BIO203 Transcript

8/10/2019 BIO203 Transcript

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2014 12 4L26 Respiration 3

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dioxide, this reaction gets pushed to the right, and we have an increase in hydrogen

ion in the area. This is the relationship -- the link between carbon dioxide and

hydrogen. So in tissues that are metabolically active that are producing carbon

dioxide, we see that there is also hydrogen ions being produced and this is an issue.

One of the things I want to mention to flashback to talking about hemoglobin is

that, notice, that carbon dioxide is influencing hemoglobin in two ways. One way

is a carbon dioxide is binding to hemoglobin, not to the heme molecule, but to the

protein, to the amino acid part of the hemoglobin, and this alters the affinity for

hemoglobin to oxygen, making hemoglobin release oxygen.

But the other way the carbon dioxide now indirectly interacts with hemoglobin is

through the production of hydrogen ion. So the hydrogen ion itself also binds to

proteins, particularly hemoglobin, and the hydrogen ion binds to hemoglobin and it

also alters the affinity for hemoglobin to oxygen, and that was the Bohr shift that

we talked about last time, the effect of pH on hemoglobin. Some carbon dioxide

alters the affinity of hemoglobin for oxygen, causing hemoglobin to release oxygen

both because it binds directly hemoglobin and because it leads to the production of

hydrogen ion, which binds to hemoglobin.

Multiple things going on here, multiple sites for interaction in the system here.

Notice that this reaction, this bicarbonate buffer system reaction is reversible. It

can go in either direction, depending on how much carbon dioxide is present, or

how much hydrogen ion is present. We are to focus mostly on manipulating carbon

dioxide in this nights lecture.


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I showed you a slide like this for oxygen. Let's look at the same thing for carbon

dioxide. This is a cartoon from out of Silverthorne. The top half of this picture is

meant to taking place in the systemic circulation, and the bottom half of this

picture is meant to depict what is taking place in the pulmonary circulation.

Let's start at the top in the systemic circulation. So cells are metabolically active.

They are producing carbon dioxide. Carbon dioxide diffuses out of the cell into theinterstitial fluid, and into the plasma. Once the carbon dioxide is in the plasma, of

course you can dissolve in plasma, which I've mentioned before, but the carbon

dioxide primarily diffuses into red blood cells, and in red blood cells in encounters

carbonic anhydrase, causing the production of carbonic acid and the dissociation

into bicarbonate ion and hydrogen. Also the carbon dioxide can bind to

hemoglobin. These are the things we talked about last time and the numbers of the

same here as we have in the previous slide.

In terms of the production of hydrogen ion and bicarbonate ion the hydrogen ion

ends up being bound primarily to hemoglobin, and this plays the important role of

basically buffering the hydrogen ion, so the pH does not change that much. The pH

goes down a little bit in the systemic circulation compared to the pulmonary

circulation, but because there is so much hemoglobin present, the hemoglobin

binds a lot of the hydrogen ion that is being produced by the bicarbonate reaction.

The other thing I want to point out is that the bicarbonate ion itself does not stay in

the red blood cell, but rather it is exchanged via a transport system with chloride,

so that the chloride comes in and bicarbonate ion leaves the red blood cell. This is


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This is the last of the diagrams of the circulatory system. And now we have all the

numbers on here, and we have all the things we just talked about. This is right out

of Silverthorne. I recommend that you curl up with figure 18-12 over the weekend

and make sure you know what the numbers are in each place, and understand why

the numbers are what they are, and you should be able to explain everything that

we just talked about at the end of Tuesday's lecturers and now.

I will turn our attention to something else for the rest of tonight


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I want to introduce the idea of respiratory drive, which is the desire to take a

breath, and I will talk about what is controlling respiratory drive. What is

responsible for making us want to take a breath? The respiratory system is very

interesting because it is under a lot of different influences. At one level we have

voluntary control over the muscles, over the diaphragm and intercostal muscles. I

am exercising that voluntary control right now, talking to you. I am doing control

of expiration, making intelligible noises that provide insight to you about

respiration.

On the other hand though, remember, that the respiratory system is a breeze or die

system. If it is not working you die. So the nervous system has an absolutely

fundamental responsibility, which is to make sure that you do an inspiration that

leads to seven times a minute at rest or more if you're active. This has to happen no

matter whether you're awake, sleeping, running, laughing, whatever you're doing.

So what we see in the respiratory system is this range of functions. So there is a

range of things that the respiratory system does and I've tried to organize them

from involuntary down to voluntary and in between. I am not try to give you acomprehensive list. I'm trying to point out just how varied the activities are. What

we will focus on now is this one up here, the involuntary responsibility of the

nervous system to make sure that we have proper levels of oxygen, proper levels of

CO2, and pH in the plasma. That is, one could argue, the principal function of the

respiratory system.

So the question I'm going to ask is how is this regulated? How does this happen?


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Lets start by looking at how we actually generate an inspiration. How does the

nervous system make the inspiration happen, and how does the nervous system

make it happen 10, 11, 12 times a minute? The way it happens is that there is a set

of cells in the brain that are spontaneously active, that generate a rhythm that is

responsible for our basic respiratory rhythm.

I have a silly cartoon appears showing the brain and the brain stem. I have some

yellow dots in this figure. One dot at the level of the pons, the lower dot is at the

level of the medulla oblongata. These are the key areas, particularly the medulla

oblongata for generating rhythm. We'll talk about that more in just a minute. These

areas project down toward motor neurons that are located in the spinal cord, and

those motor neurons project out to muscles that are associated with breathing,

diaphragm, intercostal muscles, etc. They're the ones that generate that.

The act of breathing causes things to happen, the movement of gases, the

movement of tissues etc., and this causes sensations or provides for sensory

feedback, and their sensory receptors that are located in key places which will talk

about in greater detail in a few minutes. But the sensory receptors provide

feedback to the brain on the status of respiration, and then can modulate respiration

on a breath by breath basis. The point being to maintain homeostasis with respect

to oxygen partial pressure, carbon dioxide partial pressure and pH in the plasma.

I've drawn kind of a rough schematic here with different circles. This red circle


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here is meant to represent a collection of neurons that are located in the medulla

oblongata. That is the lower dot right here in the lower part of the brain stem.

These are the neurons that are rhythmically activate that generate the basic rhythm

of respiration.

How do we know that? In the old days the original physiology experiments were

brutal, and they would take and animal and make cuts in the animal. Imagine that

this is a cat or a lower mammal, and we would just make it cut through the brain

and say is this animal still breathing, and the answer is yes. Then we make

another cut in the brain and see if its still breathing. And you do it and you keep

making cuts, and eventually you get down to about here and then the animal stops

breathing. So that's basically how they established that the medulla do it is to keep

place for generating the rhythm.

One of the points I'm trying to make by telling you this is that injury to the brain

stem and the spinal cord can interfere with respiration, particularly if the injury is

below the medulla. So for example let's say there is an injury that is about this

level, in the upper spinal cord. The medulla may be intact but now the medulla is

no longer able to communicate with the motor neurons in the spinal cord, telling

the motor neurons when to generate action potentials and when to cause an

inspiration. The end result is that the individual can no longer breathe. This is what

happens of the highest cervical spinal cord injury, and those individuals then need

to be on ventilators in order to stay alive, because they are no longer able to

generate effectively the rhythm and activate the skeletal muscles appropriately in

order to achieve inspiration and expiration.

This is this connection here that I'm talking about. Your neurons in the medulla

oblongata that are projecting down to the spinal cord, particularly motor neurons

that are involved in causing respiration. These motor neurons project out to

muscles, and when the muscles contract they cause inspiration or expiration, but

they cause changes in oxygen levels, changes in our carbon dioxide levels, and

they also can cause changes in the physical size of the lung. We talk about

inspiration been expanding the thoracic cavity, stretching the lung. This provides

sensory feedback to the medulla to alter the rate and depth of breathing. We will

talk a bit about what is going on with this.

In addition of course to medulla is receiving input from higher centers, most

notably a set of neurons that are located right above it in the brainstem and the

pons. Is an important respiratory center, but there is also input, from lots of other

higher centers. The hypothalamus for example, the cortex, etc. So this is the basic

loop though, and the rhythm is generated predominantly by the cells in the medulla

oblongata. Lets look at some reflexes that are involved in controlling respiration.


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We will cut this down slightly. We start with the inspiratory neurons in the

medulla. They are projecting into respiratory motor neurons in the spinal cord, and

have an excitatory effect on the motor neurons, causing him to fire action

potentials. Those action potentials propagate out to the muscles, and cause muscles

to contract, i.e. diaphragm, inspiratory intercostal muscles etc., and the effect,

we're just going around the same basic thing we said before, causes some change.

In particular I want to emphasize that one of the things that happens. Inspiration is

the stretching of the lungs. Remember we talked about how the lungs are elastic;

they really want to be smaller Ii there left to their own devices, and by expanding

the thoracic cavity it stretches the lungs. The lungs have stretch receptors in them,

and we have seen a number of examples of stretch receptors in this course already.

Prof. Cabot talked about stretch receptors that were involved in the baroreceptor

reflex. I talked about stretch receptors that were involved in muscle length

monitoring and spindles, which are stretch receptors.

This is another example of a stretch receptors. What happens when the stretch

receptors are activated is that they activate sensory fibers that project into the

spinal cord, and in this case the input to the neurons in the medulla, the respiratory

center is inhibitory. That makes them become less active. It does not actually turn

them off, at least not for any particular period time, but it make sense of them slow

down. This is a negative feedback mechanism. So activate motor neurons, activate

muscle, cause stretch of the lungs, and the stretch causes the respiratory center to

decrease activity on the motor neurons. It is a negative feedback system. It is a

system that comes into play with lung stretch, and so it is a feedback mechanism to


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help terminate inspiration. You inspire, you activate stretch receptors. That inhibits

inspiration. You stop inspiration.

This reflex is called the Herring-Brewer reflex after two guys. The question thatyou should be asking yourself is how important is this reflex? Is this a reflex that

actually is important every time we take a breath, or is an important only under

special circumstances? It turns out that this reflex is not very important. It does not

actually stimulate, it is very difficult to demonstrate this reflex, particularly in

adults, and that sure, it is playing a role, probably with very extreme inhalations,

but on a breath to breath basis this reflexes not played a critical role in regulating

breathing. But physiologists love to talk about this reflex because it is another

example of the stretch reflex, and we love stretch reflexes in case you haven't

noticed.

Far and away the most important reflex for controlling respiration are the

chemoreceptor reflexes and they come in two basic varieties. Peripheral

chemoreceptor reflexes and central chemoreceptor reflexes. We will start by

talking about peripheral receptors, and then we will switch and talk about centralchemoreceptors.

I will give away the punchline and tell you that, by far, the central chemoreceptors

are the important ones. They're the ones that are really sensitive, that are

responding on a breath to breath basis. The peripheral chemo receptors, while they

can have a very strong effect, are not very sensitive to the levels of carbon dioxide

and the levels of oxygen that you typically see in a healthy adult.


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Lets look at the table up here. I've listed for a couple of animals the location of

peripheral chemoreceptors. Notice the names. Carotid body, carotid, carotid. You

see the pattern? Their chemo receptors that are associated with the carotid arteries

or a structure called the carotid body, which is right next to the carotid arteries, and

their monitoring oxygen and carbon dioxide in the plasma. They're monitoring the

blood gases going to the brain, perfect sense. You absolutely want to have some

monitoring system to give you feedback as to the levels of gases in the plasma

going to the brain, because the brain is really important, particularly oxygen

because the brain needs oxygen in order for individuals to remain conscious.

In fish, we also see them in gills, which is important, but fish have a slightly

different circulatory system. I will not talk about it too much today. Notice what

they respond to. Decrease in oxygen partial pressure, increase in carbon dioxide

partial pressure. So these receptors are being activated under conditions where

ventilation is insufficient.

If you're not breathing enough then you the partial pressure of oxygen is low, the

partial pressure of carbon dioxide is high, and that is going to be of the stimulate

these receptors. So this feedback system here, this chemo receptor system is one

that senses low ventilation, and then triggers a system to increase ventilation, to

increase respiratory drive.

Now, lets ask the same question we've already asked me before and Ive already

given you the answer. Is this an important feedback mechanism for regulating

breathing on a breath-to-breath basis? The answer is no. How do we know? It is

not because the reflexes are not potent. If you activate these reflexes, if you get the

oxygen level low enough this could have a really strong effect on respiration. But

the key here is that it is hard to activate them.

The reason why is because the chemo receptors are not very sensitive to changes in

oxygen and carbon dioxide in the range that you normally see in a healthy adult.

That is, the point I'm making right here. In order to activate his peripheral chemo

receptors for oxygen, the oxygen level has to get down to about 60 mmHg. In

arterial blood. What is the normal partial pressure of oxygen in arterial blood, well

its around 100 mmHg. So for the partial pressure of oxygen in arterial blood to be

at 60 mmHg, this means that this individual is in trouble already. So when thesereflexes get activated this is when things are already pretty bad off. They are not

important. They do not play key role in regulating breathing on breath-to-breath

basis.


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This is where the action is. Essential chemo receptors are located guess where? In the

medulla oblongata. This is an MRI of a human and I have a little arrow going to the

medulla oblongata. This is where the chemo receptors are. Gee, that is where the neurons

are that generate the rhythm for ventilation, for respiration.

It turns out that they are the same cells. The cells that generate rhythm are also responding

to signals related to blood gas levels. How do they do that? Let's take a closer look at it.

The key here is that they respond predominantly to changes in hydrogen ion. This is the

most critical or the most important stimulus for these chemo receptors. It is a hydrogen ion

concentration in the cerebrospinal fluid that is important to activate these receptors.

Wait a minute, I said blood gases, then why are we talking about hydrogen ion?

Hold that thought, I will come back to it. You should be asking yourself that

question. So this is a cartoon of the medulla oblongata and the pons. This is out of


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the Silverthorne textbook. This is just to show you, it is actually pretty

complicated. There is actually more than one set of neurons in the medulla that are

responding, that are important for generating rhythm, and there is a dorsal

respiratory group. There is a ventral respiratory group. Theres a subsection of the

ventral group that is probably the most important for generating the respiratory

rhythm, and most likely that the chemo receptors are in the dorsal respiratory

group, but basically what you want to keep in mind is that the action is in the

medulla oblongata. There are dedicated nuclei there that are important for

generating respiratory rhythm, and they respond to hydrogen ion concentration.

And they're very sensitive. They respond quickly and they're very sensitive to

changes in hydrogen concentration.

How does this work? You should already know the answer. What is the

relationship between carbon dioxide and hydrogen ion? It is the bicarbonate buffer

reaction, that if you have an increase in carbon dioxide and that gets converted toan increase in hydrogen ion by carbonic anhydrase and the bicarbonate buffer

reaction. So that happens anywhere where there is water and carbonic anhydrase.

So it happens in the blood and it happens in the cerebrospinal fluid.

So this figure here, also out of Silverthorne, this red tube up here is meant to be a

cerebral capillary. So this is the circulatory system, and it is right up against the

cerebrospinal fluid, and then below the cerebrospinal fluid is a surface of the


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medulla. The key here is if we have an increase in CO2 in the organism, because

were not breathing enough, that will cause an increase in CO2 in plasma, inside the

cerebral capillary.

Of course the CO2 will produce an increase in hydrogen ion in the capillary as

well, for mechanism we just talked about. But the hydrogen ion that is generated in

plasma is unable to diffuse into the cerebrospinal fluid. The reason why is because

of the blood brain barrier. The blood brain barrier is due to endothelial cells that

are close to each other and there are no fenestrations between the endothelial cells,

and so even small charge molecules like hydrogen ions are unable to diffuse out of

the circulatory system into the cerebral spinal fluid.

So how does increasing the CO2 in plasma lead to an increase in hydrogen ion

concentration in the cerebrospinal fluid? The answer is really simple and real

obvious. Carbon dioxide diffuses readily out of the plasma. It is able to go through

the blood brain barrier no problem at all, and when it gets into the cerebral spinal

fluid, it then undergoes the same bicarbonate reaction, forming carbonic acid

dissociating into hydrogen ion and bicarbonate ion. Now this hydrogen ion is free

to bind to hydrogen receptors and activate the chemo receptors in the medulla

oblongata.

A point that I want to make here is that plasma has tremendous buffering capability

for hydrogen, because there's a lot of protein in plasma, particularly hemoglobin. A

big increase in CO2 in plasma, yes it produces quite a bit of hydrogen ion, but that

hydrogen ion gets largely buffered by the protein. But the same increase in CO2 in

the cerebrospinal fluid produces an increase in hydrogen ion in the cerebrospinal

fluid, but there is very little protein in the spinal fluid. It is a clear solution, and the

so there is very little hydrogen ion buffering capability in the cerebrospinal fluid.

So this causes a large change in the free hydrogen ion concentration. So there's a

big change in hydrogen, much bigger than you would expect based on a pH change

in the blood for example. And this hydrogen ion can then trigger the chemo

receptors in the medulla in order to increase respiratory drive.


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This is a summary figure of what we just talked about, and I'm not going to walk

through the whole thing with you. This is also in Silverthorne, but I want to point

out the two biggies. One is were talkubg about two different types of chemo

receptors, peripheral chemo receptors and central chemo receptors.

The peripheral chemo receptors absolutely when they're activated they can have a

very strong effect on ventilation, and the effect is to increase ventilation. But thesereceptors are not very sensitive. In order to actually activate them the oxygen

sensitive ones, the partial pressure of oxygen has to get low. This is a very low

number for arterial blood.

The other chemo receptors are responding to predominantly hydrogen ion in the

cerebrospinal fluid. This figure shows also CO2, and they're very sensitive. They

respond very quickly to changes in hydrogen ion concentration, and they have a

very strong effect on ventilation, leading to an increase in ventilation. Of course

increasing ventilation causes an increase in PO2. It decreases PCO2 and negative

feedback to the system. So were talking here in both cases about negative

feedback, homeostatic mechanisms, but the important take-home message here is

that it is a central chemo receptors that provide the most sensitive response to

changes in blood gases, and provide breath to breath regulation of respiration.


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What I want to do for the rest of today is to work through a case study or an

example, and we are going to highlight just the facts that we talked about. What

are things that can change the partial pressures of oxygen and carbon dioxide in

organism? And how does that affect ventilation or one measure of ventilation? The

example I want to use or the case study is something called shallow water

blackout, and you're probably familiar or you have heard of the term or if youve

looked at the exam from last year because I asked a question on shallow water

blackout.

Shallow water blackout as the name implies, it occurs when people are free diving

underwater. By free diving I'm talking about taking a breath and then going

underwater. I am not talking about scuba diving. That is a very different scenario.

But in the case free dive, once one is holding their breath underwater one of the

things that can happen, and very often is fatal when it does, is someone can lose

consciousness underwater and that is what they mean by shallow water blackout. It

is called shallow water because it tends to happen close to the surface, I will talk

about why that is the case.

Theres a lot of information about shallow water black out on the Internet. If you

Google shallow water blackout you'll get a whole ton of sites. I came across a very

interesting description, or narrative about shallow water blackout that I want to

share with you, and then we'll talk about it in some detail.


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*Collins reads slide* That's a significant dive.

*Collins reads slide* This individual, the scuba instructor, notice, has now suffered

shallow water blackout.


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What are the characteristics? Loss of consciousness. Strikes most commonly,

within 15 feet of the surface. This is an important point and one we will come backto it a little bit later. Blackout occurs without warning and is associated with

amnesia. Typically if the individual recovers, they wake up and they go what

happened Where am I? Why am I in the boat? I was under the water and the next

thing I know youre on top of me pressing on my chest. Equally important here is

that they had no warning that it was going to happen. They just lost consciousness

without even knowing that they were in danger of losing consciousness.

You see almost all of these risk factors in the narrative that are just share with you

a moment ago, which is actually why a chosen narrative, because I wanted to

illustrate or highlight those risk factors. Risk factor number one, hyperventilation

before diving. This is a biggie, and this is one that we will focus on in the next 10

or 15 minutes. I will define for you the term hyperventilation.


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Intermediate level experience. The narrator there was a scuba instructor, so I

imagine that person was experienced. The interesting point here is that this

typically happens to people with experience. It is not associated with the novice

diver. I go for my first breath, dive in and I get shallow water blackout. No, it tends

to happen with people that have experience, that know what they're doing.

Physical activity while diving. This is another really important risk factor. Think

about why would physical activity while diving put someone at risk for shallow

water blackout? We will specifically address the point.

Young and competitive goal oriented diving. So a bunch of guys competing with

each other is trying to stay down longer, each trying to do better than the other.

And of course that feeds into physical activity and etc. Were not going to address

these last two too specifically but it should be obvious why these are risk factors

once were done talking about this.

Whenever I show the slide I have to make the following comment which is that I

think this slide in this picture is meant to illustrate someone who just experienced

shalowl water blackout. My feeling is that this is a staged photograph because I

cant imagine that a photographer underwater would see someone unconscious

underwater And go Oh look, hes dying! Id better take a picture. But it gets the

point across.


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In this activity that we are going to do together. I think you will gain some insight

as to what is going on during shallow water blackout. This is something we have

all done. We've all held our breath and we all have an idea as to how long we can

hold our breath. So were going to the three situations. We are not actually going to

do it because I don't want people feinting in the aisles, but what I want to do thisfor you to think about and imagine if you're doing what were going to do.

A. Holding your breath after normal relaxed breathing. So you're just breathing

and then you hold your breath. How long can you hold your breath.

B. After breathing deeply for 15 seconds. By that I mean deep breath, deep breath,

and doing it for 15 seconds. What I'm trying to do here in this month is to create a

situation of hyperventilation. I remember we talked about, we defined, alveolar

ventilation as the amount of fresh air getting into the alveoli per minute. So

hyperventilation is an anything that increases alveolar ventilation. There are a

couple ways to do it. One way to increase alveolar ventilation is to breathe morequickly. Another way is to breathe more deeply, and what I'm saying here lets

breathe more deeply. So this is a model for hyperventilation, increasing alveolar

ventilation.

C. After breathing deeply in and out of the paperback for 15 seconds. This is meant

to be a model for hypoventilation, and so if you're breathing in and out of

paperback, yes, you may be breathing deeply, but youre not breathing fresh air.

The more that you breathing into the paper bag, the less fresh the air is, so you're

getting less and less fresh air into the alveoli so it is an example of hypoventilation.

We are not going to do he first one. The first one is our starting point I decided for

you to think about it. But I do want you to be thinking about the other two. What

about the other two? What about B, and C, and then we'll fill in this table together.


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We will fill in this table and for normal breathing whatever your normal happens to

be, I will ask you during normal breathing what happens to the CO2 content in

plasma? What happens to the 02 content in plasma? And how long can you hold

your breath after normal breathing?

I put lines here because that is the starting point for each of us. If we are to go

around the room and have people just try to hold their breath, what we would see is

there'd be this huge variability. Some people would be able to hold their breaths for

a long time, particular if theyre swimmers, and some people wouldnt be able tohold their breath for a long time particularly if theyre smokers..

Our activity is going to be to fill in the squares. First we will talk about deep

breathing fresh air. What does that do to the carbon dioxide content in the body, or

in plasma? What does deep breathing fresh air do to the oxygen content in plasma?

What does hyperventilation due to CO2 in oxygen and then after hyperventilation

what does that do to your ability to hold your breath? Can you hold your breath for

a longer or shorter period of time? Then we would do the same thing for the C as

well.


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So you think that oxygen content would increase if you hyperventilate, and you

would be wrong. In fact, it has no effect on oxygen content. Oxygen content is not

affected by hyperventilation. Let's do the follow-up question. How about carbon

dioxide?

It decreases. Here's the dilemma. When you hyperventilate, youre bringing more

in and out of the lungs, you're bringing more air in and out of the respiratory

surface, and yet it has no effect on oxygen content in plasma, but it has a very

strong effect on CO2 content. It is lowering CO2 content in plasma. What is going

on? Why is it happening? This is an important point.


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Lets look at this figure. First let's look at the axes. We're looking at a figure of alveolar

ventilation, which we have already defined on the x-axis, and alveolar partial pressure of

gases, and the red line is oxygen. The blue line is carbon dioxide. Were looking up partial

pressure of gas in the alveoli. This is just what you would expect.

If we hyperventilate, in other words, we increase the alveolar ventilation, were moving in

this direction on the graph. We are starting at the dotted line point around four, which is

our example last time. If we go right here, of course what we see is that the partial pressure

of oxygen increases. You would expect that. And the partial pressure of carbon dioxide

decreases. You would expect that as well. But how is it that the partial pressure of oxygenis increasing, but the content of that oxygen is not changing? Why is that the case?

The reason that is the case is because what determines the content of oxygen in the blood?

The saturation of hemoglobin that determines the content of oxygen in the blood. It is this

relationship right here that we looked at last time. So let's start here at 4 L per minute,

which is basically at rest, we see that the partial pressure of oxygen is around 100, which

are the numbers we talked about last time. If we go to 100 mmHg on this graph here and go

up, we see the hemoglobin is essentially 100% saturated.

What happens if we increase of alveolar ventilation to 5 L per minute or 6 L per minute,

like really crank it? What we see is that we can get the partial pressure of oxygen up 115

mmHg. It is not on the graph here, but we could go all the way to the right all we want. Wewill not get any more oxygen onto hemoglobin because the hemoglobin is already

saturated. So hyperventilation does not do anything in terms of really increasing the oxygen

content of the plasma. You would think it would, but that is not what it is doing. What

hyperventilation is doing however is blowing off CO2.


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By that I mean, and I drew this one not nearly as nice, but if you imagine that this

line is meant to be the blood brain barrier and that this is the CO2 in the alveoli,

and this of course equilibrates with CO2 in the blood. The CO2 can diffuse across

the blood brain barrier and then enter into the bicarbonate reaction and CSF, which

we just talked about before.

If were decreasing CO2, partial pressure of CO2, we are just pulling this whole

system to the left. Were blowing off CO2. The end result is that we are removing

hydrogen ion from the cerebrospinal fluid. The hydrogen ion is going back intocarbonic acid. CO2 is being pulled out in the way of CO2. The technical term for

this is blowing off CO2. That is the term. That is what the physiologists say.

So hyperventilation blows off CO2 and as a result it increases the pH of the

cerebrospinal fluid, I.E decreases hydrogen ion concentration and it decreases

respiratory drive. So hyperventilation, no effect on oxygen content, big effect on

CO2 content, and on the pH of the cerebrospinal fluid.


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The answer is that it increases. As a matter fact it increases significantly. And we

also know this, because we all have done it. We all know that if you hyperventilate

before taking a breath, you can hold it for a longer period of time. The reason why

is not because there is more oxygen, it is because you have less CO2. Therefore

you are starting at a lower level of CO2 in your body and it takes longer to build

the CO2 up to the point that it activates the chemo receptors in the medulla,

causing you to want to take a breath.

So this is populating the middle row. Decrease CO2 content, no effect on oxygen

content, increase breath holding time. Now lets do the same thing with

hypoventilation. What happens if you breathe in and out of a paper bag for 15seconds?


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It decreases. The key here though is that it goes down, but it does not go down a

lot. It goes down a little bit. It decreases but is not super impressive.

CO2 levels increased dramatically in plasma during hypoventilation. So let's look

at this again.


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So lets start with oxygen. Hypoventilation on this graph here, we are decreasing

alveolar ventilation, so we're going from the left the dotted line. Of course when

we do that we see the partial pressure of oxygen goes down, and the partial

pressure of carbon dioxide goes up in the alveolar space.

Of course the same numbers are going to be true for arterial blood. But now, look

at the oxygen hemoglobin dissociation curve and let's just pick a number, lets say

3 liters of air per minute. That will be about 70 mmHg of oxygen. That is the

partial pressure of oxygen if you hypoventilate that much. We go to 70 on this

graph here and we come up, and yea, it is down about 7% or something. It is

dropping, but it is not dropping a lot. Theres not a huge change in oxygen.

The take-home message here is that this is hemoglobin. Hemoglobin is binding and

buffering oxygen, and in order to see changes in oxygen content in the blood, you

have to have a big change in partial pressure of oxygen, because were sitting up

here on the flat part of the hemoglobin saturation curve. So were not going to see

big changes in oxygen either with hyperventilation or even with hypoventilation.


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But in the case of carbon dioxide, that is not the case. Just like we are able to blow

off carbon dioxide by hyperventilation, hypoventilation produces a huge increase

in carbon dioxide in the body. Because there is can a be a big increase in the partial

pressure of CO2 and that will push all these reactions this way and cause an

increase in hydrogen ion concentration in cerebrospinal fluid and the net effect of

that will be decreasing pH, but, functionally speaking an increase in respiratory

drive.

Absolutely. Breath-hold time decreases markedly following hypoventilation.


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Try it sometime. Do tonight when you go home. Try re-breathing in and out of the

paperback and you will find that you almost cannot even get 15 seconds, because

after you do for a while you'll feel like you're not getting any air and you'll have to

try and take a deep breath. Then try holding your breath after doing it, you may not

be able to hold your breath at all. It is a very strong stimulus for increase in

respiratory drive.

Question. Why do people breathe in and out of a bag? What happens is if people

have elevated anxiety, or theyre really nervous, one of the symptoms of that is

rapid shallow breathing. They don't do it on purpose but they just start breathing

really quickly with very shallow breaths. If you think about what happens when

they do that is that you are actually hypoventilating, because if you breathe very

shallow breaths youre basically just moving the dead space around, and you're not

getting a lot of fresh air. So even if youre breathing really quickly, you're not

getting fresh air, but the problem is the individual when they start doing it they feel

like they cannot breathe. They feel like they need to take a breath and they cannot

stop breathing quickly, and the way you break it is you have them breathe into g

the paper bag.

You drastically increase the carbon dioxide content in their body and that makes

him take a deep breath. And it breaks the cycle. So they stop breathing quickly,

and now they're able to recover from that, or they keep doing it until they're better.

The reason that it is confusing is because people think sometimes breathingquickly is hyperventilation. It is not. One can breathe very quick shallow breaths,

but actually be hypoventilating.

So now we have done this row right here, and rebreathing or hypoventilation

increases CO2, drastically lowers oxygen but not very much, and of course has a

huge effect on breath hold time, making it much smaller and in many cases people

cannot even hold their breath.


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One of the reasons I like this figure is because I got it from Wikipedia, and yes I

look at Wikipedia sometimes. Now lets talk about what's going on with shallowwater blackout. What is going on when someone is underwater holding their breath

and why do they pass out? Or might be a reason for passing out?

What were looking at here on the left is an individual breathing normally and then

holding their breath underwater, and I'll be more specific in a second. On the right

an individual is hyperventilating before holding their breath and going underwater.

Normal breathing on the left hyperventilating on the right.

In the green panel this is before diving, before breath holding. Once we get to this

point the individual has now gone under the water, they're holding their breath and,

this is time, on the y-axis, and notice that red line is the oxygen content in theplasma, and the blue line is CO2 content in the plasma.

So now the individuals breathing normally, and they then hold their breath and go

underwater, and as soon as they hold their breath the oxygen content starts to drop.

Because of metabolism. The CO2 content starts to increase because the

metabolism is producing CO2, and notice that even though this is a negative slope

and that's a positive slope its basically inverse slopes of each other. For the same

amount of oxygen that the animals using content wise the animals producing CO2.

This yellow part here called the blackout zone is the level of oxygen at which the

individual can no longer maintain consciousness. So if the redline gets into theyellow area the person blacks out. Now this dotted line is the level of CO2 that is

needed to stimulate the respiratory center in the brain to tell the person to take a

breath. Now remember that it is the CO2 that is stimulating breathing. It is oxygen

that is needed to stay conscious. We have two different things, but they're

covarying here.

So now, person goes underwater, they're holding their breath. Oxygen levels start


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to go down, CO2 levels start to go up, and the key thing here is that the CO2 gets

to this critical level where the brain says oh I need to take a breath. Respiratory

drive increases in the maybe the person can hold their breath a little bit longer, but

they know they have to get to the surface and then take a breath. As soon as they

do that then they restore the oxygen and blow out the carbon dioxide. The key

thing here is individual never gets into the blackout zone and the individual

maintains consciousness the whole time that theyre diving.

On the right-hand side we have a different situation. Before diving, the subject is

hyperventilating. What does hyperventilation do? Nothing to the oxygen content,

so the oxygen content stays the same, and what happens to the CO2 content? CO2

content drops and it drops a lot during hyperventilation. So now the person starts to

breath-hold dive. As soon as they start to dive the same thing happens. Oxygen

level start to go down. CO2 levels start to go up, but notice that the person started

from a much lower CO2 level, following hyperventilation.

Now the good news is that it's going to take longer for the CO2 level to take get up

to where the person wants to take a breath, meaning increased breath holding time.

The bad news is that it is very possible that this would take too long and that the

oxygen will drop into the yellow zone before the CO2 level gets up and tells

individual that is time to take a breath. When that happens shallow water blackout.

The person loses consciousness before they have an opportunity to take a breath,

and they don't even know that they need to take a breath, because the CO2 level is

not high enough to trigger it.

Question: Why is it called shallow? What is the part of the shallow water

blackout? Excellent question. Hold that thought.


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This is a summary slide. Hyperventilation. This is now addressing the risk factors.

Hyperventilation is a significant risk factor because it causes a decrease in CO2

without an increase in 02, and therefore there is a marked reduction in respiratory

drive. And there is the opportunity for an individual to basically run out of oxygen

before they get high enough CO2 where they think they need to take a breath.

Why is physical activity a factor here? Because it is related to metabolism. If

someone is underwater and physically active doing stuff, then it increases their

metabolism. They're utilizing oxygen more quickly. Why would that make a

difference? It makes a difference because in addition to just having some kind of

chemical cue, a sensor cue that you need to take a breath, we kind of know how

long we can hold our breath.

If you're underwater for a while if you go all my goodness it's been 2 min. for the

sense, but if you're physically active while you're underwater then you lose the

perspective. You may be using up oxygen faster than you realize, and so if you are

just kind of relying on, well, I can stay in there for this amount of time you can

make serious mistake. Increased physical activity while diving is a risk factor

because it basically means that individual is going to use more oxygen in a shorter

period of time.

To address your question about shallow, what is going on in terms of shallow

water? The key thing here is that it very often happens during the ascent of a dive.

To understand why that happens you think about the role of external pressure on

the body. So remember that if someone is diving into water and they go deep that

the water pressure gets greater and greater the farther down you go, but what is the

effect of the water pressure on the individual?


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It presses the surface, but it also increase pressure of everything inside the body,

including all the gases that are inside the body, even the gases that are dissolved in

the fluid and so as someone dives down and they are using up oxygen and the

partial pressure of oxygen is going down in the individual, but now you have this

external pressure that is squeezing on it, that is going to artificially elevate the

partial pressure of oxygen from the blood. Just because a relative pressures.

So on the way down the pressure is a good thing, because it helps keep the

pressure, partial pressures of oxygen high, but on the way up is just the opposite. It

is a bad thing, because as someone is coming up theyre using up oxygen and the

oxygen pressure is dropping, and the external pressure is dropping which is

causing a further drop in the partial pressure of oxygen, and this really gets worse

right at the surface.

So when someone gets closer to the surface they can experience a very low driving

force for oxygen exchange. Theyre going to get it almost to zero and then the

person can lose consciousness really quickly. So having changes in external

pressure while doing this exacerbates the situation, and that's why, that is a

hypothesis for why people tend to lose consciousness near the surface on the way

up.

[picture slide]

I have a treat for you guys at the end of the semester. I'll show you a video. It is

going to star William Trubridge. He's a native of New Zealand and up until

recently he may still hold it was the world record holder for free dive without finsto depth and he set a world record a couple years ago where he went 100 meters

and back up without fins and on a single breath of air. This is a picture of

Trubridge, right there. He champions the Dolphins. He is trying to raise money for

dolphin support, and we're going to show you a video of him setting the world

record in free dive a couple years ago, and I'll show it to. It will last about 5 min.

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BIO203 Transcript