Transcription
Hey guys, what's up? So we are talking about anemia. So please go ahead and watch previous videos in the playlist first. Today we'll talk about iron studies. But first, to understand iron studies, we need to understand iron absorption. By iron studies, I mean things like serum iron, TIBC, ferritin. First, iron saturation. Iron studies is one of the most confusing topics. I'd like to make it easy. You have to know that, except for epithelial shedding and menstruation, the body has no method to get rid of iron. Okay, so iron absorption is heavily regulated.
Now let's get to the nitty-gritty: iron absorption. This is heavy stuff. I'll do my best to make it simple, but let's get the short story first. Iron has two sources: either you eat it in your diet, or you destroy your elderly or senescent RBCs. RBCs, hemoglobin, heme, and globin. Heme has iron and protoporphyrin. So heme has iron, but for now, let's talk about the one we get in our diet. Iron in the stomach—that's a big deal. Let's zoom in. In the stomach, we have hydrochloric acid that will transform iron from the ferric to the ferrous. Okay, to ferrous instead of ferric, thanks to hydrochloric acid and also vitamin C. Okay, so we end up with the ferrous iron. That's fine. So what will happen to this ferrous iron? It will go into the duodenum, pass through the enterocytes—the cells that line the duodenum from inside—to the bloodstream. And in the bloodstream, it will bind to transferrin, the carrier protein for iron. That's the short story. There is a very long story that we'll discuss now. But first, I'd like you to know something: there are two types of iron. The ferrous, 2+, is called the heme iron. The ferric, 3+, is the non-heme iron. Remember when we have talked about that red blood cells? They have hemoglobin, and the hemoglobin carries what? Oxygen. This hemoglobin, hemoglobin has iron, Fe 2+. This is the ferrous. Okay. There is a mnemonic to remember that: Fe2 carries O2. Fe2 carries O2. The ferrous state, the heme in the hemoglobin carries the oxygen. Fe2 carries O2. And we have said that in the small bowel, the duodenum, which one is absorbed to the small bowel? It's the ferrous, Fe2. There is a mnemonic for that: Fe2 goes into the enterocyte. So, mnemonic number one: Fe2 binds O2, and mnemonic number two: Fe2 goes into the duodenum to get absorbed. This is so cool.
Now let's focus on the duodenum, then we'll focus on the blood vessel, then we'll see the fate of iron on the transferrin. Now let's talk about the enterocytes. So we have the ferrous. Only the Fe2 can go into the duodenum, the enterocyte. So iron, the ferrous state, can go inside the enterocyte by two channels: either the heme carrier protein 1 or the divalent metal transporter 1, or DMT1. Okay. No matter which channel, the fate is kind of the same. The iron, the ferrous, can choose to get stored as mucosal ferritin in the cytoplasm of the enterocyte and then get shed, okay, with that normal epithelial regenerative shedding. Okay, to stool, iron will be lost to stool, and this method. Okay. By the way, that's why cancer of the small bowel is rare because unconsciously regenerating them, the cells will not be staying still for a long time. So there is less risk of mutation because when the cell stays for a long time, there is increased risk of mutation. But that's a completely different subject. Let's go back to iron. So, first method: to be stored as mucosal ferritin and get shed in the stool. The other method is to go through the door—the porta. Porta means door. Ferro-iron porta, door. I and protein. The protein that acts as a door for iron: ferroportin. This ferrous gets outside of the enterocyte, gets converted to the ferric by some compounds. Okay, then we have ended up with the ferric. The ferric will go in the blood vessel. Okay, and iron cannot be left free; it's dangerous. Why? The Fenton reaction. The Fenton reaction. So it has to be bound to something. What's that? A plasma protein called transferrin. In means protein, fer iron, transport, transportation—a protein for transportation of iron. That makes sense. This ferric on the transferrin has to face either to go to the bone marrow to the erythroid precursors to help form new RBCs, as we have said before in our video about hematopoiesis, or it can go to the liver as ferric, stimulate a protein called hepcidin. This is a regulator, an inhibitor. When it senses that there is a lot of iron coming in, so let's decrease the absorption of iron. Hepcidin is a regulator, an inhibitor, and it does that by two mechanisms: either to go to the door, the ferroportin, till this gate to shut closed—"Please, I don't want more iron"—or go to the macrophage that's storing iron—"Until please, macrophage, dear macrophage, do not release iron." That's so cool.
So, in brief, what's happening here? I have iron in which state? The ferrous state. And this iron in the ferrous state will go inside the enterocytes by two channels. When it comes in, it has two options: either to be stored at mucosal ferritin, get shed in the stool, or go through the door called ferroportin. When it goes to the ferroportin, get converted to the ferric, bound to transferrin, and then goes either to the bone marrow or to precursors for new RBCs, hematopoiesis, or go to the liver, stimulate the hepcidin, which will inhibit further absorption of iron, either by shutting the door or inhibiting the macrophage from releasing iron. That is cool. But what is the Fenton reaction? The Fenton reaction: chemistry. When iron is left free, it's dangerous. It generates free radicals, which damages tissue. So the mnemonic is: if Fe is left free, by the Fenton reaction, gives this hydroxyl free radical. It's called the Fenton reaction, and the hydroxyl free radicals are freakin' bad. I call this the F mnemonic.
Let's focus more about the hepcidin and the regulation of iron absorption. So we have said that when we have a lot of iron coming in on the transferrin, hepcidin gets stimulated and up-regulated—i.e., the level for more hepcidin to stop iron absorption in the duodenum and to stop iron release from the macrophage. That makes sense. Okay. The opposite is also true: when iron in the transferrin is less, hepcidin is down-regulated—less hepcidin forms, so there is increased iron absorption, increased iron release because there is no inhibitor. I'm afraid to absorb and release more iron to the iron serum. Increase in the serum iron increases. That's it. We have said before that iron, okay, gets absorbed where? In the duodenum, enterocyte. It has a sensor. Sensor, why? Because the absorption of new iron depends on the total previous iron storage in the body. It's heavily regulated. It has a sensor to sense the transferrin carrying iron. The HFE gene helps this enterocyte get activated and absorb iron in the ferrous state. Remember when hepcidin prevents more iron from getting absorbed? There is only one way for iron to get shed with the enterocyte in the stool because iron, remember, as we said, has two fates: either to go at mucosal ferritin or to go up through the ferroportin and stimulate hepcidin. If hepcidin shut the gate, I have only one option: to be stored at ferritin and get [ __ ] in the stool. That's it. For our next time, we'll get some details about the iron studies. But for now, you have to subscribe to get new videos as they come. Thank you very much for your support, and see you in the next video.