0:00 Armondo Hasirungan, Biology and Medicine videos, please make sure to subscribe, 0:05 join 0:05 the forum and group. 0:07 For the latest videos, please visit Facebook, Armondo Hasirungan. 0:13 In this video, we're going to look at iron physiology. 0:16 The iron is essential element metal that we need in our body to perform many 0:21 physiological 0:22 processes. 0:23 We get our iron by eating food. 0:26 Our daily dietary requirement of iron is between 10 to 20 milligrams. 0:32 So here I'm drawing iron as Fe3+, because Fe is the chemical symbol for iron, 0:39 elemental 0:40 symbol for iron. 0:41 Iron goes down the esophagus into the stomach and then will travel into the 0:45 small intestine 0:46 where it will be absorbed. 0:48 Before we continue on, we have to know that in our bodies we have two main 0:52 forms of iron. 0:53 We have the ferrous iron, Fe2+, and the oxidized iron, ferric iron, Fe3+. 1:02 Anyway, let's go back to the small intestine here and zoom in. 1:08 So here we have the lumen of the small intestine. 1:10 And here I'm drawing the intestinal cells known as enterocytes. 1:15 So iron travels through the stomach and arrives in the lumen of the small 1:20 intestine. 1:21 It's in a Fe3+ form, a ferric iron form. 1:25 Because this is usually the form it comes in when we take a consumed iron. 1:31 But the thing is, we cannot actually absorb iron in the ferric form. 1:35 It has to be converted to ferrous iron. 1:40 And so what happens is we have an enzyme on the top of our enterocytes on the 1:45 apical 1:46 surface known as vitamin C ferro reductase. 1:52 And to add to this, on the apical side we also have the iron transporter, you 1:56 can say, 1:57 known as the divalent metal transporter 1, or DMT1 for short. 2:02 And this is a co-transporter. 2:05 So the ferric iron gets reduced by vitamin C ferro reductase to the ferrous 2:11 iron. 2:12 And then it's in the ferrous iron form that it is able to be absorbed by the 2:16 enterocyte 2:17 through the DMT1 channel. 2:21 And the DMT1 is a co-transporter, so hydrogen is also taken in. 2:27 So this ferrous iron, what happens to it? 2:29 Well, the ferrous iron can be oxidized back to ferric iron. 2:39 Iron that is stored in cells are stored as ferritin, Fe3+, or ferric iron. 2:46 The ferrous iron Fe2+, can also be transported to other cells around the body, 2:51 to the liver 2:52 and to the bone marrow. 2:56 Iron leave the cell through the basal surface through a transporter called fer 3:03 roportine, 3:04 or IREG1. 3:07 Iron has to be converted to the ferric form, in order to be transported around. 3:14 And so once outside here, an enzyme, Hephaestin, converts the ferrous form into 3:20 the ferric form. 3:24 Here I'm drawing the circulation, the blood. 3:28 Within the blood, we can find red blood cells here, erythrocytes, the mature 3:33 red blood cells. 3:35 We also find many protein carriers. 3:40 One such carrier protein that we have to know is called transferrin. 3:46 When transferrin is not bound to anything, it's known as apotransferrin. 3:53 But the role of transferrin is to transport iron around the body, as iron is 4:01 unable to 4:02 travel by itself. 4:05 So here we have transferrin bound to two ferric irons. 4:11 So transferrin carries two ferric irons around our body, via blood. 4:18 So what are the fates of these irons? 4:20 Well, they have two main fates, main fates. 4:24 Most of these iron goes into erythropoasis, in the bone marrow, the production 4:29 of red 4:29 blood cells. 4:30 75% of the iron absorbed goes into the production of erythrocytes. 4:36 So here we have erythrocytes with transferrin receptors. 4:40 And why does red blood cells need iron? 4:43 Well, iron is used for hemoglobin to carry oxygen. 4:48 And once iron is used by the pre-red blood cells, the pre-red blood cells can 4:55 then become 4:55 mature red blood cells and enter circulation. 5:02 Transferrin can also transport some of the iron about 10 to 20% to the liver. 5:08 So the transferrin will bind onto the transferrin receptor, which will allow 5:13 the iron to enter 5:14 the liver. 5:15 And then the liver can then store iron, if you remember, in the ferric form, as 5:23 ferritin. 5:24 Now let's have a closer look at how transferrin binds to the transferrin 5:29 receptor on the cells 5:31 and how iron is stored within these cells. 5:36 So let's zoom into this area here. 5:39 Here we have the intracellular fluid of the liver cell. 5:42 And then we have the extracellular fluid of the liver cell. 5:45 Here we have transferrin bound, which has two ferric irons on each of them. 5:53 And here we have our transferred receptor on the outer cell membrane. 5:57 When two transferrin molecules bind onto the transferrin receptor, this will 6:02 cause the transferrin 6:03 receptor to endositize the two transferrin, forming a vesicle. 6:11 When the vesicle has formed, hydrogen ions will then enter the vesicle, causing 6:16 a decrease 6:17 in pH within the vesicle. 6:19 Our decrease in pH will cause the expression of the Divalent Metal Transporter. 6:24 As well, the decrease in pH will cause the ferric irons to detach from the 6:31 transferrin. 6:33 And so here we have the ferric iron detached from the transferrin. 6:37 And we have here the DMT being expressed. 6:40 The ferric iron will be reduced back to ferrous to be released into the cytosol 6:47 , to carrying 6:48 a hydrogen with it. 6:49 The ferrous iron can then be oxidized back to ferric iron and then be stored as 6:55 ferritin 6:55 within the liver cell, in this case. 6:59 The vesicle containing the transferrin molecule and the receptor will slowly 7:04 make it sway to 7:05 the outer cell membrane infused with the outer cell membrane, where it will 7:09 release the transferrin 7:11 back into circulation. 7:13 So here as I've drawn in the liver, iron is stored as ferritin. 7:18 The liver can also release iron back into circulation through the ferric port 7:23 and transporter. 7:25 And the iron is released into circulation down to transferrin as well. 7:35 Now that we've learned how iron is absorbed, how iron is stored, and how iron 7:38 is released 7:39 into circulation, let us learn at what factors regulate iron concentrations in 7:45 plasma. 7:46 Hepsidin is the master iron regulator and is produced and secreted by the liver 7:51 . 7:51 Hepsidin enters circulation and has many functions. 7:54 Its main function is to inhibit essentially the function of ferroportin, which 8:01 are the 8:01 transporters that play a role in iron release into circulation. 8:08 So hepsidin prevents iron to be released into circulation and therefore its 8:14 main goal is 8:15 to decrease plasma iron concentrations. 8:19 Hepsidin also functions on the spleen macrophages. 8:24 Why is this? 8:25 Well, if we zoom into the spleen, we know that the spleen contains many macroph 8:32 ages. 8:32 Now when a red blood cell becomes old or becomes damaged, the red blood cell 8:37 will enter the 8:38 spleen and then these spleenic macrophages will then engulf the damaged or old 8:43 red blood 8:44 cell and digest it. 8:46 It will digest it into smaller materials, one of which is iron. 8:56 Iron then can be released back into circulation and be recycled for erythropo 9:01 ases in the bone 9:02 marrow. 9:03 However, hepsidin will block ferroportin and therefore block the release of 9:10 iron into 9:11 circulation. 9:13 And thereby decreasing plasma iron concentrations. 9:20 Hepsidin not only works on ferroportin, but it also inhibits the absorption of 9:24 iron from 9:25 the lumen of the small intestine. 9:28 So that is important to know. 9:34 So what stimulates hepsidin release? 9:36 Well, inflammatory cytokines such as interleukin-6 will stimulate hepsidin 9:41 production and release. 9:43 An increase in plasma iron concentration, while iron bound to transferrin, will 9:48 stimulate 9:49 hepsidin release because hepsidin will then reduce or decrease plasma iron 9:56 concentration. 9:58 Some bacterial components or pathogen components such as lipopolysaccharides 10:01 will also stimulate 10:02 hepsidin production. 10:06 But the main regulator of hepsidin production is the HFE protein. 10:17 Now the HFE gene, also known as the hemochromatosis gene, makes the HFE protein 10:26 . 10:27 What does the HFE protein do? Well, the HFE protein will interact with other 10:33 proteins 10:34 to regulate iron absorption through the production of hepsidin. 10:43 If there was a mutation in the HFE protein, so a mutation of the HFE gene will 10:53 actually 10:55 result in a disease known as hereditary hemochromatosis. 11:00 And this disease is where you have iron overload when you have too much iron in 11:05 the tissues. 11:10 So how would a mutated HFE protein result in iron overloading tissues? 11:16 Well, to understand this, we have to flashback and remember what hepsidin does. 11:22 Remember hepsidin blocks ferroportin transporter here. 11:28 And it also prevents the absorption of iron from the intestine. 11:32 Its sole goal is to decrease plasma iron concentration. 11:37 Okay, but if HFE protein doesn't work, that means hepsidin will not work. 11:44 And therefore hepsidin cannot prevent or inhibit the absorption of iron from 11:49 the small intestine. 11:51 And therefore the body will absorb a lot of iron from the intestine. 11:55 And so you have excess iron in tissues. 11:59 And this can lead to severe consequences. 12:05 I hope that made sense. 12:07 Now iron does not all come from vegetables or meat. 12:13 Iron also comes from hemoglobin and myoglobin, which are found in red blood 12:20 cells. 12:21 So hemoglobin in the intestine can be broken down to heme and globin by 12:26 digestive enzymes. 12:28 The heme can be absorbed by the enterocyte through a transporter, possibly HCP1 12:36 . 12:36 The heme is the component of the red blood cell that contains iron. 12:42 Heme in enterocytes is oxidized to bilirubin and iron. 12:46 And therefore iron can then be stored as ferritin. 12:50 Which is the ferric form. 12:53 Some things to point out in this diagram is the divellid metal transporter 1, D 12:59 MT1, which 13:00 is important in the absorption of iron. 13:04 But DMT1 is also responsible for the absorption of other metals, including zinc 13:11 , copper, and 13:12 cobalt, amongst many other things. 13:15 Also, if you do not eat enough iron or consume enough iron or don't have enough 13:22 iron in 13:22 your body, you can suffer from iron deficiency, which leads to anemia or iron 13:29 deficient anemia. 13:31 Menstrubleeding is the major root of iron loss in women. 13:36 And therefore women typically require 50% more iron than men. 13:43 So that concludes the video on iron physiology. 13:46 I hope you really enjoyed it. 13:48 If it was too confusing, I hope you can watch it again and try to understand it 13:53 , I guess. 13:54 Thank you. 13:55 Bye.
