- Polycytemia vera is a very interesting
disorder that we can talk about here.
The name itself means that we have a lot or
a variety of cells in the bloodstream
and while we have a variety of cells that are overproduced
from the lesion or the defect I'm about to talk about
we mainly think of this as a red
blood cell disorder because the red blood cells are
what cause the majority of the signs and
symptoms we're about to talk about.
So to review, here's your femur and remember
the bone marrow is in the shaft of long bones,
this is what produces these pluripotent hematopoitic
stem cells, which are stem cells that can produce all of the
cells in our blood, and I think you remember there are two
lineages that come off of the pluripotent hematopoitic
stem cell.
There's the myeloid stem cell and there's also the
lymphoid stem cell we won't cover here, and the
myeloid stem cell can produce four different things.
I'm not going to talk about them in detail right now,
but we're going to discuss them in a minute, but
the main pathway I want to talk about for this
video is the one that will start off by producing
this proerythroblast right here and after several other
forms this will eventually become what we know and love
and the erythrocite or as we also call it a red
blood corpuscle, or a red blood cell, and
I think you know a lot of what happens through here.
The red blood cell goes to the lungs to get oxygenated,
it will take the oxygen then and deliver it to a bunch
of places around the body that can include the liver
in this example right here, so I want to write oxygen there.
And then become deoxygenated again, and I think you can see
this would be a cyclical path where you would just keep
pumping red blood cells into the circuit which would be
pretty bad over time, but we've got other organs that'll
help us regulate that.
Say this red blood cell gets deformed over time as it passes
through the body, at that point, when it flows through the
spleen instead of passing through the splenic
artery and coming out the splenic vein, it'll get
destroyed because it's a useless red blood cell now
if it's in this form and it doesn't pass through your
capillaries and other networks in your body very well.
So the spleen will destroy it, so that's how we get rid
of excess red blood cells we don't need.
Well what if we're living somewhere in Colorado,
really high up at a high altitude where there's a little
bit of oxygen and we need to have more red blood
cells floating around in our system.
Our kidneys help us do that, they detect the amount
of oxygen that's in the blood.
If it's not a lot of oxygen, they'll release a hormone
that's called erythropoietin that will tell the bone marrow
hey we need more red blood cells, let's pump out some more
of these stem cells and eventually make more
proerythroblasts and erythrocites, so those are the life
and times of a red blood cell, but what happens with
polycythemia vera is that you have a mutation right
here in a protein that's called a jak2 kinase, it's a
non-receptor tyrosine kinase that regulates cell division
of this myeloid stem cell, it's part of the machinery
that makes sure that we don't overproduce this stem cell.
But, with a mutation to the jak2 kinase, we get set in the
on mode all the time, which means we keep producing
proerythroblasts and we get a whole bunch
of these guys right here, which means we end up
getting a lot of red blood cells.
So much that we don't know what to do with and
they go everywhere in the body, and there are
certain signs and symptoms that we can look for
that are related to the presence of these red
blood cells in our body, as well as the other
cells that come from the myeloid stem cell lineage.
First, if we have a lot of red blood cells, a lot of them
will end up getting deformed and so the spleen will
have to do double duty, sometimes quadruple duty
and will get so much bigger to accommodate the
number of red blood cells that come its way,
that results in spleno, meaning the spleen,
splenomegaly, splenomegaly which just means
you have a huge spleen, or a mega-spleen.
And the same thing happens to the liver,
when this defect happens it's not just in the
bone marrow, that can also effect other parts
of the body that have the potential to make
hematopoitic stem cells.
The liver is one of the organs that does it
mostly when you're a little baby and a child
but it's supposed to stop that when you get
older, but the liver will be told to keep on producing
these cells causing it to become big as well and
causing you to have hepatomegaly, a mega liver.
Another issue that can arise is due to these
proerythroblasts right here, I'm drawing in
the nuclei just to emphasize that they are
nucleated initially when they're made,
but over time we lose the nucleus as we put out
red blood cells because the red blood cells don't
have nuclei.
Some of these proerythroblasts can make it out
into the blood stream and end up going to the spleen
where they would definitely be recognized as weird,
because they shouldn't be there, and they'll get
destroyed which will get these particles that come
from the nucleus to be extruded and dealt with,
but the problem is when a lot of these build up,
this can produce what's referred to as gout.
And you may have heard of gout before,
all it boils down to is a disorder where you
have an increased amount of uric acid
that gets deposited in your body which leads
to pain there and uric acid is just a metabolyte
of deoxyribonucleic acid, or DNA, and so increased
DNA breakdown will result in increased uric acid
being built up in the body.
Another issue you can have are what are called thrembotic
event, so thrembotic events are something that can be
picked up or discovered on a physical exam.
Thrembotic events, and I'll color it in purple to relate
back to the platelets because these are the culprits
here, thrembotic events are due to a blockage of vessels.
So, for example, this hepatic vein right here, that drains
blood from the liver and it's supposed to go to the
inferior vena cava, can get blocked off by a platelet
thrombus right there, and that can produce what's
called hepatic vein thrombosis, which is actually most
commonly caused by polycythemia vera.
If this happens in the eye you can also have retinal
vein thrombosis, which would be really bad, what do you
think could happen if a vein in your retina becomes blocked?
I think you guessed it, you could become blind in that eye.
Another issue you can have is what's called vessel
congestion, so vessel congestion, if you think
of congestion, in your nose, it gets really stuffy,
your vessels get stuffy as well.
If you imagine a face, I'll draw it right here, with some
eyes and a nose, what can end up happening is that you'd
have really, really rosy cheeks and kind of a full looking
face, kind of like what Santa Claus actually looks like.
And sometimes this will be described as a plethoric,
a plethoric, meaning a lot of, plethoric or a ruddy face,
but the really key sign or symptom that's often seen is due
to a cell I haven't talked about yet in the lineage, so
the myeloid stem cell produces all of these guys down
here in addition to something called a mast cell.
A mast cell, and this is the culprit
for most allergic reactions.
Mast cells contain granules that store something that's
referred to as histamine.
I think you've heard of histamine before.
It's the main chemical that's released in allergic
reactions, so in polycytemia vera, these mast cells
will release histamine to cause what's called pruritis,
or itchiness on bathing.
And the reason why this occurs, high temperature or
increased temperature from hot water showers cause
degranulation of these mast cells.
So how do we get to the bottom of things?
How do we diagnose whether a patient has
polycytemia vera or something else?
Well one of the first tests you can do is to check
to see whether they have the jak2 kinase mutation,
because this mutation is present in all types of
myeloproliferative disorders that we've talked about
previously, and combined with the signs and symptoms
we've talked about here, that'd be a slam dunk diagnosis.
Other things you can do is order blood labs, like a
hematocrit, which should be elevated if you've got
polycytemia vera, the hematocrit will tell you roughly
how many red blood cells you've got in your body.
Additionally, you'll see things like increased basaphils
so one of these other things that can be produced from
the myeloid stem cell.
In polycytemia vera, basophils aren't that common in
the bloodstream, so if they're increased that's very
suggestive of polycytemia vera.
And the same thing goes with neutrophils and platelets.
And as a last resort, what we could do, is get a bone marrow
aspirate, or a sample from the bone marrow to see if
we are producing a bunch of extra cells that would be
indicative of polycytemia vera.
So how would we treat this?
Well, as I mentioned, the red blood cells are the main
problem in polycytemia vera because there's so many
of them causing vessel congestion, so the first thing
you'd want to try and do is what's called phlebotomy.
Maybe you've heard of a phlebotomist before.
It's the person that draws blood for labs.
So phlebotomy would be to blood let or release
some blood from your body to make sure it's
not so congested.
If that doesn't work, the next thing you can do
is add on a drug that's called hydroxyurea and
the reason why I'm coloring it the same as gout
is because this will decrease the amount of uric
acid that's made by preventing proerythroblast
production and it does so by interfering with the
machinery that's supposed to produce your
deoxyribonucleotides, the DNA.
And now if that doesn't work the next thing
that we can do is give a drug that's called
interferon alpha, which does sort of the
opposite actually.
This will increase the destruction of proerythroblasts
which could, unfortunately, cause symptoms of
gout because of breaking down all of these nuclei
in addition, but thankfully this is sort of a final measure
or the last line thing that we'd want to do for
polycytemia vera.