CSB346H1 Lecture Notes - Lecture 6: Intracellular Ph, Phrenic Nerve, Control Of Ventilation

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26 Mar 2013
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CSB346 Lecture 6 Central Chemoreception (February 12, 2013)
Slide 1
- We want to move away from how the rhythm is generated.
- We want to think about how the rhythm is affected by stimuli that we know are critical.
- We are going to talk about central chemoreceptors.
Slide 2
- We talked about how the pre-BötC is responsible for generating the rhythm.
- The rhythm is sent to the respiratory MNs (e.g., hypoglossal and phrenic). Those muscles
generate the force that enables muscle contraction so that ventilation can occur.
- Respiratory frequency multiplied by volume gives you ventilation.
- How does CO2 get sensed?
Slide 3
- CO2 is the most powerful stimulus for breathing. Oxygen is critical. You breathe to acquire
oxygen, but you breathe because CO2 makes you breathe.
- Breathing depends not only on the pre-BötC to generate it, but it also has to have input from
other things that detect changes in O2 and CO2 level. It is important that you are constantly
monitoring how much O2 is in the arterial blood supply going to the brain and how much CO2 is
in the blood supply. If there is too much, you need to breathe more quickly to get rid of it.
- A chemoreceptor is a receptor that senses the chemicals (e.g., O2, CO2, pH, H+).
- O2 chemoreceptors are mainly external to the brain. CO2 is detected both by the brain and by
the carotid bodies.
- Central chemoreceptors are sensing CO2, pH, or H+ that are located in the brain.
- CO2/pH levels are related to acid-base balance in the blood and brain. Their levels reflect
adequacy of lung ventilation to tissue metabolism.
o If you are running and you slow down your breathing, your working tissues are
metabolising more quickly because you are exercising, producing more CO2, and if you
are not exhaling the CO2, it starts to build up in the body. CO2 levels go up. pH goes
down. This is because you are hypoventilating. Lung ventilation is designed to meet
metabolic demands. If you are producing more CO2, it is a powerful drive to breathe
more rapidly, not because you want to acquire more O2, but because you want to get
rid of the CO2 that you are producing because it can change your pH balance. pH is
highly regulated. The respiratory system is the rapid way by which pH is regulated.
Slide 4
- These were experiments that were done in lambs.
- VT stands for tidal volume. ML stands for the amount of air in each respiratory cycle. The lamb is
breathing in and out.
- How much of this ventilation is due to CO2 itself?
o For a long time, people thought you were breathing in and out because you were trying
to get O2. But CO2 is the most important signal that was driving you to breathe, not O2.
- They took the blood out of the lamb and went through an extracorporeal loop. He took out the
same amount of CO2 that the lamb was producing just by normal bodily metabolism.
o This is when the lamb is letting O2 go into its lung so that CO2 levels are fluctuating
across the respiratory cycle.
o He started to switch so that the lamb’s blood was prevented from going to the lungs.
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o He added the O2 and took out the CO2 of the blood. It is called an extracorporeal lung.
- As soon as the lamb got switched, so that its lungs are no longer in control of how much O2 is
being added and CO2 is being removed, you can see that breathing becomes slower and more
shallow (e.g., the volume of each breath is going down).
- Then he takes control entirely of how much CO2 and O2 the lamb has in its arterial blood supply.
o He kept both of them constant. He provided the amount of O2 required to keep
metabolism constant. He took out CO2 so it never fluctuated.
o The lamb completely stops breathing.
- This demonstrates that when CO2 falls below a particular threshold, you don’t breathe. If you
are provided the right amount of O2 and you have no fluctuation in CO2 (e.g., constant; he is
taking CO2 out in the same rate that the lamb is producing CO2), the lamb stops breathing.
o He did a whole bunch of other tests to show that it was CO2, and not O2.
- CO2 is the stimulus that is pushing you to breathe rhythmically. Without that stimulus, your
brain seems to say “I don’t need to breathe anymore because I have enough O2 and I don’t
have CO2 building up in my venous blood supply, so why would I spend energy breathing.”
- This study shows you that CO2 is an important signal for the brain to listen to. When the signal
isn’t there, you didn’t seem to generate the effort to breathe. There was no need.
o Metabolism drives ventilation.
o When metabolism is not fluctuating (e.g., the metabolism is not reaching the), then
what is the point of breathing? When metabolism goes up, you breathe more quickly.
When it drops below a certain threshold as it does in these experiments, you stop
breathing.
o CO2 production is a powerful stimulus to cause you to breathe.
Slide 5
- This is the same experiment done in humans.
- They told the patient to hyperventilate. You are blowing CO2 off more rapidly than you are
producing it. After they stop hyperventilating, they stopped breathing for a second.
o Like in the lamb, when they got rid of the CO2, the brain doesn’t feel the need to
breathe because there no CO2 build up that is signalling the brain to cause you to
breathe in and out.
- This experiment prompted a whole series of experiments.
o Why would this happen?
o Why would patients stop breathing when they hyperventilate?
- They showed that the exact same hyperventilation caused almost 1 minute without breathing.
o They got the patient to fall into stage I sleep. Then the machine hyperventilated the
person. When they hyperventilated the patients, they stopped breathing for up to 60
seconds.
- They repeated the same type of intervention at a different sleep stage, called deeper sleep.
- When CO2 levels fall (e.g., 40 mmHg 33 mmHg) by hyperventilating, you stop breathing.
o CO2 levels are extreme tracked by the brain. When they fall below a particular value,
you seem to stop breathing.
o The brain listens extremely carefully to CO2.
o A drop in CO2 is signalling the brain to not listen or to not generate respiratory rhythm.
- O2 level do not change during hyperventilation.
o Remember in the O2 dissociation curve, Hb is 98.5% saturated. Breathing faster at sea
level doesn’t do much to get more O2 into the system.
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Slide 6
- Increases in CO2 are extremely powerful.
o The two previous experiments looked at dropping CO2 levels in the venous blood
supply, in which you seemed to stop breathing.
o What would happen to breathing if CO2 goes up?
- Look at the slope of the line.
o The X axis is how much arterial CO2 you have in mmHg.
o The graph is how much ventilation is going on relative to how much CO2 is in the blood.
o It goes up a little bit, breathing goes up. It goes up a little bit more, breathing goes way
up. It goes a little bit more, it goes shooting to the roof.
o The steeper the curve, the more powerful the stimulus is having on breathing.
A tiny change in CO2 causes a massive change in breathing.
If CO2 goes down, you stop breathing.
If CO2 goes up a little bit, you breathe incredibly heavily. Ventilation increases
massively.
- The rat is breathing in and out with room air.
o When I give the rat 7% CO2, the breathing goes up in terms of frequency (e.g., the
number of breaths per unit of time) and height (e.g., amplitude or tidal volume).
o Ventilation is tracking how much CO2 the rat is producing.
Slide 7
- Where are the central chemoreceptors in the brain?
- The overall levels of blood flow are an index of how active certain parts of the brain are.
- He used NMR.
o He looked at overall levels of brain activity.
o He would take a patient, give them a whiff of CO2 in hypercapnic air, and he would see
some part of the brain light up. This would tell him that it is the part of the brain that is
sensing CO2 changes.
- The whole brain went wild.
o Not surprising because one of the most immediate responses to a high amount of CO2 is
panic.
- Look at how bright the brainstem gets (e.g., yellow). The yellower it is, the more excited the cells
appear to be in that area. The ventral portion of the brainstem seems to be quite activated.
Although there was a lot of activity in the brain, there was still an enormous amount of
activation in the ventral portion of the brainstem.
o This is an area that we know that seems to be involved in sensing CO2, at least in cats.
o This was one of the first pieces of evidence to suggest that the brainstem is also noticing
changes in CO2.
- How do you know that the central chemoreceptors are not in the periphery?
o There is a group of people who get cancer in the carotid bodies. The carotid bodies are
important in detecting CO2 and O2. Some people get cancer and have to get them
surgically removed.
Slide 8
- He got a collection of patients who had their carotid bodies removed.
- If there are important receptors in the brain that detects CO2, either patients without carotid
bodies won’t notice CO2 or something will change.
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Document Summary

Csb346 lecture 6 central chemoreception (february 12, 2013) We want to move away from how the rhythm is generated. We want to think about how the rhythm is affected by stimuli that we know are critical. We are going to talk about central chemoreceptors. We talked about how the pre-b tc is responsible for generating the rhythm. The rhythm is sent to the respiratory mns (e. g. , hypoglossal and phrenic). Those muscles generate the force that enables muscle contraction so that ventilation can occur. Respiratory frequency multiplied by volume gives you ventilation. Co2 is the most powerful stimulus for breathing. You breathe to acquire oxygen, but you breathe because co2 makes you breathe. Breathing depends not only on the pre-b tc to generate it, but it also has to have input from other things that detect changes in o2 and co2 level.

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