flowing from the lungs to the left heart.

When we travel through the circulation observing velocity and cross-sectional area it possible to see that: in the aorta, the blood leaving the left heart has a high velocity and low cross-sectional area and more the circulation branching the larger the cross-section area and the lower the velocity. At the levels of capillaries there is the maximum of cross section A in combination with the lowest value of velocity in order to exchange waste and nutrients with the tissues that are perfusing. In the vein circulation, the cross-section area is decreased while the velocity increased to the right heart. In the lung circulation is possible to observe that the cross section area of lung in the capillaries is even larger respect to the cross-section A in the whole body: it serves for the gas exchange.

Pressure: low pressure is observed in the left atrium and it becomes pulsatile pressure with high amplitude in the left ventricle due to the systolic blood pressure. In the aorta, the blood pressure fluctuation becomes smaller, between the systolic and diastolic pressure. Then in the arteries pressure the pulsatility is disappeared arriving at a steady pressure. Pressure gradient remains intact through the capillaries until reaching the right atria and ventricle: this means that the pressure at level of capillaries is low but there is a pressure drop over the capillaries until arriving in right heart. The same occurs for the pulmonary circulation: pulsatile pressure is observed in the right ventricle, the same with low amplitude in the pulmonary arteries and again it travel to the capillaries and lung where the blood is oxygenated and constant pressure drop is observed. Pulsatile pressure occurs only in the first part of the systematic system as well in the lung circulation.

Typical pressure values: these values often occur in the human body, but they can dynamically vary in the circulation depending on many factors.

Microcirculation: consists of small arteries, arterioles, capillaries, venules and small veins.

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Wall composition varies depending in where we are in the circulation (vedi composizione e diametro di vaso e lumen).

Large and small arteries and veins differ in the relative expression of these structures. The compositions of the wall of blood vessels have functional consequences: elastic fibers accommodate and smooth fluctuations in blood flow; smooth muscle regulates the diameter of the blood vessel, thus controlling arterial resistance and venous capacitance; collagen is not very elastic and helps to prevent overdistention; composition of arteries, from large to small: amount of elastic fibers and collagen is going down and the amount of smooth muscle is going up.

All blood vessels, except for capillaries, consist of three layers: tunica intima, tunica media and tunica adventitia. In figure is showed a small artery. Tunica media and adventitia are separated by external elastic lamina while the tunica media and tunica intima are separated by internal elastic lamina. Both of lamina are fenestrated so fluids can pass and it is relevant for vascular function.

Tunica media: supplies mechanical strength and contractile power to blood vessels. Spindle-shaped smooth muscle cells are embedded in a matrix of elastin and collagen fibers, so they can contract and relax changing the diameter of blood vessels. Two sheets of elastin, the internal and external elastic lamina, mark the boundaries of the media. It is specifical important that, myo-endothelial junction facilitate diffusion of the chemicals produced by the endothelium to the smooth muscle cells in the media.

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Tunica adventitia: consists mainly of connective tissue without distinct outer border. One of the main purpose is to tether the vessel loosely to surrounding tissue, in this way the blood vessel is free to move. Sympathetic nerve terminals can release noradrenaline, to regulate local resistance and blood flow. This means that the neuronal transmitters of sympathetic, branch of the autonomic nerve system, diffuse through the fenestration into the media and influence the smooth muscle cells. In this way local resistance of blood changes with the diameter and blood flow can be influenced. Large arteries and veins have “vasa vasorum” to take care of the perfusion of blood vessel wall itself.

Medium-sized artery (muscular artery) and medium-sized vein – comparing a medium-sized artery and medium-sized vein is possible to observe some differences: the arteries have a circular shape and are not able to change its shape while the vein partly collapses. In other word the arteries are best compared with a garden tube and the vein is best compared with fire tube. Veins are really able to store blood, if there is something to store, if not veins partially collapse and have a small lumen where blood can flow, not very different from the lumen area of arteries.

Travelling in the direction of capillaries, it is found elastic artery, muscular artery and arteriole:

• Elastic arteries accommodate the stoke volume of the heart and smooth the blood flow, and it is called Windkessel effect.
• Conduit\feed arteries (e.g., coronary arteries) deliver blood to the organs. They can dilate and constrict, regulating blood flow due to the large amount of smooth muscle cells.
• Terminal arteries (100-500 μm) and arterioles (10-100 μm) dominate the resistance of the circulation. The proximal resistance vessels are richly innervated and sensitive to local concentrations of metabolites. The innervations are mainly sympathetic, and metabolites have effect on constriction or relaxation of these terminal arteries and have a strong influence the perfusion of an organ.

Looking at the transition from arteriole to venule through capillary bed the most important observation is that: there are several direct connections between arteriole and venule, means that blood can directly flow from the arteriole to the venule site without passing the capillary bed. It is called arteriovenous anastomoses that serve heat exchange, they are found in the skin, regulating body temperature, and in the nose (warm inspired air).

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There are several types of capillaries, some of them are open for fluid (sinusoid); fenestrated are found in the kidneys but, in the heart as well as skeletal muscle, there are continuous capillaries.

Capillaries (4-7μm) serve the exchange of O2, CO2, nutrients, metabolites and fluid between blood and tissue, so it is important that the blood flow is low to facilitate this exchange. Some O2 exchange occurs in arterioles upstream of the capillaries; some fluid exchange occurs in postcapillary venules.

The transit time of a red blood cell through a capillary in the systemic circulation in 0.5-2 seconds, allowing the cell to unload O2 and take up CO2.

At veins site there are large vein, medium-sized vein and venule not very different in composition.

Veins and venules contain 2\3 of the circulating blood and are called capacitance vessels. Capacitance of the venous bed is controlled by sympathetic activity that can give vasoconstriction in the venous vascular bed.

In limb the intima has a semilunar valve to prevent backflow, a sort of resistance against gravity.

This discussion about the anatomy of the circulation would be incomplete if the major pathology of circulation, the atherosclerosis, would not mention at least. It can cause vascular stenosis and obstruction, ischemic heart disease, myocardial infarction, cerebral infarction, heart failure and so on. Ischemic heart disease and stroke are the leading causes of death globally in the last 15 years.

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14 – circulation – physical concepts

Physical concepts play an important role in the control of circulation.

This is the list of symbols and units in which they are usually expressed, useful to quickly understand the descriptions that belong to the lessons.

Complex organisms require a circulation. Circulation requires a pump (or two pumps, if we want to consider the heart as two pumps). But what is the pumping action of the heart exactly? What is the heart doing: it generates pressure or flow? Anyway, there is no flow without pressure. For this reason, we first consider the relation between pressure and flow in the circulation. (we will see during this lesson: resistance, viscosity, laminar/turbulent flow, compliance, wall stress and matching of venous return and cardiac output)

Resistance

If we want to push a bolus of blood through an artery, we need a certain pressure difference (ΔP) to cause a certain flow. Ohm law is applied:

• For electricity: ΔV = I ∙ R voltage difference (ΔV) is given by current (I) times the resistance (R).
• For hydrodynamic: ΔP=F ∙ R: pressure difference (ΔP) is given by flow (F) times the resistance (R).

Circulation has parallel and serial resistances (the whole circulation made by many vessels). Serial resistances have to be added, while for multiple resistance ranged in parallel the reciprocal of the total resistances can be found by adding the reciprocal of the individual parallel resistances.

Hemodynamic systemic vascular resistance is the resistance that heart experiences when pumping blood from the left heart (aorta) to the right (the inflow of the right atrium) heart. The arterial is the beginning of the systemic circulation and venous the ending of the systemic circulation, this is a combined resistance of many parallel and serial resistances. The only part that is excluded is the resistance of lungs circulation. = Ohm law flow is pressure differences divided by resistance. Applied to the circulation means that the cardiac output (CO) is equal to the difference between arterial blood pressure (P ) and venous blood pressure a(P ) divided by the systemic vascular resistance (SVR):v ( − ) = Often time it is assumed that the venous blood pressure is zero, not really true because it is a few mmHg, very close to zero. However, if we assume that it is zero, we get the simpler relation: = = And assuming that the arterial blood pressure equals the mean arterial blood pressure (MAP) we have:

In the figure below it is shown the relationship between the MAP, CO and SVR. Given by the equation:

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= ∙ + = ∙ or, simply, if we assume that the central venous pressure (CVP) is zero:

Green line – if we assume that CO is the controlled variable in the circulation, then it would mean that change in SVR would have immediate and strong effect on blood pressure: increase of SVR would increase the MAP. Decrease of SVR would decrease the MAP.

Blue line – if we assume that MAP is the controlled variable, so it is more or less kept constant in the circulation (that is more likely than CO), then SVR would have immediate importance for the CO: increase of SVR would decrease the CO. Decrease of SVR would increase the CO.

If we take a look at the blood pressure signal, that can be measured at the level of the brachial artery, we see the peak that indicate the systolic blood pressure (SBP), then a pressure wave called dicrotic notch, that is actually a reflection of the pressure wave at the resistance vessels for the peripheral circulation in the arm (the pressure wave reflects back and give the dicrotic notch). Then there is minimum point that indicate the diastolic blood pressure (DBP). It can be seen from the figure also the mean arterial pressure (MAP), nothing else than the average of the blood pressure signal over one complete cycle, and the difference between the SBP and DBP, so called pulse pressure.

If we want to assess roughly the MAP, having only the SBP and DBP values without figure:

1 1 = + ∙ ( − ) = + ∙ ( )3 3

Viscosity

Viscosity – the viscosity resistance in a tube with a given length and diameter is described by the Poiseuille-Hagen equation (in our case the tube is represented by the blood vessel).

Knowing that the resistance is equal to the pressure difference divided by the flow (R = ΔP/F), if we compute the resistance starting from the original formula we obtain:

4 8 = ∙ ⟶ = ∙ 48

It can be noted that resistance (R) is proportional to the viscosity (ƞ) and length (l), while it is inverse proportional to the forth power of the radius and this is the most strong mechanism through which the circulation can adapt its resistance (by changing the diameter of the blood vessels).

Suppose that for one blood vessel the diameter would halves, so there would be a vasoconstriction, then the resistance of the blood vessel goes up. Thus, vasodilatation and vasoconstriction are two very strong mechanisms to regulate vascular resistance.

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Red blood cells (RBCs) play an important role in the viscosity of blood. Viscosity increases with the increasing of the haematocrit (=volume RBCs / total blood volume).

For lower values, the first increase of viscosity is caused by the fact that red bloods cells stick a little bit together, then for high haematocrit values viscosity increase because red blood cells start to collide and deform.

However, there exists a normal range, which within a person is not really constant but dynamic because the amount of fluid in the blood is varying (e.g. water).

The lowest viscosity corresponds to the viscosity of pure plasma (plasma without any red blood cells) that is higher than the water as it can be seen from the figure on the left.

Poiseuille has already observed that viscous resistance decreases in smaller (<1 mm) blood vessels.

Suppose that we have blood that has a viscosity of 3.0 cP (‘centipoise’) in larger blood vessels, the same blood flow though smaller blood vessels the viscosity decreases. This happens for a series of effects, the main is the actual concentration of blood cells.

The accumulation of red blood cells is show in the figure below. In smaller blood vessel there is a layer of plasma in between the red blood cells and the wall of the blood vessel, and this actually reduces the viscous resistance to the viscous resistance of plasma (that it is lower).

There are many strange effects playing role in small vessels, for instance such a plasma layer can skimmed at the branching point, so in corner the blood is touching the wall, then the red blood cells get a spinning movement and they spin towards the center of the blood stream causing a new plasma layer along the wall.

Laminar/turbulent flow

Laminar/turbulent flow - parabolic laminar flow profile with low velocities of blood:

When we increase the driving pressure, and thus increase the amount of flow (there is a linear relationship between driving pressure and flow velocity given by the formula F= ΔP/R), and at a certain point we reach the Reynolds number, the blood stream will change from laminar into turbulent flow.

From figure we see that the relation change, this means that resistance through blood flow increases in turbulent flow.

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ρRe = v ∙ D ∙ The Reynolds number can be computed: η

With large blood vessels (high D) it is much easier to get turbulent flow, while with high blood viscosity makes more difficult to get turbulent flow.

Compliance

Compliance – relation of the filling of the fluid container and the pressure in that fluid container. More precisely, compliance is the amount of volume that must be added per unit pressure increase. The more compliant (“elastic”) a vascular bed is, the more filling volume is required to generate pressure.

The definition of compliance is change in volume (ΔV) divided by change in pressure (ΔP): =

• Zero compliance: fixed volume, that means that the contained cannot be filled. The pressure will be endlessly increasing possibly but compliance is zero because change in volume is zero.
• Infinite compliance: the container accepts any volume that is injected in it. The pressure increase will remain zero.
• Finite compliance (the situation usually meets): some extra volume increases some extra pressure. In fact,