 chemical regulation of respiration is kind of feedback control system which changes the rate of ventilation depending on the changes in the chemicals which are important for respiration that is the partial pressure of oxygen partial pressure of carbon dioxide and pH. So like any negative control system we have a sensor which senses the concentrations of these chemicals so these are known as chemoreceptors then there is a control center and in case of respiration this includes the neural centers of respiration which are present in the medulla and pons and finally there is a response and responses will change in the rate and depth of the ventilation. So in this video we will be talking about these chemoreceptors what are these chemoreceptors where are they present how they respond to changes in the partial pressure of oxygen carbon dioxide and hydrogen ion concentration. Well there are two types of chemoreceptors based on the location so there is a peripheral chemoreceptor and then there is central chemoreceptor. Now peripheral chemoreceptor is located at two places so there is a carotid artery so at the bifurcation of the carotid artery there is presence of carotid bodies so these carotid bodies are the sensors then in the arc of aorta so above and below the arc of aorta there is presence of aortic bodies. So both these carotid body and aortic bodies are the peripheral chemoreceptors. On the other hand central chemoreceptors these are located in the ventral surface of medulla and these are separate from the neural centers of respiration. So let us first discuss about how these peripheral chemoreceptors act. By the way though we have written that there are two types of peripheral chemoreceptors that is carotid bodies and aortic bodies what is found is that that carotid bodies are the main peripheral chemoreceptors. Fine so let us see the functional anatomy of these peripheral chemoreceptors. Now these receptors have two types of cells so there is a type 1 glomus cells the cells in receptors are known as glomus cells so there is type 1 glomus cell and then there is type 2 glomus cell. Now these type 1 glomus cells are the sensors and while these type 2 glomus cells are the supporting cells so you see how these supporting cells are covering these sensor cells so they are providing kind of support to the sensor cells. Now these sensor cells you see there are certain characteristics of these sensor cells first of all they have these vesicles which contain the neurotransmitter so the neurotransmitter which is present is dopamine. Then these sensors have something known as O2 sensitive potassium channels oxygen sensitive potassium channel so when oxygen will be present these channels will be open so we can call it as like oxygen gated potassium channels presence of oxygen opens the potassium channel so oxygen is present in physiological condition that means the investing state these potassium channels are open so two things one is oxygen sensitive potassium channels and second thing is there are vesicles containing the neurotransmitter dopamine and you also note that these glomus cells are making contact with certain nerves and these are the sensory branches of cranial nerve so in case of a carotid body the cranial nerve is a ninth cranial nerve while in case of aortic bodies it is the 10th cranial nerve that is the vagus nerve which makes contact with these sensor cells fine. Now it is the presence of these O2 sensitive potassium channels because of which these glomus cells are capable of sensing any change in oxygen concentration or rather let me say partial pressure of oxygen so what happens that if partial pressure of oxygen decreases in that case you see these O2 sensitive potassium channels are going to close isn't it because we are saying that O2 is keeping the channels open so if partial pressure of oxygen decreases and these glomus cells actually they have lot of blood flow so the amount of blood flow which goes to these glomus cells is very very huge so the oxygen requirements of the cell is met by dissolved oxygen only right so that is why they sense partial pressure of oxygen since the dissolved oxygen is responsible for the partial pressure of oxygen so when partial pressure of oxygen decreases there will be less entry of oxygen into the cells right and this will cause this O2 sensitive potassium channels to close so once these potassium channels close potassium will not be able to move out of the cell see potassium gradient is always from inside to outside because in all the cells inside potassium is more right outside it is less so if the channels close potassium will not be able to move up from inside to outside before it was moving so that means a positive ion remains inside the cell and this leads to depolarization let's summarize a little bit here so what has happened that decrease in O2 causes the closure of the O2 sensitive potassium channels this leads to decrease in efflux of potassium ions so potassium ions remain inside the cell this causes membrane depolarization very important right so always we see that influx of sodium ions causes depolarization here what we are telling is that there is decreasing influx of potassium ions and that is causing membrane depolarization now with membrane depolarization there is opening of L type voltage gated calcium channels so yes there is presence of calcium channels also on these glomer cells and they open and once they open calcium enters from outside to inside the cell that is there is calcium influx this causes the movement of the vesicles towards the membrane there is fusion of the vesicle and there is release of the neurotransmitter that is the dopamine now this dopamine goes and acts on the receptors which are present on the nerve cell membrane that is the D2 receptors okay and because of this there is change in the potential there is increased firing of the afferent nerve endings and from there the information goes to the control center that is the metallurgy neural center and there is increase in rate and depth of ventilation so what we are seeing is decrease in oxygen has led to increase in rate and depth of ventilation because of which there will be rise in the partial pressure of oxygen isn't it so yes this is a kind of a negative feedback control system by which changes are being made in rate and depth of the ventilation based on the chemicals now when we talk about peripheral chemoreceptor remember that oxygen is the most potent stimulus for the stimulation of the peripheral chemoreceptor so oxygen is the most potent stimulus though they also respond to partial pressure of carbon dioxide and H plus ions right so they respond to all three stimuli but oxygen is the most potent stimulus and for changes in carbon dioxide they are responsible for only 30% of the response rest of the responses brought about by central chemoreceptors right and H plus ions the response to changes in H plus ions is brought about only by peripheral chemoreceptors right not by central chemoreceptors so oxygen most potent stimulus then these respond exclusively to oxygen and hydrogen ions this response is not brought about by central chemoreceptors and partial pressure of carbon dioxide 30% of responses by peripheral chemoreceptors and rest of the responses by central chemoreceptors now this response to oxygen which we were talking about let's see it bit to graphically so in this graph if you see x-axis is showing the partial pressure of oxygen and y-axis is showing the alveolar ventilation and here we are saying the partial pressure of arterial oxygen why because these peripheral chemoreceptors that is the carotid bodies and aortic bodies they are located in the arteries so they are going to sense the arterial oxygen isn't it yes so this is arterial partial pressure of oxygen now you see that when the partial pressure of oxygen is above 100 the alveolar ventilation you see is one so here one we are considering the normal alveolar ventilation at rest so here hardly any change in alveolar ventilation is there then there is little bit change in alveolar ventilation as a partial pressure of oxygen decreases from 100 to 60 but from 60 millimeter mercury onwards so this partial pressure is in millimeter mercury from 60 millimeter mercury on what you see how much there is a steep rise in alveolar ventilation so it is only after the partial pressure of oxygen falls to less than 60 that peripheral chemoreceptors respond maximally and cause a steep rise in alveolar ventilation that is first point second point is that when we are considering this graph we have assumed that partial pressure of carbon dioxide is normal and hydrogen ions is also normal pH is also normal and they are maintained at a constant level if they are changing then the response to this oxygen is also going to change because we said that how peripheral chemoreceptors are responding to all the three stimuli so suppose the partial pressure of carbon dioxide increases say suppose it becomes 44 millimeter mercury in arteries normally it is 40 millimeter mercury so if it becomes 44 millimeter mercury in that case so these peripheral chemoreceptors will start responding bit early to hypoxia so that is point number two third point what we see is that if we actually see the number of the carotid body impulses right so let me draw it suppose I make another graph and see the number of the carotid body impulses what we see is that there is little steeper response that means for it the graph goes something like this so for this particular graph for the sixth axis will be carotid body impulses okay so here we see that the number of impulses which are occurring they have started rising much before but the alveolar ventilation is not changing with equivalence to the carotid body impulses alveolar ventilation is changing only after the fall in partial pressure of oxygen to less than 60 millimeter mercury why is that well this is because when we talk about carotid body impulses what it will do is that even though there will be change in the alveolar ventilation by its action on neural centers in physiological condition when partial pressure of carbon dioxide is not controlled this increase in ventilation is going to decrease the carbon dioxide levels and if it decreases the carbon dioxide levels then this decreased carbon dioxide will in turn inhibit the alveolar ventilation so physiologically despite increase in the carotid body impulses the alveolar ventilation increases seen only after 60 millimeter mercury so that is the first reason that why this mismatch is there there is another reason also actually hemoglobin which is there it is weak acid compared to that of oxy hemoglobin okay so when partial pressure of oxygen decreases the amount of oxy hemoglobin is becoming less and deoxy hemoglobin is more and that means weak acid is more that means pH is also more that is we are moving towards alkalosis but very little bit but we said earlier that pH also affects ventilation so if there is a bit of alkalosis then also there will be decrease in alveolar ventilation so these are the two reasons that why carotid body impulses do not match to that of the alveolar ventilation quickly three main points we saw that alveolar ventilation increases tremendously after the fall in partial pressure of oxygen is to 60 millimeter mercury and beyond second this graph is also dependent on the partial pressure of carbon dioxide so this 60 millimeter mercury and beyond is when the partial pressure of carbon dioxide is normal if partial pressure of carbon dioxide is increased in that case we will see the shift of the curve and third there is mismatch between the carotid body impulses and the alveolar ventilation that is the carotid body impulses start increasing much earlier but it is not matched by increase in alveolar ventilation this is because as soon as alveolar ventilation changes there is fall in carbon dioxide and there is also increase in pH because of less oxy hemoglobin and this leads to decrease in alveolar ventilation which is kind of counteracting the increase in alveolar ventilation fine so these were the main points about the ventilatory response to oxygen now let's move to central chemoreceptors as already said that peripheral chemoreceptors respond mainly to oxygen and central chemoreceptors do not respond to oxygen their response mainly to carbon dioxide and these central chemoreceptors are present on the ventral surface of medulla so how do they respond to partial pressure of carbon dioxide actually what happens that these central chemoreceptors are stimulated by hydrogen ions in CSF okay hydrogen ions in CSF not in blood so you see what happens that carbon dioxide which is present in blood diffuses via the blood-brain barrier since it is a gas it can diffuse through the membrane and it diffuses via the blood-brain barrier and reaches the CSF and in CSF this carbon dioxide combines with water in presence of enzyme carbonic anitris and forms H2CO3 now this H2CO3 dissociates into hydrogen ions and bicarbonate ions now these hydrogen ions which form these are the ones which stimulate the chemoreceptors they stimulate the medullary chemoreceptors but you see what has happened that the carbon dioxide is kind of trapped because as it moves to the CSF it forms H2CO3 which dissociates into its ions but this hydrogen ion which forms it cannot go back into the blood why because there is blood-brain barrier ion cannot cross that blood-brain barrier while gas can cross and secondly you see that it is a hydrogen in CSF to which is responding which is formed due to carbon dioxide it is not the blood hydrogen which can cross into the cerebrospinal fluid why again it's an ion it cannot cross the blood-brain barrier just like that so that is the mechanism of stimulation of central chemoreceptors by partial pressure of carbon dioxide so we say that the physiological stimulus for chemoreceptors central chemoreceptors is partial pressure of carbon dioxide so this is the physiological stimulus why the primary stimulus the main stimulus which is stimulating the central chemoreceptor is hydrogen ions in CSF so two terms are there physiological stimulus that is partial pressure of carbon dioxide in blood and primary stimulus that is hydrogen ions in CSF but why is that the central chemoreceptors are more effective for partial pressure of carbon dioxide and not peripheral chemoreceptors this is because even the periphery there are a lot of buffers so there is buffering which is occurring at the periphery while in case of CSF the protein concentration is very less proteins cannot cross the blood-brain barrier so protein concentration is very less and that is why central chemoreceptors can respond effectively to changes in the partial pressure of carbon dioxide so this is one reason that carbon dioxide is important to minute to minute changes in the ventilation it is not oxygen oxygen we saw that how only when the partial pressure of oxygen falls below 60 millimeter mercury in that case the peripheral chemoreceptors are responding so it is more like an emergency measure but the minute to minute changes which occur in the rate and depth of ventilation it is due to the partial pressure of carbon dioxide changes but with that also remember one thing that this response of central chemoreceptors is prone to adaptation because over a period of time if there is presence of chronic hypercapnia chronic increase in the carbon dioxide in that case what happens that more and more bicarbonate there are certain exchanges there more and more bicarbonate enters into the CSF and this can buffer the changes in hydrogen ions in CSF so if there is presence of chronic hypercapnia then there is adaptation which occurs to the response to partial pressure of carbon dioxide fine now let us see the characteristic of the response we saw the graph in case of response to changes in oxygen now let us see the graph in response to changes in partial pressure of carbon dioxide so if we see here x-axis is showing alveolar partial pressure of carbon dioxide and y-axis is showing ventilation in liters per minute now remember that even here though the term alveolar is used because when we are trying to determine the response we can get only the alveolar sample so that is why alveolar partial pressure of carbon dioxide is used but it is generalized to arterial partial pressure of carbon dioxide because if alveolar partial pressure of carbon dioxide is more naturally arterial partial pressure of carbon dioxide will also be more right so concept wise you can consider it as arterial also fine now you see the ventilatory response to increase in partial pressure of carbon dioxide is almost linear right this is almost a straight line so this is very important as I was saying that minute to minute ventilatory changes occur due to changes in the partial pressure of carbon dioxide now when we were seeing the graph of responses to oxygen we saw that if partial pressure of carbon dioxide increases how will the graph change so similarly let us see that what will happen if the partial pressure of oxygen changes right so you see that just let us see just one graph here where partial pressure of oxygen is 100 millimeter mercury that is normal right so we get a linear graph right now you see that there is another graph where partial pressure of oxygen has decreased it has become 80 millimeter mercury then there is another where it has become 60 millimeter mercury so you see how the graph is changing actually the slope of the response is changing right so if we see a particular partial pressure of oxygen same between say 45 millimeter mercury and just try to draw a line connecting these graphs with these points what we see that when partial pressure of oxygen is 100 millimeter mercury the response is this much okay but when partial pressure of oxygen has decreased to 80 millimeter mercury you see how the response has increased isn't it to 60 when it has the response has doubled for the same partial pressure of carbon dioxide so the slope of the response is changing so that is first point in this graph but second point you see what is the second point all of these graphs are meeting at a single point that is 37 millimeter mercury now this value you will see different in different books some may give 35 millimeter mercury some have given 37 millimeter mercury this is because the characteristic of the response varies in different individuals but the point here is that all of the graphs meet at a single point at this point is known as apnea point okay so if the partial pressure of carbon dioxide becomes to less than 37 millimeter mercury right this point so this is less than the normal partial pressure of arterial or alveolar PCO2 so if it becomes 37 millimeter mercury what happens to ventilation ventilation has become zero there is no ventilation so there is apnea so this is known as apnea point and you see this is occurring despite decrease in the partial pressure of oxygen but when the partial pressure of oxygen decreases to below 60 millimeter mercury till 60 okay right but when it decreases below 50 millimeter mercury what we see that yes some ventilation is present why is it so because of the stimulation of the peripheral chemo receptors so this is the third point with regard to ventilatory response to partial pressure of carbon dioxide along with the effect of partial pressure of oxygen on these graphs so in summary if we say that how will be the ventilatory response to partial pressure of carbon dioxide that is rise in partial pressure of carbon dioxide and fall in partial pressure of oxygen we say that the response is more than additive or what is known as synergic more than additive so in simple terms if we say some arbitrary numbers if we take say suppose if PCO2 increases one unit and ventilation increases by one unit if PO2 decreases by one unit and ventilation increases by one unit but if both decrease suppose a PCO2 increases by one unit and PO2 decreases by one unit then we say that the ventilatory change will be how much one plus one two no it doesn't happen like that ventilatory change becomes three so that is what it is that the ventilatory response is more than additive it is synergic finally what is the ventilatory response to hydrogen ions well the ventilation just increases linearly with the rise in the hydrogen ions and it is very important because hydrogen ions cause change in pH and when pH changes then the functioning of all the cells will be affected so hydrogen changes are very tightly controlled so there is linear increase in ventilation with increase in the hydrogen ions and if we see what will be the effect of both PCO2 and hydrogen ion changes on ventilation that means PCO2 is also increasing in hydrogen ions also increasing then the effect is additive PCO2 and oxygen we saw that the effect was more than additive in case of both PCO2 and hydrogen the effect is additive so that was all about the chemical regulation of respiration thanks for watching the video if you liked it to press the like button share the video with others and don't forget to subscribe to the channel physiology open thank you