Transcribed by Stephen Holt Lecture 17- Gas Exchange by Dr.

Pavlov

April 2, 2014

[2] All right so we should probably start the lecture. So this the third lecture of the respiratory and physiology part and the title of todays lecture is Gas Exchange and transport. [3] Today well be talking about pretty much about similar processes like ventilation, diffusion, and circulation but in some more details and I will put some more numbers on this and it becomes a little bit more in depth but nothing really major so pretty much the overall objective of this is to understand in some more depth mechanisms of oxygen and carbon dioxide transport throughout the respiratory system. And again its anywhere from lungs and to the cells so like just to break down what kind of topics well be reviewing today. So first well look again at ventilation in some more quantitative ways so well just introduce a couple of important equations which describe this process and then well look again into diffusion. Again diffusion we talked about already so well look just to refresh, you know like Ill talk about Henders(?) law just to remind you from what was yesterday. Then well look at pulmocirculation again in some more details and look at some numbers how pressure and how blood is actually pumped and then well look at some very important subject which is you know the relation between these two; ventilation and perfusion because if you recall they need to be matched and now I will show it in more details like coordinate these two processes and in time. And the last will be a little more of what we havent talked, itll be like biochemistry, we will look at oxygen and carbon dioxide in blood and this will be a little bit not like all this pumping business or breathing in and out but its a little bit more of biochemistry, how these molecules can be dissolved and cured by blood. [4] So again to review the processes as we talked about it a number of times already. So again there are 3 major steps of oxygen in the lungs. Like getting in and out through ventilation, diffusion, and then blood picks it up and carries it to the cells. And here it gets used up. And then here O2 gets produced and gets in the blood and go backs here, diffuses and goes out. [5] So before we go into some processes, I want to kind of introduce you to some numbers. And this is specifically for oxygen. And I guess one of the things about these numbers thats nice to remember them thats like driving school youd need to know speed limits. So they dont really mean much, but its useful like you know for example the oxygen pressure you know in the atmosphere. And you know the oxygen pressure in venous. So here is the atmosphere, the arterioles, venous. Theyll be coming up especially in the second lecture and in your kind of experience youll need to get an idea what the typical pressures are for normal conditions. So I guess one of the messages from this plot other than just introducing these numbers

Transcribed by Stephen Holt

April 2, 2014

is also to show the example thats actually oxygen transport from the outside into the mitochondria into the cell for usage. Its really kind of a cascade where pressure always drops and this is not really intuitive because at some point it was believed gas transport might be an active process but this is a good illustration that its not. That really all respiration is about is diffusion down the pressure gradient and this is a very important concept in respiration that it really is all the respiratory system does is kind of just passively allows gases to go in and out and this is a key principle of this. So there is no waver where carbon dioxide or oxygen gets actively pumped against the gradient or anything like that. So its usually all passive going from 160 down to almost 2 ml Hg in mitochondria. [6] So again this is the numbers again. To look at and to keep in mind and again just remember them and we just talked about oxygen how it drops so its anywhere from atmospheric going to humidified air so it drops here because you need to humidify and its replaced partially by water and then going alveolar and this is expired air. And the same for CO2 its also some useful numbers and there is also like really zero in the air like when you inspire. And alveolar its more or less stable at 40 and again this is also important numbers. So I guess 100 for oxygen and 40 for CO2 are important and the rest are just random barometric pressures and not really all that critical. [7] So again looking at the extra pump, so we see this contour a number of times and just kind of remind again in the context of todays lecture so that there are like 2 volumes. So actually in the airways we have 2 groups of volumes. So we have this gas exchange volume which is the major and we have this air conduction volume where gas in not really exchanged in where its just used for air to go in and go out. [8] And these volumes are related to each other in such a way that you would have like actually here it kind of looks kind of smaller but this is gigantic volume of alveolar gas exchange happening and this is called alveolar volume. So this is about 3000 mL and there is this stoop here that is actually called anatomic dead space. Anatomic dead space corresponds to this conduction part of the lower airways and it is much, much smaller than the gas exchange area so you can appreciate that here its roughly like 5% of the volume compared to the total volume of the lungs. And what is important to know this volume so if the dead space and other other gas space because actually what really matters when we talk about ventilation actually is how much air was delivered into gas exchange system so this is like. So dead space is used just to kind of, well its dead so nothing useful happens there except it provides the passage. So really what were interested to when it comes to physiology is how much air is been exchanged between alveolar and environment and this space essentially needs to be subtracted.

Transcribed by Stephen Holt

April 2, 2014

[9] And this is critical consideration when we introduce alveolar ventilation. If you remember the first lecture, I gave you an example of the total ventilation of the lungs which you essentially take total volume and multiply it by the number of breaths you take. But it was not really very useful parameter; what is much more useful is alveolar ventilation, which is really how much air has been exchanged with you know, the extra lungs where it has been used up. And this parameter it needs to be taken into consideration the dead space. So its probably very straight forward equation and I would imagine its easy to grasp concept. So pretty much you just subtract from the total volume the dead space. So with each breath its kind of wasted and youre left with the useful ventilation. This is one of the kind of key equations in the whole business and the definition of if it is the volume of air per unit of time. And here obviously this different volume so the respiratory volume, tital volume, and dead space volume which needs to be subtracted from tidal. So this is the first way to look at alveolar ventilation so this is the exact definition of the process. [10] But there is also another way to introduce the equation and this is very important as well. So the equation here is called alveolar ventilation equation. And you can look and also I encourage you to look at this equation in the test book because its not that complicated but I think its important to understand it. So what it says here is actually what you could do is introduce you know look at the ventilation as the rate of production of CO2. And what it is so for example you would have so there is no CO2 in the environment so its really close to zero. So pretty much all CO2 that is produced has to go out of our body. And it has to go out of our body is through alveolar ventilation. So this is essentially the relationship. So this is the amount of CO2 produced or the amount of CO2 expired which is pretty much the same thing because it really cant accumulate anywhere. And it will be proportional to alveolar ventilation and the fraction of CO2 which you would have in alveolar space right in the air which is in alveoli. And this is very important because it will directly lead to other ventilation with the production of CO2. And the way you can also rewrite it. So this is the fraction of CO2 and this is the partial pressure of CO2 multiplied by certain parameters. So this is essentially what I mentioned, so this is the percentage of CO2 in the alveoli so normally it would be like 40, so this kind of establishes alveolar ventilation not as a kind of volume of breathing in/out but as a rate of CO2 production so essentially its partial pressure of CO2 so pretty much alveolar ventilation is proportional to rate of CO2 production vs the proportion to partial pressure of CO2. So please keep this equation in mind and essentially what it tells you that the more CO2 is produced, the faster ventilation will be. And Ill just drop this information for now, its an important equation but I really will not be asking about it; you should just be aware of the relationship between CO2 production and O2 production, its not really a subject of todays lecture I just put it in because I felt its important to mention but its more like metabolic states of how much oxygen you consume and how much CO2 you produce is based on your metabolism. But anyway dont worry about this , but lets look back to this example so how this other

Transcribed by Stephen Holt

April 2, 2014

ventilation can be exemplified in the real example and this would be how rate of CO2 production compares to the alveolar ventilation. So Ill just focus you on two points. So this is alveolar pCO2 which is capped at 40 under normal conditions and as well see in the next lecture actually what our organism is trying to do is try to keep pCO2 as stable as possible, you know around 40 in alveoli. And here there are 2 conditions, one is resting and one is mild exercise. And what the difference is pretty much as I mentioned so like CO2 production is directly related to energy demands. So pretty much you pretty much always have some food in your organism which needs to be used and if you exercise you burn more food so you consume more oxygen and produce more CO2. But actually if you exercise or not, actually what the organism is trying to do is keep pCO2 at 40 and here you can see the difference between 2 conditions. So based on this equation so pCO2 stayed the same and what changed is the rate of CO2 production from 250 to 750 and essentially what happened is the alveolar ventilation tripled. So this is a specific example how you can link metabolism of the organism like the rate of metabolism to the rate of energy production to the rate of alveolar ventilation. So theres a straightforward link. [11] And so now just to go back to diffusion again we talk quite a lot about it so I guess I dont want to spend too much time but I want to mention again the rate of diffusion is proportional to the difference in pressures across and barrier and the diffusion coefficient and this is like again the wall of the capillary and like to see how its going to exterior alveoli(?) [12] Just reminder again that the equation we just looked is defined by a fixed law and key points here is as we talked about the surface area should be like as big as possible and then the thickness should be as small as possible for the gas exchange to occur in an efficient way. [13] And I just wanted like in comparison to the previous lecture I just wanted to spend a little bit on oxygen diffusion. As I mentioned, so this is the normal process of oxygen exchange in the capillary. So this is the partial pressure of oxygen in the blood as it goes through from left to right to the contact with alveoli and as you can see within 25% of the travel it gets saturated under normal conditions and then it just kind of keeps going like this. And here I give you a couple more examples which are one is just an example of the abnormal diffusion exchange so it could be like in some conditions like if you have buildup of liquid in lungs like pneumonia perhaps. So you have some abnormal diffusion which could make it harder for the oxygen to get in and what would happen is this process would slow down. And as I mentioned so there is a lot of resource problem in this case even if diffusion is kind of compromised youd still be fine because all you care about is how much oxygen gets on the exit. So pretty much this will be not too bad but if it gets worse the diffusion can become more problematic and this would lead to incomplete exchange of blood

Transcribed by Stephen Holt

April 2, 2014

and this could create problems. And here I just wanted to mention this is kind of mythological part I just talk about carbon monoxide as a method to measure the efficiency of diffusion. And normally carbon monoxide is a poison and later Ill talk about it as a poison process but pretty much I guess how you could use it here because for example if you were to trying to assess the diffusion you will not really pick it up if something abnormal because it will be like really the blood will be oxygenated if you just look at oxygen so you will think its not too bad. But actually if you look at carbon monoxide you can add like really little amount of carbon monoxide and it will be such a small amount that it will really be zero in blood. And you can add a little bit in the breathing air so not to poison the person and so what will happen is that it will be like zero here and it will be a lot in comparison in alveoli. And what will happen is it will be diffused in the blood and it will not be limited because it is so low here so essentially it will not be limited by concentration because here for example diffusion will stop because you saturate blood with oxygen but in case of carbon monoxide and its little so it will keep diffusing and will keep going up and then you will know actually measuring carbon monoxide in the blood and you would know how much of the gas you would have and then you will know how efficient diffusion is because if it is abnormal this line essentially if it was like really good it would be somewhere here and then progressively will go down just by peaking at the end point you can tell where there is a problem with diffusion or not. [14] And just to kind of complete with this diffusion business is kind of again this is like simple slide which is the opposite of oxygen saturation of the blood. So this is kind of CO2 depletion of the blood. And here again these numbers will be coming up a few times. So you see this 40 mL of mercury which is normal alveolar CO2 and here you have 2 parameters, so when blood arrives and oxygen is being used and CO2 being produced at about 45mL(also important number.) And then it starts gas exchange again it equilibrates so quickly within like 25% of the travel time it goes from 45 to 40 and then its kind of gets to this normal basal level which can kind of travel through the system and pick up more CO2. [15] So now going back to kind of the next step which is pulmonary and systemic circulations so well look at it a little bit so Ill just remind you from yesterday. So there are essentially 2 circles. One is systemic so this is the presentation of the heart. And one is systemic circulation so its going through organs back to the heart and this is first circle. And then there is this pulmonary circle so this pulmonary circulation when it goes through lungs and as I mentioned the key point is that it is low pressure and the lungs receive total cardiac output on like the systematic organs. [16] And this is just a breakdown of what happens with the pressures and again this is something I want to show. So pretty much there are 2 stages, so this is the heart

Transcribed by Stephen Holt

April 2, 2014

beating, so systolic and diastolic and its relatively small difference when you go from 25 to 8 and when it reaches pulmonary capillaries there is essentially no pressure drop. So you can see really when it says pulmonary capillaries its almost like flows effortless right? So then it also drops slightly after capillaries to the left atrium and here is the reason. Why it is so slow. I also mentioned the capillaries in the system they kind of need to form this big network and essentially [17] This is an example and this can probably might make it clear why special blood flow in capillaries is so kind of effortless because its really formed this huge network. So you can imagine actually one is kind of venous and one is arterial side so its hard to tell which of these two kind of blood vessels is which but you could see so pretty much if we mention that blood flows from here to here then you could appreciate it actually. So this is capillaries. So essentially its not even a flow through the tube right but is like the flow through almost continuousthey call it sometimes this blood blanket or something like that. So it is really like effortless and the purpose of that like I mentioned is you need to have really big contact area between alveoli and capillaries so you need this big surface and it gets really slow and nice. Well its not that slow actually but really theres not much pressure drop. [18] So now doing some arithmetic on that. So we talked about ventilation and about the resistance of the airways and there is pretty much also similar type of equations which described the circulation. So really there is a lot of analogy. Well I kind of forgot outputwell this is supposed to be cardiac output sorry about that. But in anyway the idea here is you have this cardiac output so its how much blood is pumped which would correspond in lungs to ventilation if you wish. And there is this delta p is the difference in pressure between different sides of the heart and you have this PVR(pulmonary vascular resistance). So essentially the same kind of resistance of the airways and they link in the same simple way. So you have this cardiac output so the more you pump, and it will be directly proportional to PVR. So pretty much the heart coefficient is so the more pressure difference you need to create to make pumping happen. [19] And this is one of the important concepts about PVR so pretty much what I guess is one of the important things you need to understand and I mentioned about it briefly about it in the last lecture. That actually PVR is not static but can be regulated by blood pressure and this is a fairly simple comcept so you have this arteriole and venous pressure so its pressure inside the blood vessels. And you can see that actually PVR drops quite dramatically you know in both cases. So when you increase the pressure that it will be arteriole or venous you see this gigantic drop in, well not that dramatic, but in PVR and this is easy to understand since we talked about blood vessels that they are like really quiet and not very strong in term of the walls and the more blood you pump they tend to expand and they allow kind of the

Transcribed by Stephen Holt

April 2, 2014

more pressure applied from the inside so they tend to expand and then the blood can just flow through more easily in this case. [20] And this also brings.I mean this concept of blood vessels and capillaries in lungs being so flexible and so you know so variable in diameter and the resistance. It also kind of brings in the concept of the zonal model of pulmonary circulation. And what it is that it tells you that in vertical standing lungs the blood flow will be different in different areas of the lungs right. So what you can see here so pretty much these capillaries are surrounded by alveoli and you would have like a few parameters. So you would have alveolar pressure, you would have arteriole pressure inside and then you would have venous pressure right? And what happens here you would haveby the way the small letter is always applied and the large applied to air so its a little bit confusing; I mentioned theres this terminology when you have you know this values which are pretty straightforward. The only not straightforward thing I guess is here because you can choose arterial and alveoli because theyre both a but just to keep it kind of simple when it goes to blood its always small letters when were talking venous or arterioles and when it goes to air its always capital letter right? But you can see here there are 3 conditions. Vertical standing lungs and what is happening in zone 1 is you have alveolar pressure will be bigger than arterial pressure and it will be bigger than venous pressure so what would happen here essentially is this capillaries will be collapsed just because theyre so flexible so essentially what will happen is the arterial pressure kind of squishes capillaries and you will not have any blood flow. And then as you go down so what happens the arterial pressure starts to go up as well as venous pressure because again just because of the gravity so the blood kind of pushes down so its kind of easy for the heart to pump it here so its pretty much so essentially the blood is pushing down its own way. So whats happening here in zone 2 which is transitional zone what you would have is arterial pressure becomes bigger than alveolar so the blood starts to kind of push through the capillaries but not much because some times they still collapse as pressure drops in the venous end and you will have this transitional zone when blood can go through not as easily but its already starting to kind of leak through so you can get some blood through in the second zone. And third zone is like when both alveolar and venous pressure, sorry arterial and venous pressure is bigger than alveolar pressure. So they kind of expand and they can restore blood flow. So again this is one of the important concepts of the zonal model of pulmonary circulation and youll have this in your textbook, maybe with a different cartoon but the same thing. [21] So and then another important equation in terms of oxygen transport in the cardiovascular system is the link between oxygen consumption by the organism and the cardiac output. So this would be somewhat similar to the alveolar ventilation(?) equation and what it tells you is that were not looking at the rate of ventilation but at the rate of oxygen consumption. So its how much oxygen we use. And it will be proportional to the cardiac output which is the amount of blood pumped through

Transcribed by Stephen Holt

April 2, 2014

the organism and it will be also proportional to the difference in concentration of the blood at arterial end minus concentration of the blood at the venous end. And so again I imagine this is very simple equation because what you get is total blood flow and then you just kind of subtract what you had in the input from what you have in the output and multiply essentially by volume. So you get the rate of oxygen consumption so very easy equation and this is oxygen consumption linked to cardiac output. [22] And now well go back to this cartoon because one of the important thing since we looked at the rate of ventilation and the rate of cardiac output and the rate of blood transport now what we need to look at is how they are matched. So as I mentioned so the idea is we need to deliver oxygen to the cells in a timely manner and need to get rid of CO2 as well in well coordinated process. And this coordination is the good match between the process of alveolar ventilation here and the process of the blood flow and cardiac output. So these two rays they need to roughly need to correspond to one and this is very important relationship which well look at a little bit. [23] Like right here so this is relationship is called ventilation-perfusion ratio. And this is fairly straightforward so this is ratio dividing the rate of alveolar ventilation by the cardiac output and normally this rate would be kind of dictated by the metabolism of organisms. So again it doesnt usually depend on exercise or anything like whether there is stress or exercise because they both kind of have to go up right. If you kind of change the rate of metabolism but it rather depends on not on the rate of metabolism but the type like you know what do we burn. Do we burn fat or carbon? So .8 in normal conditions but actually it can go anywhere between so pretty much this is the dependence of pretty much how this relationship how the normal concentration of oxygen pressure and CO2 pressure would depend if you change this ratio. So if you have normal condition, say .8 in normal working respiratory system then it would correspond, it would bring the levels of O2 and CO2 to roughly normal which again will be coming up as I mention again and again this 140. So for pCO2@ will be roughly 40 mm mercury and for O2 it will be roughly 100. So this is normal but it can go anywhere like regardless if something happens and Ill give you examples on the next slide. But I showed you two extremes so for example if you have some areas of the lungs which are not perfused which is called dead space so pretty much alveoli exchange is nice, its pretty normal but this essentially tends to be at zero and what this leads to is you have oxygen in the alveoli which do not have blood flow so they dont really give away oxygen so it will be closer to what you inspire but you have zero pCO2 in this place and like and the opposite is true. So for the shunt what you would have here is you would have alveoli which do not get any ventilation but you will have blood which will have normal perfusion which would have zero because so pretty much this ratio when you dont have ventilation but have perfusion it will turn to approach to zero and here will have opposite effects. So youll have very low oxygen and you have increased amount of CO2 so it really

Transcribed by Stephen Holt

April 2, 2014

will be correspondent to venous CO2 because youre not taking up CO2 out of it right. So there again will be a lot of other margins and this ratio can be anywhere in between these two extremities. [24] And here Ill just kind of show you an example from your textbook of how this can be happening. So there are 3 conditions shown here and well look at the partial pressure of oxygen here so the normal would be around 100 and this corresponds to this ratio here which again is roughly 1. So what you would have is normal alveoli so you have normal ventilation and normal perfusion and you get it around 100 here. And then what happens for example if youll get no perfusion right so the perfusion gets really problematic so it drops to only 1 so what youll have in this area in the blood so you would have like quite a load of oxygen because you have a lot of oxygen but pretty much there is no new blood coming with low oxygen so it will be equilibriated at much higher level just because there is no gas exchange happening here and you would have much bigger partial pressure of the oxygen in this case and the opposite is true for this case here when you have some dead space when you would have air is not coming so perfusion is good but ventilation is not that good. So what is happening here is you would have a much less oxygen. So here the oxygen concentration would be approaching the oxygen concentration, the venous blood, and thus you would have an outcome, right? And this is important part and Ill mention some just in one slide how actually organs can deal with that because I guess the problem is the end you would have the mix of the blood, some of them coming from normal places and some coming from places for example that are not perfused or not ventilated well and in the end you will have blood which will the sum of 2 and will be not very well oxygenated and will be not very good for the organism and the way to deal with this is [25] Actually for the organism so what it actually can do and Ill explain in a second what it will try to do is try not to, it will try pretty much to exclude this blood, it will try not to have blood in this capillary because this area is not good because its not ventilated so theres no gas exchange so it will try not to pass blood through this area. [26] And how its done it is done by the process of vasoconstriction and this this very important way for the organism to try to deal with this area of poor ventilation and here is just an example. What it tells us pretty much, lets not worry about pH, like pH is important but it doesnt really illustrate the point. Like I said theyre all very similar. So lets look for example at pH 7.1 and this is pulmovascualry resistance. So pretty much what you can see in normal oxygen it will be like 200 or whatever. And then as it drops, if it drops below some good level which would happen if you lose good ventilation, so the oxygen levels will start dropping because you will not be getting new oxygen so what would happen here is you get this huge increase in pulmovasculary resistance. So huge increase in the resistance of this particular

Transcribed by Stephen Holt

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capillary which is not ventilated well so essentially what this means is that blood will stop flowing through this area right? [27] So this is more graphical example of how this actually is happening so pretty much if you have the model of 2 nice alveoli and 2 capillaries flowing by and everything is fine so everything will be flowing and mixing like good normal blood. And then what would happen if this alveoli stop beings perfused for whatever reason, so it kind of becomes hypoxic so theres less suction here. So what would happen is it would cause this lower oxygen would cause the constriction of this capillary and in the end point what you will see is you will see much less input from this capillary to that and overall for the organism it will be really good deal because the end of the day you will be like getting here the same nice blood which is almost not contaminated by deoxygenated blood. So this is a process of vasoconstriction and again this example is not very good so if you kind of open this up for no good reason what you could get actually is you could get , without real if you can open it this capillary will not really help and will not be good because it will start mixing and it will be kind of bad for the organism because its getting a lot of deoxygenated blood. But again lets not worry about this part for now, lets focus on these two. [28] So anyways now we will go to the last part of this lecture and this is how oxygen actually gets carried by the blood. After diffusion is finished so pretty much after we received oxygen into the blood it needs to be carried to the target cells and this is a very simplified model of how this happens in kind of in blood vessels so if you mention this will be oxygen molecules. So this will be alveoli. So this will be air phase, this will be liquid, blood and what is happening is you would have oxygen diffusing into the blood but its not the only thing that happens to oxygen. After its located in the blood, so essentially in the water it gets bound to the protein of hemoglobin and essentially the bulk of the oxygen carried in the blood is not carried as a diluted molecule but rather carried in the form when it is bound to the proteins. And this protein is called hemoglobin. [29] And the importance of this process can be illustrated here so where you will have, this kind of gives you the relative amount of oxygen which is transported by blood in dissolved ways. So this would be dissolved oxygen here and this is bound to hemoglobin and as you can appreciate, so its like essentially nearly 100% of oxygen is transported like. So this slide here corresponds to this event of oxygen bound to hemoglobin. And only a very little part is dissolved oxygen. And here is one very important concept is this oxygen dissociation curve. So one of the important things here is to remember the numbers. So this pretty much, the saturation of hemoglobin with oxygen is not linear its more somewhat sigmoidal. We wont talk about it but it kind of reflects the cooperative activity. Theres more than one oxygen molecule bound to hemoglobin so thats why it kind of has this shape because its cooperative. But for now dont worry about it but lets just look how this

Transcribed by Stephen Holt

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hemoglobin can bind and release oxygen. So this process is actually really tightly linked to the pressure of oxygen or in this terms we can talk about concentration but lets talk partial pressure. So pretty much its related really tightly to this and you can see 100 which is normal arterial pressure of oxygen. So when blood is completely oxygenized like pretty much all hemoglobin will be bound to oxygen. So it will be very efficient. So you kind of loaded your cargo here when you get a normal arterial oxygenation. And another key parameter is venous oxygen which is around 40 and this the end point where hemoglobin arrives back to be reoxygenated. And thats pretty much how oxygen gets released as it travels through the arteries and veins and through the organism and this is very important because it tells you how much oxygen can be released and used up by the organism. [30] And here are some illustrations why this graph is important and why its regulated. Heres some examples what would happen if you have different conditions. So for example this curve can be shifted to the left and to the right depending on the need of the body in the oxygen. So what happens here, as I mentioned the pressure of the mole is the same, it will be between 100 and 40 on each end of the system but what happens here like depending on conditions. Like Ph change, or temperature, or CO2 increase, what they will do is they will signal to the organism that it needs for example more oxygen. For example a drop of pH tells a lot of walking is going or more CO2 produced so we need more oxygen and what happens is the curve of hemoglobin will shift to the right. And so pretty much what you see is alveolar end and this is venous end. And so the same cycle of the pumping between 100 and 40 in normal conditions it will drop after 50% of oxygen but if you have the striped shift what will happen is through the cycle you get pretty much 50% more oxygen released and delivered to the cell. And this is very important concept and the opposite is true. So if you dont need more oxygen you can have this foot outside cycle so the hemoglobin just pass by the cells without releasing oxygen. And this is very important concept in terms of understanding how dynamically the supply and demand of oxygen can be regulated by this association and dissociation of this oxygen from hemoglobin. [31] And then another example of how this curve can be modulated is oxygen in blood and pathological conditions. And here just two types of events. So here you see the normal oxygen release through this curve. Between 100 and 40. So this is how much oxygen is being used up by the organism and its all fine. And then you would have 2 conditions: one is like CO poisoning and another is anemia and you can see there is pretty much in anemia you would have like just less blood cells so pretty much in this example half of the amount of hemoglobin compared to the normal conditions. So as you can see its not really kind of like for that particular case is not really that terrible because you can still get enough oxygen released. It just happens at the different level in terms of total hemoglobin but since you have this reserve in this case you would have still, if you drop oxygen concentration it will be released from hemoglobin. But its quite different for CO poisoning, what it does is it poisons,

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it takes off the binding sites for oxygen on the hemoglobin and it kind of changes the affinity of oxygen to hemoglobin and you can appreciate here that it will be much more problematic. So if you go from 100 to 40 you get this release here and this release in anemia but in the case of CO you only get this small point right, because the whole curve kind of shifts to the left. Because the affinity of oxygen to hemoglobin has changed so its kind of holds on to it more tightly. And you can see you get really small release of oxygen in the same normal condition. So to get back the oxygen you need to drop the concentration below any reasonable amount. And this is important problem which illustrates the danger of CO poisoning because actually you would not be able to et your oxygen out of the hemoglobin and it is a fairly dangerous process. [32] So this is pretty much the last, well prevent this slide and then take a break. So this is like the amount of carbon dioxide in blood in comparison to oxygen. And I guess I just wanted to illustrate here just one very simple concept that actually carbon dioxide changes much less compared to oxygen. So this is the difference in partial pressures of oxygen which is like 100 to 40 between arterious and venous ends and its much, much different for CO2 when you have the drop only of 5 mm Hg between arteriole and venous. And this is one of the interesting things about carbon dioxide is that it is very tightly regulated and in the next lecture Ill kind of illustrate why and because one of the things I should allow carbon dioxide is so stable because it is used by the respiratory system as an indicator of how well it functions so it kind of keeps it more or less stable so the things are kind of can respond if something abnormal happens and carbon dioxide is somehow compromised it could signal the system that it could change the metabolic rates and the rates of respiration. So lets maybe take 5 minute break and well talk some biochemistry on how its transported.