BLOOD VESSELS

So this is the heart, and we’ve got to move fluid from the heart, and there are points along

the way where blood is diverted from the main vessel out to some organ. Then within the organ,

blood is divided up into the internal spaces within the organ, and the vessels become very

complicated little systems which are the capillary beds. Then everything comes together and

eventually the blood is returned back to the heart.

As you are leaving the heart, the major vessels that leave the heart are only to transport,

and in the beginning all the blood is in one vessel, the aorta. All the blood that is leaving the

heart is coming out of one very large vessel, kind of like being on the turnpike; the turnpike is

not there to let you navigate around your neighborhood, like to get down from your house to

Starbucks, that is not the purpose. You are not going to get from your driveway to Starbucks by

taking the turnpike, but you will get from NJ to CT taking the turnpike; once you have gone a

certain distance on the turnpike and you want to get to some local town, you are going to exit off

the turnpike and get onto a different system of roads, and eventually some system of roads will

take you into your neighborhood, and then eventually they will be able to deliver you to where

you live. The same thing is with this system: in the beginning we have what are called

conducting vessels, they just conduct, or move, and the characteristics of the vessels necessary to

do that are very different from the characteristics of the vessels that are going to deliver oxygen

and nutrients to the cells, however despite the differences in function, all blood vessels are

constructed the same way. If I took a piece of a blood vessel and I looked at its cross section, it

would have some kind of internal space, called the lumen, and the lumen would be surrounded

by an internal lining—if someone was wearing a tunic, what would they be wearing? It is like a

robe that covers you, and there are a couple openings for appendages to stick out of, and a place

for your head to stick through it. There are coverings on the lumen: there is an internal tunic,

that is called the tunica interna, a middle tunic, the tunica media, and an outer tunic, tunica

externa. A vessel can be constructed out of one or more of these tunics. The biggest vessels

have all three of these layers. The inner layer that surrounds the lumen is just simple squamous

epithelial cells; it is just an inner lining, with maybe a little connective tissue holding it together.

The tunica media is smooth muscle; it allows the vessel to change its characteristics and its

diameter. Vessels that can change their diameter have this ring of muscle, and there are two

terms that describe changing the diameter of vessels: vasodilation, which is to make the opening

bigger, and vasoconstriction, which is to make it smaller. Blood vessels that can change their

diameter are going to have this muscular layer. The outermost layer, the tunica externa, is there

to reinforce the wall of the vessel, to make it stronger and to attach it to other things, and it is

primarily connective tissue. The type of vessel it is will determine the characteristics of these

layers.

When you are close to the heart, where the blood pressure is highest, where the blood

volume is flowing greatest through that area, you are going to have a very big lumen, not much

muscle, and a lot of connective tissue around the outside to strengthen the wall of that vessel.

When you get down to the conducting vessels, which are just for moving blood and not

distributing it, there are going to be very big vessels, strong walls, and not a lot of muscle. Then,

when you want to divert off of the conducting vessels into some organ, you are going to enter

into a distributing artery, and these distributing vessels have muscular walls. (If you have ever

gone out to run or workout right after you ate, sometimes you will get these cramps, because the

blood is in your digestive tract and all the other organs have a reduced amount of blood going to

them. When you go out running, you want to shift everything around, and sometimes you get

local areas where you are not getting proper oxygenation, and you will get a cramp.) You go

from conducting vessels to distributing vessels, and then once you get inside the organ and you

need to distribute the blood to the whole area of the organ, you get into what are called arterioles.

Arterioles are almost all muscle, because they can be totally shut down when you are not

oxygenating and delivering blood to the organ. Eventually you go from an arteriole to a

capillary bed, and it is only in the capillary bed where we actually allow the cells of the body to

come in contact with the contents of the blood. All these other vessels are simply to get blood to

the cells, and it is only in the capillary bed where there is any kind of exchange of gasses or

nutrients with the cells. So, you go from conducting to distributing to arterioles to a capillary,

and it is only in a capillary where gases and nutrients can be exchanged.

Looking at the capillary bed: if this is the arteriole coming into the capillary, the other

side is a venial leaving the capillary. There is a way to bypass the capillary all together, so there

is a channel that goes through the middle of the capillary, called the thoroughfare channel. The

actual capillaries, the tiny little vessels come off the beginning section of the capillary bed.

There are little muscles that control the movement of blood into the capillary called precapillary

sphincters. The blood enters into the capillaries, and fluid can leave the capillary, gases and

nutrients can leave the capillaries, and the capillaries come back and join back up with the

thoroughfare channel. The blood then drains into the venials, and the venials join up with each

other to form veins, and small veins join to form big veins, and eventually the blood is drawn all

the way back to the heart.

A shunt lets something go from one place to another, and so to shunt something is to

divert it from one place to another, hence the thoroughfare channel is a vascular shunt: it allows

the blood to go from this side to the other side and bypass the capillaries. You do not need blood

going to your capillaries all the time, so most of the time the blood is going right through the

middle and never going into the capillaries, because the little precapillary sphincters are closed.

Conditions where you do not need blood going through your capillaries would be like right now,

where your muscles hardly have any blood going through them, because you are not running or

bicycling or swimming. Your metabolic level is so low, most of the cells are hardly using any

oxygen or nutrients, so enough blood is there to keep them alive, but most of your capillary beds,

even 95% of the capillary beds in your lungs right now, are bypassed, because you do not need to

absorb that much oxygen, simply because are not doing anything.

When the capillaries come back together, they form venials, and the venials become

veins, and the veins become bigger veins, and eventually the blood goes all the way back to the

heart. Now one thing about the arteriole side verses the venial side: on the arteriole side you

have this big pump that pushes the blood from the heart out to the capillaries. The heart, when it

is contracting, generates maybe 120 mmHg of pressure; by the time you get down the capillary

bed, the pressure is down to about 20 mmHg. If it took you 120 mmHg of pressure to push it

from the heart all the way out to the capillary bed, how do you get it to come back, when there is

no pump at the end? We need some mechanism to move the blood back to the heart: the primary

mechanism for pumping blood back to the heart is that the veins are integrated into your

muscles, so as you contract your muscles, the muscles compress the veins. If this is a vein here,

and it is surrounded by a muscle, when that muscle contracts, it compresses the underlying vein,

pressurizing the blood. That is fine, except for the fact that when that blood is pressurized, it just

moves away from the place it is going to be squashed, so you have to have a way to make the

blood go one way. The veins have little flaps, valves, so if blood is compressed, it is going to be

pushed through the valve going towards the heart. The valve only opens one way, like a door

only opens one way, towards the heart. When the blood is being pressurized, the valve behind

the blood being pressurized with be closed, and the valve ahead of the pressurized area will be

opened, and the blood will move forward. The primary mechanism for returning blood back to

the heart is the skeletal muscles simply compressing the veins, fluid in the veins becoming

pressurized and then moving forward. (If you have ever taken a long plane flight and taken your

shoes off, and you go to put your shoes back on and your feet do not fit in your shoes anymore, it

is because a lot of the fluid that was in your circulatory system has not been returned back to the

heart and a lot of the fluid is in what is called the interstitial space, which is the area between

your cells, and you need to get up and walk around and compress your veins with your muscles.)

BLOOD PRESSURE

Let us talk about blood pressure, how it works, and how it is regulated.

Veins generally do not have muscle in their walls, they are very distensible, they expand,

so at any given point, a lot of your blood is just pooling in your veins. When you are inactive,

your veins act as a reservoir, and the veins will stretch out and blood will pool in the veins, and

that is where a lot of it is stored. (For individuals that stand for long periods of time, say their

job requires them to do that, sometimes the vessels in their legs will actually expand, and

sometimes they will expand to the point where the valves do not work very well anymore, so

they start getting blood pooling in the vein like a varicose vein. That is because there is so much

blood in the vessel that the valve does not function well enough to stop back pooling.) Veins are

not muscular; they are primarily for conducting fluid back to the heart. The reason why they are

not muscular, and not particularly thick, is because there is not a lot of blood pressure there. On

the other side, close the heart, the vessels have to be very thick and very strong because pressure

is greater.

If I have a vessel with fluid moving through it, the fluid has pressure, and the pressure

that we measure as blood pressure is the force that the blood is applying to the wall of the vessel.

Blood pressure is just a force. If we want to measure blood flow, if I want to make fluid flow

from A to B, I first have to have a pressure gradient, which is a difference in pressure between A

and B. The pressure on side A of the vessel has to be greater than the pressure on B to get blood

to flow in that direction. Also, anytime fluid is moving inside of a vessel, there is some

resistance to that fluid moving because the fluid is in contact with the inside of the vessel, and

you can view it almost as friction. In order to get flow, I need a pressure difference that is going

to overcome friction, or resistance, inside the vessel. When we measure blood pressure, it is

going to be a function of the resistance of the vessel and the pressure gradient through the vessel.

If I am going to get blood to flow through the body, the movement of blood through the

body requires a pressure gradient, and I need some source of that pressure gradient, which is the

heart. Here is the heart, and here are some conducting vessels, then distributing vessels, then

arterioles, then capillaries, and then venials, then veins, more veins, and then back to the right

atrium of the heart. If we look at the pressure near the heart, depending on the individual, the

pressure will vary between 120 and 80 mmHg of pressure. During systolely, the pressure in the

heart is very high, and diastolely it is lower. As we move away from the heart, the pressure

drops, first of all because the fluid is encountering resistance running through all of these vessels,

and on top of that, it is being spread out over more and more vessels. If you are in the

Mississippi river, the main channel of the river is moving very fast, but when you get to the

delta, at the Golf of Mexico, the river is hundreds of miles wide, and the flow is almost

unperceivable, you cannot even see it moving. The same is the case with your blood: it is all

concentrated in one place in your heart, in the aorta, but as you spread it out over more and more

vessels, the pressure is being distributed through all of those vessels. You go from 120 mmHg,

and by the time you get down the capillaries, it is about 40 mmHg, and by the time you get back

to the heart, it is virtually 0.

We have to move blood throughout the entire body; we have the heart to push it down,

and we have what is called the skeletal pump, the skeletal muscles, to pump it back to the heart.

What makes it move initially is cardiac function; blood pressure is a function of what the heart is

doing. You might remember from yesterday that cardiac output is equal to stroke volume times

heart rate, and stroke volume is equal to the amount of blood in the heart before it contracts,

which is endiastolic volume, minus the amount of blood left in the heart after it contracts, which

is endsystolic volume. Blood pressure is related to heart function in the following way: blood

pressure is equal to cardiac output times peripheral resistance, which is essentially friction, the

physical forces opposing the movement of blood through the vascular system. When we want to

talk about regulating blood pressure, any variable that can be controlled by the body can change

blood pressure. If we change heart rate, we change blood pressure; if we change the amount of

blood in the heart before it contracts, we change blood pressure; if we change the amount of

blood in the heart after it contracts, we change blood pressure; if we change the resistance in the

system, we change blood pressure.

One quick comment about peripheral resistance: resistance is related to the cross

sectional diameter of a vessel: the smaller the vessel, the greater the resistance. In your big

vessels, there is very little resistance, but when you get out to your small vessels, the resistance

gets much bigger. Remember, for some vessels you can change their diameter, and so you can

actually increase resistance and change blood pressure by changing the diameter of the vessels

by activating the smooth muscle in the vessel wall.

Let us talk about how to control blood pressure and what part of your body does that.

There are a couple different ways to do it; one thing about blood pressure is that it can be

controlled on a short term basis, for very short periods of time, and short may be minutes, maybe

hours, but you can also control it over a long period of time. Short term control usually involves

the nervous system or certain types of chemicals made by the body. If you want to control your

blood pressure over the long term, and you want to raise it or lower it and keep it at a higher or

lower pressure, what you need to do is change blood volume, and this is done by the kidney. If

you have a greater volume of blood you are going to also have a higher stroke volume and higher

cardiac output, therefore you are going to have a higher blood pressure.

Let us first talk about short term regulation of blood pressure. Essentially on the short

term, what you do is change what the heart is doing, and if you change what the heart is doing,

you are going to change cardiac output; if you change cardiac output, you are going to change

blood pressure. The first mechanism for short term control is by the sympathetic and

parasympathetic systems. When the sympathetic system is activated, heart rate goes up; if heart

rate goes up, cardiac output goes up, which then causes an increase in blood pressure. When the

sympathetic system is activated, it also causes the heart to contract more fully, so if the heart

contracts more fully, the amount of blood left in the heart goes down because more blood is

ejected, then the stroke volume increases, the cardiac output increases, and blood pressure

increases. When you change cardiac output, you change blood pressure. When the

parasympathetic system is activated, heart rate goes down, therefore cardiac output is going to go

down, and blood pressure is going to go down.

There are other brain based mechanisms, and these are considered autonomic, which

means there is nothing you can do about these things. An area of your brain called the medulla

has an area called the vasomotor center. One part of the vasomotor center system is a connection

between the brain and the muscular walls of your arteries. The vasomotor center is sympathetic,

therefore it causes vasoconstriction, so when the vasomotor center is activated, you vasoconstrict

your blood vessels, and the decreased blood vessel diameter increases resistance, so it is the

vasoconstriction that increases the peripheral resistance which is going to increase blood

pressure. When you activate your vasomotor center, you cause vasoconstriction of the arteriole

blood vessels, peripheral resistance goes up, and blood pressure goes up. All of these brain

based mechanisms are short term; your brain does not want to spend its whole day worrying

about blood pressure, it is going to think about other things like texts to send and checking

facebook, and all the important things, it cannot be worried about this.

The next short term control results from the activity of your baroreceptors; barometric

means pressure. Baroreceptors are in the large vessels of your heart, your carotids and jugulars,

and they are mechanical receptors in the vessel wall, so when the vessel is stretched, the

baroreceptor is activated. You do not want this giant bolus of highly pressurized blood rushing

up to your brain, so we need to control the blood pressure leaving the heart on its way up the

brain, and that is why the baroreceptors are located in the vessels just outside the heart. When

blood pressure goes up, we activate our baroreceptors, which then reduce the activity of the

vasomotor center, which then causes peripheral resistance to go down, which then causes blood

pressure to go down. It is kind of a reflex to reduce the blood pressure that is on its way to the

brain. Essentially, what you do is you inhibit the vasomotor center, the vessels dilate, and

pressure goes down. (That is why sometimes if you stand up really quickly and accelerate the

blood above the heart, you might get a little lightheaded for a second, because your vasomotor

center just shut down and you dilated all of your blood vessels, and pressure dropped very

quickly, so now you don’t have any blood going to your brain—not any, I’m exaggerating here,

but enough to feel like “whoa, I’m a little lightheaded here.”) This mechanism is available to

work at all times, but should you have high blood pressure on the way to the brain at any given

point? Probably not; this is more of a protective mechanism, it is not there to moment to moment

regulate your blood pressure.

The next thing we want to talk about are chemical mechanisms. A lot of these chemicals

are hormones usually released from secretory cells that are released into the blood stream and

that then affect different components of the circulatory system. They can affect what the heart is

doing or the blood vessels themselves. There are several of them, but we are going to try to keep

it as straightforward as possible.

The first one is a hormone produced by your posterior pituitary called ADH,

antidiuretic hormone. If I put you on a diuretic, what would it do? You would have to urinate,

you would lose fluid from your blood stream; blood volume would go down, and if blood

volume goes down, which variable is going to be affected? EDV is going to go down, you will

have less blood going back to the heart because you have less blood, and if you have less blood

to pump, you pump less blood, therefore stroke volume goes down, cardiac output goes down,

and blood pressure goes down. Why is urinating related to blood volume? The fluid from your

bloodstream goes into the cellular components of the kidney tubules, the nephrons, and they

process the fluid and return it back to the body. On a moment to moment basis, you push 149

mL of blood out of your circulatory system into your nephrons per minute. The nephrons will

cover up to 148 mL and then 1 mL becomes urine, maximum, per minute. Without hormonal

regulation, however, without controlling this process, you actually produce about 30 mL per

minute. ADH controls the amount of fluid that comes out of your kidney tubules back into your

blood; that is why it is an antidiuretic hormone, because it reduces the loss of water as urine and

returns the fluid back to the bloodstream. ADH increases blood volume, which increases EDV,

which increases stroke volume that increases cardiac output, that increases blood pressure. For

example, alcohol is a diuretic ; it blocks the affects of ADH, and so it becomes a diuretic .

Without ADH, you produce 30 mL of filtrate per minute; your bladder only holds about 300 mL

comfortably, at 600 mL you have some sense of urgency and are seeking out the appropriate

place to deal with that sensation, and at 900 mL it does not matter where you are.

Another hormone is aldosterone. This hormone is produced by another endocrine gland

called the adrenal gland. Aldosterone also affects blood pressure in a very complicated way: it

increases the amount of sodium you take out of your filtrate, so it increases sodium in your blood

—how does that regulate blood pressure? It increases sodium reabsorption from the kidney

filtrate, which increase solute concentration of the blood, which activates osmoreceptors,

osmolarity receptors, and that is what causes ADH to be released. Aldosterone does not really

do anything directly to blood pressure, but it causes you to recover sodium from the filtrate of

your kidney and put it back into your bloodstream, and that increases the solute concentration of

your blood, which increases its osmolarity, which activates osmoreceptors to make the solute

concentration of your blood to go down, this simply increases blood volume, which dilutes it and

makes the solute concentration normal again. Then ADH essentially increases blood volume,

which then causes the pressure to go up.

The next hormone we want to talk about is angiotensin II. When blood pressure goes

down, there is a specialized region of the kidney tubule, the JGA, the juxtaglomerular apparatus,

that releases rennin. What rennin does is it causes angiotensinogen to be converted to

angiotensin I, which is converted in the lung to angiotensin II. Angiotensin II acts on the blood

vessels, causing vasoconstriction. What happens if blood vessel diameter goes down?

Peripheral resistance goes up, which then causes an increase in blood pressure. angiotensin II

then acts on the adrenal gland to cause aldosterone to be released, which causes sodium to be

reabsorbed, which increases solute concentration, which activates the osmoreceptors, which

cause ADH to be released, ADH then increases the reabsorption of water, which increases blood

volume, which increases EDV, which increases stroke volume, which increases cardiac output,

and therefore increases blood pressure. This is the rennin-angiotensin-aldosterone mechanism.

So angiotensin does two things: it causes the vessels to constrict and causes aldosterone to be

released. What is particularly elegant about it is that the same organ that is controlling blood

volume, the kidney, is the one that says, “hmm, blood pressure is dropping, let me release some

rennin too,” so we get this other chemical being released by this organ that is actually regulating

blood pressure that says, “hey we need to regulate blood pressure here, we will release some

rennin,” and starts this whole process.

There is another factor called ANP, atrial natriuretic protein, made by the atrium. What

does the atrium receive? The blood coming back from the body; if blood pressure is high in the

blood coming back from the body, the right atrium is going to get stretched, and it does not want

to be stretched, it is a low pressure structure. If blood pressure goes up, then you release ANP,

which then blocks the effect of ADH. It does not stop ADH from being released, it blocks its

effect, which would be to increase blood volume. Blood volume goes down, EDV goes down,

stroke volume goes down, cardiac output goes down, blood pressure goes down. Notice,

everything else increases blood pressure, but ANP reduces blood pressure.