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Iron absorption physiology

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Iron in the diet exists primarily in two forms: heme iron, found in non-vegetarian foods, and non-heme iron, which is less efficiently absorbed. The body absorbs approximately 25% of dietary heme iron compared to only about 5% of non-heme iron. Absorption mainly occurs in the duodenum and the proximal part of the small intestine, where specific cellular mechanisms determine how much iron enters the bloodstream. Once inside the intestinal epithelial cell, non-heme iron must first be converted from its ferric form to the ferrous form by an enzyme called duodenal cytochrome B, allowing it to cross cell membranes via the divalent metal transporter 1. In contrast, heme iron bypasses this initial conversion step and enters the cell directly through a specific heme transporter before being broken down into its iron component inside the cell. Once inside the intestinal cell, the fate of the iron depends on the body's current needs. If iron stores are sufficient or demand is low, the iron remains within the cell, where it is stored as ferritin. When these cells eventually shed from the intestinal lining due to rapid turnover, this trapped iron is lost in the feces rather than being excreted through a dedicated pathway. Conversely, when the body requires more iron, such as during increased red blood cell production, erythroblasts produce hepcidin-inhibiting factors that prevent the release of hepcidin. This allows the ferroxidase enzyme hephaestin to function alongside ferroportin at the basolateral membrane, facilitating the export of iron from the cell into the plasma where it binds to transferrin for transport to tissues like the liver or bone marrow. The regulation of iron absorption is critical because the human body lacks an active excretory mechanism to remove excess iron; therefore, controlling how much is absorbed is the primary method of maintaining iron balance. Several factors influence this absorption process, with increased demand being a key driver that suppresses hepcidin levels to enhance uptake. Nutritional components also play a significant role, as vitamin C helps maintain non-heme iron in its absorbable ferrous state, whereas substances like milk, phytates found in tea and coffee, and tannates can bind to iron or alter its chemical state, forming insoluble compounds that prevent absorption. Additionally, adequate gastric acidity is essential for converting dietary ferric iron into the more absorbable ferrous form, highlighting how diet and physiological conditions collectively determine the body's iron status.
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Iron in diet is present basically in two forms either in heem iron form. Hemiron is present in non-vegetarian diet or as non-heam iron. So this hem iron actually is better absorbed than non-heem iron. So non-veg diet whatever iron is there as hem iron that is better absorbed and approximately 25% of this iron is absorbed but in non-heem iron only 5% of the iron in diet is absorbed. Now the absorption takes place in jodinum mostly and some part of proximal small intestine other part of small intestine as well. Okay but mostly it is covered uh it is happening in durina. Okay. So here this is the luminal side of intestine and this is the basolateral side. So here what we see that uh this is the dural epithelial cell and there is vi projecting on this intestinal uh border we have the this reductase enzyme is there. It is also known as gyc basically diodinal cytochrome B. Okay, doden cytochrome B enzyme is there which converts the feric form of iron into the ferrris form. Now this is important. Why? Because it is the ferrris form of iron which can cross the membranes. So always you see it will be the ferrris forms of iron which will be crossing the membranes. But it is transported and stored as feric forms right. So by this enzyme dural cytochrome B the feric ion is converted to ferosion and then this ferrraion moves into the cell in the intracellular compartment via another transporter that is dalent metal transporter one. Okay, divalent because this is two valencies there, right? So dalent metal iron is a metal dalent metal transporter one. So this moves inside into the intracellular compartment of the cell. Now he iron hemiron there is another transporter direct hem transporter. So it will directly transport he from the lumininal site to the intracellular compartment and within the intracellular compartment there is a enzyme heem oxygenase which will act on this he and remove the globin part and the ferris part separately. Okay. Now this ferris has two pathways either it can go out of the cell that is one or it can remain within the cell right now that depends on the requirement of the iron. So if the iron requirement is more this iron will go out of the cell. If body doesn't need iron then the iron remains intracellularly in this intestinal epithelial cell. Okay. So what I'm trying to tell you here that absorption of iron absorption of iron is regulated depending on the requirements. So how this regulation is brought about. So first let us see how it is getting absorbed. So on the basolateral side of this intestinal epithelial cell we see there is a transporter that is feropotin. So this feropotin basically transports this ferris form outside and along with this feropos uh feropotin there is another protein attached heestin. Okay. So here it is shown separately but you will see other books it will be like this. So if this is feropotin you will see that they will show one diagram where heestin another protein is associated with this feropotin and this is much better way of depicting why that you see that as the transport of iron occurs in the ferrris form by the feropotin immediately this iron is converted into the feric form. So it is associated movements uh they are occurring simultaneously iron is moving out and this ferrris form is getting converted to feric form immediately and uh this heestin is responsible for conversion of ferrus to feric form. Then this feric binds to the protein transferin which is present in the plasma. So iron is transported aspheric form combined with transferin and this transferin either goes to the cells where it is required where the iron is required or it goes to the storage site and the main storage site for iron is liver. Okay. So either it is taken by the epito cells or it goes to the iththroidid marrow because the iron is present in the hemoglobin. So where it will go? It will go to the developing cells which will form ithroytes the RBC. So that is eriththroidid mar. Okay. So that's what we discussed that how iron is absorbed. Peropin associated with feesin. Right. Now if the storage form of iron is more. So here say suppose liver has already lot of storage of iron is there. So in that case liver releases a protein that is hepsidin. Hepsidin it releases. Now this heepsidin goes and blocks this feropin one. Okay. So if this feropotin transporter is blocked, will iron move from the intracellular compartment to the basil site? No, it won't be able to move. So it will remain intracellularly and intracellularly it will be converted from ferrris to feric form and it will be stored as mucosal feritin here. Right now in some time there will be loss of this epithelial cells. So there is shedding of dural epithelial cells and the intestinal cells turnover is very high. So with the loss of this intestinal epithelial cells the iron which is present here that will also be lost. Okay, understanding. So very important fundamental concept it is that absorption of iron is regulated in our body. We don't have any excrettory regulated pathway for iron. It is the absorption which is regulated and this here with the iron which is trapped here if the iron requirement is fulfilled in the body if there are adequate stores and the iron which is trapped here this is also lost along with the epithelial cell. So this is known as there is a term for this mucosal trap mucosal trap of iron. Okay. So that was about the iron absorption. We saw that intestinal epithelial cell there are transporter for hem hem transporter is there. Then for non-heam iron first it is converted from feric to ferrus by dycb enzyme jodal cytochrome B and then ferrus is transported intracellularly by talent metal transporter one and then it moves from the intracellular site to the vasolator site by feropotin one which is associated with hephestin and this feropotin one can be blocked by another protein that is hepsidin. Now this is very important to know because it has significance in another disease that is hemocchromattosis that we are going to discuss later. Okay. So that was about the iron absorption we have discussed. So what are the factors which affect iron absorption. There are factors which increase the iron absorption and there are factors which decrease the iron absorption. So increased iron absorption occurs based on the demand. Okay. So when there is increased demand for example if there is increased synthesis of RBC so the eriththroidid precursor cells which are there that is the pronormal blast they will divide more so that means iron requirement will be more so in that case these ariththroblast produce a protein that is okay and thiserone actually inhibits hepsidin so this hepsidin which we talked before okay which is inhibiting feropotin so it is not allowing iron absorption to occur. So this ariththroblast actually produce ariththreron which blocks uh which inhibits hepsidin. So that heepsidin is not able to act on parapotin and iron absorption can continue. Okay. So that's how ethoid hyperplasia increases iron absorption. Then next component is vitamin C. Vitamin C actually keeps dietary iron in ferris state. Okay. So it is keeping it in reduced state in the fer state and we have seen that non-hemir iron is absorbed in fer state. Then the factors which decrease iron absorption include milk. Okay. So suppose you have given iron supplementation to somebody and they take milk along with that then iron will not be absorbed. Okay. Then phitates and tanates these are basically present in tea coffee and these phitates tanates bind to non-hem iron and form nonabsorbable insoluble compounds. So obviously iron will not be absorbed. Then decreased gastric acidity. So that is also important because acidic environment actually facilitates the conversion of feric to ferrus form. So if acidity is less this is not going to take place and the dietary iron will remain in feric form so it will not be absorbed. So that was about the iron absorption in the diodnum and the factors affecting the iron absorption. Thanks for watching the video. If you liked it do press the like button. Do share the video with others and don't forget to subscribe to the channel physiology open.