 So, if we take somebody's blood, spin it down to separate red blood cells from plasma and then divide the overall amount that's red in the tube by the overall concentration of red blood cells in the mixture, we get this value called MCV mean cell volume, which gives us a rough idea of the average volume this person's red blood cells. If they have heaps of cells, but the cells individually are small, the overall concentration will go up, but the overall amount that's red, otherwise known as the hermitocrite, will go down, resulting in a lower MCV. Alternatively, if there aren't many RBCs, but the ones that are present are big, the overall concentration comes down, but the hermitocrite might stay relatively normal, resulting in an increased MCV. So in the hospital, we look for anemia by checking for low hemoglobin levels, hemoglobin abbreviated to HB here. MCV, on the other hand, gives us important information about what's actually caused their anemia. Let's consider if the MCV is low for a start. We have a normal red blood cell here, about 7 microns wide. The average volume of the red blood cells is low, will end up with micro-cytic red blood cells. Now, why would this be? So the volume of a normal RBC is mostly made up of hemoglobin. If an RBC is small, doesn't have enough hemoglobin, and in most cases, that's because we're lacking in a critical element required to produce hemoglobin, that's iron. So if we have not enough iron, we have not enough hemoglobin, we have small RBCs. Hemoglobin usually looks like this, four separate structures making up this overall protein, but there's a certain set of genetic diseases which can bump out one of those constituents, known as the thalassemias. There's a spectrum of severity when it comes to the thalassemia, but the universal quality that they share is some degree of hemoglobin synthesis dysfunction. If we've got that, we've got not enough hemoglobin per RBC, we've got small RBCs. When the body's in a state of chronic inflammation, the liver is forced to hold onto its iron stores that it would otherwise give up for red blood cell synthesis. So if we have Crohn's disease, or rheumatoid arthritis, we have this prevalent of inflammatory cytokines which cause a kind of iron deficiency anemia, and we call this anemia of chronic inflammation. You'll also hear the misnomer anemia of chronic disease, but that doesn't describe the problem as accurately. Okay, so if the MCV is high, the RBCs are called macrosidic. RBCs have had some fundamental problem with their synthesis of DNA. In a normal red blood cell precursor, DNA is replicated so that the cell can eventually split like this, but at the same time hemoglobin is constantly being produced, which is then shared between the two divided cells. But if the DNA synthesis process is interrupted in some way, the replication is slower, but the production of hemoglobin continues at the same rate. So much hemoglobin being produced, this cell gets swollen, packed out, and even when it finally divides, it's got too much hemoglobin. It ends up macrosidic, chock-a-block, not what we want. The spleen will see these massive RBCs as defective and will chop them out of the circulation and will end up with anemia. Two major players in the synthesis of DNA are B12 and folate, so if we have a deficiency in them, we'll end up with macrosidic anemia. You have to be very malnourished to get to that point though. If you have celiac disease, however, you're at much greater risk because celiac disease often primarily affects the distal ilium, this bit of the small intestine, and that's the point where B12 is absorbed from your food into your blood. If that part of the small intestine is diseased, you'll have reduced B12 uptake in your greater risk of this kind of anemia. This B12 absorption is actually mediated by a molecule that's produced in a stomach, which we call intrinsic factor. If you have a congenital deficiency in this hormone, you'll develop macrosidic anemia. Quite severely, in fact, for that reason this is historically called pernicious anemia. Something else that can mess with your folate levels is too much alcohol, and I've clearly drawn that out here as the MOG4 to be as clinking. Alright, and lastly, certain drugs can cause broken DNA synthesis. They're easy to remember because that's what these drugs are designed to do. Methatrexate is a chemo drug that partly inhibits DNA synthesis to stop the growth and division of rapidly dividing cells. AZT, the HIV drug that stars in the film Dallas Buyers Club, as well as other chemotherapy drugs, function to disrupt the synthesis of DNA throughout the body. So it's no surprise that they too can cause macrosidic anemia. If the MCV is normal but we still have anemia, then we have what we call normalcytic anemia. The most common cause of this is blood loss. So as a quick summary, we've covered three types of macrosidic anemia, which are all due to some kind of deficiency in hemoglobin. We have three types of macrosidic anemia, which are all due to defective DNA synthesis. And we've covered one type of normalcytic anemia, a direct result of losing blood. We'll cover the hemolytic anemius next, so keep an eye out for that. But for now, thanks for watching, hit subscribe, and we'll see you next time.