hello and welcome to the second part of the video for the lecture on the control of breathing and the control of insulation the introduction of it just before this lecture was about the respiratory centers medulla and the emblem and the pons and how feedbacks were actually affecting those battery centers so today I want to cover the two most important the central chemoreceptors and Pio chemoreceptors I talked about them really briefly before and I'm starting with the the central chemoreceptors because they are the most important proportionally they represent around 80 percent of the controller ventilation seventy-five to eighty percent depending on the publication so I'm not gonna go in too much details I just want to give you as you can you'll see here just few slides on what I think is the most important and what I would like you to children and and to remember so the most important trigger are the central chemoreceptors are going to be a change of hydrogen ions there's a change of pH I already mentioned before that the central chemoreceptors they are called central because they are in your brain they are actually on each side of the medulla base of the Madeira between the medulla and the spinal cord so that's what we usually said they are bilateral in ventrally so in the front of the medulla central chemoreceptors are surrounded by the CSF here so the CSF is the cerebral spinal fluid and it's me just write this down say more spinal fluid and actually you know this is the liquids that surround your brain and is between your brain and your skull and this will have a very important role actually for the function and for the action of the central chemoreceptors so you keep that in mind because well we'll talk about this again just just after but it's not blood the central capacitors are actually not surrounded by blood they are surrounded by this this simple spinal fluid which is actually mostly water so where they are you can you can see here is actually not not human but it's a cat there's a lot of studies and research shall be done for the respiratory system and it's peaceful for the nervous system also on cats so you can see here the rostral part of the medulla and the colored part of the Madeira and the central chemoreceptors are actually right there there's two major part of the ventral part of the front part of the of the Madeira if you see here you have this power cords and over here you would have the brain so maybe you you will be curious about to know about how do we know that two central chemoreceptors how do we know that the specific location of the medulla actually actually has specific receptors that are sensitive to chemical at the journey of studies that was like a century ago or more were actually taking brains and in Madeira so they knew the scientists knew at that time that there is the respiratory centers but it didn't know exactly where they were and they actually didn't know if they were stimulated by something so what they did was to take me to learn brains of cats to expose them by surgery basically and they were using a service plan of fluid that was either increase of pH or decrease of pH an increase of carbon dioxide or decrease of carbon dioxide or changes of oxygen and when they were dropping this fluid with a change of pH example the lower pH so that was the most important one when they were dropping this fluid on the medulla of cats and they figure out that there was part of the medulla they were starting to sound impulses starting to son the whole impulse if you see here on the graph on the side here you have numbers ok so 9 10 11 12 those are nerves I mean I saw those nails are coming out of the medulla very specific clusters on the medulla and when they were dropping this liquid on the the medulla they started to recount no impulse coming from do Snell's here and they say oh if you drop a lower pH liquid then your impulse coming from the nerve the gloss of angle nerves falling apart which is the nerve number nine yeah so that's how they the dupioni of studies at the beginning of what we call electrophysiology obviously now we have much better way to do that but this particular graph is actually coming from the spur on your studies okay so what is what the role of the central chemoreceptors they are very important for the respiratory phase is very important when you inspire and that's why if you remember I told you that the spra phase is the most important compared to the expiratory phase because the inspiratory phase is the one that we control to expert with it so they are responsible for when we call the ramp signal which is basically very easy to understand if you have a curve like this okay and everybody every aspiration is the car going up and expression is the cap going down for the ramp going up like this for the aspiration the central chemoreceptors are known to be very important for that part so what does it mean exactly central chemoreceptors are sensitive to change in pH we could just you know stay at that level of understanding but I want you to be able to understand that a little bit better understand the mechanism behind this how exchange of pH can actually activate a molecule how is that possible actually the central capacitors are made of two senses molecule one is called a medium and another one is called a histidine okay so here you have a medium so imidazole is this molecule here it doesn't really matter to know exactly what the chemistry behind this molecule but what's important is that when the pH change me so for example if you go from a pH 7 to pH 6 okay obviously the pH 7 will be Monica natural pH 7 point 4 and 6 would be a very low pH when you when you lower the pH you add adult anions okay it's because you increase the numbers of atoms and ions that your pH start to decrease and this extra other anions is actually going to come and bind to a specific site on the imitation so you see here the emitter zone has a active site or binding sites for a lot anions so when this hydrogen is around and is produced let's say during a physical activity because you are per friend lactate okay for the opponents a classic example then you you increase the Virgin Islands and the site of Reliance comes and bind to this first molecule but that doesn't do anything by itself basically that is not activate a molecule that doesn't do anything what's the activation phase is actually that now this histidine is going to be able to be binding to another bigger molecule called the imidazole so you can recognize here the the molecular immediate the students here and in that case now without the adult anions okay if you don't have the address anions here there's no way for this molecule to bind to the second one okay so this simulates all here I cannot bind to the histidine but because you have the bridge of the Atocha Lions molecule now now this mark is going to bind and is going to connect to two part of the STD and the connection between this two part of histidine is actually going to start to create a action potential so that's how the depolarization is going to start and that's how actually you can start to have a depolarization that sends a neural signal to the rest of the respiratory centers and so you get the idea about the importance of the change of pH and the importance of the hydrogen ions being the link or the bridge if you want between the images on and the HDD without the change of pH there is no possible binding of the medium on Easter day but when you have the PA version ions then you create this link and it's possible for this to connect together and the connection between the two creates the jeopardize it me so that's for the that's for the mechanism but maybe an even more important question is why this is happening why do we have a change of pH dance this change of pH resulting in a change of hydrogen ions especially at the brain level especially at develop dose set working chemoreceptors so I think maybe you've you've seen that before but I can I can just go back to this quickly you know this is what we call the buffering system or the AC basic relation when you produce carbon dioxide because of the activity because of the domestic economy our work for example because during during exercise you produce carbon dioxide here okay in the blood and so you have a on this graph you have two blood with the capillaries you have the cell when a fluid and the brain what you see here I'm drawing here with our own is what we call the blood brain buyer okay so it's the buyer yesterday is the limit the border between the blood and your brain and this blood-brain barrier is actually very tight there's not many things that can cross the blood-brain by there's not many nutrients or waste on the feeds or molecules that can really cross this this body but one thing they can do like that is able to cause he's come on damn time because you remember carbon dioxide is very soluble and it was it's going to be able to cross from the blood to the blood-brain barrier and end up in the cerebral spinal fluid in the CSF and that's where the properties of the CSF is going to be important compared to the blood because interest yourself you can have carbonic anhydrase on sign okay so let me write this down cow per Nick I need to a is okay so maybe you're hoping this sign before but the carbonic anhydrase is the enzyme that he is going to be able to combine carbon dioxide and water okay by combining those two together is going to move to multiply the combination okay so you know the role of an awesome is to increase the speed of a chemical reaction it's going to increase the speed of this combination between carbon dioxide and water and the result of that is carbonic acids yeah carbonic acid can then be decomposed into hydrogen ions and bicarbonate ions that's about the basic of the buffering system you know also that this carbonic anhydrase enzyme is able to go this way so to combine carbon dioxide and water but it's also going to be able to go the other way it's going to be able to take bicarbonate ions and others in our hands and produce more carbon dogs so it's going both ways but for now let's not make this more complicated let's just look at this this direction where carbonic the company can enjoy his work is going to combine water and carbon dioxide and police erosion ions then disillusion ions is going to change the pH in the cell wall spinal fluid the peers can start to drop because you produce the hydrogen ions and then the mechanism that we've talked about before he's going to reach those two molecules the histidine and the emitter is all and it's gonna be in the link between the two creating this reaction to work to it is if you want it's like a key that's going to open the lock and hydrogen ions is the key and it's going to unlock the stimulation of the central chemoreceptors one one thing that I really would like for you to to understand is this reaction of the carbonic anhydrase and carbon dioxide's that is going to transform physically into a Tottenham is happening only at the CSF level and not in the blood in the it's happening in the blood but not as much in the blood there is a buffering system that prevents the build-up of hydrogen ions in the cerebral spinal fluid because there is no perfect system not much of a buffering system the perfect system is made out of proteins to help ourselves to what blood cells the president sounds everything you have in your blood in the syllable spinal fluid we don't have any of that it's mostly water so because there is not much of a buffering system this reaction of the communicated race that will switch the carbon dioxide into a torch and it's gonna happen much more than if it was happening in a blood and that's why the central chemoreceptors can be stimulated because they are in the CSF and would not be stimulated if there were actually in Dublin yeah so that's really an important points that I wanted you to to remember okay so does evolution do sir I'm sorry do sir central give acceptance will be very important for the change of hypercapnia hypercapnia being the increase of basically the partial pressure of carbon dioxide's in your arteries indirectly conducting and driving the change of pH so those will be mostly central chemo signals they are other chemo receptors that are also important for the response for hypercapnia but also the the drive of the respiratory centers in order to send feedback to the respiratory centers in general is the peripheral chemoreceptors okay so that's the one can you see now to pay for chemo receptors depending on the literature or they might be I would say between 20 and 30 percent responsible for the change in carbon dioxide but they are 90 percent responsible for the change in oxygen this time okay so in response to hypoxia when you have a decrease of oxygen in your blood the resulting increased ventilation is mostly due to the categories so let's see that now what are those special chemo receptors they are very special cells very special cluster of cells they are the only cells in your body that are able to monitor the level of oxygen and they are very conveniently located at the bifurcation of the internal and external county's arteries mostly and also like I said in the after the principal the most important work in my acceptance ah and in the county level yeah so well used mostly the term counted bodies or carotid bodies or Volcom acceptance and that basically means the same thing it's not like the Arctic bodies are not important but they represent less than ten percent not the of the the role of the performance at all in the after actually one of the most important receptors are the bow receptors not really the chemoreceptors so the bow receptors are sensitive to pressure and again that's logical because the after is just right at young I did the outside of the other heart just outside and that's why you study had the most important change in pressure okay so where do scout it but is you see here the outer outside of your heart and then you have the cow eats the right and the left coyote that goes up and you have here right there to bifurcation okay so I could actually just suckling you can see I'll show you after a a picture of a real dissected counted bridge so you have an idea Ducati breeze all right now so they're very small actually but they are very important they are elevated by the groose of angkor now that goes directly here in the respiratory centers okay so they are stimulated we say by a decrease of pao2 and the estimation goes straight into the medulla and straits and signal to the respiratory centers in return to that is also the article is here but well we are going to develop that much okay so here's a picture I want to show you so you have a better idea of where those cotton bodies are and you see they are very tiny here right here and right here those are it's gorgeous they'll be dissected and you can see this little cluster of of cells very red because actually the petrochemicals are proportionally if you just take into consideration their size they are the most elevated and the most oxygenated organs in our body so they are they want to visit the most blood and the other one also to receive the most oxygen compared to the other size so they are made of two different subject as you can see since 1930 by the work of a men's we know what the cotton bodies are and what they are made of not since the 30s exactly but we know about you have to understand that a bit later so they are made of two different type of cells and they are just two cells are important they all had the two the two sounds are different given wrong you see here a type 2 cell and type 1 cell the type to sell is the yellow cell here is the one that surrounds the type to do type 1 action so the type 2 I making like a membrane around this organ even though they are made of different cells different type of cells because of this type 2 cells I'll give you were to surround and basically make it like a membrane around this organ and why is that important it's because when you have a membrane that you can make a difference between the inside and the outside you can start to see if there is a difference in terms of pressure between the inside and between the outside if you want to be able to monitor a partial pressure of gas monitor a partial pressure for oxygen you need to be able to have a way or a system where you can have a difference between one environment and another and then you can sense the change so that's the that's the idea to start to sense they will be able by creating a physical barrier around the one sells they're going to be able to create a gradient of pressure basically and that's how the big carton bodies are going to be able to sense a change of oxygen I'll develop the mechanism just after the type one cells are the one that are inside and they are really the one who are doing the job so once they are stimulated by change of oxygen then their job is actually to create an oval house materials and especially dopamine you see here so to start are very tiny but they are very productive in hand they are again proportionally the one that can produce the most dopamine by itself and the dopamine is a neurotransmitter is going to be able to chew then cross the synapse here and the connection with the neurons we said grosser a group of fog on the other and send a signal directly through the respiratory centers so you get you get the idea of those organs now let's talk about the mechanism so when we talk about the central chemoreceptors the take-home message of the central capacitance was the mechanism between the media and the histidine and the wall of the Idahoans into that now for the peripheral chemoreceptors the this graph here that we're going to talk about now is the mechanism and easy button and so you need to understand that to do you have here the Glomus cell or it's actually the type one cell okay so that's the cell that is doing the job by answering the stimulation so let's say you start to exercise okay you exercise and because of the the higher demand of oxygen you start to to reduce your partial pressure of oxygen but by emerge by not by a lot but there is a small drop of partial pressure of oxygen this low drop actually the first step is that going to create a closure of the calcium channel of the potassium channel because the potassium channels are always open depending on the concentration of oxygen when this concentration of oxygen is lower is actually create this gradient of pressure that I was talking about before so in that case if let me try to make this better if the pressure here inside is more than the pressure outside then you understand that this channel here is gonna close because of the pressure and that's how the chemoreceptors are going to be able to sense the change of pressure the change of partial pressure of gas is because the change of this object click on there's four different these four different channels if you want in this potassium channel it's important to understand that too because you can you can close that channel but depending on the stimulation depending on how low the partial pressure of oxygen is this stimulation might not be completely happening so basically there is a gradual increase of the stimulation it's not that just like a black and white system where on and off system where you're gonna have less oxygen so it's already on full-blast and it's going to send signal it's actually much more nuances and clever than that I will talk about this one will talk about the physiological aspect to this perform cam acceptance but when you when you have a threshold of activation if the threshold is sixty millimeter of mercury yeah so I can tell you now but you don't need to remember until we study that more it's sixty millimeter of mercury when this the partial pressure of gas is low and a 60 millimeter McQuade and you start to have a real activation of this channel of this position channel when this potassium channel closed then it depolarize the cell and because of the depolarization you're going to open this time the voltage-dependent calcium channel and it's exactly like the script on muscle contraction that you know better maybe because of that two calcium enters the cell and stimulate the production of dopamine stimulate the pollution of neurotransmitters and you have here by exocytosis the production of dopamine that will reach the elves and is going to create this action potential from the nerves this extra for the song and then it's going to travel to the respiratory centers the Madeira mostly and activate the Esperanto a signals to increase the modulation and so you have here a pretty basic but good understanding of the mechanism by which those perform acceptors I want to sense a lower oxygen and by a cascade of events at the end we'll go to produce dopamine and stimulate the nerves and send an action potential and that's how your brain at the end is aware that there is a change of oxygen this is the drop of oxygen the last thing I can I can tell you also is that those those receptors are also sensitive to an increase of oxygen actually so lower oxygen will stimulates the perform chemoreceptors but a increase of partial pressure of oxygen will hynny beats stop the activation of those chemo isotopes so they are sensitive to both decrease and also an increase opposite partial pressure of oxygen okay so this is what I said before the partial pressure of oxygen lower by lower to sixty millimeter of mercury will be the activation of the perform acceptance Lord and that is a measure increase of demonstration at the opposite hyperoxia or a higher partial pressure of oxygen I can also suppress completely not completely I will suppress almost completely to pay for him except activity you have they are very pure understanding of the role of the hypoxia and hypoxia in the faith or concept or scouted body's response so this is a very famous article in very famous study it was obviously ex vivo so I was on cats and it was a study to see the effect of hypoxia and hypoxic so here you have the partial pressure of gas the partial pressure of oxygen in millimeter mercury and here you have the impulse of the growth of growth of our mouth the impulse coming from this nail that comes out of the perform chemoreceptors so more impulses meaning that more ducati but it's a stimulating okay that's how here we measure the simulation so what do we see here we see a positive relationship between an increase [Music] increase of let's say if we take it this way I'm gonna take it this way if we sit so a negative I think it's easier to understand you see a negative relationship between an increase of the after your partial pressure of oxygen and a decrease of the activity of the cotton bodies more oxygen you have less activity you have okay so scale here if you compare a 0 to 100 then you have a very important drop of the activities of the peripheral chemoreceptors and this drop is more gradual up to 200 and it's really flat almost at zero at the end when you reach a for 500 the power 50 millimeter of mercury has a partial pressure of gas of oxygen knowing that obviously this level of oxygen here is Supra physiological this in the body we don't have 600 millimeter of mercury as the partial pressure of oxygen what we have at the most is he on hundred and fifty one hundred and thirty hundred and five hundred and ten usually partial pressure of oxygen so here we have the inverse relationship but maybe one of the most important number that you can look at is that is clearly looking at the curve is clearly a threshold where at a minimum of partial pressure of oxygen you have a very important increase of the activity of those pr4 chemoreceptors so if I look at here and that's not by mistake okay we said around sixty is where you have a sub increase of the modulation of the ventilation a sharp increase of the impulse coming from those peripheral chemoreceptors because all of the channel of the potassium channel I'm gonna closed and calcium channel are gonna open and then you have a full production of the Pamina and full impulse going to so this techo message has this graph has mostly to take a message one is the inverse relationship between oxygen and the impulse coming from the kotse bodies or the activity of the captain bodies and second is the result which is a 16-millimeter occurring if we load this traveling sub increase of the activity of the catalyst okay so as a summary of the stimulation i said that two counting bodies are mostly are the most important sensors for the oxygen but there are other things they can also activate to scouting police in different ways so change of pH change of temperature some chemicals like nicotine's carbon dioxide and so on can can do that hypoperfusion because it decreased oxygen content and so on but all of those other stimulation barely a slight modification of the activity of despair for chemo at all in response to oxygen okay so it's not like to add on irons and those other chemicals and the temperature increase and stuff could by themselves increase the activity of this for chemo at all it takes actually decrease of oxygen and then if you add on top of that Atocha and change if you change of temperature and stuff which is actually what's happening during exercise that's why it's important to understand if you add on top of that then you can increase them even more okay so in summary the the special chemo receptors are activated by a low oxygen concentration by a low po2 I found sensor signals are scented as part of a component of the Madeira through the glossopharyngeal nerve for coffee buddies and through the vagus nerve for the RT bodies this this causes the afferent signal to be sent to the respiratory muscle causing an increase in modulation categories have a higher responsibility or greater responsibility in increasing the motivation for a decrease of partial pressure of oxygen we'll stop here okay for this for this for this lecture it would be thick enough information for for you to cover let me know if you have any questions you can always reach me and I'm always happy to talk to you directly during office hours or to answer your emails have a good one