 NPTEL series of lectures on animal physiology. So, we are in the section of respiration. So, we started with the first lecture of respiration where we talked about the structure of the lungs and how the trachea which is a cartilaginous structure splits up into bronchioles and from the bronchioles to alveoli and how the exchange takes place at the alveolar surface that was the first part and we highlighted the fact that it is the partial pressure difference of oxygen and carbon dioxide which results in the exchange of gases. Now, the word what is exactly happening is that the blood which is enriched in carbon dioxide releases its carbon dioxide and picks up the oxygen which we inhale and this whole process falls under the respiration. So, in the last class I told you that in this section we will be talking about two aspect one aspect is how we calculate the partial pressure and how we have the complete table of the partial pressures and we could see how this from higher partial pressure how it goes to lower partial pressure especially in terms of oxygen and carbon dioxide and then what we will do we will talk about how the blood and carbon dioxide is being carried sorry how the oxygen and carbon dioxide is being carried in the blood what are the different mechanisms blood employs to carry this two very very important gases which are involved in the respiration as well as metabolism and pretty much everything in our body and most importantly the buffering and in the third part we will be talking about the buffering mechanism with the blood follows in order to ensure that we do not suffer from any form of acidosis or alkalosis, but as you many people have heard or see it is extreme acid conditions which even lead to conditions like cancer and many other things. So, do alkalosis so we have to always maintain a very stable or kind of a very pH range cannot vary significantly from 7.2 to 7.3 we are slightly on the acid alkaline side, but that is the permissible limit other than certain organs in our body like a stomach what we have discussed in digestion which is extremely low pH other than that most of the body rest of the body functions at an stable pH around 7.4 7.3 likewise. So, let us start with an eyes I told you in the last class please go through the Dalton's law partial pressure. So, let us come back to section 7 this is the second lecture. So, if you put the partial pressure so there are 3 gases we are dealing with oxygen carbon dioxide and nitrogen which are present in the environment and of course, a significant amount of water vapor in the and that also exerts its partial pressure partial pressure partial pressure which we indicated by say p b. So, p b is equal to partial p stands for partial pressure partial pressure of nitrogen plus partial pressure of oxygen plus partial pressure of sorry partial pressure of carbon dioxide and partial pressure of water vapor. So, these are the 4 component which constitute the complete total partial pressure equation. So, now if you know at least one component and if you know. So, always remember this partial pressure is a function of the altitude where you are. So, if you are at the sea level so that is where it is measured if you are at the sea level the partial pressure is mostly at atmospheric pressure is 760 millimeter mercury, but if you go up in the mountains then the partial pressure the atmospheric pressure decreases because of the simple reason because all these gases what you see the concentration reduces as you go up. So, as the concentration decreases so do the partial pressure. So, at different pressure zone if you are at 760 millimeter mercury the pressure is different if you are at higher altitude pressure is different and as you go down inside the ocean then the pressure is different it goes up. So, these are the basic fundamentals we all of you must have studied at some point or other class 6, class 7 or somewhere other it is just for you guys to you know rehash and keep that in mind whenever. So, what we will be doing here while we will be doing the calculation we will be doing the calculation based on partial at the at the sea level assuming at sea level 760 millimeter mercury that is 760 millimeter mercury. So, when our assumption is very clear so when the barometric pressure at sea level I am just putting at SL at is 760 millimeter mercury and partial pressure of water I just put P P sorry since I am talking like that. So, the partial pressure of water water vapour is 747 millimeter mercury this value I give you this value. So, this value if I ask you that calculate the once again there is a confusion here at this stage I ask you please calculate the partial pressure of oxygen what you will you do this is what I am asking you to do. So, we know the oxygen concentration in air is 20.8 percent this another value is known to you and the total partial pressure is denoted by P B. So, what we do we know one of the values that is 47 which is contributed by water. So, P O 2 how to calculate P O 2 that will be 20.8 percent of 760 minus 47 and the 760 is coming the added together at the sea level. So, if you really solve this whole thing 20.8 percent and this becomes 3 4 to 6 723 and if you totally calculated it comes out to be 100 millimeter mercury. So, this is the contribution of oxygen if this is the contribution of oxygen what is the contribution of carbon dioxide P CO 2. So, for that you need to know what is the concentration of CO 2 in the air which is 0.0 which is very negligible. So, if you have to calculate then P B again it is the same thing P B minus 47 which is your contribution from water and then what P CO 2 becomes 0.03 percent 760 minus 47 0.03 percent and this value was how much you calculated was 47. So, 3 4 5 713. So, that is fairly negligible approximately almost 0 if you calculated. So, basically in the air situation is like this in the air your CO 2 contribution is fairly low is the regular air water and oxygen we have talked about partial pressure of oxygen in the air is around 150 millimeter mercury and at this point we are only concerned with these two gases because those are the ones which will help us. So, if you really form the table. So, this is what I was telling you. So, partial pressure of oxygen and CO 2 into the calculation at two different level this is P O 2 in millimeter mercury and this is P CO 2 at millimeter mercury and this is for the inspired air the air which you are inspiring inspired air. We have calculated this as 150 and this is approximately 0 whereas alveolar gas as well as I am just both the arterial blood which is the blood which is laden in carbon dioxide which is coming to the lungs for purification both of them. This is around 100 and whereas this is around 14. So, let us consider this as a common this is pretty much the same now what will happen. So, now what essentially what happens is that here you see partial pressure is higher. So, automatically oxygen gets into the arterial blood whereas here if you look at it partial pressure of carbon dioxide is much more higher as compared to the outside air. So, the carbon dioxide moves like this is essentially this is one of the most key thing what you have to kind of realize that this is how this actual this whole exchange takes place because of this partial pressure use the simple logics. So, what I expect the take home message for this particular part will be you have to have a very simple clear cut understanding of partial pressure and atmospheric pressure. If you know the atmospheric pressure if it is at 760 millimeter mercury I did the calculation but if I tell you that you are in a very high altitude say Machu Picchu in Peru or somewhere in Ladakh or Lea or somewhere in Himalayas or in Andes how you do not calculate. So, what you need to know is what is the atmospheric barometric pressure and if you know the barometric pressure and if you have these values reasonably close to it you can make the calculation. So, this these are the simple ways by which you can make all this calculations which regulates your physiology as we will go through you will see it. So, now what we will be talking about after this is how oxygen is carried in the blood. So, if you remember in the last class I told you in spite of the fact that oxygen has a low molecular weight as compared to carbon dioxide carbon dioxide diffuses much more higher as compared to oxygen. The reason being carbon dioxide is very readily soluble whereas, in the case of oxygen it is not readily soluble. So, that pose a problem for oxygen to be carried. So, oxygen needs a special treatment to be carried all along your body because it really cannot diffuse into the plasma. So, readily or even if it is diffuses it diffuses at a very low concentration which is not good enough for metabolism to take place. So, how the body handle that kind of situation the way the body handles is this. Body has a specific oxygen carrier and they are found in the red blood cells. So, whenever you go to a doctor, doctor ask you when they do a blood analysis they ask you what is the hemoglobin percentage. Generally, it should be around 12 to 14, but sometime it falls down to 7 or 8 or you know to 4 sometime even you know worst case. That means that there is some problem because your body is not carrying sufficient oxygen. So, if the body does not carry sufficient oxygen what essentially that leads to is that your metabolism is compromised, your nervous system functioning is being compromised and these are some of the natural phenomena which happens in the high landers at high altitude. Very suddenly you go to high altitude oxygen is low. So, automatically the oxygen is low the hemoglobin is not completely binding to the oxygen. So, these are the kind of situation. So, let us get into it and that will help you to realize and there will be some stark differences will come across how oxygen is being transported and how carbon dioxide is being transported. So, let us start with oxygen carrier in blood. So, here you have the red blood cells by concave disk and this I have already mentioned it has a poor solubility in plasma. This is an RBC and with an RBC you have these hemoglobin molecule sitting there just putting them at HB hemoglobin. This is a protein and we will talk about the structure of this protein and which is your oxygen carrier. So, if you look at hemoglobin molecule. So, hemoglobin molecule is something like this. It has 4 subunits like this and within the subunit it has a interesting center come to that. This is a single molecule of hemoglobin. So, these two chains this and this one is called alpha chain. These are the proteins and these two chains are called beta chains. This thing this red color thing is basically iron porphyrin. This is the one which binds to oxygen. So, that is why you will see whenever there is a deficiency of hemoglobin people say you take iron rich diet or if you have to increase your blood. They say the colloquially they will say you take iron rich diet. This is where the iron plays the role and I request you people please go online and check what is the structure porphyrin. Porphyrin is basically I will not give you the full structure just look into it. It will be something like you will come across as something like a structure you will come across like this. I want you guys to really go there go online and check how all the bonding are taking place. We have structure like this you will have the iron sitting here and one more thing I request you to look at. What is the oxidation state of iron here? Is it plus 2 or is it plus 3? Is it ferrous or is it ferric? Please look this this is the exercise I expect you people to do and there is another closely molecule to porphyrin where iron is being replaced by magnesium. And that is what is called chlorophyll they are very close to each other and chlorophyll as you know is the one which helps to trap the sunlight. So, they are very close molecules and look into it I expect you guys to look into this structure. So, this is basically the overall skeleton of porphyrin and go through it and look for the oxidation state of iron in what oxidation state of iron state stays as porphyrin and this is where this is the site where the oxygen is getting bound. So, I will not go into the technical details of it in depth because this is not this are covered in biochemistry, but I expect you guys will enjoy if you go through this. So, there are basically in one molecule I had to say say for example, one hemoglobin molecule like this one hemoglobin molecule could bind to as you if you remember in the first diagram I was doing 2 beta chain 2 alpha chain it is a site to bind to 4 oxygen molecule. So, if I put the blue as oxygen likewise so this is that red zone sorry the red zone which I was drawing in one of the previous slides. So, 4 oxygen bind this is called oxy hemoglobin which is laden in oxygen. So, basically oxygen binds very loosely out there because it cannot bind very harsh because if it binds very harsh then it would not be able to dissociate. So, basically what is happening is that before plus O 2 4 I put because there are 4 binding site essentially what is happening is that 8 B 4 plus O 8 because O 2 multiplied by 4 that makes it is O 8 is 8 B 4 coming. So, this is basically how the oxygen is binding and based on the saturation level of oxygen you can termed it as likewise if there is only. If all the 4 sites are occupied by oxygen this is 100 percent saturated if 1 2 are 50 percent if only 1 is then it is 25 percent if none this is unsaturated and based on this you can draw the saturation which is also called oxy hemoglobin dissociation curve oxy hemoglobin dissociation curve this is basically what is essentially says this on y axis you have hemoglobin saturation I was telling you hemoglobin saturation. So, it could be the 25 percent 50 percent 75 percent 100 percent and whereas on the x axis you have oxygen tension in millimeter mercury. So, this is the 50 100 150 likewise and if you draw the graph it shows an almost an S shape curve here and if you look at it somewhere here it will be the venous blood it will be the venous blood which has lower saturation of oxygen as you know that most of the oxygen is being used up by the tissue and if you look somewhere out here this is where you have the arterial blood which is filled with oxygen except the artery which is taking the carbon dioxide rich blood to the and you can to the lungs and you can see the difference in the oxygen in the hemoglobin saturation of oxygen and at this part of the curve at this part of the curve this is almost independent of oxygen concentration because as long as it has the binding sites all the hemoglobin molecule has a limited number of binding sites it has only four binding sites. So, assume a situation when all the hemoglobin in your blood in your red blood cells and plus all the red blood cells are completely saturated with oxygen. So, you do not have any other part where oxygen can bind and as we have already say the oxygen dissolving power solubility is very very low. So, ultimately there is no room for oxygen really to bind. So, under that situation this curve reaches a peak what you see a plateau the plateau is reached because there is even if you once again even if excuse me even if you add oxygen at that point of time there is no point because there is no more oxygen binding site left in the hemoglobin because they are all filled. So, when the plateau reaches it is free from any oxygen concentration. So, remember that this is very important to understand coming back to where we were. So, this is the zone which I am trying to highlight that this is completely free from oxygen and another thing which what I wanted to highlight here is that at this zone you look at it. So, what essentially is happening is what is happening here when the arterial blood is coming arterial blood and the venous blood this blood is coming with very high oxygen. And then when it goes to the tissue this is the tissue just assume this box is a tissue it gives away the oxygen and picks up the carbon dioxide. It is here you can figure out if you see the saturation zone that is what happens oxygen tension is lesser out here. And if you see the previous graph it was exactly like that and this oxygen tension changes further during two different kind of whether you are at rest or whether you are at exercise at rest your oxygen consumption is low low oxygen consumption whereas in during exercise oxygen consumption is much more higher. So, automatically the saturation goes much more faster. So, remember that at the lower part of the graph where basically the venous blood is having a lower oxygen tension. So, see that graph and that graph is reached very fast when you are doing a lot of exercise. So, this is something which I expected people to you know understand from here I will move on to the next slide where basically some of the facts what I expected you guys to understand is that there is 15 gram hemoglobin is present in 100 ml of blood this will help you knew all kind of calculations. So, this is basically what we talk about how much hemoglobin is present and that each hemoglobin can carry 1.34 ml of oxygen this is very important. And the oxygen content of arterial blood at 100 percent saturation is 20 ml oxygen per 100 ml of blood these are some bits and pieces of information which will help you to do any kind of calculation. So, that is why I wish to highlight that this is very important for all the calculation purpose if you know these values it will be fairly easy to do any kind of calculations after the oxygen. So, we talked about the hemoglobin and talked about the porphyrin structure of hemoglobin. Let us talk about how carbon dioxide is being carried in the blood. So, in case of carbon dioxide there are 3 different mechanism there is no specific as such there is no specific carrier that of course, hemoglobin does bind to carbon dioxide and it called carboxy hemoglobin just like the oxy hemoglobin when oxygen binds to the hemoglobin. There is also whenever oxygen is being thrown out and carbon dioxide binds to it that is called carboxy hemoglobin. So, apart from carboxy hemoglobin there are 2 other routes by which carbon dioxide is being carried. So, what we will do now we will enumerate all the different routes by which carbon dioxide is being carried out is being carried all over the body. So, let us get back to the carbon dioxide by blood and this is very readily soluble in the blood as I have told you. So, first is as I will discuss all of them separately as a bicarbonate as a bicarbonate iron which is HCO 3 minus in plasma this is one route the route 1, route 2 a carbamino compound which is formed when CO 2 and NH 3 group of protein which is essentially we are talking about carboxy hemoglobin there is a third way of carrying which is as a dissolved molecule. This is the easiest because it has the highest solubility I have already mentioned that these are the 3 different ways by which carbon dioxide can be transported. So, how it does in the bicarbonate because that has another significance in pH that is why I will come back to that when CO 2 plus H 2 O when these 2 mix there is an enzyme which is present in the body which is called carbonic anhydrase what carbonic anhydrase is called carbonic anhydrase does is that transform it into H 2 CO 3 to go to the next page to complete the reaction then H 2 CO 3 basically has the ability to dissociate H plus H CO 3 minus. So, if I put the whole reaction in perspective then this is like this CO 2 plus H 2 O reversible reaction this is what C A carbonic anhydrase comes into play H 2 CO 3 and then from here it breaks down to H plus plus H CO 3 minus and this carbonic anhydrase is present in only in the RBCs it is not present in plasma mark my word not present in plasma. So, this reaction has to take place inside the RBCs and if you have to do a complete outline that which of these component is contributing how much for carbon dioxide travel then you will see. So, let us enumerate them one is the bicarbonate we talked about bicarbonate or amino compounds and then you have dissolved CO 2. So, this is 10 percent dissolve one carbamino compounds that is carboxy hemoglobin likewise is 30 percent and the major chunk is in the form of bicarbonate and this is very important that bicarbonate is the one which carries the maximum amount of it. Now, from here what I will come to the concept of T H how T H is being regulated. So, this is a very important fact you have to realize the P. So, I in the beginning of the lecture I told you that T H is exceptionally essential in terms of maintaining the proper homeostasis of the body. So, the T H is we will go back to that reaction if you remember the reaction as just I draw carbon dioxide plus water making HCO 3 and then HCO 3 is H 2 CO 3 H 2 CO 3 is dissociating into H plus and HCO 3 minus. This reaction is one of the most fundamental reaction and depending on forward reaction backward reaction rate of forward reaction rate of back reaction because you have two control zones. This is the one which helps to maintain the P H and that is what we are going to deal. Now, how this particular reaction helps to maintain the P H of the body coming back to the. So, the P H of the arterial blood is held constant by the. So, this is the one which is helping in the whole buffering by the buffering action of HCO 3 minus and CO 2 this is very important CO 2 this is a system which helps in our all our buffering and by blood protein which is mostly blood protein which is involved in this is the hemoglobin. This is something which you have to realize and this could be stated by the Henderson-Haschelbach equation. Please go through this those of you have forgotten it basically using Henderson-Haschelbach equation we can formulate it that P H of the blood can be calculated by adding a constant adding. So, remember this adding a constant adding a constant term to a to a variable term given by the logarithm of the ratio of the HCO 3 minus concentration to CO 2 concentration and if I put the mathematical equation here that will be P H is equal to 6.1 plus log of HCO 3 minus molar concentration divided by concentration of CO 2 this is very very important and if you see that if you see a value of log 20 which is equal to 1.3 the P H of blood at that situation will be 7.4. So, in order to have a 7.4 what will be the situation is. So, whenever HCO 3 minus upon CO 2 is 20 that is 6.1 plus log 20 which is equal to 6.1 plus 1.3 makes it 7.4. So, what are the so if you look at it. So, these values if you know the Henderson-Haschelbach equation right that P H is equal to 6.1 plus log of HCO 3 and CO 2 upon CO 2 then you can make this whole calculation without any problem and this is exceptionally essential and what are the implications of Henderson. So, let us talk about the implications of it I am just putting H H Henderson-Haschelbach equation the P H of the blood can be maintained at around normal level of 7.4 by balancing operation of renal system which is your kidney system which actually regulates which as you come to the kidney you realize this which actually regulates HCO 3 minus concentration and respiratory system which regulates your carbon dioxide concentration. So, this is exceptionally important for you able to realize that these are the two situation which regulates the P H. So, you have an interplay of kidney or the renal system and respiratory system. So, this is regulating CO 2, this is regulating HCO 3 minus as long as these are properly balance your P H in the body will be balanced. Another thing for you to important to remember is that P H of the blood as this is just the direct implication of it will deviate from 7.4 which is the normal value whenever your HCO 3 minus is to CO 2 ratio of 20 is to 1 shifts either upward or downward. If for example, if your HCO 3 minus is to CO 2 ratio is more than 20 is to 1 then we are hitting on to situation called L Colossus it means the body is alkaline. Whereas, if HCO 3 and CO 2 ratio is less than 20 is to 1 and we are hitting into acidosis. So, this is what you have to remember very clearly and there are couple of more terms which are very essential acidosis could be because of this is basically higher level of CO 2 and lower level of HCO 3 which is basically called metabolic acidosis. And this is called respiratory acidosis because for the simple reason that CO 2 percentage is governed by the carbon dioxide. So, whenever CO 2 percentage goes down or goes up it is at the respiratory acidosis or alkalosis. Whereas, in the case of HCO 3 concentration which is regulated by the kidney it is basically the metabolic acidosis or metabolic alkalosis. So, these are the aspect which we covered today we talked about the partial pressure of carbon dioxide and oxygen in the air which we inhale and the level of carbon dioxide and oxygen in the blood. Then we talked about the carriers of oxygen carriers of carbon dioxide and then we talked about how this CO 2 HCO 3 buffer system helps to maintain the pH of the body. So, these are the overall things and kindly go through the notes which I have given you here and that will help you to understand and always be very clear about your basics. Thanks a lot.