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 nonvolontaile substance with

the external milieu and the other part of circulation is

specialized in exchanging gases.

THE HUMAN CIRDULATION

It has a various number of variations which includes:

1. 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.

2. For functional reasons, the blood flows through an arrangement of parallel and serial pathways, in the

liver case.

3. Blood takes many parallel pathways from left to right heart

4. In most cases, the blood flows through two capillaries in series, for instance upper limbs.

5. For functional reasons, the blood flows through an arrangement of parallel and serial pathways, in the

liver case.

6. 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. 1 Circulation

7. 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 crosssection

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 crosssection 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.

2 Circulation

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; ccomposition 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

3 Circulation

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 ηm) and arterioles (10-100 ηm) 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 relaxatoin 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). 4 Circulation

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 02 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 infraction, cerebral infarction, heart failure and so on. Ischemic heart

disease and stroke are the leading causes of death globally in the last 15 years.

5 Circulation

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 pression 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:

6 Circulation

= ∙ + = ∙

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 – 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

= ∙ ⟶ = ∙ 4

8

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. 7 Circulation

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/TURBOLENT 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 Raynolds 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. 8 Circulation

ρ

Re = v ∙ D ∙

The Raynolds 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 – 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,