Liver Function Tests (LFTs) | Retired

what's up ninja nerds in this video today we're going to be talking about liver function tests sometimes referred to as liver biochemical tests we're going to talk about a lot of stuff before we get started if you guys like this video you benefit from it it makes sense please support us and the best way that you can do that is by hitting that like button commenting down the comment section and please subscribe also if you guys want some amazing notes some awesome illustrations to follow along with during this video go down the description box below we have a link to our website where you guys can get access to all of those things let's hop right into it and start talking about liver function tests or liver biochemical tests so when we talk about these liver tests we want to look at these tests in a couple different ways there's a bunch of different components of these liver tests the first thing we want to look at is the tests that tell us about hepatocellular injury so you know the liver cells most of the parenchyma of the liver is made up by these cells called hepatocytes they make up like 80 percent of the liver parenchyma we also want to know if there is any hepatocellular injury what types of particular enzymes would be leaking out of these cells the other thing that we'll talk about is biliary injury so we have these different things called bile ducts and there's particular enzymes or substrates which are found in those biliary ducts that if they're elevated in the blood they could be indicative of biliary injury so again we're talking about these liver biochemical tests and we're looking at liver enzymes we're particularly looking at these in the sense when there is injury to what types of parts of the liver the hepatocellular component the apatocites are being damaged or the biliary ducts are being damaged so let's talk about the hepatocyte first and then we'll start talking about the biliary stuff a little bit after so epatis cellular injury when we take and consider whenever there is some type of injury to the liver the most common things that we'll discuss today usually is if we take a look we actually zoom in on this liver and we'll look at the cells that make it up this is our hepatocytes the hepatocytes if they are injured right so there's some type of damage to these apatocites and what could be the damage what could be the damaging factor the damaging factor is usually some type of necrosis so there's some necrosis of the actual liver cells and there could be many different reasons as to why there can actually be necrosis there could be infection there could be sepsis there could be a lot of different reasons there also could be massive amounts of inflammation and that inflammation of these hepatocytes may also cause them to become destroyed or injured when these hepatocytes become injured in a particular way they maybe become more permeable and when they become more permeable they allow for very specific types of enzymes that are found in these liver cells to leak out and when they leak out they may leak out into the bloodstream and they may become elevated in the bloodstream and this is something that we test when we think or suspect that someone has a liver injury so again whenever there's some type of necrosis of these hepatocytes which are again the cells that make up the liver or there's massive amounts of inflammation of these hepatocytes they become more permeable and allow for these enzymes to start leaking out of them and into the blood and we can test that as a parameter for liver or hepatocellular injury what are these enzymes that are super important that are very high concentrations in our liver cells the first one that i want you guys to know is this blue one here this is called a s t now ast is a type of amino transferase right so it particularly is involved in amino acid metabolism particularly taking like aspartate and converting it into a different type of molecule that we can use for gluconeogenesis or different processes so this is called the amino transferase but particularly this is an aspartate type of amino transfer so that's one of those enzymes that are released from the apatocites the other one is called alt now alt is actually referred to as an alanine amino transfer same thing as the ast it's involved in amino acid metabolism that we're utilizing to take and convert alanine to different substrates that we can use for gluconeogenesis so either way both of these are involved in amino acid metabolism in some parts also in gluconeogenesis so what is the significance of these well before i actually talk about that there's something else that you have to realize between these two enzymes ast it is released from the liver whenever there's liver injury hepatocellular injury but also ast is non-specific and it can be released from other tissue cells that have been injured what are those tissue cells because that becomes very important when we're measuring lfts and our ast is super super high and our alt is just a little bit high that might make us think there might not just be a solitary liver injury there could be something else going on or something else that's causing that rise what is that thing so you know in conditions where your red blood cells actually pop open and they undergo a process called lysis they may spill out some of these enzymes because these enzymes this ast can be found in red blood cells what is that process called when you pop open red blood cells hemolysis so if there's certain types of hemolysis or hemolytic reactions this may also cause a small bump in the ast your skeletal muscles these are also containing certain amounts of ast and if there is any destruction of these they may leak these out into the bloodstream what is it called when you actually bust open particular skeletal muscle cells what are that called rhabdomyolysis so there may be a condition called rhabdo we're just going to put rhabdo for right now but it'll be rhabdomyolysis another one is you know there's particularly these enzymes that are also found in the myocardium of the heart so if there's an injury to the myocardium of the heart it also may release these ast molecules that accumulate into the actual bloodstream what does this call when you actually damage the cardiac tissue of the heart you know what that's called a myocardial infarction so one of the big things to remember is that if patients have these very very high ast levels so again one of the big things to remember is if the ast levels are super super super high you want to consider there could be a liver injury but there could also be hemolysis rhabdomyolysis or myocardial infarction that's also going on and so we have to think about that in our differential generally what we say is whenever the ast over the alt ratio this ratio here is greater than or equal to five it more likely supports the above causes such as hemolysis rhabdo or mi that's an important thing to think about there's another particular thing that we want to think about with ast you know ast not only increases in situations of liver injury hemolysis rhabdomi there's something else that also causes it up in the ast in comparison to the alt you know people are drinking lots of alcohol lots and lots of alcohol alcohol consumption alcohol abuse in those situations of alcohol abuse okay sometimes what can happen is when you look at the ast and the alt ratio if it's greater than two this may suggest some type of excessive alcohol consumption or alcohol abuse so this may suggest lots of alcoholic types of liver disease so these are things that i want you guys to think about here whenever you're having a patient who has hepatocellular injury there's injury to their hepatocytes they're leaking out asd and alt but please be remembering that ast is not only released by liver cells when they're injured it can be released by red blood cells skeletal muscles and cardiac tissue the other thing is whenever that ratio of ast over the alt is super super high you're thinking about all these other organs all the ones that we just talked about so you're thinking about hemolysis rhabdomi but if the ast over the alt is greater than two you might want to start thinking is there a possibility that there could be alcohol intoxication or alcohol abuse or alcoholic related liver disease and those are things to be thinking about okay go to the alt next the alt is way more specific okay so it's way more specific for liver injury so that is a really important thing here so if we have someone who's alt is much greater than their ast we're definitely thinking liver related injury so these would be things that we'll talk about a little bit later such as patients who maybe have viral hepatitis or ischemic hepatitis where they have some type of autoimmune hepatitis in those cases where we'll talk more about hepatitis okay where there's some type of hepatitis this may be the likely cause of their elevation in alt and ast but particularly more specifically in elevation in the alt in comparison to the ast okay so we have an idea here about what we really need to understand here about liver injury particularly hepatocellular injury whenever there is necrosis inflammation of the epadocytes it can leak these enzymes ast alt ast is particularly non-specific for liver injury you can also have that elevated hemolysis rhabdomi as long as the ast is super elevated above the alt where the ratio is greater than equal to five it's likely coming from another source besides the liver but if the ast is greater than the alt by the ratios greater than two think about testing for alcoholism or asking in their history about any alcoholic abuse that could be causing this liver disease so these are things to be thinking about okay now that we've covered these hepatocellular injuries what is the next thing that we should think about we should think about biliary injury and what kind of tests we can utilize for this so let's come down and talk about this process all right so now let's talk about particular tests that we can look at for biliary injury so we sometimes call these biliary injuries like holy stasis or some type of cholestatic process and all that means is that there's a reduction in biliary flow for whatever reason maybe it's due to a decreased production of bowel maybe there's a blockage that's obstructing the bioflow that's kind of the whole process we want to know what is causing that issue and so generally again one of the particular things that i told you to think about here is there's maybe a decreased production of bile or there's maybe something that's obstructing the biliary flow it's more common that there's usually some type of obstructive process that is up you know basically blocking the biliary flow so let's imagine for a second that here's there's a blockage right so there is a obstruction here that's present within the biliary ductal system when there is that obstruction present what happens is that you have particular molecules that are present in your biliary ducts naturally and what are these molecules well the first one here in black this one here is called ggt okay gamma glutamine transferase so that's this particular molecule here the pink one over here this is another really interesting one and this one is actually going to be called alkaline phosphatase which we abbreviate alp and then the last one that i want you guys to remember here is this one in green and this one in green here is actually a very interesting molecule and this one is called bilirubin okay it's called billy rubin so there's a bunch of different molecules that's present within our biliary ducts let's say that's imagine for a second there is an obstruction of the biliary flow so normally the biliary flow will actually your hepatocytes naturally they actually make a component they make all the substances that are important for bile and that bile should naturally kind of flow downwards and out through the biliary duct and eventually into the intestines well imagine there's an obstruction that's blocking the biliary flow and now all this bile is starting to back up back up back up back up into the actual what into the circulation okay so if some of these molecules are actually backing up backing up backing up into the circulation they may just go ahead and just have this process where they flow right back into the blood circulation and this may cause an elevation of particular enzymes that are present within the blood and again what enzymes may actually increase within the blood there may be an increase in ggt there may be an increase in alkaline phosphatase and there may be an increase in bilirubin we're just going to put billy for right now so bilirubin so this is something that you could see with an obstructive process so an obstructive process you may see an elevation in alkaline phosphatase bilirubin and ggt now another particular interesting thing here is that sometimes if there is inflammation of both the apatocites and the biliary ducts for some reason so there's injury to both of these nearby so the small docs and then the apatocites nearby sometimes if there's nearby injury you can also leak some of these other molecules that will actually leak into the bloodstream and what are these molecules that could potentially leak into the bloodstream ast right you can have some of that leaking into the bloodstream as well as this other molecule here called alt and so sometimes when you're thinking about biliary injury you all automatically say oh the only real thing that would actually if there's a biliary injury like where there's an obstruction whether there's inflammation of these biliary ducts or whether there's inflammation of the nearby hepatocytes in the biliary cells it should only produce ggt billy and out phos elevation that's not necessarily true in these biliary entries because these biliary ducts are nearby hepatocytes if there's inflammation of the biliary ducts there's likely going to be inflammation of the apatocites if there's inflammation of the hepatocytes but also can leak out ast and alt so also remember that okay so let's say that we have this process where there's an obstruction it's obstructing the flow of biliary flow right so you're going to have this up in these particular enzymes these are the ones that i really want to focus on let's talk a little bit about ggt what is it we need to know about ggt well ggt again is this thing called gamma glutamine transferase it's important within different pathways that are involved in the biliary flow process ggt is really interesting because whenever ggt is elevated it's a little bit more specific it's a little bit more specific than alk foss that's kind of where it gets its benefit where the some of the literature will say ggt is a little bit more specific for biliary injury in comparison to alkaline phosphates i'll explain why in a second but it's important to remember that a lot of different things can elevate your ggt but why do we use ggt the particular reason why we would do this is that we have someone who has an elevated alk floss and you want to confirm it's a liver problem it's a biliary problem because ggt is more specific for liver injury than alkaline phosphatase if alk foss is elevated you would check a ggt to confirm that it's actually the liver problem it's a biliary problem problem is though is that sometimes what's not realized is that ggt can be elevated by a couple other things besides liver injury sometimes in patients who have profound alcohol abuse they can also have an elevation in their ggt or if they have some type of underlying diabetes mellitus where there's a insulin resistance in certain situations this also can elevate the ggt so it's important to realize that why do we use the ggt ggt is one of the enzymes that's present in our biliary ducts if it's increased in the blood that means that there was probably something that was obstructing the flow or was inflaming or decreasing the biliary flow process and causing that ggt to up within the blood okay the reason we use it is a little bit more specific for biliary injury than alkaline phosphatase so if someone had an up in their alkaline phosphatase you would check agt to see if that's elevated and if it is elevated you can at least say with some degree of certainty that it's likely from the liver and not from another source that that alkaline phosphatase is elevated okay so that's the first one so ggt done again what is it telling me that there is some type of decreased flow there's an obstruction there's no movement of biliary flow and the biliary substances are moving back into the bloodstream okay second thing is bilirubin bilirubin is really interesting because when we talk about bilirubin it's actually somewhat of a complex pathway so if we take for example where the whole bilirubin process comes from let's say we have these cells here these are called your macrophages right now your macrophages are they're eating types of cells they're big eaters so what they do is they actually phagocytose old and defective red blood cells when they break down the red blood cells they break down the component that we need within the red blood cells called hemoglobin and they break it down into amino acids which is the protein component into a heme component and that heme component actually gets broken down into a molecule called bilirubin now bilirubin when it's actually released from these macrophages and into the blood it's bound to make some like plasma proteins like albumin but it's not technically conjugated okay so what is this type of bilirubin that's just floating within the bloodstream that just got released okay it got released from the macrophages this type of bilirubin that's actually floating in the blood before it got to the hepatocytes this is a very different type of bilirubin this bilirubin is called there's two names for it unfortunately it is either called unconjugated bilirubin we're just going to put billy sometimes in the clinical world we actually refer to this as a indirect billy or eye billy okay so the indirect ability or the eye billy now once that bilirubin is actually released into the bloodstream it binds to the albumin the albumin will transport the bilirubin to the apatocites and take the bilirubin up into the hepatocytes now it's going to be taken into these cells so it's still unconjugated bilirubin in the actual hepatocyte there is a very special cute little enzyme and this enzyme is called ugt what is this enzyme called it's called ugt and what ugt does is it takes the bilirubin and puts something onto the bilirubin to make it conjugated to make it very polar where it can be put into the bile and we're going to mark it as this little red molecule here and that red molecule is called glucoronate it's called glucoronate what happens is now that this is actually conjugated we can put this into the bile as a component of it right so now i have my bilirubin which is bound to what the glucuronate this type of bilirubin is a very different type of bilirubin this one is actually referred to as conjugated bilirubin okay but oftentimes we call this the direct billy or the d billy the combination of these two if you add both of these two together give you what's called the total amount of bilirubin that you would have the ones that is really important that we want to think about in these biliary injuries though is the d billy because where is that actual bilirubin now this one right here it's in your biliary ducts so when you think about this it's really really important we'll talk about a little bit later is when there is an elevation in the bilirubin you have to differentiate which type of bilirubin is actually elevated is it the unconjugated or the indirect bili that's just bound to albumin that came from hemolysis or is it the bilirubin that was actually conjugated in the liver and put into the bile and this is called your direct bili the combination of these two though is referred to as your total billy now what's the problem with this bilirubin why is this son of a gun such an issue well the problem with bilirubin is that sometimes this bilirubin whenever you have high levels of bilirubin and they spill into the blood these high amounts of this bilirubin molecule can get deposited into different tissues and give it a very interesting type of hewish discoloration and we call this like a jaundice discoloration so some of this bilirubin will get deposited into the skin like the palms of the hand soles of the feet and this may produce a jaundice type of appearance or it may deposit into the sclera and again give a jaundice type of appearance sometimes we call that icterus but either way that's one of the really really important things to remember about this bilirubin process okay so we have an idea now that whenever there's biliary injury whether it's an obstruction or again let's put this down here whether it's an obstruction or there's an inflammatory process there's some type of inflammatory process so it could be obstruction it could be inflammation of the biliary ducts this may cause a reduction in biliary flow causing it to back up into the blood or if there's some type of hepatocellular injury in nearby biliary injury this can also cause that backup of these substances ggt billy and alkfoss along with it there's hepatocellular injury alt and ast now last thing to think about so we talked about our ggt we talked about the bilirubin my friends now what we have to finish off talking about is this alkaline phosphatase the alkaline phosphatase is another molecule that can be increased in the blood due to an obstruction of the biliary ducts inflammation of the biliary ducts or just a decreased flow of bile maybe because there's some nearby hepatocellular injury and biliary duct injury small little biliary ducts if the alkaline phosphatase increases what does that tell me again we already know it tells me that there's some type of obstruction here's the problem with alkaline phosphatase remember i told you that it's not as sensitive for liver injuries the reason why is there's other conditions that can increase your alkaline phosphatase you know what these conditions are or what organs that if they're injured or there's some type of increased process going on in them that they can also up your alkaline phosphatase you know in patients who have a lot of bone turnover tons and tons of bone turnover you know there's a condition called paget's disease i'm just going to put down one of them but any kind of high turnover disease such as in a condition called paget's disease there's lots and lots and lots and lots of bone turnover they will naturally have an elevation in their alkaline phosphatase so if you see a patient has an elevation in their alkaline phosphatase what should you think about well i could order a ggt to see if that's definitely coming from the liver but i could also go looking to see if there's any kind of bone processes that i got to look think about okay that's why alkaline phosphates is not as specific if it's elevated consider checking a ggt to confirm it's coming from the liver because that is more specific and the alk foss is can actually be elevated from other organs other organs that it can actually come from is kidneys so if there's certain types of increase in kidney turnover like in chronic kidney disease or some type of acute kidney injury or here's another one pregnancy so in certain types of pregnancy you know that one of these organs here that actually just basically is giving a lot of the blood supply and removing waste product from the baby there's this organ here called the placenta the placenta in pregnancy likes to increase a lot of alkaline phosphatase so if someone's pregnant they may also have a jump in their alkaline phosphatase so these are things to think about so when we think about alkaline phosphates just remember one of the big things for this one not specific to liver so what we should follow up on is checking that ggt to see if it's elevated there is other ways that you can check there's different types of alkaline phosphatase and so you can fractionate them just like you fractionate bilirubin and say is this alkaline phosphatase the type of it actually coming from the liver we don't technically do that unless you're in some type of special hepatology center but either way these are the big things that i need you guys to understand that if these enzymes are elevated ast alkaline phosphatase bilirubin ggt and alt they are markers of injury to what types of cells the hepatocellular component the apatocites more specifically ast alt and if the ggt the bilirubin and the alkaline phosphatase are elevated this is likely a damage or inflammation obstruction of their biliary ducts or nearby small hepatic duct inflammation due to hepatocellular dysfunction now that we've covered that and we talked about the tests for liver injury let's talk about the tests that tell us about the true function of the liver all right let's now talk about tests when we're actually talking about liver function tests you can actually look at some of the functions of the liver right so we talked about injury to the liver ast alt ggt alkalos bilirubin technically bilirubin also is a marker of function too because technically again the liver enzymes the ugt has to be able to convert the unconjugated bilirubin into conjugated so in a way we could also say that the bilirubin synthesis is technically a hepatic function as well however let's talk about particularly three things that tell me a good amount about liver function one of those is albumin so you know the liver is a protein factory right it makes tons and tons and tons of proteins one of those proteins that the liver actually synthesizes is a protein called albumin now what we need to know about the liver and whenever it's injured before that is what albumin does and then once we know what it does we can say okay if it's injured obviously there's going to be a decreased production of albumin so naturally what albumin does is imagine here i have some albumin molecules that are inside of the bloodstream okay what the albumin does is it creates something called an osmotic gradient okay which the whole point of that is to pull water into your blood vessel to keep the actual uh well we'll put blood vessels we'll put blood vessel it's to pull and keep the water in the actual bloodstream in the intravascular that that's its job now if there is a condition in which the liver is injured you know usually whenever the liver is injured it's usually going into failure or they're having cirrhosis so usually when we see liver failure or complete liver failure severe liver injury so again what would be particular things that we would see these particular issues in is when someone has liver failure right maybe they're in acute liver failure maybe they're an acute on chronic liver failure or they have some type of true cirrhosis so in these situations the liver function is declining significantly in other words imagine if multiple multiple hepatocytes were damaged if multiple hepatocytes were damaged are they going to be able to make albumin properly no so if someone has multiple fibrosis of their liver in other words a lot of the parenchyma is replaced with fibrous tissue fibrous tissue can't make albumin and if a lot of their liver cells are injured or damaged in an acute liver failure or an acute on chronic liver failure they don't have as many hepatocytes to be recruitable to make albumin so whenever this happens the albumin levels will drop and albumin tells us about liver function generally over a span of about two weeks because that's about it's half life so now if albumin levels in the blood drop precipitously what's going to happen to your ability to keep water and pull water into the bloodstream so your ability to pull water into the bloodstream now is going to be reduced so all of this is going to be inhibited you aren't able to keep the water into the bloodstream and so instead the water starts staying in the interstitial spaces so it accumulates in the interstitium and when it accumulates in the interstitium there's particular areas that it likes to accumulate in certain areas one is it loves to accumulate in the peritoneal cavity if it accumulates into the peritoneal cavity this causes a condition such as ascites it also loves to accumulate in the interstitium of the lower extremities causing petal edema so these are things to think about whenever someone has severe liver failure whether it be acute acute on chronic or fulminate complete cirrhosis of their liver where their ability to make albumin is decreased they lose the ability to maintain this osmotic gradient and keep the water in the blood vessels and so the amount of actual water that's in the blood vessels is less so their intravascular water is lower and their interstitium amount of water is much higher which precipitates this findings of ascites and pedal edema what do we call this condition whenever there's low albumin levels within the blood we call this hypoalbuminemia and this can sometimes be seen in liver failure you know another condition that you can also see lower levels of viewing besides liver failure because you'd have this on your differential on the differentials you should also be thinking about what are the conditions that can lower albumin so the differential for low albumin should be if somebody has some type of renal failure like what you know there's a condition called nephrotic syndrome so if they have some type of nephrotic syndrome this can also cause a drop in albumin because they're losing a lot of that albumin into the urine or if they have some type of malabsorptive syndrome so they have some type of gastrosis so in other words there's some type of abnormality within their gi tract where they're not able to absorb a lot of that albumin and if they can't absorb the albumin that might be an issue and so there's some type of gastrosis or some type of malabsorptive syndrome that's occurring so they're either losing or not absorbing the albumin across the gi tract peeing out the albumin or in liver failure they're not making albumin so these are things to think about on your differential okay in another future video we can talk about something called a protein gap you can use that for differentials we're not going to talk about that here i believe that's beyond the scope so what i want you to know is that liver function can be measured by albumin and if albumin levels are low these are the things that you can see you can check the albumin on their actual um particularly from a cmp there's a their comprehensive metabolic panel and you can look at their level of auburn and if it is low think about these particular cases you can also check something called a protein gap which looks at their total protein minus their albumin and if there's a lot of protein that's in that gap sometimes you can think about other conditions like multiple myeloma sepsis autoimmune hepatitis things of that nature but we're not going to go that far we'll talk about some of those things in future videos okay so we got albumin as one of these things that tells us about functional liver what is something else that can tell us about functional liver something else is the coagulation proteins we call this the pt or the inr let's come down and talk about that now all right so another one is this concept of a pt inr right so you know what else the liver makes it makes a lot of different types of coagulation proteins and the ones that you actually do need to take the time to remember is it makes these proteins called factor 2 which is also known as thrombin factor 7 factor 9 factor 10 protein c and protein s i don't know what happened another comma there but these are the big big coagulation proteins now the big thing that you actually have to understand about these proteins is these proteins are pro coagulants all right so they want to induce clots right that's their whole job they're not anti-clotting or anticoagulant proteins they're particularly pro coagulant proteins so they want to induce clots i think that's the easiest way to remember here here's the big thing that you can't forget though these proteins such as factor 2 7 9 10 c and s these not only do they induce clots but they're important but they actually tell us about certain types of pathways right and so one of the things that they do is they tell us about the amount of time it takes for us to be able to bleed or clot and so particularly one of those main factors is factor seven and factor seven is involved particularly within the extrinsic pathway and because it's involved in the extrinsic pathway it tends to be more particularly tested in something called your pro-thrombin time or your inr so it tells us about how long it takes for the activity of the extrinsic pathway to occur and induce a clot formation so the longer time it takes for you to induce a clot the longer the pt or the higher the inr the quicker you can induce a clot that's going to occur faster the lower the pt the lower the inr here's the big thing about these proteins these proteins in order for them to be synthesized they are very dependent upon a molecule that we get across our gi tract from diet and from bacteria and this molecule is called vitamin k so vitamin k is very important we get this across our gi tract what happens is this will get taken across our gi tract and it will get taken into the liver and once that vitamin k gets into the liver it's necessary in order to stimulate this process so these proteins cannot be synthesized without the presence of vitamin k here's what happens though and this is why i'm mentioning this vitamin k process when someone develops liver injury right they actually have some type of liver failure right so we've already kind of gone through this process but they have some type of liver failure so in other words they have liver failure whether this be acute liver failure whether this be an acute on chronic liver failure or whether most of their hepatocytes have been replaced by fibrous tissue their ability to make these proteins decreases so if that happens you this will result in a decreased production of factors 2 factor 7 factor 9 factor 10 c and s your ability to induce clots is going to decrease if you take a long time to induce a clot the time it takes for you to actually clot will actually be again measured via this thing called the pp and inr and so that will go up the problem with this though is as your pt and inr goes up you have a higher risk of bleeding so high risk of bleeding and sometimes we refer to this as a coagulopathy so this is a type of coagulopathy so why am i telling you this when someone has a very very acute liver failure acute on chronic liver failure cirrhosis and they have this decrease in proteins they're at high risk of bleeding particularly gi bleeds brain bleeds a lot of different situations like that and so how do we determine that the reason why their actual ptinr is due to their liver failure and it's not due to a deficiency in vitamin k well here's what's interesting we test these patients and so to determine if it's vitamin k so is vitamin k the issue how do we know so here's what we do we bypass the gut so we give them iv vitamin k if you give them iv vitamin k and it's due to the vitamin k that is the issue this will actually stimulate the liver to make increase the factors 2 factor 7 factors 9 factors 10 and c and s those will up if these increase what will that do to your actual ability to clot it'll increase your ability to clog what will that do to your ptnr if you can actually increase your ability to clock the time it takes for you to clot is going to be decreased so that'll do what to your pt inr that'll drop it that'll prove that process however if you do this process where you give them iv vitamin k and the liver is damaged so in this case you have the opposite pathway liver is damaged if the liver is damaged can you make these particular proteins no and so there is still a decrease in factors two factor seven factors nine factors 10 c and s if that happens and there's less of these factors are they going to be able to induce clots no if they can't induce clots what happens the time it takes for you to actually clot off it increases and so you'll still have the sustained or elevated inr despite giving them iv vitamin k so that's one of the tests that we utilize to tell us what is the issue so one of the big things for this is that whenever somebody has very significant liver failure acute acute on chronic or full minute complete cirrhosis their ability to make these proteins declines and they have high risk of bleeding and what again do we call this high risk of bleeding whenever you have very little of these proteins in the blood to be able to kind of stimulate these clotting processes they're supposed to be utilized if they're not being utilized now you have higher risk of bleeding because whenever you have these actual breaks within the blood vessels you're not going to be able to properly clot and blood can actually increase in this risk of actually extravazating or increasing the risk of bleeding what is that called this is called a coagulopathy so this is called a coagulopathy quagulapa see and again this is due to the liver as the problem okay so that's one big thing about liver function obviously if your liver function is going down the higher risk of bleeding higher risk of ascites and petal edema there's one more other function of liver you know the liver makes a very interesting hormone uh it's a hormone called thrombopointing i'm going to put t-p-o okay thromboplatine thrombopointing tells your actual bone marrow hey bone marrow we need to increase the synthesis of platelets son of a gun we need to increase the synthesis of platelets so tpo will tell the actual bone marrow to increase the production of platelets now if you have as you guys have noticed the trend here a patient with liver failure whether this be acute whether this be acute on chronic or whether they have complete fibrosis of their liver now most of the actual parenchyma is filled with fibrous tissue fibrous tissue can't make tpo damaged liver cells can't make tpo so tpo levels drop if tpo levels drop you can't stimulate the bone marrow to make platelets platelet levels will then subsequently drop if platelet levels drop in this situation this is called what thrombocytopenia so what i really want you guys to understand here is that sometimes a patient can have high risk of bleeding so they can have elevated pt inr they can have low platelets and because of that sometimes it may think oh man this person is in what's called a dic disseminated intravascular coagulation and that sometimes is a little complicated to differentiate and to separate and so what we do is is whenever you have a confusion of someone having something like dic because of low platelets high ptinr they have a higher risk of bleeding so they may be anemic they may have low red blood cells they're actually may have this low pt high ptinr low platelets what we do is we actually say okay how do i differentiate that it's actually not dic so is it dic sometimes what we may do is we check a level that the liver does not a protein of the coagulation cascade that the liver does not make and this is called factor eight if factor eight levels are actually low that tells us that it was not likely from the liver and this is likely from particular a dic type of process and that's one of the big things to think about the liver does not actually make factor eight and so that's one of the things that we can think about my friends we've talked about the tests of apatocyl and biliary injury we've talked about the tests of hepatic function now we actually have to think about the patterns of these things these lfts and say okay i have a patient who has injury to their parasites what are the enzymes that are going to be elevated and what are the causes that i have to be thinking about and how do i test for those so let's do that next all right so let's talk about the approach to a pedocellular injury right so a patient has come in they're having maybe some particular like right upper quadrant abdominal pain they're having some fatigue they're having some nausea they're having some maybe even some episodes of vomiting just generalized malaise and you're thinking about okay let me order a cmp or order some lfts i want to see what's going on with that liver all right when you do that and you order that cmp you're looking for particular enzymes that may be elevated particularly within the bloodstream now with the pavocellar injury what are those enzymes let's re you know space repetition here and then on top of let's think about what types of causes what is the differential behind someone having an elevation in these particular enzymes and then once we think about what are those causes what are the tests that i should send out reflexively to rule these particular conditions out okay all right so first things first you have some type of hepatocellular injury we've already kind of gone through this there's two particular enzymes that are located here within these liver cells and again there is ast right and alt and we've already discussed that whenever there's hepatocellular injury whether there's inflammation necrosis and we'll talk about the things that lead to those two particular processes these enzymes are going to be increased in the bloodstream so there's injury to the apatocites right and we'll talk about what things injure the apatocites when they're injured it increases the ast oh let me usually this one is alt keep it the same color alt alt is elevated and ast is elevated okay now here's the other thing that you really want to remember sometimes if there's a little bit of inflammation that's involving these hepatocytes it may actually kind of cause a little bit of inflammation and irritation to the nearby biliary ducts as well and so sometimes if the biliary ducts are a little bit injured and they're a little inflamed because of the nearby inflammation of the apatocites this may cause a little bit of leakage of particularly a little bit of alkaline phosphatase a little bit of ggt to up within the blood as well just minorly right so we can put like a plus or minus elevation of the alkaline phosphatase it may be very minimal okay but there's definitely going to be huge jumps in these the alt is going to be really high the ast will also be really high so these are the big things to think about now one more thing remember i told you that bilirubin is found in two places we're going to do a different color here so bilirubin we can have that bilirubin which is in the actual liver cells and the bilirubin which is in the biliary ducts remember when i drew that little red molecule which contains the glucuronate onto it that was indicative of the conjugated bilirubin or the direct bilirubin whenever there is injury to the epanocytes or there's enough inflammation of the nearby ducts from the inflammation of the apatocites you can also cause another molecule to leak into the blood and again look here you have liver injury this molecule can leak right into the bloodstream as well what is this molecule that if it's elevated into the bloodstream whether it be from this process or from this process what is this called this is bilirubin right but what kind of bilirubin we have to specify this is an increase in what's called the d billy the direct or conjugated bilirubin nonetheless though what are the enzymes that i really really need you to remember the most common elevation whenever there's a powder cellular injury the most common ones the most important ones is if you see an increase in ast an increase in alt you may see a increase in the d billy as well and there may or may not be a minimal elevation in the alkaline phosphatase in the ggt but primarily there should be elevated ast elevated alt and an increase in the d billy okay once we've seen that okay so our primary thought process we get our cmp the cmp shows us an increase in ast an increase in alt and an increase in our d billy and maybe a minimal increase in out foster ggt but nothing really special we have to say okay what could be the reasons for this what could be the causes behind someone having this type of increase ast alt and d billy because i know there's a there's got to be a hepatocellular injury here process right so i think about very specific causes the first one is there a viral hepatitis present okay so the first one i want to think about is is there a viral hepatitis and there are so many different types of viruses that can actually cause this however it's relatively easy to think about all of your hepatitis viruses such as testing for hepatitis a virus hepatitis b virus hepatitis c virus hepatitis d virus and you can even throw off a hepatitis e virus so throwing off a hep panel may be kind of one of the first steps in this process this would be the first thing that i would do there is other viruses that can cause viral hepatitis they are just way less likely unless the patient is immunocompromised they in other words they have some type of like organ transplant they're on immunosuppressants they're on chemotherapy they have hiv aids in those situations so i'm going to put down immuno suppressed in some way or immunocompromised in some type of way if they are you can test other particular types of enzymes such as you can test something called cmv cytomegalovirus ebv or you can also test another one like herpes simplex virus or varicella zoster virus however it's relatively unlikely to be these particular conditions it's more likely going to be these types of viruses that'll lead to this massive elevation in alt and ast okay and again i want to really stress that it's more particularly an increase in the ast and the alt and again you may get a little increase in the d billy okay viral hepatitis is one another particular cause that i want to be thinking about in the differential here is is there an autoimmune hepatitis so is this a possibly an auto immune hepatitis so there is some type of auto antibodies that are attacking the liver and causing massive amounts of inflammation of the liver right so we know that viral hepatitis will cause massive inflammation of the liver autoimmune hepatitis will cause massive inflammation of the liver what are particular types of auto antibodies that i should be testing for in these patients we can send off a bunch of different labs so one of the ones that you start off with first is what's called an a a and anti-nuclear antibodies you can also send off another one which is called an anti-smooth muscle antibody you can also check something called an igg titer or level and these are generally going to be most of the tests that you would need to diagnose someone with autoimmune hepatitis however often if these tests are positive you may end up resulting in checking something called a biopsy to actually confirm the reason why is whenever you have someone with autoimmune hepatitis you don't want to indirectly just start them on steroids you want to make sure that you confirm that they have autoimmune hepatitis because they're going to be on these steroids for a decent amount of time so it's definitely something that's important to confirm so we have two particular causes that have caused this massive hepatocellular injury causing a bump in ast alt and an increase in d billy maybe a small increase in ggt and outfloss okay what else could be causing this drug induced injuries there is so many the list is literally so long and what we'll do is at the end of this video if you guys go down in the description box i'll have like a little link that you can click on that will actually give you the most common drugs to remember in these processes but for right now let's talk about some of the big ones that are important for your exam and some that are actually important particularly in real life so whenever we have these patients who have these massive elevations in astlt we can send off a hep panel we can send off the anti-nuclear asma and igg titer if we think that it is some type of drug or toxin induced hepatitis okay so some type of drugs are toxin-induced hepatitis we can send off obviously right away what i can send off a tox screen and a tox screen maybe give me a lot of the drugs that maybe the patient is taking that they weren't technically honest about or whatever it may be usually the ones that i'm definitely including in this is i'm going to be checking an apap level so an acetaminophen level i want to know is that really high because this is one that is very very scary and usually whenever they have high acetamino acetaminophen overdoses these can definitely cause a very intense and significant elevation in the lfts so what i want you to remember is whenever you have this acetaminophen overdose so in patients who have apap overdoses these can produce massive i mean massive like greater than a thousand for the actual and the ast and alt levels so it's definitely important to be able to really really consider that whenever somebody comes in you're checking their lfts and you see a massive greater than a thousand bump in their lfts especially the ast and alt definitely don't hesitate to order an apap level or acetaminophen level to make sure that they haven't had an overdose another one is alcohol induced right so alcohol induced is another one so if someone's drinking tons and tons of alcohol this will also cause a bump in there at lfts one of the things that we already talked about a little bit though is that you may see the asts you're gonna see huge jumps right maybe in the thousands but we're gonna see that the ast to alt ratio may be greater than two so they'll have these huge bumps maybe close to a thousand from the drug-induced liver injury however the ast over the alt ratio may be greater than two another thing that i can check is the ggt may also be elevated which will help and support me in this process of an alcohol-induced liver injury okay so there's definitely an important thing to think about here for these drug toxin induced there's so many drugs the list is like never ending so it's also important to take into consideration go through their medication list and figure out which one of these if i look through my list and i compare and say okay oh i see that's a drug that's definitely one that causes a common one that can lead to a patient or a polystatic injury or some type of process like that okay so we have viral hepatitis autoimmune hepatitis drug and toxin-induced hepatitis what is another one another one that i want you guys to remember is this one is actually due to some type of vascular hepatitis right so this is usually some type of vascular induced hepatitis so vascular induced hepatitis and there is many different types of causes for this one i want to talk about three particularly and i have a perfect diagram here to kind of set it up for you so there's a problem with the blood flow the vasculature of the liver you know in patients who have severe right-sided heart failure like they have right-sided heart failure so imagine here's your heart if the heart was up here you have a structure here called the inferior vena cava right right below the heart when someone has right-sided heart failure what happens to the pressures on that right side it backs up and so blood can actually back up into the inferior vena cava and into the liver and when all of that kind of fluid backs up and deliver it caused the liver to get congested and very swollen in a way and that swelling or congestion in that nature that causes the apatomegaly is enough to cause liver injury so that could be one particular reason is someone may have some type of right heart failure or a volume overload type of situation and so it's important to go and check their echo on these patients right so what would be a good thing to check on these patients if i think that they have right heart failure or volume overload i can easily just do a echo the other thing that's important here this one's the the bad one is let's say that you have a clot right here you have some hepatic veins and you have a clot within these hepatic veins and the blood flow that's supposed to be coming into the hepatic system that's supposed to be going into the liver the liver will filter it and then put it into the inferior vena cava and take it up to the heart there's an obstruction due to a clot or some type of structure that's occluding the actual blood flow through the hepatic veins and that's definitely going to alter the actual blood flow to the liver enough to cause injury what is this condition here called whenever you have big clots within the hepatic veins that obstruct the blood flow into the liver you know what this condition is called this is called bud chiari syndrome this is called bud chiari syndrome and bud chiari syndrome is usually due to clots that occur within the hepatic veins that reduce the blood flow into the liver and that can cause liver injury now how do we test for blood chiari syndrome you know we do we actually send these patients to get a right upper quadrant abdominal ultrasound and we put on doppler flow so we do doppler flow and what we're looking for is when we put on the right upper quadrant ultrasound we may see some enlargement of the hepatic veins maybe a little bit of enlargement of the hepatic veins proximal to where that occlusion is and we may see less blood that's flowing distal past that actual obstruction of the hepatic vein so if you throw color doppler here you may see blood flow if you throw the color doppler here you may not see any blood flow past that area of where the occlusion is in the hepatic veins or reduction in blood flow and so that's a good test to think about for these patients so we have again two things here we have right heart failure as one thing to think about generally you can just check an echo you can also check their ivc to look to see so you can do an echo and an ivc ultrasound to see if that's dilated and plethoric you can do a right upper quadrant ultrasound with doppler flow to look to see if there's any decreased flow through the hepatic veins due to clots in blood chiari syndrome here's the next one so the next one is you have some type of decreased flow of blood through the arterial system into the liver what could be a condition where you have less blood that's actually flowing into the liver through the arterial system this could be due to what's called shock so we call the sometimes shock liver or ischemic hepatitis so you can see this in patients who have some type of profound hypotension so this could be in sepsis this could be in cardiogenic shock in these types of situation where a patient is extremely hypotensive and they're not perfusing their organs very well that can definitely lead to a situation where they have a massive elevation in their lfts and so what you want to be thinking about is looking to the clinical context of these patients have they had some type of shock state have they have been diagnosed recently with cardiogenic shock have they been diagnosed recently with septic shock if they have it's likely their cause of this massive elevation and their lfts okay especially if we've gone through and we've ruled out that there's a normal right upper quadrant ultrasound with doppler flow we've ruled out that there's any kind of right-sided heart failure symptoms and we're kind of left with oh they just recently were in shock on multiple amounts of pressers and that's one of the reasons why okay we talked about these let's come down and talk about these last two here all right so we've gone through and we've talked about some of the most common causes so the reason why i'm coming down here to these last two is these are actually one of the most least common causes or the ones that you don't really want to go looking for as the cause of a massive acute elevation in someone's lfts to greater than a thousand so if anybody ever comes in they have this massive elevation of ast and alt within the thousand range you want to go looking for viral autoimmune hepatitis drug-induced hepatitis or some type of vascular-induced hepatitis if it's less than a thousand it's it still could be these situations okay and it could be these but again if it's greater than a thousand it's unlikely to be these last two that i'm going to talk about here but these still are somewhat common in certain scenarios especially this one so there's one other type of hepatitis that can be due to someone having you know there's something called metabolic syndrome and a metabolic syndrome some of the classic features that they tend to be hypertensive they tend to have hyperlipidemia so they may have high levels of ldl and triglycerides they may have some type of increased risk of diabetes so they have high blood glucose levels and their bmi is on the upper range in these situations this increases the risk of something called non-alcoholic fatty liver disease sometimes it's also referred to as non-alcoholic steato hepatitis okay so sometimes you may see these kind of like interchanged it's non-alcoholic fatty liver disease or non-alcoholic steatohepatitis in these situations you can actually say that whenever you're trying to think about these as a particular cause you obviously could check a lipid panel you could check their glucose and you could think about their obesity like risk factors however particularly you shouldn't always depend upon these things because sometimes these patients may have some of these other confounding factors in their history as well so generally if someone has a negative evaluation in other words what do i mean i've worked them up for viral hepatitis it's negative i've worked them up for all these hepatotropic viruses it's negative i did an ana anti-smooth muscle igg titers and a biopsy to confirm and there was no autoimmune nature all the drugs that they've been taking and none of them caused it their apap level was normal their alcohol level was normal their top screen was normal their echo showed no kind of uh evidence of right heart failure no evidence of plethoric ivc they're a right difficult ultrasound with doppler flow is normal they haven't had any kind of shock events if that's the case and i have another thing so a negative evaluation as above and their ast tends to be greater than their alt this also can help in the support of a patient who may have some type of non-alcoholic fatty liver disease so one of the ways that i could definitely diagnose this is i could definitely go ahead and confirm so if i have someone with a negative evaluation as we talked about above their ast and their alt are greater their ast is greater than their alt and i do a biopsy that would be to confirm and it would show lots of liver cells that are riddled and filled with a lot of fat molecules and so this is something to think about in your patient who has a lot of these risk factors where they have a very high level of hyperlipidemia hyperglycemia they have obesity a lot of the risk factors for metabolic syndrome negative evaluation as above ast is still elevated but it's much more greater than the alt and you confirm on biopsy that there's a lot of steatohepatitis present this would be the diagnosis now the last one that i want to talk about which is again something that you should not go looking for in an acute liver failure is some type of hereditary cause okay so there's a lot of different diseases that are hereditary in nature so there's some type of genetic component here that increases the risk of deposition of particular types of molecules or ions into the liver cells that cause a lot of necrosis and a lot of free radical reactions so one of those is hereditary conditions is there's genes that increase the level of iron within the liver cells you know um there's a condition where there's very very high levels of iron and this accumulates in the liver cells it increases the free radical reactions and causes destruction of the liver cells what is this condition called when there's high levels of iron this is called hemo chromatosis so in patients who have hemochromatosis these can cause high levels of iron these high levels of iron can increase the reaction of reactive oxygen species that can cause destruction of the hepatic cells injury of the hepatic cells and then over time can lead to potentially cirrhosis however it is not something that's going to cause an acute elevation of lfts in the 1000 range it's not that common if you had this suspicion and they're coming out as a chronic kind of condition of like elevated lfts in a chronic type of situation then you can send off iron studies so in other words everything's going to be elevated right they'll have an elevated iron elevated transfer elevated ferritin and their iron binding capacity will be lower because most of the proteins are saturated with iron and the other thing is you can do what's called an hf e gene study to look to see if that's positive that's the hemochromatosis gene so if you have a suspicion of hemochromatosis whether you have someone with these kind of like middling chronic elevations in their lfts and they have some type of hereditary component associated with it you can go looking for hemochromatosis if you check their iron studies iron's elevated transfer is elevated ferritin's elevated tibc is low and the hfe gene is positive the other thing that you can check for is something called copper and so if copper levels are super elevated there is a condition in which this is elevated and this is called wilson's disease so this is called wilson's disease in wilson's disease there is some type of mutation within the proteins that actually are important for excreting copper into the bile or into our feces and we can't excrete that copper and so then copper accumulates within our liver cells within the blood and so what we do is and again copper also causes lots of free radical reactions and damages liver cells so how do we diagnose wilson's disease for the love of goodness if you have a patient who has an acute elevation in their lfts and they're old do not look for wilson's disease because you're looking to write a case report because this is more likely common in younger pediatric patients that you'll be thinking about this type of condition and it is super unlikely to cause acute elevations within your lfts as much as we want to will that into existence it is not going to happen so wilson's disease you check their copper levels in the blood and it's going to be high so they can have high copper levels in the blood and in the urine and you can check something called the cerulo plasmin and this often is low ceruloplasmin is a protein that binds onto copper if this is actually bound to tons and tons and tons of copper the free level of ceruloplasmin is going to be low the other thing is why we should not be checking these things in an acute liver elevation is because sometimes ceruloplasmin is inadvertently positive or elevated i'm sorry inadvertently low and you start thinking oh they have wilson's disease no it's just non-specific it's not a great test for looking at wilson's needs sometimes you may have to get biopsies for these two conditions to really kind of confirm so sometimes you may need a biopsy okay so my friends what i really want you guys to get out of this is if someone comes in to your clinic or they're in the hospital you check a cmp or lfts they have a huge elevation their ast or alt a little elevation in their d belly and maybe plus or minus this small elevation they're out foss and ggt think hepatocellular when you think about a cellular you think viral autoimmune you think about drug induced or toxin induced you think about ischemic or vascular causes those are the ones that are going to cause the massive acute elevations greater than a thousand if it's not greater than a thousand it's it could be potentially any of these again but it also you want to go thinking about these if it is greater than a thousand do not think about these okay now the last thing that i want to talk about to really ease your mind help you guys to say okay zach i'm still kind of struggling because you said that there could be an elevation the alk foss and the ggt and the alt and the ast and all these other ones how the heck do i know if it's truly hepatic like hepatocellular or if it's biliary is there a way i got you all right so how do i really kind of like hammer down like zach i'm kind of still you said that there could be like an elevation of a lot of these things like ast alt d billy and even that outfloss and the ggt well yeah i did say that right but again the more important thing was that there was a more marked elevation of the ast and the alt way more than the alkaline phosphatase in the ggt so there was an individual i don't know who it was but he came up with a very interesting equation to help you sift these things out if you're really struggling and so it's called the r value and so the r value is we take this r and we make it equal to a lt again the reason why we pick alt in comparison to asts alt is more specific for the liver and divide that by the upper limit of normal of whatever alt is okay so you take alt divided by the upper limit of normal of alt and then you divide that by the alkaline phosphatase so alt was definitely more specific for what kind of injury hepatocellular injury alkaline phosphatase was way more like generally utilized and for biliary injury but again remember what i told you about the biliary injury alkaline phosphatase can be elevated in conditions such as patients who have some type of placental pro you know process so they're pregnant or it can be elevated in high bone turnover or in renal failure and things of that nature but again we still utilize alkaline phosphatase as a marker of colic or biliary injury and so we take alkaline phosphatase and we divide that by the upper limit of normal of alkaline phosphates here's the reason why top number or the the numerator tells us of hepatocellular injury particularly the bottom number tells us about biliary injury more particularly if we take this and we put this into different like whole numbers and we say okay the r was greater than or equal to five that likely means that this numerator was really high and so if that's the case it's likely hepatocellular okay and the reason why is that this numerator was the larger number okay if the r is between let's say it's you know somewhere between two to five in that case we're going to say that this is likely going to be what it could be a mixture so if it's kind of like two to five it could be a mixture because there's maybe an elevation in alt and a good elevation in alkaline phosphatase so this could be a mixed picture of both hepatocellular and colic injury but if the r value is less than two it means that this bottom number is really really high and there is significantly large levels of alkaline phosphates way more specific for biliary injury and so in that case it's probably cole static in other words biliary injury and so this is the ways that we can definitely look at this and say okay this has more of a hepatocellular picture when the alt is markedly elevated it could be mixed when there's a big elevation alt and a big elevation in alkaline phosphatase where they're kind of like evening each other out or it's likely cholestatic when there's a massive elevation alkaline phosphatase and only maybe a little elevation in the alt so that's the basic way of kind of putting that into a formula okay now that we've talked about that we have a good idea of how we can actually quickly check these things let's now talk about how can we approach biliary or cholestatic injury it should be straightforward now so in patients who have some type of biliary or cholestatic injury there's two different ways by which this can happen one of the more common reasons is there's something called a extra hepatic obstruction so there's something called an extra hepatic duct obstruction so what do i mean by this so i have a patient who has some type of obstruction within the biliary ducts outside of the liver so extra hepatic meaning outside of the liver those biliary ducts that are outside of it there's something that's obstructing them what could be the things that are obstructing them let's start all the way down here well you have a particular organ that's nearby the biliary ducts and this is called your pancreas so in sometimes when patients have very large cancers of the pancreatic head so they have some type of pancreatic carcinoma particularly of what of the head of the pancreas this is enough to be able to apply some compressive forces onto the biliary duct trying to collapse that biliary duct okay another particular reason is you have someone who has some type of malignancy right so you know there's like maybe a cancer that's involved particularly the biliary duct cells so there's some type of cancer here that's involved in the biliary duct cells this is sometimes referred to as a cholangio carcinoma so it's called a calangio carcinoma so that could be one reason and that's actually obstructing the biliary flow another one is there's some type of excessive amounts of fibrosis so lots and lots of fibrosis that are occurring of these particular areas and whenever it's actually having a lot of fibrosis it's causing these little strictures so you know if you have a lot of fibrosis it's narrowing the lumen of these biliary ducts and really causing a reduced flow of bile that can cause a stricture there what is this called this is called primary sclerosing cholangitis okay so primary sclerosing cholangitis another type of condition is you could have a stone so you know like whenever you have some type of stone let's say here is a gall stone that's getting stuck within the bile duct and whenever it gets stuck in the bile duct it kind of like squishes there in that area and obstructs the biliary flow this is called chole and this is usually due to some type of gallstone and all of these situations what's the common denominator is that you're reducing the biliary flow through these extra hepatic ducts if that happens go back and think about what are the particular molecules that are primarily found in the biliary ducts that's why we stressed it so much the pink one that's here this is alkaline phosphatase what was the other one we used which was the black color that was the ggt that was in there and then the other one which we did is green but we we also kind of used the blue but it was the bilirubin and what type of bilirubin is this that's in the biliary ducts conjugated also known as direct bilirubin if these things can't move downwards where are they going to flow my friends they're going to flow backwards and into the bloodstream and so what will become elevated within the bloodstream you'll have an elevation of what types of molecules in sequence here you'll have an elevation a marked elevation in alkaline phosphatase you'll have a market elevation in ggt and you may have a market elevation in the conjugated or we also call this direct bilirubin so let's actually let's be more specific again we should write what kind of bilirubin is this this is the conjugated or we actually if we're measuring it this is called the direct bilirubin so we call this the d billy we should be very specific in these situations this is definitely highlighting some type of holy static process because again if you plugged it into the r value your out phosphate alkaline phosphatase is going to be super elevated you may have some small increase in these hepatocyte injury with a lot of the ductal dilation and actually causing the backflow sometimes that can actually squish down on the ducts and cause a little bit of inflammation at small ast alt elevations but nothing spectacular in these cases if your alkaline phosphatase is super high if it's really high it's going to cause this overall r value to be a lot lower less than two supporting more of a cholestatic process so if i have a patient who's presenting with right upper quadrant abdominal pain maybe they're even a little bit jaundiced because of this massive increase in the direct bilirubin they're having maybe some nausea they're having maybe some vomiting all of those kinds of things what would i go ahead and test for i'm going to want to find the obstruction and so the best thing to do in these situations is to send this patient for what's called a right upper quadrant ultrasound so i'll send them for a right upper quadrant ultrasound and what i'm looking for is if there's an obstruction here this with these obstructions that are present it'll show ductal dilation proximal to the obstruction and that will tell me oh there is my cause i have my cause i know that there's some type of ductal dilation and that's causing this backflow and there's a backflow due to a colidocolothiasis a primary sclerosing cholingitis a calangiocarcinoma or a pancreatic carcinoma of the head in these situations i know that there's doctor dilation but does that tell me what the cause is does that actually definitely delineate oh i see ductile dilation i know it's this this this or this no we may have to further go ahead and look into other tests so we may do something called an ercp and in this situation in endoscopic retrograde chlangio pancreatography we shoot dye up through that actual biliary system and sometimes it may show us a little bit more of an ideal situation of what's going on and we can therapeutically treat them sometimes we may do something called an mrcp and this is utilizing an mri to look at the entire calangio the biliary system in the pancreatic system as well sometimes you can even do like a ct of the abdomen as well you can also consider maybe a ct of the abdomen but either way these are things that i'm going to go thinking about and considering another thing that i could also test for with primary sclerosing cholingitis as a specific one here is primary sclerosing cholangitis can give you particular antibodies that are somewhat positive so sometimes they can check something called an a a and that may be positive i can check something called an anti-smooth muscle antibody and that may be positive but what i may actually go looking for is something called a p anchor and so if these are positive and i also have evidence of ductal dilation which is present on right upper quadrant ultrasound and maybe i even have it supported on ercp or mrcp then i may go thinking about primary sclerosing cholingitis okay so that is how i would go about diagnosing these particular issues is get imaging right upper quadrant ultrasound look for ductile dill if you see ductile dill you know that there's something that's obstructing these biliary duct systems extra paddock wise go ahead and maybe perform further evaluation such as an ercp or an mrcp maybe if you want to you can do a ct of the abdomen and if you want to add on some tests to look for primary sclerosis and cholingitis you can add on these auto antibodies as well okay now that we've done that let's talk about the next thing which is there's not a extra hepatic obstruction there's intra-hepatic problems or hepatocellular types of problems and we have to investigate that all right so the next type of situation that we have to talk about with the biliary or cholestatic injuries is very interesting so we talked about extra hepatic obstruction so obviously now we're talking about ducts that are inside of the liver that are becoming more of the problem right so the intraopatic ducts so if there is some type of issue where there is intra-hepatic kind of obstruction or damage or inflammation these could be problems where there be a reduction in biliary flow correct so one of these conditions that is relatively obvious to think about is you have these auto antibodies and these auto antibodies are attacking these small little ducts that are inside of the liver the intrapatic ducts and they're doing the same thing as primary sclerosing cholingitis they're attacking these areas and causing little inflammatory strictures to occur in these small ducts in this situation where these autoantibodies are attacking the liver right so particularly they're attacking these small hepatic ducts what is this condition called where they're only attacking the intraopatic ducts and they do not attack the extra paddock ducts and cause these strictures this condition is called primary biliary cholangitis primary biliary cholangitis in primary biliary cholingitis where there's auto antibodies that are attacking these small intraopatic ducts this condition if you had someone who you did an ultrasound for they had no ductal dilation then you've actually ruled out any kind of extra hepatic obstruction the next thing you can consider is testing for these auto antibodies so you can do the whole a a you can do the whole anti-smooth muscle antibodies but what's the true winner in this situation here so i wouldn't even waste my time doing these i would go ahead and send off right away what's called an anti anti-mitochondrial antibodies if this is positive you've already established and clinched the diagnosis of primary biliary cholangitis so again how do i go about this particular diagnosis i have a patient who has these auto antibodies what type of auto antibodies anti-mitochondrial antibodies that are attacking these small intrapatic ducts causing inflammation and strictures and fibrosis of these small ducts if they're causing strictures or inflammation and narrowing these small ducts again what are these particular molecules that are present in here what's this one that's going to dump into the blood alkaline phosphatase will be elevated again what's this other molecule in black that'll also be kind of blocked off and dump into the blood ggt will be elevated what's this other molecule in green that's also going to be in these small biliary ducts the d billy will also be elevated okay so in these situations it's just like what we talked about above the only difference is in these patients i would go ahead and let's say that i follow that same process i see this this clinches my thought to say order a right upper quadrant ultrasound i do that and it's negative for ductal dilation if it's negative for ductile dilation my thought process is is it is not an extra hepatic obstruction if it is not an extra paddock obstruction it's some type of intra-hepatic process so it divides me into two thought processes one is this is intra-hepatic process it's an intra-hepatic issue and then we call this sometimes intra-hepatic cholestasis or the last situation which is super rare very rare is something called infiltrative diseases infiltrative diseases in these situations that's my process so i have someone who has an elevation in the aop the ggt and the d billy just like we saw up there now generally in extra paddock obstructions these elevations actually tend to be a lot higher they tend to be a lot higher particularly in the extra paddock obstructions and the intraopatic intraopatocholi stasis and the infiltrative diseases they tend to be more particularly predominantly elevations in just your alkaline phosphatase most specifically and you may have small increases again in your ggt the d billy may be a little elevated as well just a little bit but you know those the big one is your alkaline phosphatase and these types of conditions either way i go through the same process i get my right upper quadrant ultrasound if there's ductile dill it's extra paddock if there's no ductile dill then there's intraopatocholi stasis or the super rare infiltrative diseases okay so intrapaticholysis has already talked about one of those particular situations so on this side of the diagram we're talking about what types of causes here on this side we're talking about intra hepatic cholestasis we've already mentioned one of those particular causes one of them is primary biliary cholangitis is causing these little strictures and fibrosis of the small intrapatic docs that's one particular reason the other reasons are super super interesting so the other one that i want you guys to think about here is drug induced son of a gun so there's certain types of drugs and toxins and for us to go through the list of all of these drugs and toxins is insane i'll put them down in the description box below but what happens is you know when you're making bile you have to remember that bile process guys you can't forget it so let's stick to the color that we did before here's our bilirubin it's not in the hepatocyte yet so this is called what kind of bilirubin unconjugated indirect bilirubin it gets taken up into the liver once it's in the liver there's a very special enzyme called u gt and ugt does what ugt will take that actual type of bilirubin what type of bilirubin the conjugated type of the unconjugated type of bilirubin and add on the glucoronate when it adds on the glucoronate this is now called conjugated or direct bilirubin okay there's other molecules that are used to make bile one of them happens to be bilirubin but there is other molecules that make bile other molecules that make bile is there's things called bile salts we'll just draw these here in black so there's also other molecules called bile we'll put bio salts and then again this molecule here is called bilirubin we utilize transporters to push these bile salts out into the biliary system and we also use these transporters to push out bilirubin into the biliary system okay so we're gonna have bilirubin out here and we're going to have all of our bile salts out here now when someone who has cholestasis the whole definition of cholestasis is there is a decreased amount of flow there's decreased amounts of bile that is moving through your biliary ducts if there is a decreased amount of bile that's moving through your biliary ducts there can be two reasons one is their small little obstructions like structures again primary biliary cholangitis or you're not making a lot of bile if you're not making a lot of bile that's going to mean less biles flowing through the biliary ducts what things can cause a decrease in bile production one of them is particular types of drugs or toxins and what they can do is they can inhibit this transporter from pushing the bile salts and pushing the bilirubin into the actual biliary system if there's less of this flow that could be one of the reasons if there's less of this biliary flow that also may cause a small increase in these molecules particularly within the bloodstream more specifically though we again we see that increase in the out foss because there's less flow of biliary processes now what else another one is there's some type of infection you know sepsis in patients who have sepsis and sepsis for some reason you have some type of bacterial infection right that bacterial infection activates your immune system cells and your immune system cells will produce tons and tons of cytokines it'll produce things like interleukin-1 it'll produce things like interleukin-6 2-minor necrotic factor alpha all of these cytokines what these cytokines do is is they signal particular cells and in this case it signals the liver cell and it inhibits these transporters and so this results in a reduction in biliary production and biliary molecules that are present within the bile ducts okay that is another particular issue the next thing that i want you guys to remember is besides sepsis there can also be another reason why there is a decrease in the biliary production and this is in patients who actually have high levels of estrogen you know when there's high levels of estrogen such as when someone's taking oral contraceptives or when someone is pregnant these also through very interesting mechanisms work to inhibit these transporters from putting the bile salts and bilirubin into the biliary system if we can't put them into the biliary system there's less bile within the biliary ducts and that means that there's less flow of bile through the biliary ducts now what's the problem with all of this if you can't put a lot of these bile salts and bilirubin into the biliary ducts what happens is the billy starts increasing in the bloodstream because what happens is these bilirubin molecules they don't just like to sit here in the cell so sometimes when there's lots and lots of these bilirubin molecules in the cell they start diffusing out into the actual bloodstream and so you'll get an up in their d billy you also have some of these bile salts that'll start diffusing out of the cell as well and go in depositing into tissues why is that an issue you know when there's high amounts of bilirubin in the blood and it deposits into tissues what do you get jaundice when there's high amounts of bile salts into the blood those deposits into the tissues they cause pureitis so some of the common clinical features that you really want to be thinking about and a patient who has this type of intra-hepatic cholestasis where there is either something that's obstructing the flow of the small ducts or something that's causing a decrease in the production of the flow is drugs or toxins and pregnancy this is called pregnancy-induced cholestasis and what some of the common features in these conditions is they have jaundice and they have itching they have paritis and so that may be common features to think about intraopatic holy stasis what i really think is the easiest one to remember because sometimes intraopatic holy stasis can be kind of confusing when it comes to these situations is i like to make myself relatively simple straightforward here is i get my right upper quadrant ultrasound i see no ductile dil i know that that's either this or this intrahepatic cholestasis are infiltrative diseases the main one that makes the easiest sense to remember why all of these are going up is the primary biliary cholangitis test for the anti-mitochondrial antibodies if it is you've clinched the diagnosis if it is not this then it is likely some of these other issues that are resulting in a decreased imbile production thus causing a reduction in biliary flow unless bile is actually flowing through the biliary ducts and through mechanisms that aren't completely understood there may be an up in the alkaline phosphatases up in the ggt and then again there's definitely going to be an up in the bilirubin in the blood because a lot of this bilirubin that's not getting put into the biliary ducts just leaks out and diffuses into the bloodstream okay so that's the way i would go about explaining this process after i've gone i've got a right upper quadrant ultrasound no ductile dill i test for my anti-mitochondrial antibody it was negative i've gone through and i've rolled out any drugs or toxins they're not septic i've checked their estrogen they're not taking any oral contraceptives and they're not pregnant then i go and i say okay is it an infiltrative disease because these are the rare ones an infiltrative diseases there are so many different things that actually start to deposit into these biliary ducts so these actual infiltrative diseases they deposit into these intraopatic ducts and when they deposit into the intrapatic ducts again they narrow the lumen of these small intrapatic ducts and cause these elevations in alkaline phosphatase elevations in ggt and elevations in d billy but again it seems to be more predominantly alkaline phosphatase so if i've gone through i've done this process i think it could be infiltrative diseases what do i do there's a bunch of different conditions that can deposit into these biliary ducts and whenever they deposit into the biliary ducts they start depositing into these biliary ducts they cause those enzymes to increase within the blood alkaline phosphatase ggt and d billy if these are all up within the blood i see no ductile dill i have no cause of intraopatocholi stasis i think it's infiltrative what are the particular types of diseases that can infiltrate there could be malignancies so some type of malignancy where some type of metastasis from a tumor whether it be from a lung cancer whether it be from a breast cancer whether it be from melanoma whether it be from the bone any of these have metastasized and spread and infiltrated into the biliary ducts of the liver that could be a particular cause okay another one is i have some type of granulomas so there could be casey eating granulomas or non-caseating granulomas they're depositing into these actual biliary ducts narrowing the biliary ducts and causing this backflow this could be in situations such as tuberculosis sarcoidosis the other thing is there could be lots of misfolded proteins that are depositing into the actual biliary duct tissue and again obstructing and narrowing the actual biliary lumen causing the backflow of these enzymes and this misfolding of proteins could be something called amyloid doses and then last but not least this is kind of like on the rare end is there could be certain types of actual amoebi or certain types of infections of actual like this is nasty but worms that are actually accumulating within these small biliary ducts and obstructing the flow and in these situations there could be something called ascorasis lumbricoides which is a nasty type of worm or like liver flukes sometimes those can accumulate those small little ducks and actually cause again infiltration of the ducts and then again cause obstruction and narrowing of these little intraopatic ducts causing these elevations and again alkaline phosphatase ggt and deep billy in these situations you can try and test as much as you want all these different types of things testing for tb testing for sarcoid testing for amyloid all those things one of the things i would say is it wouldn't hurt to check something called an s pep which tests for the certain amounts of proteins these misfolded proteins and amyloidosis but mostly the most important test to consider in these infiltrative diseases is you have to biopsy them and once you've biopsied them and it's positive for a malignant tissue it's positive for tb it's positive for sarcoid it's positive for amyloid or positive for certain types of worms then you know okay i have clinched my diagnosis of an infiltrative disease so whenever we have a patient to completely summate and recap this cholestatic injury which is a little bit more of a complicated one patient comes in they have super elevated alkaline phosphatase more markedly elevated than their ast and their alt they may also have elevation in their ggt they may also have elevation in their direct bilirubin if that's the case what do you do right over quadrant ultrasound look for an obstruction you see ductile dill you think it's obstruction get an mrcp or an ercp you can consider a ct of the abdomen if you think that there's multiple areas of strictures you can test for primary sclerosing cholangitis by sending off their a a am anti-smooth muscle and their uh p anchors that are positive if there's no ductal dilation and you have no extra hepatic obstruction then you're thinking it's two issues intra-hepatic holy stasis so there's either small ducts that are being obstructed or blocked or your liver cells aren't making enough bile and putting it into those biliary ducts and so that's another reason for their decreased flow if that's the case assume intraopaticoli stasis due to an obstructive cause is primary biliary cholangitis test for the anti-mitochondrial antibodies if they're positive you've diagnosed them if it's not positive you have these lower tough ones to be able to differentiate if they're pregnant think about them having higher estrogen levels that are decreasing their biliary production this is called pregnancy-induced cholestasis if there is septic that might be a thing that's causing a decrease in the biliary production and there's many different drugs and toxins that can also cause a decrease in biliary production this is the tougher one to make sense of though so go with this one and if it's not this one think about these three last one is if you've gone through you've had no ductile dill no primary biliary cholangitis you've ruled out all these drugs toxins pregnancy-induced or sepsis you finish up saying could it be the rare infiltrative diseases such as malignancy tb sarcoid amyloid or some type of infection by a worm like asteroids lumbocoities or liver flukes you get a biopsy if the biopsy comes back positive you've diagnosed your infiltrative disease and the cause for your elevation out foss ggt and d billy my friends we finish this off let's head it home with the last one which is a patient who's in elevation in their bilirubin very high enough to cause features of jaundice what could be the causes behind that all right engineers where the last part here which is talking about how do we approach those patients who have isolated hyperbilirubinemia or they have these high bilirubin levels and it's tough to differentiate what's the cause of this increase in their bilirubin levels so we've talked about issues where there was primarily increase in ast and alt the predominant one we talked about conditions where there was a predominant elevation the alkaline phosphatase and the ggt okay predominantly the last one we're going to talk about here which is again predominant elevation in the bilirubin what could be causes for that so whenever billy reuben's elevated one of the common clinical features is jaundice right so discoloration of the skin particularly kind of like orangish kind of discoloration yellowish discoloration particularly of the skin palms and hand soles of the feet and maybe even the sclera in those situations you check their cmp or you check their lfts and you see that there's a bump in their bilirubin we have to again go back to what was the cause what was the particular type of bilirubin more specifically so go back to that whole process quickly for a spaced repetition right so here we have our macrophage whenever our red blood cells are getting old or there's something wrong with the red blood cells all right so there's something wrong with the red blood cells in that situation where they're getting old they're defective there's some type of process wrong with them our macrophages are going to eat up those red blood cells and they're going to hemolyze them and release out the amino acids from the globin and release out that bilirubin which was coming from the heme pigment now this bilirubin that's released and goes into the bloodstream this is what type of bilirubin you have to remember this what type of bilirubin is this one that's in the bloodstream and it is bound to albumin this is what kind of bilirubin this is called the unconjugated bilirubin so this is called unconjugated unconjugated also known as indirect bilirubin we call this the eye billy right when this bilirubin binds to albumin it circulates through the bloodstream and then obviously can go to the liver and it gets metabolized by the liver and we'll talk about what happens there in a second now if we actually were to have this bilirubin go into the liver it would go through that particular conjugation process so let's actually talk about what that would look like so now we have this bilirubin okay it's going to the hepatocytes it spreads through the blood gets to the apatocites and the bilirubin binds on to these particular transporters when it binds onto these particular transporters these transporters bring the bilirubin into the cells okay so it brings the bilirubin into the cells of your body then the bilirubin will go through its conjugation process right so this is again indirect bilirubin or unconjugated bilirubin it will react with a very special enzyme here what is this enzyme here called again guys the ugt what does it do to the the bilirubin that's unconjugated it conjugates it by adding on something called glucoronate so now we have our conjugated bilirubin what kind of bilirubin is this for the love of goodness do not forget that this type of bilirubin this one here is called unconjugated this one here is called conjugated bilirubin again what else do we call this sometimes we call it conjugated bilirubin or direct bilirubin we're going to put d billy then this bilirubin that's conjugated gets pushed into your biliary ducts where it'll then be go and get incorporated into the biliary into your bile which will be excreted into the gi tract right so that's the generalized process of bilirubin here's what i want you guys to think about if the patient has an increase in their total bilirubin so you check their lfts right and when you check their lfts you see an increase in their total bilirubin so you see an increase in their total bilirubin you want to know is that increase in their total bilirubin due to an increase in their indirect ability or is it due to an increase in their d billy or is it a little bit of both so that's the kind of goal to figure out so whenever you check someone's total bilirubin level you want to determine is it actually the indirect bilirubin that's the problem or is it the direct bilirubin that's the problem in your lft panel typically you get this one and you get this one so all you have to do is take the t billy and subtract the d billy to get your indirect bilirubin okay so let's say for a patient you check their lfts you see there's an a big increase in their total bilirubin you subtract the t billy from their d billy and you notice that their indirect bilirubin is very high what could be causes for an increase in the indirect bilirubin we got to go back to the process anything that would cause an increase in indirect bilirubin would be something where the macrophage is breaking down red blood cells a lot or red blood cells are breaking open a lot and there's something wrong with the transporters where they're not taking in the bilirubin into the cell or this enzyme ugt is not conjugating the bilirubin so there's a problem at what steps here that would cause this disease process one is right here there's hemolysis second one there's a problem with transport third one is there's no conjugation we have to think about diseases that can cause this and how do we test and prove that the first one that we have to talk about is this one over here and this is called hemolysis so if a patient has a condition called hemolysis this is basically where their red blood cells are busting open and lysing if you had hemolysis you could check their particular a bunch of different levels one thing is if you have a molecules you may see a drop in there hemoglobin right there may be a drop in their hemoglobin because you're busting open their red blood cells and if you're lysing a ton of red blood cells you're getting rid of red blood cells and your hemoglobin within the blood can actually drop the other thing that you may see is that there's other enzymes that are released from your red blood cells during red blood cell injury you know what those are ldh so ldh may also be higher this is an enzyme that's in high concentrations and a lot of lysis or severe liver injuries and the other one is another protein here called haptoglobin so haptoglobin is a protein that binds on to free hemoglobin now remember if you're busting open your red blood cells what are you releasing out into the blood hemoglobin hemoglobin has to get bound by this protein called haptoglobin so if your haptoglobin is binding and complexing to your hemoglobin your total free levels of haptoglobin are dropping so in these patients who have hemolysis they may have low hemoglobins they may have high ldhs they may have low haptoglobins another thing is you can also check because what happens is when all of this occurs this may trigger this hemolysis reaction may trigger something called reticulocytosis reticulocytosis so it tells your red bone marrow hey there's lots of red blood cells that are getting destroyed right now we need to make more red blood cells and so when you make a lot of red blood cells you make a lot of these immature red blood cells and so your reticulocyte count may go up because your bone marrow is trying to replenish all the red blood cells that you're destroying so if you have a patient who has an increase in their indirect bilirubin so again we have an increase in the indirect bilirubin the eye billy i think hemolysis i will send off a cbc to check for their hemoglobin i'll check an ldh i'll check their haptoglobin and i'll check for the reticulocytes to see if there's an increase in the reticulocyte count after i've done all of those things the next thing that i will do that actually tends to be the best diagnostic test is if you're lysing a lot of these red blood cells and you do something called a peripheral blood smear it may show you the busted open red blood cells you know we call that whenever we do a peripheral blood smear we look at the red blood cells under microscopy we call these busted open or ripped open red blood cells schistocytes and if you have shista sites that are positive in combination with an increase in reticulocytes a drop in their hemoglobin an increase in their ldh and a drop in their haptoglobe and this may be a likelihood of having hemolysis to figure out what was the particular type of hemolytic cause that's beyond the scope of this lecture that'll be more in that hemolytic anemia type of lecture but that's one thing we can obviously say it's hemolysis the other thing is what can cause this problem with not being able to transport the unconjugated bilirubin into the cells and this also just causes this increase this would be due to drugs that actually inhibit these transporters you know there's drugs that inhibits these transporters so here this transporter is being inhibited here we're going to have this as the the other cause this transporter is being inhibited so there's transporter inhibition and this transporter inhibition is what's causing an increase in the indirect bilirubin there's two drugs that have been studied very very significantly that caused this and this is called rifampin rifampin is actually a drug that we utilize to treat patients with latent tb so what we actually found this from is patients were getting treated for latent tb with rifamp and they were having super high levels of indirect bilirubin and that's one of the things that we know the other one is if you're treating a patient who has gout and you're treating them with a drug called probenocid probenicid also has been shown to be able to increase the indirect bilirubin levels because it inhibits the transport of unconjugated bilirubin into these particular cells so how do i determine if this is the cause i just look at their drug their medication list medication history okay and again they'll unlikely have any types of evidence of hemolysis so they would not have any evidence of increased reticulocyte shistocytes uh low hemoglobin low haptoglobin and increased ldh the next one i could do here these are the super weird ones rare ones but there's a problem with this ugt enzyme so there is some type of decrease or mutation in that ugt enzyme so if i really wanted to i could go and do genetic testing for this that's causing a mutation or decrease in the ugt enzyme but the particular diseases that cause a decrease in the ugt activity one is very very very common and oftentimes in a patient who have actually proved that they do not have hemolysis they aren't having any medication history like this it's oftentimes this particular disease it's called gill bears so guild bears is a type of condition that whenever there's lots of stress or anxiety or certain types of like decrease in sleep or anything like increase in alcohol drinking it can actually decrease the function of this ugt enzyme and so they develop an increase in their indirect bilirubin the other super rare one which you'd want to go thinking about in a child is something called krigler najar syndrome so it's called kriglin najar syndrome so but these are the things that i want you guys to be thinking about in a patient who has an increase in their t billy their total amount of bilirubin but very specifically when you take the t billy subtracted d billy they have a high amount of indirect bilirubin what are you thinking about hemolysis medications or decreased ugt enzyme activity which is likely gill bears okay now that we've talked about that let's talk about the intraopatic jaundice all right so let's talk about the next type of cause behind someone having an increase in their bilirubin right causing their jaundice so we've tested them and we've said okay i'm gonna look at their t billy their total bilirubin is elevated if their total bilirubin is elevated what do we check for we do the t billy and we subtract the direct bilirubin and if the direct bilirubin minus if you do that and you actually get an increase in the indirect bilirubin we already talked about that so if you have an increase in the indirect billy then you would do the above processes right if you don't have an increase in indirect bilirubin and you look at them and they have a very high t billy and a very very high d billy then you start doing the uh the according things down here okay so that is kind of the key differentiation here is that when we check someone's total bilirubin we check their t billy it's elevated if their d billy is also super elevated and we actually have an increase in t billy and a super increase in their d billy it's likely that the cause of their increased total billion ribbon is this is the one that's increasing if we take the t billion it's really really high son of a gun we take the t billy and it's really high and we subtract the d billy but the d billy isn't the one that's really really high it's the one that's the indirect bilirubin that's really high that's the one that's contributing to this increase in t billy if it's the indirect billy it's hemolysis drugs or gill bears rarely critical in a jar if it's the t billy that's increased and the d billy that's increased it's likely an intrahepatic or post hepatic jaundice okay how do we go about these in intra-hepatic jaundice the most common causes is usually two particular issues here one is there's a transporter malfunction or there's something that's damaging the hepatocytes causing them to spill a lot of these bilirubin molecules into the blood what could be the transporter malfunction these are super rare but go back to the whole dang process of the bilirubin we got the bilirubin here this is the unconjugated the indirect gets taken into the cell when it gets taken into the cell it gets acted on by the ugt so then we have the conjugated bilirubin that's now been acted on by the ugt we need transporters that are utilized to push this conjugated or direct bilirubin into the biliary system okay if these transporters are malfunctioning due to mutations within them where they aren't able to perform this function they can't actually do this so now imagine for some reason these transporters are malfunctioning it isn't able to excrete this actual bilirubin conjugated into the biliary system so now all of this conjugated bilirubin is just accumulating inside of the cell eventually what will happen is it'll start leaking into the bloodstream and when it starts leaking into the bloodstream we get an increase in the d billy within the blood because we can't actually excrete it into the bile that would be one particular cause what are the names of the conditions where there's mutations within these transporters one is called rotor syndrome and the other one is called dubin johnson syndrome okay super rare causes unlikely going to be those that you think about but if it's a transporter malfunction usually the big thing to think about is this is primarily just going to be an increase in the d billy there will not be any issues with the ast or with the alt okay that's a big difference here so if you have a patient who's a primarily increase in their d billy and there's no increase in their ast no increase in their alt or their alk foss or anything like that also again no real increase in their outfloss either then it's likely going to be something like rotor syndrome or dubin johnson syndrome now the other cause for someone having an increase in their d billy is there's hepatocellular injury so in a paracellular injury it's the same kind of process here guys listen i get the unconjugated bilirubin or the indirect bilirubin i bring it into the cell i conjugate it by the ugt enzyme when i conjugate all of these bilirubin molecules so here's all my bilirubin molecules that i just conjugated by this ugt okay so he's already done his job he's done it well and we have tons of these conjugated bilirubin molecules in our cell and it's really ready to be excreted there's no problem with the transporter but then all of a sudden i infect this cell with a virus i damage it with auto antibodies i decrease the blood flow or i cause it to become congested i give tons of drugs that damage these cells and when i damage these cells guess what starts leaking out into the bloodstream this is going to be an increase in what type of molecule my conjugated bilirubin or my d billy what kind of things can damage these hepatocytes any of the hepatocellular injury causes so someone with a viral hepatitis like hepatitis a b c d cmv ebv hsv vzv right autoimmune so this would be those conditions where there would be an increase in the ana the anti-smooth muscle antibodies the igg titers but you need a biopsy to confirm drugs such as toxins such as what kind of things alcohol acetaminophen levels so you can check a toxic screen checking acetaminophen level check the alcohol level or some type of vascular issue they have congestive type of have had a megalith so due to right side heart failure echo positive for right heart failure and ivc is plethoric they have bud chiari syndrome due to clots within the hepatic vein ultrasound to the right upper quadrant with the doppler flow which showed decreased flow through the hepatic veins or they had a recent episode of sepsis where they're profoundly hypotensive if they have a negative evaluation they have increase in their hyperlipidemia hypertriglyceridemia increased glucose increased bmi and their ast is slightly more elevated than their alt this is more suggestive of non-alcoholic fatty liver disease which i can prove with biopsy or if there's an increase in their amount of iron deposition copper deposition these also could be particular causes and again i would have to go through iron studies and do copper studies to diagnose hemochromatosis or wilson's disease and there's another rare one called alpha one antitrypsin i didn't mention that one as well but in certain patients who have alpha-1 anthrotrypsin deficiency they may have lung involvement such as copd early onset as well as liver failure but either way i would go through diagnosing these patients who have intraopatic jaundice where they've been increasing their d billy by looking at the d billy and again checking off all of these other things is there a massive increase in their ast in their alt if there's a massive increase in their ast and their alt with an increase in their d billy what would i be more likely to suspect my friends i would be more likely to suspect this as the cause and then what do i go do i will go and i will send off all the same labs that i will send off for a hepatocellular injury hepatitis panel antibody panel drug talk screen ultrasound echo and then send off maybe some of these also tighters for hemochromatosis and copper studies boom we did it the last thing is post-hepatic jaundice so in post-hepatic jaundice we've already discussed here in post-hepatic jaundice what is the particular issue here and this one there is an elevation in the t billy but the reason the t billy is elevated is because there is an increase in the d billy it has nothing to do with the indirect billy anymore the only reason that there will be an increase in indirect ability is hemolysis drugs and gill bears rarely quickly in a jar in this case it's the increase in the d billy the reason that there will be an increase in the direct bilirubin is there is something that is causing an obstruction so there's something that's obstructing biliary flow of the large hepatic ducts there's something that's obstructing flow of the small hepatic ducts or something that is reducing the secretion of bile into the biliary ducts do you guys remember all those things that we talked about with colic injuries so if we think about it someone has a massive extra paddock obstruction so they have a gallstone they have a cholangiocarcinoma they have a pancreatic carcinoma they have primary sclerosing cholangitis any of those causes that we talked about they would have a positive ductal dilatation on their ultrasound and these situations if you're obstructing this duct all of that bilirubin that you've been secreting into these ducts so all of this bilirubin that is now conjugated it can't move this way it's blocked so it starts backing up and into the blood and then you start getting a lot of this conjugated bilirubin in the bloodstream okay so again this will cause your increase in your direct bilirubin so that's the extra padded obstruction the other issue is that you have small little ducts that are being blocked as well so an intraopatic holy stasis what was the particular condition for intraopatocholi stasis that was the primary biliary cholangitis there was inflammation due to autoimmune attack there narrowing and causing structures of these small ducts again if the bio bilirubin can't actually pass through this area if it can't pass through it'll back up into the bloodstream the other one was the super interesting one which was if there is not actual strictures or obstruction due to primary sclerosing cholangitis the weird one was that there was some type of drugs that were inhibiting the excretion of bile into the blood you couldn't i'm sorry you couldn't excrete the bile of the bilirubin or the bile salts into the biliary ducts remember that so there was drugs toxins pregnancy such as in someone who has pregnancy-induced cholestasis where they can't secrete the bile into the biliary ducts or sepsis where they can't excrete the bile into the biliary ducts in those situations if you can't excrete the bile and what's one of the components of bio that we care about in this situation the bilirubin if i can't excrete that conjugated bilirubin into the biliary dox where do you think that conjugated bilirubin is going to go well it's going to be increasing in my cells and i can't go into the biliary doc so guess what it diffuses right into the blood increasing the level of my d billy okay and that would be all of those issues with intra-hepatic holy stasis whether that be due to small strictures and primary scleros on primary biliary cholangitis or you're inhibiting the release or excretion of bile into the biliary dox in drug induced pregnancy or sepsis the last this situation which is the most rare is there is infiltrative diseases that are involving the small dox and in these situations you would have to test for malignancy you would have to test for a granuloma such as in sarcoid or tb and you would have to go looking for a amyloid deposition or some type of amoeba like ascoriasis lumbricoides or maybe like a liver fluke of some kind of thing and those situations you would require a biopsy so from all of these if i'm thinking that someone has an increase in their d billy i would also see what else that would increase in these patients because we're blocking a biliary duct please we've already gone through all of this guys if there's hepatocellular there's increase in ast and alt if there's injury or blockage of the ducts there's going to be an increase in the alkaline phosphatase in the gdt there may still be increases in their ast and alt but nowhere near as elevated in comparison to someone who has a patter cellular injury and intraopatic jaundice so there should be a massive increase in alp increase in ggt increasing their t billy with an increase in their d billy more specifically that's causing that rise in their t belly and if i'm trying to figure out what is the causes for these i will get right upper quadrant ultrasound right and this will be positive for dilation here i can then follow up with an mrcp or an ercp in this situation the right upper quadrant ultrasound will be negative for ductal dilation i can still do an mrcp and an ercp okay but usually for these it's ordering something like an anti-mitochondrial antibody to rule out primary sclerosing cholangitis primary biliary cholingitis primary biliary cholangitis okay and then also looking through their history are they pregnant have they had sepsis or is there any drugs or toxins that can cause this and then for infiltrative diseases usually the right upper quadrant ultrasound will be negative for ductal dilation i'll have negative mrcp negative ercp so negative mrcp or ercp their anti-mitochondrial antibodies will be negative and i will depend upon my biopsy to confirm this particular condition ninja nerds in this video we cover so much information about the liver function test or the liver biochemical test i hope it made sense i really hope that you guys learned a lot and enjoyed this and engineers as always until next time [Music] you

Channel: Ninja Nerd

Views: 711,479

Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: Y4Q9fI4Mze4

Length: 120min 34sec (7234 seconds)

Published: Thu Feb 17 2022