What is polycythemia vera?

- 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.