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So here's a picture of mom and a little fetus

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and at this point when the fetus is still attached by

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the umbilical cord everything that goes into the fetus

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is really originating from mom. She controls all

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the nutrients and all the oxygen that goes into that baby.

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And with oxygen in mind, there are a couple of interesting ways that the baby, in this case this little

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fetus on the right, has come up with to be able to get as much oxygen as possible from mom.

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because remember the fetus is trying to grow and it wants to make sure that all of it's tissues that are

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growing and developing have enough oxygen. So there are a couple of tricks.

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And the first trick, let me actually just draw it out for you, is simply looking at a single vial of blood.

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If we look at a single vial of blood from mom, and compare it to a vial of blood from baby.

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So let me try to draw the vials about the same height and width.

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These are the two vials. If I was to take now, let's say a little bit of mom's blood and spin it down, let's say in this little tube.

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And then do the exact same thing with the baby's blood, take some of baby's blood and spin it down.

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That spun blood, once it's spun down, would actually separate out into little parts, right?

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You'd have three different layers.

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And this first layer would be something like this. This is called the plasma.

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The next layer right below it, remember there's a little layer of white blood cells and platelets.

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And below that, right here, is a layer of red blood cells.

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Remember red blood cells are the ones that contain the hemoglobin.

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They're the ones that are going to move oxygen around.

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And in mom, the percent that this red layer takes up is about 35%.

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Meaning this whole thing would be 100%, and of that just over 1/3, or 35% exactly, is that bottom red layer.

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That's the red blood cell layer.

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So we would call this the hematocrit.

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So this is mom's hematocrit. And this is a very typical number for a pregnant woman.

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It varies depending on whether you're a man or a woman, and what age you are.

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But for a pregnant woman, 35% is a pretty reasonable number.

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Now going over here to the baby side.

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Let's draw in what baby's blood probably looks like.

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The baby has a lot less of the blood taken up by plasma

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so that layer is going to be smaller. And then the next layer, the white blood cell layer,

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that's a very small layer anyway so that's not going to change much.

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And the final layer, the third layer, is the red blood cell layer.

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This layer takes up about 55%.

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So I hope I didn't misdraw that, but that's about 55%.

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So here the hematocrit is much higher, and what does that mean?

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If the hematocrit is higher in the baby, about 55% percent, then that means that the baby actually has

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more red blood cells going around, in a given amount of volume of blood, and those red blood cells

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can then take up more oxygen because that's really the part of blood we care about when it comes

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to moving oxygen around.

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So that's one trick, in terms of tricks, for getting more oxygen.

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Simply having more of the red blood cells in a given volume of blood. Kind of the amount of red blood cells is going to go up in the fetus

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and that's kind of one trick. When I say trick that's what I mean.

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So what's another trick, or strategy, that the baby or the fetus can come up with

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to get more oxygen from mom?

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Well if we think of the amount, you can also think of the type.

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And what I mean by that is: thinking specifically about the type of hemoglobin.

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So we know that the adult hemoglobin has four units to it.

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So let me draw out the adult hemoglobin over here on the left.

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Let me first write out adult hemoglobin.

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So "Hb" for hemoglobin and "A" for adult.

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I'll write adult here so we keep track of which is which.

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And there isn't one type of adult hemoglobin. There is a main one, which is the one I am going to draw.

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But there're few different types of little (...)

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The main one, as I said, is this one,

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has a couple of alpha units, this is just a protein peptide,

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that is in some conformation we call it alpha,

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and a couple of beta units,

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and these are slightly different looking than the alpha ones

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and there's a 2 to 2 ratio, so which hemoglobin has four units

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and here you can see that you have two of each type.

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Now, on the fetus side you actually have something a little different

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so we also have over here hemoglobin, Hb,

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this time F, for fetus,

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and just as before the fetus has a few different type of hemoglobin,

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but the main one is HbF, and it's actually this one also shares that alpha units

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and has two of them just as before,

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but instead of beta unit, this one has what we call it gamma unit,

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this is the Greek letter for gamma,

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now oxygen is gonna bind and both of hemoglobin,

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both the adult and the fetus, can bind four oxygens,

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let me just draw in four oxygens here, you got the idea.

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now inside of red blood cells there's a little molecule and

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actually I just gonna sketch it out for you,

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this molecule has three carbons, let me just number the carbon one two three,

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and coming off of the two carbon, this one right here,

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is an oxygen, and coming off of that oxygen is a phosphate.

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Remember that phosphate has typically five bonds,

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so I just gonna show you what this little molecule looks like,

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in fact, the exact same thing is happening of the three carbons.

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so this molecule that exist inside of the red blood cells, it looks like this,

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has a couple of phosphates, and coming off this number one is something like this,

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so this is the little molecule, and it's called --

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and you can --maybe when you can take a stab and try to guess what it's called--

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it's called 2,3 --I'm reffering to this 2 and this 3--

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Di --because it got two phospho--

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so, Di-phospho- glyceride.

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so that's Di-phospho, and then glyceride just refers to this part right here,

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this is kind of the part that is being refered to when we say gyceride,

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so Diphosphoglyceride.

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and 2,3-diphosphoglyceride, we just fix that,

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is actually sometimes shortened down to 2,3-DPG

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'cause people don't like to say the whole thing,

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so they'll say 2,3-DPG, and that's what this molecule is.

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so this molecule 2,3-DPG, is inside red blood cells,

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and it actually helps the red blood cell get rid of oxygen,

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the way it does that is, actually is a tiny little molecule I'll draw it.

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now that you know what the whole sturcture looks like, I'll draw --it's a yellow dot,

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this is the same thing, I just make the equal sign, the equal of same thing,

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This little molecule will go and bind in the middle here,

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and it likes to bind to the beta subunits,

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actually the beta subunits are shaped so that this thing can bind very easily.

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and it nit, it sits kind of nicely between all four subunits, the betas and the alphas,

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and what it does is that actually makes the conformation or

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'the shape of the molecular' change, so these little oxygens want to move off.

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So basically what it does is that it makes it easier for the oxygen to be released from the hemoglobin.

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Now when this molecule comes around this side, on the fetus side it tries to bond,

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guess what happens, well this gamma subunits basically say, go away! go away!

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They don't want to bind to this 2,3-DPG.

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They don't have the right shape for it.

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And so they basically want this little molecule to get lost.

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And so this molecule doesn't bind as easily to hemoglobin F.

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and this result those molecules of hemoglobin don't get rid of oxygen

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nearly as easily as hemoglobin A does.

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Now why would we even have a molecule like 2,3-DPG around?

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What it would be doing there?

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well, interestingly, the level of 2,3-DPG actually go up

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in situations where you actually have more niver oxygen,

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so let's say chronically you're without oxygen.

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So the situation like that be, when you're chronically without oxygen.

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Well, let's say you live --I don't know what the-- the top of the Himalayan Mountains.

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And you know, the altitude is so high, if you got a high alitude,

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that the air itself doesn't have a lot of oxygen in it.

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and that situation your tissues are kind of always, or chronically, without oxygen.

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Now another situation could be, let's say you have lung disease.

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Let's say you have lung problem or lung disease, and it's a chronic lung disease,

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where you're always having difficulty, you know, getting oxygen to the blood.

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Well again, the tissues are really lacking of the oxygen,

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so there the red blood cells would make a lot of the 2,3-DPG.

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Or a final situation, maybe you're anemic,

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maybe you don't have a lot of red blood cells circulating around the body,

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and for anemic, the tissues are not getting as much oxygen

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as they wish they would.

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And again, in this situation you might have more 2,3-DPG.

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So 2,3-DPG, its basic job is to try-- to make sure that oxygen is left off of the hemoglobin,

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so that if you have tissue that really needs that oxygen,

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it's more easy to-- to actually deliver the oxygen to that tissue.

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So, going back to the trick for the fetus,

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you can see the fetus has different type of hemoglobin from the adult.

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So, let me draw a little curve and you'll see what this different incept doing.

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so let me sketch out a curve.

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let's just draw out a little graph here.

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this'll be the partial pressure of oxygen on this axis,

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and this'll be O2 or oxygen saturation,

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looking at how many of those spots on hemoglobin are taken up.

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so this'll be going up that way.

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let's start out with mom's hemoglobin, or adult hemoglobin,

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you know, has kind of S-shape, because of the cooperativity

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that we've talked about at the past.

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so this'll be hemoglobin adult type, or hemoglobin A.

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now, if I have, let's say, really high level of 2,3-DPG,

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let me just draw out what that would look like,

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so let's say we have a situation where that high level of 2,3-DPG,

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and it could be because of one these reasons,

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maybe live on a high mountain, or you've chronic lung disease,

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or you're always anemic, if you had one of these situations,

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and your 2,3-DPG level were really high, or higher than usual,

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then what will happen to your curve, it was actually--

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it would look like this, the curve for oxygen binding or oxygen saturation

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basically kind of shifts over to the right.

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So we call this a right shift, because the whole thing looks like it has just kind of moved over a little bit.

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And now, at any point --let's say I just choose a random point over here,

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and I choose the same point here.

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So this is the same partial pressure of oxygen, right?

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which is somewhere down here.

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Now for the same partial pressure of oxygen, my curve actually went down,

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meaning I have less oxygen bound to hemoglobin in the presence of molecule.

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and that makes sense with what we just said, because the molecule helps kick off the oxygen.

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Now what if you had an opposite situation,

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what if I actually drew out a curve like this,

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and this could be --let's say, a situation where you have a low levels of 2,3-DPG.

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Well, with low level of 2,3-DPG, you can see that this would make sense

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because now of all sudden, that molecules are not around, it's not doing anything

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to help get the oxygen off, so of course oxygen is gonna stay down to hemoglobin,

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and at the same partial pressure of oxygen, more of the hemoglobin would be bound by oxygen.

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Now, think back to the idea of fetal hemoglobin,

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remember, fetal hemoglobin we said has this gamma unit,

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and the gamma doesn't like 2,3-DPG, it doesn't like to bind to it,

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and so it says, get lost! go away!

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and so in a sense the way I drawn it for a low level of 2,3-DPG,

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I could --just this --well, erase that,

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and say, well, this is the situation in the fetus.

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The fetal hemoglobin is basically this curve, right?

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This is kind of the hemoglobin F curve.

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If you just look at the curve, it looks like it's left-shifted.

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But the-- but the real concept behind it,

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it's that it's because those hemoglobin molecules don't like to bind to 2,3-DPG,

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and so of course it's gonna go in the opposite direction of the blue curve.

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So looking at these two curves now, the white one and the red one,

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the white one represents mom, the red one represents baby,

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and the white one, if you wanna look at the point where about half of the

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hemoglobin molecules are bound to oxygen, that might be right about there,

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meaning this is about half way up to here,

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this is actually 50% of the way there.

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So 50% of the hemoglobin molecules are bound to oxygen,

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when the pressure of oxygen --the partial pressure of oxygen--

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is about 27. And for the fetus, the same kind of point of reaching half way saturation

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is reached when the partial pressure is about 20.

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So it's interesting for a lower partial pressure of oxygen,

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the baby or the fetus is able to accomplish the same thing we adult can accomplish

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at only higher amount of oxygen in the environment or in the blood.

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And this values are called p50, so if you see p50

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--if you see that term, you can remember now that the hemoglobin F p50

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is lower than the hemoglobin A p50.

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and that is --again, the actual number is 20 versus 27, or there about.

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so these are the two tricks than one, is the-- you know, the amount of hemoglobin

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or red blood cells in the fetus,

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and the other is the type and hemoglobin F binds oxygen much more tightly and has a lower p50

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~o0o~