DIP Episode 550 - The Iron Story and The USMLEs (Part 1)

Welcome my name is Divine this is episode 550 of the Divine intervention podcasts. Into this podcast we're gonna be doing what will be a two-part series and the title of this podcast is gonna be the Iron Story and the US ML Is. The Iron Story and the US ML Is. The thing is Iron is something that integrates into so many questions on the exam so I think it's useful to have a podcast or a series that truly helps you understand Iron. To be honest with you if you understand this podcast there are many things about an imi and that will click for you and Iron regulation would not sound like such a nebulous idea to you anymore. So the focus of this podcast is on being two parts. One I'm gonna give a background in Iron. I know you may be like who cares about a background in Iron but you're gonna see why that's very important and as I'm making that as I'm discussing that background I'm gonna be making a lot of different integrations and then in the next series we'll then talk about some Iron related disorders and you're gonna see how everything ties together. I'm actually really excited about this stuff. Okay so how does this whole system work? Well you're gonna consume iron. Literally you consume iron. You consume iron in your diet. Now as that club of iron moves down your throat and then it gets into your soft gas and then into your stomach. Well where does that iron get absorbed? Well it gets absorbed in the small intestine. More specifically in the doodinum.

You know there's some absorption that happens in the early part of the genum but honestly for the most part iron on the USM at least is absorbed where in the doodinum is absorbed in the doodinum and the thing is typically you reabsorb about 10% of the iron that you consume. So whatever iron consume you reabsorb about 10% of it but you can actually increase that efficiency of absorption on that certain circumstances. Again this is something that can be easily framed in a USM-Lq question. We describe a state or we describe something that has happened to a patient and then they start giving you some arrows that pertain to iron labs and you have to figure out what happens to the rate of absorption. Well that rate of absorption of iron obviously if you bleed your body is gonna be like oh no I've lost some iron. Let me reabsorb some more. Or if you're a child that's growing think about it kids that are growing they need like a ton of iron. I mean think about it a newborn how much blood if you take a CBC on a newborn how much blood do they have not very much what if you're an adult you have like five liters of blood yeah they're gonna need as you're green as a child you're gonna need a lot of iron right if you have your main sees a woman as she approaches a menstrual cycle or she's menstruating the amount of iron she reabsorbs in the doodina naturally goes down.

So if you have just a bleed you're menstruating whatever you're gonna have these increases you can literally double the amount of iron you reabsorb in the doodina when you are in any of these states. So now the key thing to understand is how does this iron actually getting to the entire site well the thing is that iron it comes in on the typical side of the entire site through a transporter known as DMT1 DMT1 I may wonder define what does DMT1 stand for? Well DMT1 stands for DIVALENT METAL TRANSPORTAL ONE DIVALENT METAL TRANSPORTAL ONE LITERALLY DIVALENT METAL TRANSPORTAL ONE. So why do you think I'm really emphasizing I could have just said DMT1 I moved along what do you think I keep saying DIVALENT DIVALENT DIVALENT well DIVALENT means it has a VALENC of two and if you have any kind of recollection from general chemistry in college so you mean like an iron that is in the two plus state yeah that's exactly what I mean so that tells you that if this transporter only works with DIVALENT IONS what form of iron will be best reabsorbed in the gut?

Well I hope you're telling me oh the viney has to be the fairest form of iron the two plus form of iron that's the only form that can be reabsorbed the three plus form cannot be reabsorbed very efficiently because hey this is a DIVALENT METAL TRANSPORTAL not a trivalent metal transporter and the thing is this transporter that reabsorbs iron two plus is also useful for reabsorbing other DIVALENT IONS right so things like copper things like zinc things like manganese stuff like that so DMT1 will help you reabsorb that iron into the enterocytes the enterocytes are the cells that line your GI tract and then for that iron to go from the enterocytes to the bloodstream it has to bind to a protein known as ferroportin ferroportin ferroportin F E W R O P O R T I N is like a port for iron and then it literally takes that iron that it's bound and then releases it into the bloodstream but the thing is the bloodstream is kind of a rough neighborhood for iron iron is very reactive it's literally like an iron I O N in this case right so it's super reactive you don't want super reactive stuff just kind of floating around in your blood you know there's all these issues with stuff like I don't know like ferroretical damage that's not ideal so iron and also it's not just very soluble to be moving around like that in blood so he needs someone to help him out he needs a protecting group needs a helper and that helper is transferring so iron is going to be bound to transferring in the blood and that transferring then kind of shoves it around in the in the blood now what are some key things to know about transferring well the thing is transferring you know since it has the ability it's a protein has the ability to take on iron that means there is this whole thing called transferring saturation that we need to worry about and I'm gonna talk about it more detail as we proceed in this podcast

but basically transferring is about 20 to 45% saturated with iron so if you take all the transferencing in the body look at all the binding sites for iron about 20 to 45% of those sites are filled with iron now that tells you something if you notice them my transferring saturation is less than 20% it means that you must be kind of short on iron that's why transferring saturation is low in iron deficiency anemia but if this transfer in saturation happens to be some really high number some number over 45% you know some people use 50% then you know that I probably have a little too much iron makes you think of some kind of iron overload that's one now another thing to know about transferring is that your red blood cell precursors they have receptors they have transfer receptors that can bind transferring why would a red blood cell precursor want to bind transferring well obviously want to do that if you want to suck up that iron if you want to suck it up and you know use it to make red cells or store the iron or whatever and then also don't forget that transferring can interact with your macrophages remember macrophages are a very big place where iron is stored in the bone marrow so macrophages can store and not just macrophages in the bone marrow honestly macrophages in many parts of the body but macrophages they can bind transferring and they can suck up iron for for storage right and in fact these receptors that you see me or these transporters you see me talk about in the entire size things like DMT1 and and fair reporting your macrophages also have those things which makes sense right because again macrophages need to bring in iron and store it but macrophages also would like to pass off that iron to people that would love to use it so it would make sense that they should have fair reporting for also passing off that iron just FYI just something I figured out kind o

f throw that in now one thing I want to talk about you may notice this more of a teaching and integration podcast you know kind of throwing a few questions in here and there I just think that's the better format to go over this material but the thing is what are some factors that can modulate the iron that you consume and how it's absorbing the body what are some factors well I'm sure you've heard of this pesky thing known as hip siding hip siding is something that's released by the liver and there is actually quite a number of triggers for hip siding but there are two big ones I want to talk about today number one is if you have an inflammatory state that's the one many of you learning medical school you know you have an inflammatory state you'll make your release a ton of hip siding but another thing that triggers the release of hip siding is that if there is a lot of iron in your liver so there's actually something I want to talk about because many people think that iron is only stored in the bone marrow that's not true you know iron is stored in many parts of the body but big big ones to know for sure are the bone marrow the liver and the spleen right BLS bone marrow liver and spleen those places are big time stores of iron so if your liver says that man I have like a little too much iron on my hands your liver is gonna be like you know what I'm gonna release more hip siding so an increase in liver iron stores increases hip siding production and what in the world does hip siding do what the thing is hip siding combined to ferroporting remember that transporter on the basal surface of your intestinal enterocytes hip siding combined ferroporting and when you bind ferroporting it prevents ferroporting from releasing the iron that it has into the bloodstream so you may wonder so divine like if I can't release this iron into the bloodstream isn't it gonna just hang out

in the enterocytes yes it's gonna hang out in the enterocytes so you may wonder okay divine if it's just hanging out there how's that helping me with not getting iron in well the thing is your enterocytes are replenished fairly frequently after a few days those enterocytes get sloughed off right remember enterocytes they have they're very metabolically active so the body replaces them fairly frequently I mean think about it they're they're they're kind of labile cells in a sense right they are not very strong right they they last for a while and they're gone so as those enterocytes slough off you're just literally gonna like just get rid of that iron poop it out and and stuff like that so just something to kind of keep in keep in mind so that's one thing so we've kind of talked about the hip siding story I will say more things about hip siding when we get to leader parts of the spot cast or you know in the in the next part of the spot cast but another thing that also affects iron absorption is the form it's absorbed in right so like I'm sure many of you have heard this that oh if you take oral iron it is recommended that you drink some orange juice with it well why do you think that that's some bit of advice well there isn't get that advice is that orange juice you know contains vitamin C and another thing for vitamin C if many of you know is is a scorpic acid not only you may see for a scorpic acid is a scorpite it's just the salt form of it remember salt is when you take like a metal and an iron right so an a scorpite is an iron it can bind to iron itself and you know like iron a scorpite or whatever I'm just kind of making that up but a scorpite is a salt but basically something that loves to bind iron and when you bind iron in that form very very easy to reabsorb very very easy to reabsorb in fact iron that is complex with a scorpite easy to reabsorb in the GI tr

act so why is it that a scorpite helps well the thing is vitamin C is a very powerful reducing agent to powerful reducing agent and remember when I talked about that divelent metal transporter one so the thing is iron may be in the three plus form and that three plus form can't really get reabsorb that's the ferric form it's the two plus form the ferrous form that's heavily reabsorbed so the thing is vitamin C can convert iron from the three plus form the ferric form that's not reabsorbed to the two plus form the ferrous form that's taken by DMT1 and that makes it easily reabsorberable so that's one of the reasons why oh if you're taking an oral iron supplement drink orange juice is gonna make that iron is gonna basically increase the bioavailability of that iron I can see a pharmacology a question in there somewhere about increasing iron bioavailability again the USML is the stocking trade is to just take something something simple that you know and just put it in terms that you may not think about or you may not consider if the understanding and the foundation is not is not there so what's an integration can make with this well think about methemoglobinemia you see a person they consume like dapsone or they consume like primal queen formalaria remember primal queen is the thing that kills those hypnozoid forms of plasmodium that you know vivaxano valley that hang out in the liver that lead to maintain the liver or dapsone remember you can use dapsone for many things right can easily treat dermatitis or perteformis in celiac disease you can use it as one of the ways you deal with with the most serious your vetsy so it's a very powerful oxidant so you can take iron from the two plus from putting the three plus form and that can cause methemoglobinemia so how can you fix that problem typically the first lecture means methelym blue methelym blue is gonna convert the thr

ee plus iron to two plus iron but and a good adjunct or you may not if you don't see methelym blues and answer your exams is to consider just given vitamin C because vitamin C powerful powerful powerful powerful reducing agent convert iron from the three plus form to the two plus form again good integration to know for your exam now another thing that modulates iron absorption I think it's actually kind of important to understand that there are two forms of iron from your diet there's two forms of iron from your diet is hem iron and there's non-hem iron there's what him iron and non-hem iron so what in the world is hem iron well hem iron is iron that you'll find pretty much in meat in fish and in poultry in meat in fish and in poultry non-hem iron is iron that you find in like fruits in vegetables and nuts why is this distinction very important this distinction is extremely important because non-hem iron is not reabsorbed as efficiently as hem iron in fact hem iron is reabsorbed with like three times more efficiency than non-hem iron basically if you consume him iron so you consume like meat fish poultry about 30% of the iron in that iron you consume this reabsorbed versus non-hem iron where it's like more like 2 to 10% so that's just really really low right so if you want to really look up on iron it's probably be loading up on like fish poultry meat stuff like that you know seafood lean meat favorite rich sources of of hem iron and then another thing to also consider is I said that your your iron is so the dietary iron is reabsorbed in the duodenum so why does it get reabsorbed in the duodenum well the thing is your microv lie remember the microv lie is an typical surface modification for your duodenal cells that increase the surface area and makes it possible for them to reabsorbed a ton of stuff well that's not the only story there the thing is there's actually an

enzyme on your microv lie known as ferric reddoctase ferric reddoctase well look at the name ferric reddoctase it takes ferric that's three plus iron reddoctase it reduces it remember reduction is when your oxidation number gets less positive right if you remember that from general chemistry in college so ferric reddoctase is gonna take the three plus you know it's gonna basically reduce ferric iron to ferrous iron so that it gets easily reabsorbed so you can already begin to see why people that have malabsorptive disorders like celiac disease may have issues with iron deficiency anemia because their microv lie has been destroyed in an inflammatory process so you've pretty much got rid of like ferric reddoctase so you cannot reduce ferric iron so you cannot reabsorb that iron and then that ultimately becomes a problem right so that's something you want to kind of keep at the back of your mind for exams right and you can also see why again you know people that have celiac disease they have just many of them are absorptive issues so it's something you want to keep in mind right and then just on a more non-specical level and I promise we're getting close to the end of this path one because I don't want it to be too long because it's kind of a complex topic with many parts but again I want to make sure that you understand it and you're good to go but basically some other things that increase iron reabsorption is again if you have less hep siding and again well you have less hep siding well not in a super inflammatory state less iron stores in your liver right or if you have hypoxia if you have hypoxia that triggers the release of rethrough poison you want to make more red blood cells because when you're hypoxic your blood oxygen carrying capacity is just heavily reduced literally it's heavily reduced so the thing that happens is that essentially that iron if you're hypox

ic you what is like man I I need to make more red cells you know so that list even if normally I have like 12 hemograms of hemoglobin or whatever let me make it like 15 so that even if the hemoglobin is not as saturated as it should be if I have more carriers available I can move more stuff around I mean think about it like a person that has COPD right those people the surface especially like in physical the surface area of the alveoli is heavily diminished so they have less surface area they have less diffusibility so the ingredient is high I mean so yeah it's high it's high right because the PBG to the oxygen the alveoli cannot equally breathe very well the oxygen in the in the vessels in the opponent capillaries right so the hypoxic right that's why those people have a lot of very thorough poises so when you have high levels of epoch that's going to increase your absorption of of iron in the in the dodenum so it's something to keep in mind okay now next day I want to talk about with iron again I told you that this is just a foundation lane podcast the second one lots and lots of integrations but let's talk about how the spleen kind of factors into all of this stuff well because the spleen actually plays a big role in iron metabolism and the key thing to know about the spleen is that I like to think of it as like a quality control region of the body where you deal with red cells it's like a quality control region right so the spleen as we know contains a lot of macrophages you know have all these plate macrophages and the thing is one of the things they do is they they take and they destroy old red blood cells right they take they destroy old red blood cells you know they pretty much just kind of look at those red cells and say hey how's this red blood cell doing you know is it a good red cell is it young is it old they kind of do that quality control if you're an o

ld red cell they they destroy you right and as they destroy the red cell they're like I'm not just gonna destroy you but I'm gonna take the useful stuff out of you right I kind of think of the spleen sometimes it's like a good digging organ is like hey red blood cell coming here destroys the red cell and then sucks up the iron out of it literally sucks of the iron out of it but it's kind of useful because that iron that is sucks up again because it's these macrophages remember I said that those macrophages have those DMT1s and ferroportines they can literally recycle that iron and return it to your storage pool of iron right so it's not all bad but that should help you remember one of the reasons why we can do spleenectomy as a treatment for hereditary spherocytosis because those spherocytes yeah they're not amazing but they work okay but the spleenic macrophages being a quality control thing they're like this spherocytosis it doesn't it doesn't look like a normal red blood cell so what do they do to those red cells they destroy them that's why if you do a spleenectomy then you take those spleenic macrophages that are crushing these red cells out of circulation and voila problem solved all of a sudden or if you think about it the spleen plays a role in destroying red cells in other disorders like like G6 PD deficiency right again think of all these things like bite cells and whatnot right or think of the spleen because the spleen is so heavily intertwined with red cells you think of the auto spleenectomy getting sickle cell disease again all these things are just kind of linked together in one way shape or shape or four all right now next thing I want to talk about with iron is the storage right iron is stored and the thing is if you want to think about iron stores again I said what are three main places iron stored in the body and the bone marrow in the spleen and in

the liver there are two basic ways that iron is stored there's short-term storage and there's long-term storage okay there's what there's short-term storage and there's what there's long-term storage so how's iron stored well the short-term storage is in the form of ferritin ferritin many people think iron stores yes ferritin is a good measure of your iron stores but it's more short-term because it's limited right but in terms of long-term storage the long-term storage form of iron at least this is the way I think about it is as hemocidering hemocidering is almost like limitless and its ability to store iron I just like to think of ferritin versus hemocidering as being like your checking account versus your savings account you know ferritin is more like your checking account you know your checking account you can see you can kind of store some money you're checking account but it's called a checking account because you want to get immediate access to that money if you need it you just write a check and boom good to go but your savings account is more long-term you put money in your savings account that you know that you know what I kind of want to keep this for you know for emergencies or whatever you know it may not be is something we easily be able to tap into but it's there if you need it and I think I want to make some integrations here with hemocidering because the thing is since hemocidering is a form of iron and remember iron can you know is colored it's kind of like a colored iron you know is a colored iron I.O.N.

in a sense if you think about it if you have a disorder when you where you bleed or you have iron extravacetin from your from your you know your bloodstream your blood vessels like your capillaries that can cause like almost like skin hyperpigmentation so whenever iron is kind of leaking out of your capillaries and you have skin hyperpigmentation what do you think is causing that skin hyperpigmentation it's the iron in the hemocidering is that is literally the iron in the hemocidering right so say for example if a person has like hair district hemocurmitosis why do you think they you know many of you remember the bronze diabetes bronze diabetes well what do you think the bronzing of the skin comes from it's pretty much hemocideroosis of the skin right because that iron in hemocidering is just you have this iron overload it's kind of staining your skin but honestly that's not the only thing what if a person has like you see a lady that is old and she's like postmenopausal and you know she has like this skin hyperpigmentation in her lower extremities and she says that her legs are swollen by the end of the day well I hope you're thinking of varicose veins remember in varicose veins you're because your veins have valves those valves are incompetent so they can't take blood back convincingly towards your upper body so the blood just kind of stays right as the blood is kind of staining your vessels remember increasing hydrostatic pressure you have more extravacation so you have hemocideroosis and bone there you go right so just that that's stasis dermatitis what's the mechanism behind the dermatitis dermatitis in stasis dermatitis it's hemocideroosis it's what it's hemocideroosis of a person is bleeding right again you're gonna have that skin hyperpigmentation right for that for that reason right so again just something to keep in mind again all these things they may look

like minute mute points until it shows up on you example you're like hmm they find it actually talk about that and the thing is when you have this kind of foundation when you're studying diseases and pathologies like everything just kind of clicks in your brain just kind of makes sense just kind of makes sense now the last thing I'm gonna talk about here today and this is the last thing let's look at some iron labs I do have a podcast on iron labs so it's gonna be like a quick just brought over view but I want to bring in some kind of bio statistical association here right but we know serum iron is just pretty much a measure of how much iron you got in your serum total iron binding capacity it just means hey how much iron do I have the ability to bind essentially in my serum that's the way I think about it total iron binding capacity is literally how much iron do I have the ability to bind in my serum and the thing is if you combine these two labs you can actually get your percent transferring saturation from that you can literally get your percent transferring saturation from that so how in the world do we calculate percent transfer in saturation percent transfer in saturation is literally calculated by taking your serum iron and dividing it by your T I B C your total iron binding capacity I'm gonna tell you this right now your percent transferring saturation is the most sensitive test for determining your body iron stores I'm gonna say that again your percent transferring saturation is the most sensitive test for determining your body iron stores in fact if they give you a question on your exams on screening for hairdryer hemochromatosis and you know the USM at least you know the MBM Es and what they do the these devious things they do if they put percent transfer in saturation as an answer and they put ferritine as an answer many resources you can even and actually

honestly either one is fine but if they give you both as answers and you have to pick one then you have to put on your bio stats hat and pick the one that is more sensitive the one that has the higher negative predictive value in this case percent transferring saturation okay it is more sensitive it is more specific for determining your total body iron stores right ferritine is good but is not great right it may be decently sensitive but is not particularly specific right so it has a very low positive predictive value for looking at your iron stores because there are many other things that increase your ferritine right if you have liver disease your ferritine is gonna go up if you have a state of inflammation your ferritine is gonna go up right if you have cancers certain cancers certain malignancies your ferritine is gonna go up right so again if you're comparing these two labs both of them are decently sensitive although the one that's more sensitive is your percent transfer in saturation but if you're looking at both in terms of specificity your percent transfer in saturation is more specific your ferritine is less specific is less specific because there are other things that can elevate your ferritine besides just you having good iron stores so you just something want to keep at the back of your mind right literally the same mantra they test it with like D dimer versus like a CT angiogram for example for for a PE right a D dimer is very sensitive for PE right has a very high negative predictive value but it's not particularly specific because there are many things that can elevate your D dimer like pregnancy and stuff like that right so all these things you just kind of want to keep at the back of your mind so again just as a recap we talked about how we just kind of use this as like your quick review dietary iron absorbing the doodinum DMT1 microvli we talked abo

ut ferric reductase we talked about the iron getting to enterocytes ferroporting gets it into the bloodstream binds to transferring we talked about iron is stored in the liver in the bone marrow in the spleen we talked about this as corbite story we talked about the hip side in story we talked about hem iron versus non hem iron right we talked about the spleen and its quality control integrations we talked about the short term versus long term stores of iron we talked about some iron labs we talked about a bunch of stuff right so just kind of keep these things at the back of your mind please this stuff is very very important so we're gonna go ahead and end here if you're interested in any of my classes I have like a series of classes taking place before Thanksgiving you know it all starts next week Monday they all over zoom Monday test taking class Tuesday bio stats class Wednesday social science and ethics class Thursday so those Monday to Wednesday classes are definitely first step one all the way to step three Thursday I have the last minute review that's for step two and step three and then on Friday and Saturday I have the 20 hour class split 10 hours each day that's for step two and step three and in the first week in December I have a 25 hour step one class so these classes again if you love the way explain information you love the way making integrations you're gonna love these classes the over zoom many people have like tons of very quality notes from the class and I've had many people who are extremely well from these classes so if you're interested shoot me an email can give you some more information also for one-on-one tutoring and I also have these podcasts on the major apps you know Apple Google Spotify I have a You Tube channel where I have some videos you can check out and then I have another website called Divine Intervention Life Lessons.com Divine In

tervention Life Lessons.com where you know every week usually I post a podcast or so where from a biblical perspective I address a life lesson actually many people listen to that podcast as well it's actually an Apple podcast as well Divine Intervention Life Lessons.com and I think you'll find out to be helpful so thank you for listening to me today again putting the work learning your craft learning your medicine because again you're you're handling human life so you want to do your best in learning if you do your best as a learner you probably be better as a practicing physician so with that I will see you in episode 551 have a wonderful rest of your day God bless you and bye for now thank you

The duodenum (small intestine).

DMT1 (Divalent Metal Transporter 1).

Ferrous ($\text{Fe}^{2+}$) or two-plus state. The ferric ($\text{Fe}^{3+}$) form cannot be efficiently absorbed.

Ferroportin.

It binds and transports iron through the blood, preventing it from being highly reactive or precipitating.

Liver, Bone Marrow, and Spleen (BLS).

Hepcidin. High hepcidin levels decrease absorption.

Ferrous ($\text{Fe}^{2+}$) (two-plus state).

Ferric reductase. Celiac disease/malabsorption disorders impair this function.

It acts as a powerful reducing agent, converting poorly absorbed $\text{Fe}^{3+}$ (ferric) to readily absorbable $\text{Fe}^{2+}$ (ferrous).

Ferritin is short-term storage (like a checking account); Hemosiderin is long-term, accumulated iron deposits.

Iron deficiency anemia/low total body iron stores.

Hypoxia (e.g., COPD) or menstruation/hemorrhage, due to increased demand for erythropoiesis.

Ferrous ($\text{Fe}^{2+}$) (two-plus state).

Ferric reductase. Celiac disease/malabsorption disorders impair this function.

It acts as a powerful reducing agent, converting poorly absorbed $\text{Fe}^{3+}$ (ferric) to readily absorbable $\text{Fe}^{2+}$ (ferrous).

Ferritin is short-term storage (like a checking account); Hemosiderin is long-term, accumulated iron deposits.

Iron deficiency anemia/low total body iron stores.

Hypoxia (e.g., COPD) or menstruation/hemorrhage, due to increased demand for erythropoiesis.