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[LAUGH] Okay gang.
We continue today with the vesicles, and a couple people
didn't notice that the notes they got covered Monday's and today's
lecture, so if you happen not to bring your notes
and you want them there are a couple extra's up here.
Okay?
So anyway, the vascular system, cardiovascular system is
a pump in a closed system of vessels.
We talked about the pump.
Now we're going to talk about the vessels.
And you obviously know, you've known probably since middle grade, that
blood flows from arteries to arterials, to capillaries to veinules to veins.
And the structures of these vessels match their functions very nicely.
So both the major vessels, the arteries and the veins, consist of multiple layers
including the internal endothelial layer, which is the lining of the blood vessel.
And then there is a basement membrane.
And there is, in arteries especially elastic tissue elastic
fibers, and in the large veins, there also are elastic fibers not shown here.
And then smooth muscle.
And unlike the gut, the smooth muscle here is
all arranged in a circular fashion around the vessel.
because there's no peristalsis in blood vessels, they just constrict or dilate.
And then in arteries, there's more elastic fibers,
so essentially arteries are like steel belted radial tires.
They have to sustain, withstand large pressures.
And then some connective tissue.
So, the structure is pretty much the same all the way
through with the amount of smooth muscle and elastic fibers differing.
And as we'll see in some of the large veins, we have valves which
prevent the back flow of blood, and we'll get back to that in a moment.
But if we look now at some of the physical characteristics
of the circulation that these take the cellular properties have to match.
Of course, in the arteries there's very
high pressure, and the velocity of the blood
is very high, because the total cross
sectional area of the arteries is really small.
So you start out with simply the aorta, which is just one vessel.
And, the pressure and the velocity in the aorta is very large.
As it divides into smaller arteries there's not much of a drop in velocity.
And and pressure until you get into the
really small arterials, and these vessels have because of
their small diameter and because they can constrict As
we'll see they can have very high resistance, okay?
So because of the high resistance in the arterials there is
a major drop in velocity, and also a major drop in pressure.
Because pressure is dissipated as you push something against a resistance, right?
So then when we get into the capillaries,
we see this huge increase in total surface area.
There are, even though capillaries are so tiny,
just one red blood cell in diameter, there
are so many of them, that if you
take their total cross-sectional area It's huge, okay?
So it's sort of like a river rushing down through a mountain gorge and
them up and then emptying out onto a plane into a, into a delta.
The area over which the water is being spread is
very large, and the flow rate goes very, it goes down.
So similarly here, the flow weight is minimal in the in the capillary beds.
But the total surface area is high.
And these vessels have very thin walls, because this is where all of
the exchanges take place, the exchange of
respiratory gases, and nutrients and so forth.
Okay, then we come out of the capillary beds, the cross sectional area goes down.
So the velocity goes back up.
But the pressure continues to stay low.
And the reason for that, is that the
pressure has been imparted here by the heart.
It's been dissipated.
And now that pressure imparted by the heart
is no longer influencing the pressure in the veins.
So the question then is how do you get this blood back to the heart?
And we'll come back to that in, in a moment.
So here are some pistological pictures of
these different vesicles, here is a large artery.
You can see the, the smooth muscle fibers that are arranged around
the the the lumen of the artery, and make it possible to
constrict it, decrease it's diameter, or relax, and increase it's diameter.
And then we here have lots of elastic fibers.
That can absorb the pressure that's imparted to the blood by
the heart, and prevent the vessel from blowing out or creating aneurysms.
And here is just a magnification of these elastic fibers that are arranged
circumferentially around the artery to given, strength.
[SOUND] We go into the arterioles, and we still see a lot of smooth
muscle, and, because of the smooth muscle in the arterioles, they
can open and close to change the blood supply for individual tissues.
So because their resistance is variable,
their resistance in controlled to direct blood
into tissues where the blood's needed the
arterials are called the resistance vessels, okay?
because they have variable resistance.
And then we get into the capillaries, so
here's an arteriole feeding a bunch of capillaries.
And you can see once you get to the capillaries
the diameter is pretty small, the wall is very thin.
Red blood cells squeeze through one at a time, and
diffusion between the interstitial fluid and the plasma can take place.
So they are the exchange vessels.
And then we get into the venules, they don't
have to withstand high pressures, so they're mostly thin walled.
You can see your red blood cells flowing through a venule.
But when you get into the bigger veins, you find that they do
have a lot of elastic fibers, and they do have smooth muscle, layer.
And, the, because of the elastic fibers, and the smooth muscle
layer, the veins can vary the amount of blood that they contain.
So because their capacity to, to contain blood
can be very, they're called capacitance vessels,' kay?
Capacitance or capacity to hold a larger volume of blood.
Now when you're sitting here at rest, you don't need your blood
volume to be in circulation, your total blood volume to be in circulation.
Some of it can be sitting there in reserve.
So now when you're sitting here, about 60%
of your blood volume is in these large veins.
Only about 18% is circulating around your body in the arteries, okay?
Then when you get up and get active, there is some
contraction of the smooth muscle in the large veins, and this
blood which is essentially on a siding, if you will, it's in
storage, short-term storage, is pushed back into the central circulation.
So, capacitance vessels.
'Kay, so, one of the things I want to emphasize to you
is, the importance of these elastic fibers in the large arteries.
It's not just to keep them from bursting open, it also has
a very important role in maintaining the flow of blood around the body.
And I'll demonstrate that to you here, because I have a ventricle, okay?
And I have an aorta.
So, what I'm going to do, is show you the properties of pumping
of the blood to the aorta, because of the sistole and diastole.
[INAUDIBLE] My ventricle is not filling.
Well, we'll fill it another way.
[SOUND]
Okay.
Now let's
see if it works.
Unfortunately have an air bubble.
So here we go.
Systolic, diastolic.,
Systolic, diastolic, Systolic, diastolic, sis, we still have an air bubble [LAUGH].
An air embolysm is really a serious problem.
[LAUGH] Right.
You don't want that to happen to you.
[SOUND] I wouldn't make
a good gasoline.
[SOUND] My siphon pump wouldn't work.
Eh, try again.
[BLANK_AUDIO]
Okay.
Systolic, diastolic.
Systolic, diastolic.
You see the problem?
Your need for oxygen, your need for nutrients is continuous.
But because of the cardiac cycle, the pumping is pulsatile.
So you say, well, this isn't just, this isn't realistic.
You just have an art, just have the major artery, just have the aorta.
What if you put in some arterials.
Okay, well let's put in an arterial.
So, see
if I can find something that fits.
Okay, so here's a smaller diameter vessel, here's an arterial,Systolic, diastolic.
Systolic, diastolic.
.
Systolic, that still doesn't work, we still just have pulsatile flow.
Well, let's put in.
Let's put in a capillary.
>> [INAUDIBLE] >> Pardon?
>> They can't see you.
>> Yeah, we can't see you.
You can't?
>> Oh my god.
[LAUGH] >> Okay.
Systolic, diastolic, systolic, diastolic, systolic, diastolic.
[LAUGH] You got it?
[LAUGH] Okay, now I got to try to find the connection that'll.
Make if possible for me to put a, I just put
a bunch of connectors here.
And see what will work.
[BLANK_AUDIO]
Well, that's not going to work.
[SOUND]
Here we
go.
That should do it.
Okay.
Once again, here we have the arterial systolic, diastolic.,
systolic, diastolic.
Now let's put in a capillary.
Okay, a very small diameter capillary.
Systolic, diastolic, systolic, diastolic, systolic, diastolic, systolic, diastolic.
[LAUGH] Okay.
So let's put in, let's put in.
A you got it over there?
Systolic, diastolic.
[LAUGH] Okay.
So let's put in now an elastic arterial, or an elastic artery.
So I'm going to go back down here and put in an elastic artery,
which is simply a balloon which has elasticity, you remember that.
And, replace our capillary,
or arterial at our capillary.
Okay, see if that holds together.
Systolic.
Systolic, diastolic, Systolic, diastolic.
Whoops.
I have an air bubble again.
These air embolisms
are a problem.
There we go.
Get that air out of there.
Okay, there we go.
Systolic, diastolic.
Systolic, diastolic.
Systolic, diastolic.
See it works.
[LAUGH] So the important thing is that these elastic
vessels enable the, the kinetic energy of the
heart that's being imparted to the blood during
systolic to be absorbed, and then replenish that.
Or replace that, or return that energy to
the blood during diastoly, so the blood keeps flowing.
Okay, so those valves in the veins, those valves are found
in the veins that are below the level of the heart.
Okay?
And those valves prevent the back flow of blood.
So blood can flow in the vein towards the
heart, but it can't flow backwards because of the valves.
This is something you can demonstrate on yourself.
You know, if you have a vein in your arm that you can just put your hand on.
And, and, and push the blood through the vein.
As long as you're going towards the heart
you don't see any bumps occurring in the vein.
But, if you try to stroke it in the
other way you, start seeing little bumps or swellings.
Along the vein, because what you're doing is you're trying to push the blood in
the opposite direction, and the valve closes and
you get a little swelling of the vein.
Okay.
So what, the, the presence of these valves plus the squeezing of the veins
by the muscles, as you're active result in pumping the blood back towards the heart.
So even though there's no, no pressure imparted to the
blood from the heart down in the lower part of the
body, as you're active the muscles contract and act as
an auxiliary pump to pump the blood back towards the heart.
So this is why if you have soldiers that have to stand at attention
for a long period of time, or if you have guards like a Buckingham palace.
They may be, they may look as if they're stuck still, but
what they're doing is they're consciously
isometrically contracting the muscles of their legs.
If they don't after a little while they'll just kill over
because they're not getting enough blood supply back to the brain.
Okay.
So, here is another very important property of the blood vessels and that is
the exchange of fluid between the plasma and the interstitial fluid, okay?
So, blood comes in to the capillary beds
under pressure, and these capillaries are highly permeable.
So, there is a large eflux of fluids out of the capillaries.
So small molecular weights and water are continually
moving out of the capillaries into the interstitial space.
So, why don't you just become a big bag of water, and blow up?
Because, at the other end of the capillary bed, where
pressure is low The fluid is being returned to the capillaries.
So, the question is how does this happen?
And a long time ago this guy, Ernest Starling,
came up with a hypothesis which is called Starling's Hypothesis.
And, for the last 120 years or so, every student in physiology has learned
that this is the mechanism whereby your
interstitial fluid gets back into the circulation.
And if you're asked that question on the MCAT exam, or
the Graduate Record exam, be sure you know the wrong answer.
Okay?
The wrong answer,
which is essentially Starling's hypoth, that's not totally wrong.
I mean, there's some truth to it, but the Starling's
hypothesis says that on the arterial end of the capillary
bed, the pressure is high, and therefore, there is filtration
of the blood, as we've seen before, into the interstitial space.
But as you go through the capillary bed, the pressure is dropping, and eventually
you get to the point where the osmotic pressure of the blood, in the
capillary is higher than the osmotic pressure of the interstitial fluid.
Why?
Because large molecules, such as proteins, can't get out of the blood.
So the, what's called the colloid osmotic pressure, or
the osmotic pressure due to large molecules, large protein
molecules, is a force that pulls the water back
into the, on the venous side of the capillary bed.
Okay?
Now, the alternative hypothesis is that, that movement
of bicarbonate into the blood, because of the
carbonic and hydrase in the endothelial cells, and
the carbonic and hydrase in the red blood cells.
That influx of bicarbonate into the blood plasma, creates a phenomenon
called solvent-solute drag, and it essentially is pulling, the
solvent, the water, with it, as it moves away, from the walls of the
from the endothelial cells, moves into, the plasma.
And it's creating a drag force that pulls water with it.
And the guy who came up with this probably about 20 years ago now.
Had a lot of difficulty in getting this idea accepted.
He could not get it published, and even got laughed at by physical chemists.
And this is another story like the
Helicobacter pylori that, it's hard to change dogma.
You may have some good evidence, but unless you can get
it out there and people to consider it, it gets ignored.
So he felt so strongly about his hypothesis and his findings in
his experiments, that he wanted to be sure they were engraved in stone.
And that's what he did.
He had his tombstone made before he died, and on his tombstone it says,
he is a physiologist who recognized the diffusion of
bicarbonate ions as the principle osmotic effect in Starling's hypothesis.
[LAUGH] So I hope someday you feel so strongly about
one of your ideas that you go to that extent.
So anyway, okay.
Talking about pressures, what about the most common pressure
we deal with, with the cardiovascular system, blood pressure?
I'm sure you all have had your blood pressure taken, or you've
taken someone else's blood pressure, and it's really a very simple process.
The pressure in the larger arteries is
increasing and decreasing with systolic, diastolic, systolic, diastolic.
So what the blood pressure measurement method is, is to put a cuff
around the upper portion of the arm let's say, it could be somewhere else as well.
But it's where you can occlude a large artery.
An artery which is close to the heart and therefore
reflecting the pressure that's imparted to the blood by the heart.
So here are the biracial artery is being occluded by this pressure cuff.
So when you listen to the sound of
blood flow through the artery below the pressure cuff.
When the blood is just flowing you don't hear anything, okay?
If you occlude the artery, so here is
essentially the pressure which is being produced by the
heart, if you totally occlude the artery, you
don't hear anything here because there's no blood flow.
And if you slowly lower the pressure of the cuff, you'll eventually get a little
bit of blood squeaking through at the peak of systolic.
And the vessel is essentially opening up a little bit and slamming shut.
Opening a little bit and slamming shut.
And it's that slamming shut of the vessel that gives you the first heart sound.
That you, or the first sound from the stethoscope here,
that you're using to listen to blood flow through the arm.
So that then equals the systolic pressure because it's the peak
of the systolic pressure that's able to squeak through the occlusion.
And then you gradually lower the pressure in the cuff.
Until, eventually there is continuous flow of blood, a continuous swoosh
sound of blood and then the, the pressure at which that swoosh
becomes continuous is the diastolic pressure, okay.
Okay, so the really important question that we brought up at the
very beginning of the lecture yest, on Monday, is what is regulated?
So many things are being transported by the cardiovascular system.
What is it that provides the information that is
necessary to change the function of the cardiovascular system?
Well first of all, at the very, very
basic cellular tissue level, blood flow is autoregulated.
And, you know, we've seen this before.
And that is that when waste products build up in a tissue bed.
Those waste products have an influence on the arterials, so those waste products,
such as excess hydrogen ions they're also local hormones which can be produced.
[UNKNOWN] what they do is they cause relaxation of
the smooth muscle on the arterials, and as a result.
There's more pressure on the arterial side of the
capillary bed, and blood flow increases to the capillary
bed, bringing in more of the nutrients that are
necessary or taking away more of the waste products.
So keep in mind that flow equals pressure divided by resistance, okay?
So, in this case, what we're doing is we're decreasing the resistance.
And as a result, with a particular blood pressure being imparted
to the ar, arterials by the heart, you can increase the flow.
Okay?
So, this is good for a local capillary bed, but what about your whole body?
How does the cardiovascular system respond to the demands of the whole body?
I'm sure you've been in a situation in your dorm, where you're trying to take
a shower, and all of a sudden five people flush the toilet at the same time.
What happens?
The water pressure goes down.
Right?
So the same thing is true for your whole body.
If you open more, and more, and more capillary beds, because
there's more and more tissue demand, the central pressure will fall.
Because just as in the periphery, also in
the center, the flow equals pressure divided by resistance.
So when we're talking about systemic circulation,
we're adding together all of these capillary beds.
That are practicing autoregulation.
Okay.
So, what is driving the overall flow of blood is the mean arterial pressure.
What is the mean arterial pressure that you would measure in the
aorta or in one of the major arteries close to the heart?
And it's that mean arterial pressure which is then pushing blood
through all of the different smaller
arteries, and arterioles and capillary beds.
So the critical, the critical factor is mean arterial pressure.
What does that equal?
Well, that equals the cardiac output.
And the cardiac output is liters of blood per minute, let's say.
Times the total peripheral resistance, the resistance
of all of those capillary beds added together.
So you can see that if all of a sudden, all of the capillary beds open up.
Total peripheral resistance goes down mean arterial pressure goes down.
On the other hand, if something happens to your heart
and the cardiac output goes down, mean arterial pressure goes down.
Okay, so what influences the total peripheral resistance?
Well we've just seen several of them.
Local factors buildup of waste products, hydrogen ions in the local tissues.
Autonomic nervous system can influence the resistance in individual
capillary beds, and we saw that of course in the case of the the kidney.
And hormones, and we saw that also in the case of the kidney, how hormones
can influence the dilation constriction of arterials,
and therefore contribute to the total peripheral resistance.
Okay.
So what about cardiac output?
Well cardiac output equals the product of two factors.
The heart rate, how many beats per minute, and the stroke
volume, how many milliliters of blood per beat the heart pumps out.
So the heart rate, we know is controlled by the
autonomic nervous system, sympathetic speeds
it up, parasympathetic slows it down.
[BLANK_AUDIO]
The, sympathetic nervous sys-, or the autonomic nervous system, especially the
sympathetic nervous system, also has an effect on the stroke volume.
So that if there is sympathetic activity, the heart tends
to beat stronger, and therefore, the stroke volume goes up.
But there is also another factor which
is called the Frank-Starling law of the heart.
And this demonstrates the Frank-Starling law of the heart.
Very simply, the more you put into the heart, the more you get out.
You say, yeah, that doesn't say very much.
Well, it does because the more you put into the
heart, you more, the more you stretch the heart, and
when you stretch the heart, that increases the force of
the contraction, and that's the Frank-Starling law of the heart.
So, the filling of the heart is
measured here as the ventricular end diastolic volume.
Okay, so at the end of sistolic, or excuse me, at
the end of diastolic, what is the volume of the ventricle?
Now, if you're trying to push lots more blood through
the system there's lot of return coming from the Venus side.
That endiostolic volume is going to be higher.
'Kay.
So the stroke volume is proportional to the end-diastolic
volume over a fairly large range of, of volumes.
Okay.
So at rest, 'kay your end-diastolic volume is not
that great in your stroke, in your cardiac output.
Stroke volume is not that great.
When you get to exercise your end-
diastolic volume gets bigger because you're pushing more
blood back into the heart, and the
heart is responding by increasing it's stroke volume.
The reason for this, is that at rest the overlap of the actin and myosin fibers
are not optimal for generating the max, the largest contraction,' kay.
So if you stretch it a little bit, that optimization is improved.
And as a result, the subsequent contraction of the heart is more forceful.
So the bottom line is that anything that increases venous
return is going to increase cardiac output by influencing stroke volume.
So, we still haven't asked what's regulated, what is the information?
We talked, when we discussed respiration, about the chemo sensors in the medulla.
The sensors responsive to hydrogen ions predominantly, and the
chemo sensors on the aorta, which are responsive to oxygen.
And in addition to influencing
respiration, they also influence heart rate.
'Kay.
So that if
there is a signal here that there is not enough, that there's too much CO2 in the
blood, or there's a signal here there's not
enough oxygen, or the blood flow is too low.
That influences medulary cardiovascular control center, center neurons
to increase the sympathetic output to the heart.
Okay?
Now in addition to these chemo sensors there
are also stretch receptors in the great arteries.
And these stretch receptors are responsive to blood pressure.
Because the higher the blood pressure, the higher
the systolic pressure, the more they are stretched.
And these neurons, these stretch receptor neurons, are
active all of the time.
So, when you are simply sitting around, these stretch receptors are firing.
They are not silent.
They don't have to be stretched maximally to increase or to start firing.
Okay?
So they're normally at the midpoint of the mean arterial pressure curve.
So here we're looking at the firing rate, mean arterial pressure, just sitting here
at a normal systolic pressure there at the midpoint of their firing rate.
And then if the pressure goes up, they increase their firing rate.
And if the pressure goes down, they decrease their firing rate, 'kay?
So there's constant information coming from these barrel
receptors depending on what the mean arterial pressure is.
So what do they do?
They feed into the medullary cardiovascular control center.
And when, and actually what they do is they
inhibit the sympathetic output from the cardiovascular control center.
So if pressure goes up, they inhibit the sympathetic and
release inhibition on the parasympathetic, and it slows down the heart.
If pressure drops due to haemorrhage let's say, what happens
then is they activate the sympathetic, and the sympathetic has a
direct action on the pacemaker nose and on the muscle
it's self to increase the heart rate and the stroke volume.
But in addition, the sympathetic nervous system
can activate the adrenal gland to release epinephrine.
And epinephrine has a very powerful effect on heart rate and stroke volume.
So it looks like the major information which is being used here, is
the pressure in the great arteries, 'kay.
So there are also other control elements
besides these neural ones, the sympathetic and
the para-sympathetic, there are hormonal influences on
blood volume, blood pressure, and heart rate.
So, here is the vicious circle that we have to deal with.
If you have a fall in arterial pressure, let's say you have a
haemorrhage, or you have a heart attack and you're not pumping enough blood.
Decreased blood flow to the tissues means local accumulation of metabolic waste,
means that autoregulatory response of decreasing
the resistance in the capillary beds.
As a result our arterial pressure falls even more.
Okay.
So you could see how this is a vicious circle.
The fall in arterial pressure leads to a decrease in total
peripheral resistance, and therefore a decrease in arterial pressure.
Okay?
So what are these hormonal influences?
We have, we saw the neural influences, which are rapid.
They are immediate influences, but the hormonal influences
operate over a longer time frame so, we talked
about the kidney responding to a drop in
blood pressure by releasing rennin, from the juxtaglomelular cells.
The renin activates angiotensin, and what angiotensin does, as it's
name implies, is that it causes peripheral blood vessels to constrict.
So you cause the peripheral blood vessels to constrict.
That's going to increase the total peripheral
resistance, and therefore increase the mean arterial pressure.
Okay.
We also saw when we discussed the kidney, how the kidney excuse me, the
changes in the osmotic pressure of the blood, lets
says a rise in osmotic pressure of the blood.
Can cause the hypothalamus to release vasopressin,
this is another name for ADH, antidiuretic hormone.
And as the, this name implies, vasopressin, it also causes peripheral
vasoconstriction, increasing the total peripheral resistance, 'kay?
So, both of these hormonal mechanisms will cause a
rise in arterial pressure to compensate for this loss.
Now in addition to the mechanism we talked about in the kidney and the
osmotic pressure of the blood the hypothalamus is also sensitive to
firing in these arterial stretch receptors, these baroreceptors.
So, when blood pressure goes up, it inhibits the release of vasopressin.
And, therefore, you're going to pee out more volume and reduce
the total blood volume which helps to bring the pressure down.
If, on the other hand, the barometric for the baro, the stretch
receptors decrease their firing rate, the baro receptors decrease their firing rate.
That is going to relieve, in addition, on the release of vasopressin, which will
promote the reuptake of water and conservation of fluid volume.
And remember also that the angiotensin causes thirst.
So that not only helps preserve fluid volume,
and preserve blood pressure by putting the volume
into a smaller circulatory volume it also tends
to increase the total volume by increasing water intake.
Okay.
So that's how it normally works.
What happens when it doesn't work normally?
And it's worthwhile paying some attention to this, because as we started out,
said that cardiovascular disease is responsible for 40% of all deaths.
And you tend to hear a lot about various forms of mortality.
And just sort of assume that well,
cardiovascular disease, that's something that's going to happen anyway.
Not much we can do about.
But indeed, there's a lot we can do about it.
So the problem of cardiovascular disease of any kind,
is that it causes the heart to pump less blood.
So it is essentially the failure of the
heart to meet the circulatory needs of the body.
And why might that be so?
Well, the heart muscle can be responsible for this.
Decreased contractility.
And if you have a heart attack, and part of
your heart muscle is not getting enough oxygen and nutrients.
Therefore, you can have decreased contractility.
And of course if that is sustained for a long
period of time, a portion of that myocardium can die.
And then you have a permanently impaired cardiovascular system.
So acute myocardial infarction, heart attack, blocking of blood
vessels, the coronary blood vessels can result in cardiac failure.
Over a longer period of time, there
are chronic conditions that decrease cardiac function.
For example, coronary artery disease.
The accumulation of plaque.
Cholesterol in the coronary arteries that decreases the ability to
perfuse the myocardium and provide it with enough nutrients.
Another condition we'll talk about which is a genetic condition that's very
common in the population and most of us Don't know whether we have
it or not, because it rarely raises it's ugly head but that's familial
hypertrophic cardiomyopathy which we'll give you more details on in a moment.
Another cause of cardiac failure, or inability of the
heart to pump enough blood is damaged valves, and
this is usually the valves into and out of
the left ventricle which are subjected to the highest pressure.
So the mitral valve or the aortic valve can become leaky, or can malfunction.
And then conditions which result in total permeability of the vascular
beds, called shock, result in a huge decrease in blood pressure.
And essentially what's happening is that the fluid is leaking out into all
the tissues of the body, and the return to the heart is, is decreased.
Okay, so shock is another possible cause of failing,
causing the heart to fail to pump enough blood.
'Kay, just a quick look at coronary artery disease.
Here is a large artery, which you see is very largely occluded by
this proliferation of smooth muscle over this plaque consisting of, cholesterol.
And here you can see a vessel which is also almost totally occluded.
As a result of the build up of, of fatty plaque in the wall of the vessel.
And here is actually a vessel in place, and it's not been fixed.
So you can actually see the plaque through the through the vessel wall.
You see the plaques here that are forming in the walls of the vessels.
And we know now that these plaques can start to form in very young individuals.
You don't have to be an old codger
to start getting cardiovascular disease and plaque formation.
So one of the problems with plaque formation, is that
it causes an irregularity in the flow of the blood.
And it causes actually rupture of the endothelial wall.
So, if we allow this plaque to build up it can actually rupture the endothelial wall.
And then the clotting proteins, which are circulating in the
blood, can be activated and cause the formation of a clot.
Okay?
So if you have the formation of a clot around
one of these plaques, that plot, clot can break loose, and
it's going to go downstream and as the arterioles get smaller
and smaller, eventually it will stop because it's, can't get through.
And that's a thrombosis, and here you see a thrombosis in a major coronary
artery, and that is the common cause of a heart attack, lack of blood
flow to the myocardium which is fed by that particular artery.
And here's the consequences of a heart attack, here you see healthy.
Ventricular tissue and then here we have scar tissue which is the result of dying
of the myocardium that's been deprived of blood because of a coronary thrombosis.
So you can imagine that this ventricle is not going to be able to pump.
Nearly [COUGH] as efficiently as a ventricle in
which the myocardium is healthy, all the way around.
This kind of damage can occur to different
locations in the heart, because we have multiple
coronary arteries, so the artery which gets clogged
by a clot determines what the nature of the
heart attack will be.
Okay, so this phenomenon of hypertrophic cardiomyopathy is
a genetic condition, and as I said it's actually very common in the population.
And it most, it doesn't affect most of us.
But it tends to affect athletes.
And it affects athletes because, what the, mutate and there're a number of mutations.
It could be a mutation in one of
several of the contractile proteins in the sarcomere.
That make up the sarcomere.
Okay, of the cardiac muscle.
But what it does is it causes the muscle contraction to be less efficient.
And actually you can get as a, as a result you can get sort of a almost
mixed up arrangement of cardiac muscle cells as a result of the
effort of these fibers to overcome their inability to contract.
So, why is it more common in an athlete?
It'll, if someone is exercising to a very high level, frequently.
And their heart is not very efficient.
The heart hypertrophies.
The heart gets bigger because, there is an
effort to increase the ability to meet the demands.
You've all heard, I'm sure, of the athlete's heart.
So, athletes tend to have bigger hearts, and it's the result of, of
pushing their, cardio vascular system to high levels all of the time, okay?
So here's a particular case.
Reggie Lewis, who was a star with the
Boston Celtics, he collapsed in a couple games.
He was diagnosed by is doctors as having no problems whatsoever.
This was just maybe fainting, or they didn't give a particular reason.
Then one day he was playing a pick up
game with some kids and he collapsed again and died.
And it was found that the cause
of the death was this familial hypotrophic cardiomyopothy.
Okay.
And that's why most of the individuals
that die of this, die right after exercise.
Either during exercise, or right after exercise.
So why?
This hypertroph, hypertrophy of the heart is
predominantly, of course, of the left ventricle.
So you can see the normal myocardium of the left ventricle.
And here you can see a hypertrophic cardiomyopathy,
an enlargement of the muscle of the left ventricle.
And what can happen is, this muscle hypertrophy can get so extreme.
That of course the volume of the left ventricle is very much decreased.
So that's counterproductive.
But in addition, it can interfere with the conducting fibers, which are
going down the, the septum between the left and the right ventricle.
So here you can see a normal heart.
Here's the size of the left ventricle, and there, here's an FHC heart.
You can see the volume of the ventricle is very much reduced, but importantly this
thickening of the wall can infringe upon and obstruct
the conduction of action potential down conducting pathways.
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So there is an argument that people should be geno
typed for whether or not they have one of these mutations.
As information that would be perhaps relevant when you decide whether or
not you're going to going into major athletic effort in competition or not.
Other people say, well, it's not something that everybody should know about,
because they should make their decisions on what they want to do.
So, it's an example of, of ethics that
are derived from human genome capacity an, and information.
So, let's go to now from the athletic to the old codger
which is frequently suffering from congestive heart failure.
So here you have a condition of cardiac failure from a young individual who is
extremely healthy, a peak athletic, and someone who is aged and incapacitated.
So what do these two conditions have in common?
In both cases, it's an imbalance of supply and demand.
The tissues need more blood, and the heart, can't supply it.
Okay?
So, an imbalance of supply and demand.
So in the case of the FHC, the hypertrophy is a mechanism to increase supply
in resid, in response to the increase demand
of high high metabolic activity, high exercise levels.
And of course the decrease can, the decreased contractility.
But in Congestive Heart Failure there's an overload on the heart, 'kay.
The heart is not able to pump out the blood which is coming back to it.
So the heart has to work against a unfavorable pressure gradient in order to
supply blood to the body, and I'll show you how that actually plays out.
So, first of all, the cardiac failure can
be left heart or right heart, or both, 'kay?
So, depending on whether it's left heart or
right heart, the effects are going to be different.
If, of course, it's the left heart, a major
problem is going to be that there is a
return of blood coming from the pulmonary circuit, and
the heart is not able to pump that blood out.
So if the right ventricle is healthy and pumping
at high pressure, it's going to result in pulmonary hypertension.
Increased pressure, in the vessels of the lungs.
And as a result, you get a fusion of fluid into the
into the the, the, the, the, the, the thoracic cavity.
So, here you can see the result of that
infusion here by the the shadedness of, of this x-ray.
In a normal individual, you'd have rather clear boundaries between the lungs and the
cardio, the the, the cavity containing the heart.
Okay?
So on the other hand, if it's left heart.
Oh, that was left heart failure, if it's
right heart failure, then essentially what's happening is
the heart is not able to accommodate all of the blood coming back from the body.
So you get damming of the Venus blood in the systemic circuit.
You get effusion of fluid then from the veins are on the venous side, so you get
accumulation of fluid in the extracellular spaces in the throughout the body, so.
So, short term consequences.
This is essentially what we just said.
The right heart failure.
Abnormal high systemic venous pressure, so you get
congestion, in the various organs of the body.
Which therefore have higher venous pressure, higher
venous resistance than they should, and as
a result accumulation of fluid, for example,
in the abdominal cavity which is called ascites.
Left heart failure, you get backup of blood into the pulmonary circuit,
so pulmonary hypertension, and therefore effusion
of fluid into the, into the lungs.
Diminished perfusion to vital organs, so as
a result, the auto-regulatory response is the organs,
are going to be, demanding more blood, and the heart is incapable of delivering it.
So fatigue, weakness, faintness, because the lack of, of adequate blood supply.
And once again systemic edema because eventually things get
backed up so that the venous pressure throughout the body is increasing.
So this is the condition Congestive Heart Failure.
So generally it's the left heart which fails.
And then if the left heart fails, then the problem progresses to the right heart.
Once again, if you're not able to supply
the tissues of the body with enough nutrients.
And you're not able to supply the myocardium
with enough nutrients you're eventually going to have this
injection in the systemic circuit, and failure of
the right part as well as the, the left.
Okay, so what are the consequences of these events, these conditions?
So, let's look at what happens to acute,
to an individual with acute heart failure, okay?
So this is a heart attack.
And the immediate effect, of course, is there's
going to be a sudden decrease in cardiac output.
So if we go down and we, once again, look at the
Frank Starling Law of the Heart, and now instead of ventricular volume.
We're going to look at right atrial pressure.
And course you realize that these things are completely related.
So you can look at the Frank-Starling law,
either in terms of ventricular volume or atrial pressure.
And you're looking at the same thing, 'kay?
So normally we sit right here.
And here's the normal Frank Starling relationship, 'kay?
And the right atrial pressure is normally very, very low.
And the cardiac output is, at rest, is up here at maybe six liters per minute.
'Kay?
So what happens with the heart attack?
The heart muscle is damaged, the heart muscle cannot
contract efficiently, and therefore the cardiac output goes down suddenly.
So, now we're on a new relationship, okay.
Because we're not able to pump out the blood which is returning to the heart.
The right atrial pressure increases.
Okay?
So we're now down in this position here, with the acutely damaged heart.
So the very first thing that happens is we get a big, sympathetic response.
The autonomic nervous system is, getting the information that, tissues are
not getting enough are not getting enough nutrients, not getting enough blood.
So sympathetic activity goes up, and that strengthens through the mechanisms we just
saw, that strengthens the heart and increases the cardiac output.
The heart rate goes up, the stroke volume goes up as much as it can.
And in even in the damaged heart.
Now if you're in this condition for a period
of time, you may eventually get some recovery, you may
get some repair of the heart tissue, and you may get some additional
compensation without the continued sympathetic activity.
So this is a partially recovered heart, it's not back to where it should be.
There is an abnormal high of right atrial
pressure and there is a decrease cardiac output.
So,
if an individual reaches this partially recovered
condition, obvious he's going to be considerably impaired.
But is the patient going to live or die?
So that's the critical question.
What is enough, what is adequate, what
is sufficient cardiac function to maintain life?
Well the critical variable is the function of
the kidneys, which we talked about last week.
So what is necessary to maintain normal glumerular filtration
is an output of about five liters per minute.
Okay.
So that output of five liters per minute sets a critical threshold for survival.
If the heart function can recover adequately to get above the cardiac
output of five liters per minute, the prognosis for long term survival is good.
If they can't we see a series of
events which are characterized by this curve here.
Okay.
With the heart intact we move up here with the sympathetic response, we move up here.
It is not adequate, okay.
So what is happening?
What is happening is that the condition is getting worse.
And the heart is getting weaker.
And the heart is getting
overstretched because of the inability to pump out everything that's coming in.
Either from the systemic or from the pulmonary circuit.
So because of this, stretching of the heart, okay?
We move a little bit up this curve,
but it's still not enough to reach critical threshold.
And now we start getting accumulation of
fluid, in the extra cellular spaces, edema, acides.
And as a result, the situation becomes even
worse, and the buildup of waste products weakens the heart even more,
and the decreased flow can result in sludging of the blood.
In other words disseminated intravascular clotting,
formation of minor clots throughout the
body, which is going to further complicate and compromise the other organs.
And of course the hypoxia and the acidosis is also a
serious consequence, and as a result, we go into cardiogenic shock.
All of the tissues are saying we need more
blood, all of the vascular beds are opening up.
And as a result the the condition gets even worse.
We're not pumping out the blood, the right arterial pressure is going up,
and the inability, increased stretch of the heart and weakening of the heart.
Drives us to this condition which is leading to death.
So what are some of the things that you
can do, if you're sort of on this borderline condition?
Well one of the things that can be done is to, strengthen the heart.
With various medicines, to decrease the
vascular volume, which is creating problem, by
using diuretics, so you've heard of ACE
inhibitors, you've heard of inhibitors for ADH.
So, because the kidney is trying to maintain blood pressure
by preserving vascular volume, and that's compromising the cardiovascular system.
What you want to do is decrease the actions of the
kidney, the selfish actions of the kidney, and decrease the vascular volume.
So you want to have diuresis, you want to
decrease the reabsorption of water from the kidneys.
The other treatment that's shown here, is one that's been around for a very,
very long time, and it's using a
drug derived from foxglove, these plants called digitalis.
And what this drug does, this alkaloid from the digit, from the foxglove,
it slows the calcium pumps in the In the sarcoplasmic reticulum of the myocytes.
So if you slow that calcium re-uptake, you're
going to prolong the contraction of the myocardial cells.
So you prolong the contraction of the myocardial
cells you're going to get more complete emptying.
Of the ventricles and more blood forced out into the circulation.
So let's look at and unfortunately it's hard to distinguish these curves.
We're looking at the first day which is
the thin curve here, and the thin curve here.
So during, and of course what this represents is the return to the heart.
And what this represents is the cardiac output.
And the two have to be, balance.
Okay?
They have to be equal.
So, on the very first day of this heart attack, we end up over here.
So the return to the heart and the output of the heart is balanced at this right
arterial pressure, and at this cardiac output, which is below the critical level.
Okay?
So what happens with partial recovery of the heart, and perhaps digitization
of the heart with with, with the cardiac, cardiotonic drugs.
As a result, you can move into this relationship.
Okay?
Where we're getting, more efficient output of the heart.
Because of strengthening of the of the cardiac muscle.
And as a result, the right atrial pressure is going down.
Because we're able to pump more of that blood out and hopefully, we move to
a point where we're at the critical
level that the kidney can continue functioning, okay?
So it's sort of just a way of seeing graphically
what you have to think about if you want to treat a failing heart.
Now, the bottom line is, which I tried to emphasize to
you at the beginning, is that in physiology it's all interconnected.
So, homeostasis depends on the functions of all of the
organs and if one organ goes down, such as the heart.
You can see the kidney, then its going to malfunction,
and it's going to go on and on to other organs.
So the bottom line for you is,
rather than oh, well, keep everything healthy.
Live well, eat well, exercise, be healthy and.
Good luck on your exams.
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