Main content
Health and medicine
Course: Health and medicine > Unit 2
Lesson 11: Fetal circulation- Meet the placenta!
- Umbilical vessels and the ductus venosus
- Hypoxic pulmonary vasoconstriction
- Foramen ovale and ductus arteriosus
- Fetal hemoglobin and hematocrit
- Double Bohr effect
- Fetal circulation right before birth
- Baby circulation right after birth
- Fetal structures in an adult
© 2023 Khan AcademyTerms of usePrivacy PolicyCookie Notice
Fetal hemoglobin and hematocrit
Although mom controls the oxygen source, the fetus has a couple of clever tricks to get the most oxygen possible! Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
Want to join the conversation?
- Does the plasma expansion (and resultant decreased Hb concentration) during pregnancy result in a kind of moderate anemia, encouraging the HbA to bind more BPG and thus decrease O2-affinity? This would also increase the relative difference in O2-affinity between HbA and HbF, helping the fetus pick up more O2. This sequence of events makes sense, but I'm not sure if the effect is significant.(29 votes)
- Yes, it is significant :) Many women experience anemia while pregnant (in fact many doctors prophylactically prescribe iron to pregnant women). DPG levels begin to rise early in pregnancy and this results in a gradual shift to the right in the maternal oxygen- hemoglobin dissociation curve and therefore an increase in the amount of O2 unloaded in the peripheral tissues (including the intervillous space- facilitating 02 transfer from mother to fetus)(12 votes)
- I feel there is a contradiction in that both the mountain dweller and fetus need more oxygen delivered to their tissues, but one has more 23DPG and one has less than the normal adult. It was explained that lower 23DPG allows for better oxygenated tissues because then oxygen binds more tightly to Hb, and that higher 23DGP allows for better oxygenated tissues because then oxygen more readily enters tissues. It seems that one of these correlations would have to be false. What am I not understanding?(22 votes)
- If adults had HbF then the mother would not produce such high levels of 2,3-DPG. The whole goal of the mother producing so much 2,3-DPG is to cause her HbA to release more oxygen, therefore, the fetus can uptake as much oxygen as possible. If the fetus had beta chains instead of gamma chains, giving it HbA, it would then be releasing oxygen just as much as the mother but the fetus's goal is to hold onto as much oxygen as possible. So now if we grew older and still had HbF the oxygen in our blood would not be getting dispersed as easily as it should to our body tissues. So as we grow older and our HbF turns into HbA, when in low oxygen conditions our body makes more 2,3-DPG because it releases more oxygen to all the cells in our bodies.(9 votes)
- How long does it take an infant to transition to adult hematocrit levels and hemoglobin expression?(13 votes)
- The transition time from HbF to BhA varies- HbF synthesis slowly starts to decline in the third trimester and continues to decline reaching 2-3% HbF at around 6 months of age and adult levels before the age of 2 (most adults have <1%HbF, though those with blood disorders often have increased levels which may cause them have milder symptoms from their disease processes).
Hematocrit levels vary depending on age and after puberty, the sex of the individual. Levels decrease until around 2 years of age and then begin increasing again until adulthood.(9 votes)
- So the HbF O2 Saturation curve is left-shifted compared to HbA due to low levels of 2,3-DPG, meaning that there is a greater amount of oxygen binding to the fetal red blood cells at any given time. However, isn't the point of RBC saturation to deliver O2 to the tissues? In that case, wouldn't you want high levels of 2,3-DPG at some point in order to kick off O2 and deliver it it the tissue cells? Or does this un-binding of O2 for the actual delivery follow a different chemical process than just facilitation by 2,3-DPG?(10 votes)
- In an adult human if your tissues are not getting enough oxygen, you do want more 2,3 BPG, This will cause a right shift and the adult HbA will let off more of its oxygen in the tissues (which is the whole point).
In a pregnant mother, there is an even greater need for the oxygen to get to her tissues, because she needs to supply the baby's oxygen through the placenta. So the mother produces lots of 2,3 BPG so that her RBCs will unload oxygen into the placenta. Also, Fetal hemoglobin (HbF) is not sensitive to 2,3 BPG. So 2,3 BPG is lowering the affinity that HbA has for Oxygen, but not lowering the affinity that HbF has for oxygen. This allows for very efficient oxygen transfer at the placenta, to ensure the growing baby gets enough O2.(11 votes)
- Does this mean that both the mother and the baby will have the same blood type?(3 votes)
- No, the blood type will be decided in the baby by the combination of genes donated by the mother and father. This can mean mother and baby have the same one, but often is not the case. Luckily, the blood of the mother and baby does not come in direct contact in the womb.(13 votes)
- Since the fetal hemoglobin has more affinity for oxygen than the adult hemoglobin and is unresponsive to 2,3 DPG, how can HbF get rid of oxygen to supply it for the needing tissues?(6 votes)
- HbF's ability to garner O2 from maternal hemoglobin establishes favorable movement of O2 to fetal blood. It does not preclude the release of O2 to the low O2 fetal tissues. Remember, hemoglobin is a blood O2 buffer. As the PaO2 decreases in fetal tissues, HbF releases more O2 into the blood, which then allows it to diffuse into the tissues.(3 votes)
- How does foetal haemoglobin change to adult haemoglobin?
What factors act induce this change?(2 votes)- They have different sets of subunits. Fetal does not change to adult. Rather, in adults, more of the adult subunits are expressed at a genetic level and less of the fetal subunit it expressed.(5 votes)
- I have a question
1. In a fetal hemoglobin and hematocrit , you said that :when 2,3-DPG is lower, at p50 , HbF is lesss than HbA , but a graph showed 2 unit is partial pressure oxygen and O2 saturation. So partial pressure oxygen relates to hemoglobin ?
2. When a mom is anemic( or have a lung disease), how is the fetus suported enough oxygen for surviving ? I think if baby( fetus) only have 2 gamma chains in Hb not accepting 2,3-DPG is not enough condition for baby's life ?
3. When 2 gamma chains of hemoglobin( in fetal) convert to 2 Beta chains( in adult ) ( I mean the age of the baby when 2 gamma chains of Hb convert)(4 votes) - How can a mother and baby with different blood types still be healthy and not develop any immunologic responses? I read that it isn't a problem, obviously it isnt, but why isn't it?(2 votes)
- Actually, that can be a problem. It's called hemolytic disease of the newborn. It occurs when the mother is Rh- and the baby is Rh+. During the first pregnancy, its not a problem, but after the mother is sensitized, her body will attack the red blood cells of any baby she carries after. It's extremely uncommon these days because it can be prevented with an immunoglobulin injection (Rhogam) during and immediately after pregnancy, but it used to be devastating to some families.(4 votes)
- Isn't the purpose of Oxygen is to be spread in the issues anyway? So why in the normal person we don't have a lot of these 2,3 DPG?(1 vote)
- It turns out that we normal humans do have a fair amount of 2,3 BPG. Luckily for us, the body has formed amazing ways to interact between different chemical processes. 2,3 BPG is formed readily during glycolysis. As the cell needs more energy, glycolysis will convert sugars into free ATP molecules so more glycolysis makes more 2,3 BPG, indicating a need for energy and oxygen. Well, when more 2,3 BPG is available, the interaction with HbA will allow oxygen to be released at these tissues. This allows the tissue to move from glycolysis to cellular respiration and produce energy more efficiently for its work. 2,3 BPG would be considered both an allosteric inhibitor of HbA as well as a product of glycolysis. Fascinating stuff.(4 votes)
Video transcript
So here's a picture of
mom and a little fetus. And at this point,
when the fetus is still attached by the umbilical
cord, everything that goes into the fetus is
really originating from mom. She controls all the
nutrients and all the oxygen that goes into that baby. And with oxygen
in mind, there are a couple of interesting
ways that the baby, in this case, this little
fetus on the right, has come up with to be able to
get as much oxygen as possible from mom, because remember,
the fetus is trying to grow. And it wants to make
sure all of its tissues that are growing and
developing have enough oxygen. So there are a couple of tricks. And the first trick--
and let me actually just draw it out for you--
is simply looking at a single vial of blood. If we look at a single
vial of blood from mom and compare it to a vial
of blood from baby-- let me try to draw the
vials about the same height and width. 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, and then do the exact same
thing with the baby's blood, take some of baby's
blood and spin it down, that spun blood,
once it's spun down, would actually separate out
into little parts, right? You'd have three
different layers. And this first layer would
be something like this. This is called the plasma. The next layer, right
below it-- remember there's a little layer of white
blood cells and platelets. And below that, right here,
is a layer of red blood cells. And remember, red blood
cells are the ones that contain the hemoglobin. They're the ones that are
going to move oxygen around. And in mom, the percent this
red layer takes up is about 35%, meaning this whole
thing would be 100%. Let's say this entire
thing would be 100%. And of that, just over
one third, or 35% exactly, is that bottom red layer. That's the red blood cell layer. So we would call this
the hematocrit, right? So this is mom's hematocrit. And this is a very typical
number for a pregnant woman. It varies depending on
whether you're a man or woman and what age you are. But for a pregnant woman, 35%
is a pretty reasonable number. Now going over here
to the baby side, let's draw in what baby's
blood probably looks like. The baby has a lot less of
the blood taken up by plasma. So that layer is
going to be smaller. And then the next layer,
the white blood cell layer, that's a very
small layer anyway. So that's not going
to change much. And the final layer,
the third layer, is the red blood cell layer. This layer takes up about,
let's say about 55%. So I hope I didn't
kind of misdraw that, but that's about right. About 55%. So here, the hematocrit
is much higher. Now what does that mean
if the hematocrit is higher in the baby, about 55%? Then that means that
the baby actually has more red blood
cells going around in a given amount
of volume of blood. And those red blood cells
then can take up more oxygen. Because that's really
the part of blood that we care about when it
comes to moving oxygen around. So that's one trick in terms of
tricks for getting more oxygen. Simply having more of the
red blood cells in a given volume of blood is kind of
the amount of red blood cells is going to go up in the fetus. And that's kind of one trick. When I say trick,
that's what I mean. So what's another
trick or strategy-- I guess that's another word--
that the baby or the fetus can come up with to get
more oxygen from mom? Well, if we think of the amount,
you can also think of the type. And what I mean by that
is, thinking specifically about the type of hemoglobin. So we know that the
adult hemoglobin has four units to it. So let me draw the
adult hemoglobin over here on the left. Let me just first write
out adult hemoglobin. So Hb for hemoglobin
and A for adults. And I'll write
"Adult" over here just so we keep track
of which is which. And there isn't one type
of adult hemoglobin. There is a main one, which
is the one I'm going to draw. But there are few different
types that adults have. The main one, as I
said, is this one. It has a couple of alpha units. This is just a protein peptide
that is in some confirmation. We call it alpha. And a couple of beta units. And these are slightly different
looking than the alpha ones. And there's a 2 to 2 ratio. So each hemoglobin
has four units. And here you can see that
you have two of each type. Now on the fetus
side, you actually have something a
little different. So we also have over
here hemoglobin, Hb. This time F for fetus. And just as before, the fetus
has a few different types of hemoglobins, but
the main one is HbF. And actually, this one
also shares that alpha unit and has two of them
just as before. But instead of a
beta unit, this one has what we call a gamma unit. This is the Greek
letter for gamma. Now oxygen is going to bind
in both of the hemoglobins. Both the adult and the
fetus can bind four oxygens. Let me just draw in
four oxygens here. You get the idea. Now inside of red blood cells,
there's a little molecule. And I'm actually just going
to sketch it out for you. And this molecule
has three carbons. Let me just number
the carbons, 1, 2, 3. And coming off of the 2
carbon, this one right here, is an oxygen. And coming off of that
oxygen is a phosphate. Remember, phosphate has
typically five bonds. So I'm just going to show you
what this little molecule looks like. In fact, the exact same thing is
happening off the three carbon. So this molecule that exists
inside of red blood cells, it looks like this. It has a couple of phosphates. And coming off this number
1 is something like this. So this is a little molecule. And it's called, and you
maybe even take a stab at trying to guess
what it's called. It's called 2,3, referring
to this 2 and this 3. Di, because it's
got two phospho. So diphosphoglycerate. So that's diphospho. And then glycerate just refers
to this part right here. This is kind of the
part that is being referred to when
we say glycerate. So diphosphoglycerate. And 2,3 diphosphoglycerate--
let me just fix that-- is actually sometimes
shortened down to 2,3-DPG. Because people don't like
to say the whole thing. So they'll say 2,3-DPG. And that's what
this molecule is. So this molecule, 2,3-DPG,
is inside of red blood cells. And it actually helps the red
blood cell get rid of oxygen. And the way it does
that, it actually is a tiny little molecule. I'll draw it. Now that you know what the
whole structure looks like. I'll draw it as a yellow dot. This is the same thing. Let's just make the equal sign. They equal the same thing. This little molecule will go
and bind in the middle here. And it likes to bind
to the beta subunits. Actually, the beta
subunits are shaped so that this thing
can bind very easily. And it sits kind of
nicely between all four subunits, the betas
and the alphas. And when it does
that, it actually makes the confirmation, or
the shape of the molecule, change so that these little
oxygens want to move off. So basically what it does is it
makes it easier for the oxygen to be released from
the hemoglobin. Now when this
molecule comes over on this side, on the fetus
side, and tries to bond, guess what happens? Well, these gamma subunits
basically say, go away. Go away. They don't want to
bind to this 2,3-DPG. They don't have the
right shape for it. And so they basically want this
little molecule to get lost. And so this molecule doesn't
bind as easily to hemoglobin F. And as a result, those
molecules of hemoglobin don't get rid of
oxygen nearly as easily as the hemoglobin A does. Now why would we even have a
molecule like 2,3-DPG around? What would it be doing there? Well interestingly, the levels
of 2,3-DPG actually go up in situations where you actually
have more need for oxygen. So let's say chronically
you're without oxygen. So what would a
situation like that be where you're
chronically without oxygen? Well let's say you
live, I don't know, at the top of the
Himalayan mountains. And the altitude is so high--
you've got a high altitude-- that the air itself doesn't
have a lot of oxygen in it. In that situation, your
tissues are kind of always, or chronically, without oxygen. Now another situation
could be, let's say you have a lung disease. Let's say you have a lung
problem or a lung disease. And it's a chronic lung
disease where you're always having difficulty getting
oxygen to the blood. Well again, the tissues are
really lacking in oxygen. So there, the red blood
cells would make a lot of the 2,3-DPG. Or a final situation,
maybe you're anemic. Maybe you don't have a lot of
red blood cells circulating around the body. And if you're
anemic, the tissues are not getting as much oxygen
as they wish they would. And again, in this situation,
you might have more 2,3-DPG. So 2,3-DPG, its basic job is to
try to make sure that oxygen is let off of the hemoglobin so
that if you have tissue that really needs that oxygen, it's
more easy to actually deliver that oxygen to that tissue. So going back to the
tricks for the fetus, you can see the fetus has a
different type of hemoglobin from the adults. So let me draw out
a little curve. And you'll see what this
difference ends up doing. So let me sketch out a curve. Let's just draw out
a little graph here. This will be the
partial pressure of oxygen on this axis. And this will be O2,
or oxygen saturation, looking at how many of
those spots on hemoglobin are taken up. So this will be
going up that way. Now let's start out
with mom's hemoglobin, or adult hemoglobin. It has a kind of an S shape
because of the cooperativity that we've talked
about in the past. So this will be hemoglobin
adult type, or hemoglobin A. Now if I had, let's say
really high levels of 2,3-DPG, let me just draw out what
that would look like. So let's say we had a situation
where you had high levels of 2,3-DPG. And it could be because
of one of these reasons. Maybe you live on
a high mountain or you have chronic lung
disease or you're always anemic. If you had one of these
situations and your 2,3-DPG levels were really high,
or higher than usual, then what would happen to your
curve, it would look like this. The curve for oxygen binding,
or oxygen saturation, basically kind of shifts
over to the right. So we call this a right
shift, because the whole thing looks like it's just kind
of moved over a little bit. And now at any point--
let's say I just choose a random point here. And I choose the
same point here. So this is the same
partial pressure of oxygen, which is
somewhere down here. Now for the same partial
pressure of oxygen, my curve actually
went down, meaning I have less oxygen
bound to hemoglobin in the presence
of this molecule. And that makes sense
with what we just said, because the molecule
helps kick off the oxygen. Now what if you had
an opposite situation? What if I actually drew
out a curve like this? And this could be, let's say,
a situation where you have low levels of 2,3-DPG. Well, with low
levels of 2,3-DPG, you can see that this
would make sense. Because now all of sudden,
that molecule is not around. It's not doing anything to
help get the oxygen off. So of course oxygen is going
to stay bound to hemoglobin. And at the same partial
pressure of oxygen, more of the hemoglobin
will be bound by oxygen. Now think back to the
idea of fetal hemoglobin. Remember fetal hemoglobin,
we said, has this gamma unit. And the gamma
doesn't like 2,3-DPG. It doesn't like to bind to it. And so it says, get lost. Go away. And so in a sense, the way
I've drawn it for a low level of 2,3-DPG, I could just as
well erase that and say, well, this is the situation
in the fetus. The fetal hemoglobin is
basically this curve. So this is kind of the
hemoglobin F curve. If you just look
at the curve, it looks like it's left shifted. But the real concept behind
it is that it's because those hemoglobin molecules don't
like to bind 2,3-DPG, and so of course it's going to
go in the opposite direction of the blue curve. So looking at these two
curves now, the white one and the red one, the
white one represents mom. The red one represents baby. And the white one, if you
want to look at a point where about half of the
hemoglobin molecules are bound to oxygen, that
might be right about there, meaning this is about
halfway up to here. This is actually 50%
of the way there. So 50% of the
hemoglobin molecules are bound to oxygen when
the pressure of oxygen, the partial pressure
of oxygen, is about 27. And for the fetus,
this same kind of point of reaching
halfway saturation is reached when the partial
pressure is about 20. So it's interesting. For a lower partial pressure of
oxygen, the baby, or the fetus, is able to accomplish the same
thing the adult can accomplish at only a higher amount of
oxygen in the environment or in the blood. And these values are called p50. So if you see p50,
if you see that term, you can remember now
that the hemoglobin F p50 is lower than
the hemoglobin A p50. And that is, again,
the actual number is 20 versus 27 or thereabout. So these are the
two tricks, then. One is the amount of
hemoglobin, or red blood cells, in the fetus. And the other is the type. And hemoglobin F binds
oxygen much more tightly and has a lower p50.