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Course: Health and medicine > Unit 6
Lesson 8: Myeloproliferative disordersWhat is polycythemia vera?
Learn to recognize the symptoms of polycythemia vera as well as how to diagnosis and treat it. By Raja Narayan. Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT related content. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video. Created by Raja Narayan.
Want to join the conversation?
- blood was generated from bone marrow for any bone in the body?(1 vote)
- https://en.m.wikipedia.org/wiki/Bone_marrow
All of a baby's bones contain red marrow that actively makes red blood cells. As we age , some of that marrow becomes yellow or fat containing marrow and stops making blood cells. In the adult, the ends of the femur, humerus, flat bones including the ribs, cranium, sternum, pelvis, etc. continue to contain red marrow.(3 votes)
- We discussed this condition in class, and our instructor mentioned that one of the effects is an increase in bleeding (i.e. epistaxis, bleeding gums)... But this seems counterintuitive considering the blood becomes thick and sluggish. Can someone please explain this?(1 vote)
- Thanks for this question, it is an interesting one.
If you follow the Merck manual link you will see they clearly list thrombosis and bleeding under the heading of 'Complications'. As you know the increased number of red blood cells increases the chances of clotting or thrombosis. However, the bleeding is actually due to a simultaneous increase of platelets. The high number of platelets reduces the amount of a clotting factor available called von Willabrandt' s factor ,vwf. The platelets break down or lyse the vwf. Without a normal amount of this clotting factor, bleeding occurs. So, the different symptoms relate to the different cells that are created by this out of control stem cell. Typically, there is a high number of red blood cells,but an additional high number of platelets, or mast cells will cause additional symptoms such as bleeding and itching respectively. A very complicated problem! Thanks again.
https://www.merckmanuals.com/professional/hematology-and-oncology/myeloproliferative-disorders/polycythemia-vera
https://en.m.wikipedia.org/wiki/Polycythemia_vera(2 votes)
- Why can the myeloid stem only produce four things?(1 vote)
- There are aren't a lot of types of myeloid cells so the hematopoietic stem cell doesn't produce more than 4 types of cells. But, it does produce many versions of each cell.(2 votes)
- Does everyone have them? Or do only people with allergies have them?(1 vote)
- So even though the defect is before the myeloid line, not just the proerythroblast line, and you do get increases in basophil, eosinophil, monocyte and platelet counts, the chief manifestation is almost always due to polycythaemia?(1 vote)
- How do red blood cells lose their nuclei?(1 vote)
- They eject their nucleus during development.(1 vote)
- I was diagnosed with this at age 56. Why did it take so long to develop if I had this gene mutation since birth?(1 vote)
- Some diseases just take longer to develop than others. Polycythemia Vera in particular is often diagnosed in people 60 or older. This is because it takes so long to develop; it is just the way it progresses.(1 vote)
- didn't understand why the liv become big?(1 vote)
- Because the liver is a heamopoetic organ, so when stimulated (such is the case) its hematopoetic mass increases and so does himself(1 vote)
- EPO, will be increased or decreased in PV?(1 vote)
- Decreased because JAK2 mutation starts RBC production without the EPO signals and the kidney is like "whoa, we dont need anymore RBC!" thus reducing EPO to try to decrease production. (unless it is secondary Polycythemia, which is due to hypoxia, then it is increased)(1 vote)
Video transcript
- 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.