DIP Episode 114 - Comprehensive USMLE Step 1 GI Review (Part 2)

Okay, welcome. My name is Devine. I am a PGY-1 A Transitioner year resident that's ultimately going into radiology. This is episode 114 of the Divine Intervention Podcasts. And in this episode I will be continuing a review of gastroenterology as relevant to the USM-Listab 1 exam. Right? So last time we talked about like a lot of those like chemicals and hormones and whatnot that in the GI tract talked about some transporters. So let's again sort of again finish laying that GI physiology background and then we can begin to go into the diseases. So I mean we know that the big big cell in the GI tract right we have our interocytes. I remember the interocytes especially like in the at the level of the jisunum where you have a ton of microvali and that increases surface here for for absorption right and then don't forget that you have many other cell types right in your in your small intestine right. So you have like paneth cells they make like things that have anti-bacterial activity. You have your goblet cells right. You kind of see great new cause because again remember your GI tract that should deal with a lot of like acid especially from the stomach. So goblet cells sort of help with sort of help with that. And then I already talked about how during the last podcast I talked about excuse me talked about how we have the SGLT1 transporters at the level of the at the level of the small intestine where we have a lot of those transporters.

In fact we actually find those transporters in many parts of the many parts of the GI tract but remember this right when you're getting a question about like a patient let's say like you know developing country that's having a lot of watery diarrhea, watery diarrhea, watery diarrhea and they're like hemodynamicly on stable right. And maybe they've been exposed to like dirty water or water that is not clean right. Under the circumstances I hope you're thinking about Vibrio cholera right. Remember cholera right it loves to screw up with it causes like a really bad secretory diarrhea right. So why is that relevant to the sodium glucose and lense transporter right. So let's think about this for a second. So the thing is if you think about cholera right. So the cholera toxin it basically activates adenylyl cyclase right. So if you activate adenyl cyclase right you convert ATP to cyclic AMP and the thing is when you have high levels of cyclic AMP that actually operates the cystic fibrosis transmembrane at channel right. So you begin to insert more of those channels at the typical side of the intestinal interocytes right. And if you do that right that channel basically pumps a lot of like chloride ions it basically dumps chloride ions into the into the lumen of the GI tract right. And where chloride goes because it's so smutically active water will follow right.

So under those circumstances if a person has a like a cholera diarrhea they have a ton of activation because the cholera toxin activates adenylyl cyclase you make more cyclic AMP you put more CFTR channels on the EPICO surfaces of the intestinal interocytes water follows and you get a nasty nasty nasty nasty diarrhea right. So the thing is usually to and remember that CFTR channel is the thing that's mutated in an cystic fibrosis right. So if you have CF that channel doesn't work well you don't pump chloride in you don't dump chloride into the lumen of the GI tract. Water doesn't follow so you have like super sticky super thick secretions in the GI tract right. So that's why those kids tend to have like maconial ilius at birth and they tend to have a lot of them absorption as well although there's other reasons behind that we'll talk about that in a later in a later podcast. So you may ask yourself how do you treat cholera diarrhea right. You can actually take advantage of those SGLT1 transporters right. So you it's something I know this has been used a lot in developing countries right. So like ORT or O-rehydration therapy. You basically give like a salt and sugar solution right. And the thing is when you give that salt and sugar solution that sodium again you would use that SG basically you operate the activity of that SGLT um transporter right.

And that SGLT transporter sodium is going down is gradient into the cell you're essentially using that secondary active transport to push glucose into the entire site because the thing is uh the cholera toxin it messes with a lot of transporters in your GI tract with that SGLT1 transporter still works even when you have cholera right. So you can use that to sort of counter that loss of fluid and electrolytes that companies are pressing a have in a cholera. So those are all kind of high-yield things you want to understand right. And again already talked about how our dust run works especially in the colon right with those like inech channels and those are potassium channels right. So I already talked about all that stuff. So hopefully you remember that. And again I I sort of talked about this last time as well. When you go to like the your parietal cells right that you find in the in the stomach right. Remember those cells they have like hydrogen potassium uh ATP is pump on the apical surfaces that brings in potassium right. Pump potassium into the cell against its uh against this concentration gradient right. That's why it's an ETP is pumpy UZCTP and then brings hydrogen ions out in reverse right to maintain electron neutrality right. So remember if you go back to the renal videos or podcasts I don't know what it is but I do have a renal material.

If you go back to those right um you remember when I talked about carbonic and hydrates how if it's dumping hydrogen ions on one side of a cell so say for example the apical site it'll be dumping bycarp on the opposing side of the cell so like the basal lateral side. So the thing is when you're secreting those hydrogen ions into the lumen of the stomach right you actually secreting bycarp into the like into the bloodstream uh while those protons have been secreted right. So think about if you're dumping bycarp in your bloodstream that already tells you that you potentially should have some kind of alkalosis right as you're digesting food okay. So that's the pathophys behind something known as the alkaline tide. That's again one of those weird things you do need to understand for the purposes of your USMLE step one example right and then don't forget right that vitamin D right active vitamin D right so like 125 dihydroxy vitamin D that is made by one alpha hydroxylase in the kidneys right converts like calcium dial to calcium trial.

Calcium trial in the GI tract right increases the reabsorption of calcium and phosphate in the gut okay so that's one how you think you want to remember and then don't forget right that you absorb iron in the dogganum right and then you absorb folate in the gigenum and then you observe you absorb a B12 in the terminal helium right remember that's why if a patient has Crohn's disease they have like a terminal elitis right they have reduced ability to reabsorb B12 and that's why we may have a macrositic macrositic or you can be a little more specific amygdala plastic anemia remember by definition the macrositic anemia is a subset of the macrositic anemias a macrositic anemia is an anemia that arises in the cell in a full lit or B12 deficiency and remember right that iron right is only reabsorbed in the FE2 plus form right that's the fear of not the ferric from the ferric form is the FE3 plus form okay the FE3 plus form cannot be reabsorbed okay so you do need iron in the FE2 plus form and then it's reabsorbed across across the dogganum and then you can use it to make a red blood cells and helium and all that crap right and don't forget if a person has like a bypass right a bypass can be something that they can present on an envy anemia exam as a cause of iron deficiency anemia because if you bypass the dogganum guess what they are not reabsorbing anymore they're not reabsorbing iron okay so again that's very high you to know that anemia is it but divine what if I consume something that has FE3 plus ions the thing is if you consume something that has FE3 plus ions they're actually like electron transport chain like proteins like some cytochrome some cytochrome enzymes that really have the ability to reduce FE3 plus to FE2 plus okay I like the brush border of the dogganum and then you reabsorb that iron and remember right there is a drug that has the ability to help you r

educe FE3 plus to FE2 plus that's methylene blue right so if a patient has a methemoglobinemia on an envy anemia exam right methylene blue is a very good drug for that because again reduce the ferric iron to the ferrous iron right because remember methemoglobinemia it's the reason it's a huge issue is that FE3 plus has no ability to carry oxygen but FE2 plus has maximal ability to carry oxygen right so that's why reducing the iron the ferric iron to the ferrous ion helps on that those circumstances alternatively remember that having FE3 plus iron is actually not bad if a person has cyanide toxicity right because remember FE3 plus actually has very strong affinity for cyanide FE2 plus does not have great affinity for cyanide so if a person for example has been like on an nitro-perside infusion and you have like cyanide toxicity from that you can give emol nitrate emol nitrate is a powerful oxidizing agent you'll convert ferrous iron to ferric iron that ferric iron will bind up the cyanide and then from ferrous ionite ferrous ionite that can then be safely excreted okay so again these are I know like this is a G.I.

review but the thing is especially step one is just one of those exams where just being able to integrate things across multiple disciplines is super helpful so I am going to try as much as possible to try to bring in correlations from other systems as I go through as I go through G.I.

and then remember right your pancreas right kind of serves a pretty big role in a person that is in the process of a digestion right so your pancreas secretes by carpe right so that again sort of helps you deal with many of the acidic secretions that are coming acidic food or you can call it like acidic kind that is coming from the that is coming from from the stomach right and then your pancreas also secrets secrets like lipase right lipase is the thing that essentially breaks up your triglycer I remember triglycerite means you have glycerol and three attached fatty acids right to each of those hydroxy groups on glycerol right so your lipases will cleave that triglycerite into like a monoacel glycerol right so like glycerol you cleave of two of the fatty acids fatty acid chains and then you are left with one fatty acid chain attached to one of the hydroxy groups right so monoacel glycerol and two free fatty acids okay but the thing is lipase right so I mean you love this function of lipase right because it sort of helps you in the as you sort of begin to kickstack the process of a digestion of triglycerites but the thing is lipase especially lipase from the pancreas cannot survive for long in the in the in the gitract okay the gitract is kind of like a rough neighborhood so the thing is there are like bile salts that can essentially bind to lipase and make it stop working so that is where another enzyme known as cool lipase comes into play cool lipase I almost think of it as like almost like a like a what is it called almost like a beta lactamase in wait I'm thinking of this right yes so I think of this almost like a beta lactamase inhibitor cool lipase comes and surrenders itself to the bowel salts so that lipase cannot treat free okay so remember that cool lipase business as you study for for the USML step one example and the thing is many of these pancreatic enzym

es you actually make them as something called like a zymogen so you make the zymogen form of the enzyme the zymogen by definition is like the inactive form of the pancreatic enzyme so the thing is when you make that zymogen form right obviously for you to be able to work you need to convert it to the active form right the non zymogen form of the pancreatic enzyme and the thing that makes that happen is something known as tripsin tripsin is a pancreatic enzyme and it has the ability to convert the zymogen form of most pancreatic enzymes to the non zymogen form of the active form of those pancreatic enzymes right so but the thing is tripsin itself does not just show up out of thin air in the GI tract right I mean that'll be magic magic doesn't necessarily happen so the thing that happens is tripsin is actually secreted initially as tripsinogen and tripsinogen right you can see origin in the name that's also a zymogen form of the compound right so the thing is you do need to convert that tripsinogen to tripsin the thing that makes that happen is this enzyme that is floridly high ultra remember for the USML step one and it's the enzyme known as entero kinase entero kinase converts tripsinogen to tripsin and then that tripsin can go and convert every other pancreatic enzyme from the zymogen form to the non zymogen of the active form right and the thing is even that tripsin goes back like an up almost like positive feedback loop and converts more tripsinogen but the thing that initially gets you some tripsin from your pool of tripsinogen is entero kinase again you may say divine you're being too detailed and being too detailed because this is actually not being too detailed believe it or not this is the USML step one it's one of those exams where breath and depth actually helps a lot so you need to know a lot of information and you need to know it in good detail versus step

2ck that is more breath than depth you need to know a lot of stuff probably more stuff than you need to know for step one on step 2ck but you don't need to know it in as much detail as you need to for the USML is step one exam so I think that's what I'm going to say about these pancreatic enzymes but please please please you definitely want to make sure you understand all the stuff right now I already talked about the digestion of carbohydrates right in the last podcast right but the thing is how do we digest peptides right so this is actually something that's kind of high yield to understand right so the thing is remember I told you that last time that dysaccharide is is covered dysaccharides to monosaccharides and then those monosaccharides are reabsorbed across the brush border of the small intestine and then you get those into your entire site and then ultimately you get those into your circulation the thing is we actually do not reabsorb amino acids we basically do not reabsorb amino acids like monopep for example well today we reabsorb them as like dipeptides and tripeptides okay the thing is the digestion of proteins for the most part kind of starts in the stomach right remember hydro as an acidic environment right can demature a protein so the thing is that denaturation sort of starts in the stomach right so you consume a protein so let's say you go to McDonald's and eat like a wonderful chicken sandwich that chicken as it lands in your stomach the first thing that happens is it's denatured by by the hydrochloric acid that you find in the stomach right and then that kind of prepares it for preparation for digestion in the small intestine but there is actually another cell in your stomach known as a known as a your chief cells your chief cells actually secret pepsino gene that pepsino gene right is converted so that's again at another zymogen that pepsino gene

is converted to pepsin by the acidic environment of your stomach and then that pepsin actually begins to digest proteins into peptides in the stomach but again the great bulk of the digestion happens at the level at the level of your at the level of your at the level of your small intestine right and again your pancreas again please the major role in that is secrets of tonopolisis that coming to the small intestine like in coming to the doodham and then they help with chopping up those chopping up those peptides into like tripeptides and dipeptides and then kind of like the same theme as I mentioned for the carbohydrates you use sodium in the process of secondary active transport right so sodium flows down its gradient into the intestinal entero site right you use that gradient energy to at the same time co-transport amino acids to co-transport amino acids again let me be a little more specific co-transport like dipeptides and tripeptides because I don't want to say amino acids because again you do not turn amino acid right is like almost like a moon pretty much a monopeptide you do not have the ability to reabsorb monopeptides at the level of your small intestine that's a very important point to be aware of right so so yes you use that sodium linked transport to pretty much make that to pretty much make that happen and then once you're getting the ones the peptides getting to the intestinal entero site they're then pretty much squished into the into your bloodstream through like facilitated diffusion from like the basalateral surfaces of those cells and remember fatty acids right I already talked about how lipase sort of extracts the process with your triglycerides and then bile sort of helps with the rest of the process and I will kind of talk about that as we as we go along today because that's actually kind of high yield to understand and remember I will say some

more things about like this bilirubin process as it relates to the GI tract and the bowel process as it relates to the to the GI tract so yeah as we go along we will we will talk about that I guess I can even kind of give you like an introduction right now right so think about it right so you consume a triglyceride your pancreatic lipase after cool lipase sort of sacrifices it's life for it your pancreatic lipase breaks down the triglyceride into like a monogly acyl glycerol and a free fatty acid so the thing is those fatty acids they're too large to be reabsorbed across the entire site right so you need bowel um bylacets to help you like form like my something known as a micelle right around the fatty acid and then when those are micelles are formed you then passively have the free fatty acids reabsorbed across the surface of the entire site now the thing is when those free fatty acids are reabsorbed into the entire site you actually essentially form a try you like form a triglyceride back inside the entire site you from that triglyceride back using some uh some enzymes that I talked about in the bio camera reviews that you can find again it's one of my earlier podcasting like episode 50 something or whatever right so you form those things those things are known as a chylomychrons and then those chylomychrons um you then basically get them into your lymphatic system so they are like some lymphatic vessels that are closely opposed to intestinal interercysia known as lacteals so LACTEA LS so those lacteals they take those chylomychrons and uh sort of move them all around your lymphatic system ultimately they get to like your thoracic dot and one higher thing you want to remember with those is if a person has like a lymphoma right they can potentially have like a chylothorax they can have like a chylos plural effusion right so you'll be like a milky milky sort of plura

l effusion um another thing that can also cause that is if you have like a something that transects your thoracic dot that's another thing that can cause a chylothorax on mbmexamts but the thing is before you actually get those chylomychrons to uh all those like fatty acids out of the entire site you actually need to put something on them to is almost like almost like a password you sort of like put a stamp on them so that they can safely navigate and be able to like be targeted to specific parts of the body that password that you put on them are your apolipoproteins right to be a little more specific it's apolipoprotein b okay so the thing is apolipoprotein b is super important in letting your um your chylomychrons and like even like your VLDL and what not make its way out of your intestinal interocyte to the rest of the body so if you have a problem where you have no like you have like a genetic issue where you're not making apolipoprotein b guess what will happen you're never able to get cholesterol you will not be able to get like your chylomychrons out of the out of the intestinal interocyte and you begin to have a build up of those things you enterocyte okay and the thing is you may say okay to find how those that clinically present well the way clinically presents is essentially just ask yourself what will happen if your motor you're absorbing fat right you have stature right so you have like floating oily stores that's the first thing second thing is you begin to have symptoms that are consistent with the deficiency of fat soluble vitamins remember your fat soluble vitamins you can remember them with the mnemonic adec so adk so vitamin A so those kids can have like problems with the eye so like my blindness they can have like a secondary hyperparthyroidism because they are not reabsorbing because they don't reabsorb vitamin D right so if you're not reabsorbing

vitamin D you'll not have the ability to reabsorb calcium and phosphate in the gut so you'll be hypochalcymic so your pt 2 rights right so you'll have a secondary hyperparthyroidism from that and then these people can also have like bliggin right because they are not reabsorbing vitamin K and you can also have problems with like cerebellate taxi remember vitamin E is very important for proper functioning of the cerebellum so if you're not reabsorbing vitamin E right you begin to have problems with like A taxia and in addition you also begin to form red blood cells that kind of have these spiky surfaces those things are known as acanthocytes if you say like an acanthocyteosis on an NVMA exam in a patient that has tiaidoria you really want to think about a vitamin E deficiency that's actually one of the ways that classically presents because the thing is vitamin E is kind of required for maintaining the integrity of cell membranes right so if you're not maintaining the proper integrity of your cell membranes you can begin to run into trouble with acanthocytes so again those are kind of like key things you want to remember in that room and again I'll begin to build on these concepts as we get to the like the GI pathologies but I want to again give you a nice physiologic basis for remembering many of these things so that when I begin to talk about the diseases it won't be like I'm speaking Greek or anything like that no offense to the Greeks so I said that bowel right helps you emulsify your lipids right so that you have the ability to reabsorb them across the intestinal interocyte well where does bowel come from the thing is bowel comes from a very complex metabolic pathway but there's literally only one enzyme you need to remember in the synthesis of bile and kind of like biochemistry all you really need to know is the original enzyme right and the thing is you know tha

t bowel comes from cholesterol right so that's kind of like a memory hook for you to remember that cholesterol alpha hydroxylis like cholesterol seven alpha hydroxylis is like the reclimiting enzyme in the synthesis of bile right but the thing is when you make bile you actually make it as a bile acid right so remember from if you remember from general chemistry in college if an acid reacts with a base right you form like a salt and water right that's like a neutralization reaction because basically see for example you take hydrochloric acid and you react to with sodium hydroxide the cation from the base right sodium reacts with the anion from the acid so chloride and then you form a salt right sodium chloride so the same thing kind of happens with bowel right so bile acid right it's an acid itself you can actually conjugate it with mice cation like glycine or touring and those form bile salts okay you may say divine come on very good to know the the cations that go along with bile acid to make it a bile salt think again again remember I've taken many of these exams that you likely taking the future right so again again I'm not gonna say oh I saw this on my exam now that's against the law but I tell you it's very high yield to know those things and the thing is when you make those bile salts right you basically reabsorb them at the terminal helium right so if you have terminal ilial disease like Crohn's disease for example right again if you see terminal ilial disease always think about Crohn's right always think about Crohn's if you have Crohn's disease you do not reabsorb those bowel salts right and you again those people can begin to have like stiadiria like the fatty oily floating like nasty stones that are false smelling okay now the thing is um um bile um I will talk about it as well in the context of in the context of bilirubin but again remember the digestive p

art of bile remember that bile actually has some ability to break down cell membranes of bacteria that's another high yield thing you want to remember but I think the bigger discussion we should probably have relates to relates to bilirubin okay so let's kind of talk about bilirubin because bilirubin and bowel these sort of all again ultimately like come from the liver but there is a few things that happen before bilirubin makes its way to the liver so let's talk about it right so the thing is when your red blood cells don't live forever right the leaf form only three more like four months right so they live for like 120 days so three to four months for red blood cell so the thing is when your red blood cells die pretty much they release their heen but the problem is that heen your body can actually use it to do many things alternatively you also want to be able to get rid of heen right you want to be able to get get rid of it and sort of like put it out or pee it out or something so let's kind of talk about that process where you go from him to pooping or pee out him whichever floats your boat the thing is when you break down so right so when your red blood cell breaks down it forms him right so that heen the first thing that happens is there's this enzyme known as hemoxygenase the hemoxygenase are converts the heen to something called bilirubin and then the bilirubin there's this enzyme known as a biliverdin reductase it converts that bilirubin to indirect bilirubin another name for indirect bilirubin is uncondigated bilirubin the thing is uncondigated bilirubin is not water soluble right so the bloodstream is kind of like a rough neighborhood for it so for indirect or uncondigated bilirubin to be able to flow freely through the bloodstream it kind of needs a body that body is argument so it pairs up with argument and then that argument takes it all the way to the t

o the liver but there are actually some high opathologies you want to remember as it relates to this uncondigated bilirubin binding to argument the thing is if kid has like a hemolytic anemia right or let's say especially like a newborn remember newborns they have very minimal activity of an enzyme that metabolizes uncondigated bilirubin and I will get to that enzyme in a bit but it's like UDPGT UDP gluconeosil transferase newborns have very minimal activity of that enzyme so if they have any process like a hemolytic anemia that makes super super high levels of uncondigated bilirubin right because again with a hemolytic anemia you're chopping up your red blood cells so you're making like a crap ton of heme all at the same time the thing is if you overwhelm the ability of argument to bind to that uncondigated bilirubin that uncondigated bilirubin remember it's lipid soluble it's not water soluble but it's lipid soluble it will have the ability to cross the blood brain barrier and it can begin to deposit in parts of the brain like the bizoganglia right that's essentially what's known as krenicterus okay and again you can also like deposit in the skin and all that so you can have like jundis one other way they actually love to test this is with a patient that's taking trimethoprimsofamethoxazole and that is one thing they actually love to test on the usml step one exam right so for person is taking tmpsmx right tmpsmx loves to bind to argument so that's why in general you try to avoid trimethoprimsofamethoxazole in like neonates because if you give tmpsmx it will compete for binding to argument with uncondigated bilirubin so you can basically displace uncondigated bilirubin into the serum and again that will cross the blood brain barrier it can deposit in parts of the brain especially like the bizoganglia and that can begin to cause lots and lots of problems like krenict

erus okay so let's continue this journey with uncondigated bilirubin right so you make that uncondigated bilirubin you get it to the you get it to the liver right the thing is there are two phases of the of hepatocyte right so your hepatocyte are your liver cells there is a side that faces remember you have a specialized type of capillary network in your in your liver right you have like sinusoidal capillaries that's what those actually are the subject of my research in med school but but that's a different story so your sinusoidal capillaries there's one side of your hepatocyte that faces those sinusoidal capillaries there's another face of your hepatocytes that faces like your bowel docks and your bowel can alkylite okay so the thing is that uncondigated bilirubin actually comes in through on the sinusoidal capillary side of the hepatocyte and then once the uncondigated bilirubin gets into the hepatocyte it's then converted by UDPGT or UDPGT is UDP glucoronocel transfer is it's converted by UDPGT to direct or conjugated bilirubin so again indirect bilirubin is the same thing as uncondigated bilirubin and it is lipid solubon but it is not water solubon direct bilirubin is also known as conjugated bilirubin and that conjugated bilirubin is water soluble it is water soluble so one high ophthalogy you kind of want to keep at the back of your mind is if you have issues at the level of like the endoplasmic reticulum of your hepatocyte because actually UDPGT is an enzyme that's found in the ER of the hepatocyte if you have an issue at the level of the endoplasmic reticulum in your hepatocyte where you lock UDPGT you actually have something called a criglanahar syndrome and again I'll talk about criglanahar syndrome when I talk about the GI pathologies but again I want to kind of introduce it here remember criglanahar syndrome has two types right has a type one where you ha

ve a complete absence of UDPGT so those kids will have like a prominent uncondigated hyperbiliurebenemia or alternatively you can also have criglanahar type two where you have like partial activity of UDPGT right so and you may say how do you tell between those two things on an MBME usually if you give something that's processed of cytochrom P450 like a buried rate those buried rates can operate the production of UDPGT because UDPGT is kind of like a cytochrom P450 enzyme and remember that your buried rates rev up your cytochrom P450 system so if you give a buried rate to a kid that has criglanahar right and you notice that oh their uncondigated hyperbiliurebenemia is beginning to resolve that tells you that you are dealing with criglanahar type two because by giving buried rates your rev of cytochrom P450 you essentially like spursop whatever minimal activity you have with UDPGT and you make more and more UDPGT you metabolize that uncondigated bilirubin and you make more direct bilirubin so I can envisage this as a great experiment question on the US several step one ready talk about like an experiment and you'll begin to see like a decrement in a presence in direct bilirubin with the administration of a buried rate that should basically lead you towards criglanahar type two as your diagnosis so the thing is right so your UDPGT helps you make conjugate bilirubin now that conjugate bilirubin it essentially is released on the bio canaliculio you can see like bar duct side of the hepatocyte and then it goes into like your intra hepatic bowel ducts and then it goes to like your hepatic duct and then your common bowel duct and ultimately mix it with to the to the to the to the to the to the to the to the to the and then from there the conjugate bilirubin mix it with to the colon to have a bunch of stuff happen to it that we will talk about in a bit but let's again keep fo

llowing this process in a granular detail right so the thing is that conjugated bilirubin right so you give it up on the bar canaliculized side of the hepatocyte and then you get it into your bowel ducts the thing is if you have issues at the level of your bowel canaliculus that will actually cause a direct hyper bilirubinemia right it's almost like an obstructive issue it's not really an obstructive issue but it's an issue at the level of the bar canalicula because your bowel canaliculize ultimately feeding to your bowel ducts so if you have a problem at the level of your bowel canaliculize yes you've made the conjugate bilirubin but you won't be able to get it to the to the to the right so that's kind of like the pathophysiology behind like to be in Johnson syndrome and the rotor syndrome and again I will talk about those when I start talking about like the diseases of the GI tract so those people obviously again will have a conjugated hyper bilirubinemia and actually many people kind of think that oh bilirubin the most important step is that UDPGT step I mean it's it's important but it's actually not the reclimiting step of bilirubin metabolism the reclimiting step is actually that step that involves the excretion of conjugated bilirubin to the bowel canaliculized okay it's just one of those weird biochem-releafed concepts that they love to test on the USML step one so now the thing is when you then from that conjugated bilirubin it makes its way to the to the colon and the thing is your colonic bacteria they love to act on that conjugated bilirubin they can convert it to things like stercopillin they can convert it to things like uro bilinogen okay the thing is that stercopillin right think of stercopillin the first two letters of stercopillin is ST remember that ST false the ST in ST okay stercopillin actually gives you the color of your STO the thing is uro bili

nogen actually makes its way across the I mean some uro bilinogen you put it out but some uro bilinogen actually is reabsorbed in the GI tract and then it's converted to uro bilin and then that uro bilin makes its way to the urine right in fact uro bilin remember the first two letters in uro bilin you are for the first letters in urine uro bilin actually gives urine its color so uro bilin gives your urine its color right so let's kind of talk about hi you this so just give you a full warning like the next like four or five minutes of the spot cast may be a little hairy so this is probably one of those areas where you want to pay attention so let's sort of break this thing down right so first thing I said is that unconjugated bilirubin is water insoluble right that's one thing second thing is unconjugated bilirubin is converted by UDPGT to conjugate bilirubin right and then I said that because unconjugated bilirubin is not water soluble in general you should not find it in the urine right but if a person has conjugated hyper bilirubinemia the thing is conjugate bilirubin is water soluble so if you have very high levels of it in the blood you can actually find it in the urine again important to understand this things and I mentioned that uro bilinogen right and uro bilin they are all kind of like important for the color of your urine those things are made in the GI tract okay so bilirubin has to make its way to the GI tract for you to have uro bilinogen or uro bilin so why is this important this is important because occasionally on MBM is they will write the question that has like many different arrows and those questions are targeted towards getting you to elucidate the difference between a conjugated hyper bilirubinemia and an unconjugated hyper bilirubinemia so let's think about this for a second if for example let's say a person has like criglanda heart syndrome whe

re they don't have udpgt or they have like guber syndrome where they have like decreased activity of udpgt or let's assume like you have like some kind of hemolytic anemia where you're making like a crap ton of like heme right and then you ultimately make a crap ton of like bilirubin how can you sort of detect that right so let's think about this for a second if a person has like criglanda heart syndrome or guber syndrome right they lack udpgt what kind of hyper bilirubinemia would those people have do you have an indirect hyper bilirubinemia right that's kind of easy now will these people have elevated or reduced levels of conjugated bilirubin they will have decreased levels right because again udpgt is not working now for these people would you find bilirubin in their urine so think about it you have an indirect hyper bilirubinemia is indirect bilirubin soluble in water no it's not so you will not find a bilirubin in these people's urine right but let's assume that this person's indirect hyper bilirubinemia is from a hemolytic anemia right the thing is if you have a hemolytic anemia there is a you have the indirect hyper bilirubinemia is that you've just overwhelmed udpgt udpgt is around what is just working over a time because you're just overloading it with too much indirect bilirubin all at once the thing is if the cause of an indirect hyper bilirubinemia is a hemolytic anemia you'll be making a ton of indirect bilirubin right as you're making a ton of indirect bilirubin you overload udpgt but at the same time you'll actually be making a ton of direct bilirubin right because it's like there's just more flux through udpgt because there's just more literally like more fit stock for it so the thing is if you're making if you have like more udpg if you have a more conjugated bilirubin being produced you can already begin to imagine that you'll make more like euro bil

inogen and more euro bilin so you'll begin to actually find more of those things in the urine the reason i'm being super detailed here is i can in this age a step one question where they try to get you to differentiate between hemolytic anemia as the cause of an indirect type of bilirubinemia and guilbert syndrome or like regular and a heart syndrome as the cause of an indirect type of bilirubinemia so let me repeat this again if you have guilbert syndrome or criglan a heart syndrome as the cause of an indirect type of bilirubinemia you will not be able to make conjugate bilirubin if you're not able to make conjugate bilirubin you are not making anything that can make it to the colon to be acted on by the flora that you find in the colon to be converted into like euro bilinogen and euro bilin that then make its way to your urine and then show up in your urine so if a person has guilbert syndrome or person has criglan a heart syndrome they'll have an indirect type of bilirubinemia they will have no bilirubin in the urine because indirect bilirubin is not soluble in water but they will actually also have no elevations in urinary like euro bilinogurabinogen okay because the enzyme is not working so because the enzyme is not working they're not making the feedstock for euro bilinogin and euro bilin which is conjugated bilirubin however if a person has an indirect type of bilirubinemia from hemolytic anemia they don't have any problems with uDPGT right UDPGT is working just fine but the reason they have the indirect hyperbiliure bilirubinemia is because they are overwhelming UDPGT so they'll have high levels of indirect bilirubin but because UDPGT is working and you're overloading UDPGT they will also have elevated levels of direct bilirubin or conjugated bilirubin and that direct bilirubin will make its way to the colon and be converted to like by the colonic bacteria the

y are mostly like anaeropes into like euro bilinogin or euro bilinogin.

So if a person has an indirect hyperbiliure bilinemia from a hemolytic anemia they will actually have elevated levels of euro bilinogin and euro bilin in the urine okay again I know like I'm spending time on this I know this podcast is running long but again I try to tutor people to kill exams not to do okay on exams okay so make sure you understand this if I were you I'll probably rewind this but I just listen to it again it's one of those things that are subtle but it's very high yield to understand and remember but let's then contrast this with a person that has say for example they have like an obstructive process right so let's say they have like primary bilirubin and conjugated remember that's associated with with anti-malochron gel antibody and anti-malochron gel antibodies or let's assume a person has primary sclerosis in colon jaydis remember that's associated with P enca and all three different colitis or let's assume a person has like the dubbing Johnson syndrome of the rotors syndrome with a bulk analycule like I all screwed up right or let's see a person has like any biliary tract problem right so let's assume they have like a cancer of the abelary tree so like a colanducarcinoma or they have like a gallstone that's obstructing the abelary tree right or they have like an infection with I think the liver fluke and chlornorchesa synences right those things will all back up conjugated bilirubin in your GI in your in your liver right so those people have a conjugated hyper bilirubinemia because the enzyme works just fine they're making the conjugated bilirubin but as you're making that conjugated bilirubin it has nowhere to go it cannot make its way to the duodenum but if you understand what I just explained for the if you understand what I've been explaining so far then you can reason what you should observe in a conjugated hyper bilirubinemia right so obvio

usly you have elevated levels of conjugated bilirubin now conjugated bilirubin is soluble in water so guess what people that have a direct hyper bilirubinemia or a conjugated hyper bilirubinemia will have elevated levels of conjugated bilirubin in the urine so they'll have high levels of bilirubin in the urine very high you'll to know that but think about it this conjugated bilirubin that these people is it making its way to the urine it is not right it is not so and the reason it's not making its way to the urine is you have like literally a physical obstruction then it's not letting that conjugated bilirubin get it get to the colon right and the conjugated bilirubin doesn't get to the colon it will never see the colonic flora you'll never make your biline or gin you'll never make your biline so you'll never find elevated levels of those things in the urine so again I can imagine the mbme giving you a question where they will label something like ab and c and then they will give you all these hours where for example this is high this is low this is low this is high and then you have to match it to different scenarios right so again remember if a person has an indirect hyper bilirubinemia from like your birth syndrome or or criglan or heart syndrome they will have high levels of indirect bilirubin they will have no bilirubin in the urine because indirect bilirubin is not water soluble and they will not have elevated levels of european origin or european in the urine because again the enzyme doesn't work so they never make conjugated bilirubin in the first place contrast that with an indirect hyper bilirubinemia that is arising from a person that has a hemolytic anemia the uDPGT works well in those people they're just overloading uDPGT so those people have an indirect hyper bilirubinemia in addition they will also have a direct hyper bilirubinemia but because they're m

aking conjugated bilirubin that conjugated bilirubin will make its way to the colon they'll make urubinogen they'll mix tracobillin but they'll so because because of that they'll have elevated levels of urubinogen and urubin in the urine okay so again but again they will not have bilirubin right they will not have bilirubin in the urine because again that indirect bilirubin is not water soluble and if a person has an obstructive process right so they have like a conjugated hyper bilirubinemia they'll have elevated levels of direct bilirubin that's kind of obvious they'll have high levels of bilirubin in the urine because direct bilirubin is water soluble and then they will have no urubinogen elevations in the urine because again if you have obstruction when you get a bilirubin it does not make its way to the colon if it doesn't make its way to the colon it would not see colonic floor if it doesn't see colonic floor you would not make urubinogen okay so you can already see that the only thing that really does cause an elevation in urine urubinogen is hemolytic anemia but that'll be associated with an indirect hyper bilirubinemia okay so again you see the different permutations of these these things that's why you can already begin to see that this is like good fodder for the USML step one example and I mean some people can have both like mixed right so like they have a direct and an indirect hyper bilirubinemia they very rarely test these kinds of things although like remember cirrhosis can cause this if a person has like a viral hepatitis or like a like a drug hepatitis that can all cause like a mixed hyper bilirubinemia right so things that kind of all out of whack here so they'll have like a direct hyper bilirubinemia they'll have an indirect hyper bilirubinemia they'll have elevated bilirubin in the urine because that direct hyper bilirubinemia they have that eleva

ted will shop in the urine they will have urubinogen that may be higher or low it it's just kind of all over the place right so they really test that okay so those are things you kind of want to keep at the back of your mind so I see that this podcast has gone on for a long so I'm going to go ahead and stop here but again I'm almost done talking about the physiology of the GI tract in fact probably in the next podcast now finish up the like the next GI podcast I make of kind of finish of the physiology of for gastroenterology and then I'll begin to jump into the GI epithology so as I round up as I always say I do offer one on one tutoring for the USML is step one step two CK step two C.S step three the preclinical medical exams and the third year shelf exams I also do offer tutoring for the medicine in training exam and the internal medicine board exams you may say hmm the vineyard your resident how you offering tutoring for those just send me an email I'd be happy to explain why over an email over the phone and then I do also offer tutoring for college subjects right so if you have like a sister or brother that's in college and taking like general chemistry organic chemistry physics physiology biochemistry histology I do offer tutoring for all those things and then if you're a med student applying to residency so like an ERAS application or a college student applying to med school that's an AMCA application feel free to reach out to me I've been on the admissions committee of a top two med school for a year so I've shifted through like thousands and thousands of super high quality applications so I can sort of prepare you to make your application the best it can be so things like mock interviews personal statement right in application prep I can help with those things to basically help you put your best foot forward again I've worked with tons of people in this proce

ss and pretty much everyone I've worked with especially like the med students applying to med school or the college students applying to like so the med students applying to residency sorry and the college students applying to med school pretty much all of them have like matched if you're thinking about I guess a med student or I've got it into med schools like med schools of your choice most people their first choice so take that for what you will and I am really happy that that the raptors one the the MBA finals I mean how good how good was that although I do feel bad for the good in state warriors with Clay Thamson and KD having like let's call them career all three injuries if you may although I don't think Clay Thamson will have much of an issue because his game does not depend on being able to dribble he just pulls up and shoots but we'll talk about some more basketball stuff in in a different podcast have a wonderful rest of the day God bless you and I'll see you next time thank you

Enterokinase.

Vitamin B12 (Cobalamin).

Cholesterol (via cholesterol $7\alpha$-hydroxylase) and amino acids like Glycine or Taurine.

Indirect/Unconjugated hyperbilirubinemia, because the rate of heme production overwhelms conjugation capacity.

Vitamin E deficiency.

Sodium ($\text{Na}^+$) linked secondary active transport (SGLT1 mechanism).

It activates adenylyl cyclase $\rightarrow$ increases cAMP $\rightarrow$ stimulates CFTR channels $\rightarrow$ massive $\text{Cl}^-$ secretion into the lumen.

Indirect is lipid-soluble, requires albumin for transport in blood, and cannot be found in urine. Direct is water-soluble, can be excreted in bile/urine, and indicates conjugation has occurred.

Hemolytic anemia shows high indirect bilirubin AND elevated urinary urobilinogen/urobilin (because UDPGT is functional). Gilbert syndrome shows high indirect bilirubin but NO elevated urinary urobilinogen/urobilin.

Impaired chylomicron formation and export from enterocytes. Clinically presents as steatorrhea (fat malabsorption) and deficiencies of fat-soluble vitamins (ADEK).

It reduces ferric iron ($\text{Fe}^{3+}$) to ferrous iron ($\text{Fe}^{2+}$), which restores oxygen-carrying capacity. This highlights that $\text{Fe}^{3+}$ cannot carry oxygen while $\text{Fe}^{2+}$ can.

Lipase breaks down triglycerides into monoglycerides and free fatty acids. Colipase acts as a protective agent/inhibitor that allows lipase to function despite bile salts.

It activates adenylyl cyclase $\rightarrow$ increases cAMP $\rightarrow$ stimulates CFTR channels $\rightarrow$ massive $\text{Cl}^-$ secretion into the lumen.

Indirect is lipid-soluble, requires albumin for transport in blood, and cannot be found in urine. Direct is water-soluble, can be excreted in bile/urine, and indicates conjugation has occurred.

Hemolytic anemia shows high indirect bilirubin AND elevated urinary urobilinogen/urobilin (because UDPGT is functional). Gilbert syndrome shows high indirect bilirubin but NO elevated urinary urobilinogen/urobilin.

Impaired chylomicron formation and export from enterocytes. Clinically presents as steatorrhea (fat malabsorption) and deficiencies of fat-soluble vitamins (ADEK).

It reduces ferric iron ($\text{Fe}^{3+}$) to ferrous iron ($\text{Fe}^{2+}$), which restores oxygen-carrying capacity. This highlights that $\text{Fe}^{3+}$ cannot carry oxygen while $\text{Fe}^{2+}$ can.

Lipase breaks down triglycerides into monoglycerides and free fatty acids. Colipase acts as a protective agent/inhibitor that allows lipase to function despite bile salts.