Transcription
Hello. In this video, we're going to talk about hemochromatosis. Hemo means blood, chromate means color, and osis means disease. So, it's essentially a condition that causes changing of color in the blood, but not only the blood, also the tissues and organs of your body.
Hemochromatosis is essentially when you have too much iron in your body. You have iron overload, and there are many causes. You can have primary, which is the hereditary hemochromatosis, or secondary hemochromatosis.
The normal iron content of the body is about three to four grams. It exists in four main forms. The first is iron is found as storage in the forms of ferritin or hemosiderin. Here you can see it's in a ferric iron state, and this is how I'm going to depict it. And you can also find iron bound to transferrin, which is the transportation of iron in the plasma. Finally, you can also find iron in hemoglobin, which is where the majority of it is found, and hemoglobin is important because it carries the oxygen around our body. Iron can also be found in other proteins and enzymes within the body.
We get iron from certain foods and vegetables, and you know, when we eat, it goes into our stomach, and it actually gets absorbed in the area of the small intestine called the duodenum. Here, iron is absorbed via a transporter on the apical surface of the enterocytes called DMT-1. From here, iron can either be stored as ferritin again, or it can be re- it can be absorbed into circulation via ferroportin, the orange transporter here, a very important transporter.
Once iron is in the circulation, it is bound to the transporter called transferrin, and remember, transferrin is the transporter that carries iron all around the body. From here, iron can be brought into the bone marrow where we make more red blood cells. So, iron stimulates erythropoiesis, and from here, you get new red blood cells until eventually, about 120 days or so, the red blood cells die, and they get essentially destroyed by the reticuloendothelial system, and essentially a recycling process happens. The iron is once again released into circulation and bound to transferrin. It's really important to know that, you know, the majority of the iron really that we that we take in gets put into erythropoiesis because we need more red blood cells.
The remainder goes into other tissues and organs, but mainly so the liver. Here, the liver can also store iron as ferritin. The liver also produces this important protein called hepsidine. You can think of hepsidine as the main regulator of iron metabolism, as well as iron absorption and regulation. Essentially, hepsidine, hepsidine's goal is to lower serum iron. Hepatin gets stimulated or released when there's a lot of iron in storage. Secondly, inflammation can also promote the release of hepatin as well. Hepatitis goal is to lower serum iron, and it does this through a number of ways, but the most important way is that it inhibits ferroportin. So, it essentially promotes the destruction of ferropotent, both in the enterocytes, as well as in the liver, as well as in the red blood cells, and so it inhibits the release of iron into circulation, thus lowering serum iron levels.
Now, I would like to talk about the different causes of iron overload or hemochromatosis. Firstly, you know, when someone eats too much iron, this can cause iron overload, but you'd have to eat a lot for it to cause any significant complications. Secondly, you can have mutations in certain transporters such as ferroportin, and when you have mutation ferriportin, what happens is is that you can have excess ferroportin, and when you have excess ferropotent, all this iron can get into circulation.
Another cause of hereditary hemochromatosis is one affecting a gene called the HFE gene, found on chromosome 6. The genes affected include specifically mutations in the C282Y or the H63D, and this is the hereditary hemochromatosis. As we know, the exact mechanism of how it causes hemochromatosis is not well known, but it's known that it also reduces hepatin, and because hepsidine is reduced, it means that there is no inhibition of ferroportin, so you have ferroportin activated, releasing all this iron into circulation, causing iron overload.
Other causes of hemochromatosis include any sort of liver disease, chronic liver disease, be it from alcohol, non-alcoholic fatty liver disease. These cause, for whatever reason, which is incompletely understood, it also reduces hepatitis, and again, reduction hepatitis means that you cannot inhibit or stop ferropotent from working.
Another cause of hemochromatosis, which is secondary hemochromatosis, include blood disorders such as thalassemia major, or intermedia, as well as sideroblastic anemia. Essentially, what happens here is that when you have this anemia, it obviously tries to stimulate proper erythropoiesis, but essentially, what you get is ineffective erythropoiesis, which leads to suppression of hepatin.
Another cause of iron overload include transfusional overload. What I mean by this is that it's, you know, it's either iron transfusions for a person or red blood cell transfusions, such as for those who have thalassemia or myelodysplastic syndrome or aplastic anemia. And when you give someone red blood cells, they also contain iron, and because they contain iron, you can cause secondary iron overload.
So, we looked at the different causes of iron overload. Now, when you have so much iron in circulation, the plasma iron binding protein, the transporter called transferrin, becomes saturated. And when this happens, iron begins binding to other things such as albumin, citrate, acetate, and this iron is referred to as non-transferrin bound iron. And when this happens, cells will take up this non-transparent bound iron into the liver, for example, the heart, the pituitary glands, the joints, the pancreas, as well as the gonads. And here, they undergo biochemical reactions which creates reactive oxygen species, which in turn causes tissue damage, inflammation, and fibrosis.
So, for example, in the liver, it can cause cirrhosis. As well, it increases the risk of hepatocellular carcinoma. In the heart, it can cause restrictive or dilated cardiomyopathy, as well as arrhythmia. In the joints, it causes arthritis. In the pituitary glands, when you have iron depositing here, it can cause secondary hypothyroidism or secondary hypogonadism. In the pancreas, the deposition of iron can cause diabetes mellitus. In the gonads, it can, obviously, it can cause testicular atrophy, amongst many other things.
Further, one of the most earliest signs of hemochromatosis is bronzing of the skin or pigmentation of the skin due to increase in melanin deposition, as well as iron. And I want to highlight three main things here, and I want you to remember that the triad of cirrhosis, diabetes, and skin pigmentation should remind you of hemochromatosis.
The diagnosis of iron overload or hemochromatosis include one, when you have elevation of serum plasma ferritin. Two, when you have evidence of iron overload in the MRI of the liver and or the heart. For example, something not commonly used now is evidence of iron overload on tissue biopsy, and this requires iron staining. You can also diagnose it when you remove iron with a course of therapeutic phlebotomy, and this will result in normalization of the ferritin levels.
In terms of treatment of hemochromatosis, the major treatments for iron overload is phlebotomy, essentially removing the blood because when you remove blood, you're taking iron with it. However, if someone already has anemia, which is low red blood cells, you wouldn't want to take out more blood, and so an alternative is using iron chelating agents, which also reduces serum iron levels.
Thank you for watching. I hope you enjoyed this video.