Cirrhosis | Clinical Medicine

what's up Ninja nerds in this video today we're going to be talking about sosis this is part of our clinical medicine section if you guys like this video it helps you it makes sense please support us some of the ways that you can do that is by hitting that like button commenting down the comment section and please subscribe also really urge you guys if you guys have a moment go down the description box below there's a link to our website on our website we have a lot of really great things that we offer things like notes illustrations quizzes we're even developing exam prep courses so become a member and have access to a lot of that and much more let's talk a little bit about curosis so when we talk about therosis therosis is the irreversible fibrosis of the liver that leads to decline liver function and potentially portal hypertension that's the best way of describing curosis I think so let's talk a little bit about that path of physiology not go too crazy but give the basic understanding that's necessary so let's say here that we we have our liver it's got some blood supply around it right and what happens is for whatever reason and we'll talk about those reasons in detail the liver starts to undergo chronic injury and damage repeatedly whenever you hit the liver constantly it's made up of small little cells here's an example of one called the ocytes when the ocytes get injured that constant repeatedly is a rough thing because the liver does have the capability of being able to regenerate but when it's pretty frequent so we'll represent that with an up Arrow what happens is this leads to the liver particularly these small cells that are present in the sinoses we'll talk about a little bit later in the complications but they're called stellate cells and they like to lay down a lot of fibrous tissue and connective tissue that actually forms around the sinusoids and so one of the complications that you develop is called fib brosis one of the beautiful things about the liver is that the liver not only has the capability of regenerating but whenever it does get injured unfortunately uh whenever it regenerates it regenerates in these nodules unfortunately so you get a combination of fibrosis and what's called nodular regeneration if you will the combination of these things unfortunately lead to two downfalls one is fibrous tissue and this nodular regenerated tissue aren't good at performing normal liver function and so unfortunately there becomes a decline in liver function and this can look so many different ways I don't want to go too crazy down this just yet because we'll talk about that in the next part of this lecture but there will be a decline in function this could be abuin synthesis this could be Billy Rubin conjugation this could be clearance of ammonia this could be estrogen metabolism coagulation protein synthesis Etc the other component here as I told you is that you'll compress some of the portal veins so if you guys remember back to the anatomy you have What's called the portal Triad that's where you have like your arterial your venal and your biliary canaliculi what happens is the the portal vein and the arterial empty into the sinusoids if all the fibrous tissue is there it's going to squeeze and compress on that actual like cidal vessels and that's going to cause a back pressure and so what happens is over time is these patients develop what's called portal hypert tension and so what we'll do is we'll talk about these two complications a little bit later in the next component but we have to start asking ourselves the question what's leading to this fibrous tissue which will represent like this which is causing a lot of problems you're losing that synthetic function as well as some of these nodules that are regenerating here making the liver kind of like lumpy and bumpy unfortunately what is those causes I think the best way of remembering the causes is to categorize them in this particular phenotypes so the first one is what can cause direct perinal damage like it's not indirect it's like these things directly hit the Ayes and Destroy them they don't use anything else as the vehicle to perform that function I'd say by far most commonly it's going to be drugs and I'd say the biggest drug that you have to watch out for in chronic liver disease is alcohol so alcohol related liver disease that is going to be by far one of the most common causes so you really don't want to forget about that one right this one will definitely cause chronic liver injury and really kind of cause a lot of problems here we'll talk a little bit later about the ratio that comes with this one but I think the big thing to look for in the clinical history is a history of alcohol consumption sometimes you look can look at the enzyme ratio between the ests and alts but I don't think that that's all always going to be guaranteed look for the history of alcohol the other one I'd say is autoimmune so having an autoimmune hepatitis is extremely important to be able to recognize and the reason why I think this one is important to recognize is that this one we often use very specific treatments for it okay and it's usually steroids and if a patients on steroids or deards for a long long period of time lifelong you better better be to guarantee that diagnosis there's a lot of these antibodies that cause direct damage right tons of them and I think real quick it's important to remember I didn't talk about this I will talk about this one but alcohol how exactly does it cause damage we'll talk about this later in future lectures like in toxicology but what alcohol actually does is it induces something called steatosis and all that is is it causes a bunch of fat kind of globules and accumulation inside of the liver so that's one potential ways remember it can cause theosis these ones they just activate immune system cell which destroy these hepatocytes but the question is what are these antibodies that are inducing this type of hepatocellular injury here's a bunch of them and you'll test for them a little bit later but you're going to want to watch out for things like Ana you want to watch out for anti-smooth muscle antibodies um IGG particularly the soluble type and there's other ones like um anti- lkm1 but I don't think that this one is as heavy um to be able to identify but I'll quickly write it down all right so these are specific antibodies that will activate your immune system to destroy these Ayes another one I'd say this is by far going to be one of the more common causes like in general like worldwide I'd say this is one of the most common causes in the United States though and this is usually going to be viral induced and there's two particular viruses that will cause chronic AOC cellular injury they'll infect these cells and by doing that they'll kind of use these cells as the vehicle to make more cells but unfortunately during that process they rupture these cells and injure them and so this is usually going to be things like Hepatitis B virus and hepatitis C virus and I think the things that you want to look for here in the history is a patient who has unsafe sex uh IV drug abuse using dirty needles uh blood transfusions back in the day when they didn't actually completely like look at blood the way they should have but these are things that you want to be looking for and usually that'll kind of give you a Telltale sign here that this is the direct cause of aular injury and they cause direct injury themselves the last one here is interesting because it's kind of a combination of things I'm just going to put this in the category of metabolic so metabolic induced meaning that these things can cause damage in various ways all right there's one it's called hemocromatosis and this disease what it does is it really kind of lot causes a large amount of iron to build up within the body but the particular area that it loves to build up in happens to be the liver there is other tissue cells that it builds up in as well such as the pancreas and the heart and other tissues like that but this is a big one that I want you to recognize because we're talking about the liver another one is going to be called Wilson's disease so Wilson's disease this one is actually going to be uh Quantified by a large amount of copper accumulation so when patients have these large amounts of copper accumulation this can definitely these two cause free radical damage so when you increase the amount of free radicals within the body they're going to cause direct injury to these tissue cells they're going to cause changes to the proteins the cell membrane Etc so look for a patient with those Kaiser flesher Rings look for weird kind of Korea movements as well with hemocromatosis you're looking for maybe pan uh some some type of pancreatic disease um so usually kind of like a diabetes uh bronzing of their skin kind of cardiomyopathy restrictive cardiomyopathy types of findings and hemocromatosis the next one is called alpha1 antirion deficiency so alpha 1 anti-ron deficiency and this is literally what it is it says it within the name here I'll actually just use the red arrow to indicate this there is decreasing amounts of this particular enzyme that's present in the bloodstream and that causes things like osma but also these polymers build up the inactive polymers build up because you're not making this molecule in the liver and they cause direct injury to the liver so look for osma in a young person and sosis the last one is I think starting to become one of the biggest most common causes of today is non-alcoholic fatty liver disease this one in the same concept like to alcohol is that it really increases what's called steatosis so it causes massive amounts of fat accumulation with inside of the liver which can cause injury to the liver it causes them to become inflammation it's called stat hepatitis and then that chronic inflammation then leads to fibrosis this is really common in patients with obesity hypertension hyper lipidemia so kind of that metabolic syndrome picture is the one that you want to watch out for okay this is direct prle damage if you injur these cells one of the things that you may notice is if you injure these cells you may have some of these enzymes that leak out that could indicate injury and this is your a and your alt right they could or may not be elevated depends so curosis if you have repeated damage you're replacing a lot of the normal liver tissue with fibrous tissue so in the early middle stages of curosis you will have these elevated but as you get to the late stages you don't have much like hepatocytes remaining and so these levels may actually be normal so pseudo normalize okay if we come over here we talked about the direct injury to the liver cells what if it's indirect so like here I have these liver cells right here they're not being directly injured they're being kind of indirectly injured and it's because there's something else that's affecting them so what if a patient has something like right heart failure you know um right heart failure and there's not many reasons why this happens it's either an MI or pulmonary hypertension but the problem with this one is that you either can't get blood out of the heart or you can't get blood into the heart it's the same concept though right so this is impeded and so what happens is blood backflows into the venne Hava and so what we say is these patients have what's called a elevated Central Venus pressure and that elevated central venous pressure because these patients live with this chronically will cause hepatic congestion so fluid will back up into the liver and over time these cells will be subjected to such high congestive fluid and pressures that it'll start to become injured over time leading to this kind of like chronic pathway the other situation is the same thing a back pressure but it's not due to the right heart not doing its job it's due to a clot being stuck somewhere Within These hepatic veins so if I have clots here within the hepatic veins it's the same concept I can't get blood moving forward so it just backs up and congests into the liver cells and causes them to experience that for long periods of times and that'll eventually cause them to become injured chronically over time this is actually an interesting disease where you have clots within that this is called Bud kiari syndrome and it's essentially I'm going to kind of point to it in this scenario here whereas this is this scenario here right I think the the big things to remember here is that it's often associated with malignancy right so the reason why is that you could have maybe various types of malignancy sometimes it's even a cancer of the liver but they definitely increase your hypercoagulable state so this is more of an acquired one you could even have genetic ones as well so Factor five lien protham and gene mutation Etc and the other one I would remember is going to be polycythemia so it's you have too many red blood cells and they kind of just make the blood a little bit more viscous than usual they clog up the actual vessels and they can definitely become more prone to clots so these are the two ways which we cause chronic aasy injury and then this kind of Downstream negative pathway the last one's kind of funky but it's interesting because it's often forgotten about I mean rightfully so it's not extremely common but it's something to remember for biliary tract diseases that are chronic that caus like chronic inflammation to the intrahepatic biliary ducts and even some of the extra hepatic biliary Ducks what happens is when you inflame these biliary ducks you're kind of impeding bioflow and so the whole concept behind this is that in these diseases there's an increase in bile backf flow and when bile back flows the thing is that some of the contents within the bile are not supposed to be back flowing into the liver because over time some of the contents within the bile will cause injury to these ocytes it could be because of the bile pressure it could because of the chemicals that are in the bile but they're causing aasy injury and again if you put that together the concept is the same is that with heaty injury repeated repeated repeated you're going to have this same concept that we talked about bu it has to be more of a chronic kind of disease so that's why a lot of these are chronic diseases so what I want you to think about is what are some chronic diseases not acute diseases chronic diseases not due to a gallstone something that's usually due to fibrosis and inflammation so it could be something like primary biliary curosis sometimes they call this colangitis though as well so primary biliary colitis because this inflammation of the biliary ducts but it also could be due to what's called primary sclerosing colangitis and I think the big thing to remember between these two is that primary biliary colitis is characterized by only intrahepatic doct inflammation where primary sclerosing colitis can be both and I think that's one of the big differences and so let's actually kind of write that down here that this is intrahepatic I'm going to kind of put this in an abbreviation this is intra hepatic duct inflammation only and this is intrahepatic duct and extra hepatic duct inflammation so you have a combination of the two so often times when this is thought about usually the patient presents with features of johis and purtis and often times this one's associated with what think about this one being associated with Aller of colitis and then this one is usually associated with a very specific autoimmune kind of nature you see lots of autoimmune diseases associated with this one so it's often times associated with what anti- mitochondrial antibodies and I think that's some big things to remember for these so I think the last thing to kind of cover here is is we've really talked a lot about curosis in general the causes the basic pathophysiology but now what I want to do is I want to dive into this I want to talk about what are some of the downstream consequences and how do these patients present often times when their liver is just not doing a good job and they start to decompensate let's talk about that now all right my friends so now we have the patient who has curosis right we talked a lot about how the primary pathophys is there's lots of fibrosis and there's nodul regeneration because of chronic inflammation we talked about all the different things that could cause this from the direct pral damage the vascular diseases and the biliary tract diseases I think the next thing to remember is that often times in patients who have therosis often times they can be completely asymptomatic and we may not really know that they have therosis and so we kind of use this term compensated cerotic it's really when the patient starts to advance throughout their serotic stages and they start developing complications um related to portal hypertension or declining liver function that we may start to see them present in these decompensated states and so decompensated curosis is usually the way that we often think about in a patient who presents with a verical bleed or confused or kidney injury Etc and so that's really the important thing to remember so let's talk a little bit about some of these complications well the first one we said is related to portal hypertension it's really straightforward I don't think it's like crazy complicated to imagine that if you have a bunch of fibrous tissue there's a bunch of veins here's our portal vein right so this right here should be our portal vein and this portal vein is supposed to take blood into the liver via these little venules into the smaller little Triads portal Triads there's a lot of fibrous tissue around there it's going to compress on these portal veins and so what happens is the blood will actually kind of start to develop like a really large back pressure and this back pressure will be transmitted into like the the tributaries of the portal vein right so it'll back up via the super mesenteric vein it'll back up via the inferior mesenteric vein and it'll even back up via like the gastric veins and so all of this is a result of what really high portal Venus pressure so this is a response of high portal blood pressure so this is again a complication of fibrosis of the liver that's causing compression of the small portal vels when that happens the blood backs up and we already talked about it can back up via the superior mesenteric vein the inferior mesenteric vein or the gastric vein the problem arises in a couple different scenarios here when this portal blood pressure is really high it's hard to move blood in this direction the blood naturally wants to go this dire Direction but is that going to happen very well no and so what happens is our body tries to create these things called shunts and so what it may do is and this is kind of interesting here is this will kind of this like these vessels will kind of create like an alternative Pathway to kind of try to get blood to move through the liver but it just may do it an alternative way and so now here this pathway which I'm going to kind of draw here in red is the blood is going to be diverting via this shunt and then this will allow for blood to make it through the liver the problem is is that there's not going to be processing by the liver and this right here this concept of what we call here is a Porto systemic shunt the problem with this is that there's no processing by the liver because it's at a high portal blood pressure we create alternative pathways one of the particular molecules that's supposed to be metabolized by the liver and converted into something called Ura is ammonia but if it's not metabolized properly it actually will allow for it to build up within the bloodstream and this is called ammonia when ammonia really really is high within the blood stream it's called hyperemia it really loves some of the asites in the brain and it kind of gets taken into those and what it does is it binds onto something called glutamate and turns it into glutamine and glutamine is really osmotic and it pulls a lot of things into the actual cells makes them swell and so a couple different things that can actually arise in these patients they can develop what's called cerebral edemas sometimes to the point where these patients can have really elevated in cranial pressures it's actually quite terrifying and you don't want to see this but the worst the actual ammonia is the higher the risk is of brain um herniation and so that's a really scary complication often times though it doesn't usually get that bad it's usually more just altered mental status so they become confused th the terms inop so they have what's called alter mental status but here's the Telltale sign when you see these two in combo it's called asterixis so when you see them being really confused and this could range from just not really remembering where they're at disorientation maybe the hallucinating maybe they're irritable a lot of those things but then you take and you extend their hand and they have like these little flapping trimmers it's very characteristic of atic andil opathy now atic Andy opathy we definitely see this in chronic liver disease via this portal system shun it also could be because the liver is not doing its job so it's not also clearing it so there's two reasons why you can develop hepatic and sopath the other thing is that it's not just in the setting of chronic liver disease often times patients have this in the setting of a couple other things going on maybe they have SBP and that triggers this maybe they have a GI bleed and that triggers this maybe they just had a TIPS procedure which is kind of like a shunt and all you're doing is you're creating these alternative Pathways to build up ammonia and other toxic chemicals that cause and sey opathy so usually there's an alternate trigger such as a GI bleed SBP or tips procedures so remember that think about I'm not going to write them all down but try to ask yourself in these situations especially in the clinical vignette what is the trigger okay and again SBP GI bleeds and tips procedures are often times the most common triggers okay now the same concept you develop a shunt here that causes this but let's come here and kind of go step by step on our way down if the portal blood pressures are getting really high into the gastric veins these kind of give like these little branches that go to the lower esophagus and it starts bulging out these these little suckers here in the lower esophagus these are called esophagal varices the problem with esophagal vyses is if for whatever reason the pressure in this actual portal system is high enough it can cause this Blood to kind of just leak out and it can cause these guys to rupture and if you cause these to rupture you're going to have tons of blood within the upper I'm sorry within the lower esophagus that you can either vomit out or you can poop out and so often times this will present as what we call a upper GI bleed and how do upper GI bleeds generally present they often present within two ways one is hematemesis which is the vomiting of blood or Melena which is that darkish blood that's actually present within the stool CU it had time to oxidize or move through the git so watch out for this this is usually a catastrophic cause of people dying because they lose tons of blood it also can affect their upper Airway and if they have incopy and isoil varices it just makes for a mixture of a disaster this is a really important one it's often times a really big trigger for patients developing infections too because you provide an just an open route for bacteria to travel right into your bloodstream another thing here is if we come down via these mesenteric veins when these mesenteric veins are filled with all this portal pressure what you do is we'll kind of write this mechanism over here you start causing the hydrostatic pressure Within These vessels to increase so here now what's going to happen is you're going to have an increase in your hydrostatic pressure what's hydrostatic pressure that's the pressure that wants to push things out of the blood vessels and into the space well what's that space well I'm going to I highlight this that this is called the parium all right so you have two layers to your parum you have the parietal and then the visceral so this is the peronal space so if hydrostatic pressure is really really high fluid starts leaking out into this space I'm going to kind of put this in like this bluish color here so now all this fluid because of increased hydrostatic pressure which is the result of what the portal hypertension all this is going to accumulate and when that increases hydrostatic pressure leads to fluid accumulation what do we actually end up experiencing aites and so this is another potential complication that these patients will present with so not only could they come in with confusion cerebral edema asterixis not only could they come in with GI bleeding but they could also come in with a very large distended abdomen and so I some think some of the things that you want to look out for here is watch out for that patient with abdominal distension watch out for that patient who has the shifting dullness we talked about this in the aites lecture and watch out for that patient who will also have the um the fluid wave test that's positive now often times we talked about this again um in the lecture on AES but I told you that this fluid that's leaking into the abdomen if we really were to kind of dig into it deep is it rich in albumin or is it poor in albumin it's poor in albumin if we do What's called the serum aites albumin gradient and we test that I tap into it pull the fluid off what would that sag be is there going to be a lot of albumin or very little it's very little and so we often say that this is usually a sag that because there's low albumin will be greater than 1.1 okay because you're taking the serum albumin minus the what the asides album The asides albumin is very low so you're taking a big number subtracting from a smaller number okay the problem is is that when you have this fluid accumulating within the abdomen that's not very rich in albumin it's kind of like a I don't know a culture medium if you really want to think about it it's an opportunity for bacteria to just kind of hop in there and feed and create an infection and so what happens often times is bacteria can do what's called translocation and and this is usually where patients often die as well not just in the vary stage but this one here as well so what happens is the theory is here we have bacteria that are present within our git and if by any opportunity they are allowed to move to our mesentary glymph nodes and then from the mesenteric lymph nodes they move into the acidic fluid now you have bacteria in this fluid right so now I can kind of just do a little bit of a mixture here I'll kind of put like here's a bed of acidic fluid and then in this fluid I'm going to have a lot of bacteria and these bacteria will kind of cause a little bit of inflammation and so whenever you cause inflammation right you're going to inflame the peritoneum so we kind of represent that here in this red so now this pink tissue is super super inflamed and when it's inflamed it causes a lot of abdominal pain more so than usual so sometimes one of the characteristic features is the patient could present with increasing abdominal pain but the other thing is is that this bacteria right it triggers an immune reaction and so one of the things that it'll do is it'll kind of cause a bunch of cyto to be released and these cyto kindes will kind of tract in a lot of immune system cells particularly what's called polymorphonuclear lucites they're neutrophils essentially right we use that because they have all these red esine acid and the methylene blue base so this is going to stimulate these pmns and going to be like oh shoot there's a lot of infection here I'm going to start rushing into this area and try to fight off this bacteria that's one particular thing the other thing is the cyto kindes also will try to trigger an increase in your body temperature by triggering the hypothalamus so sometimes these patients will have fevers as well so I think some of the things that you want to watch out for is increasing abdominal pain fever but here's the big thing when you tap into this belly and you look for the polymorph nuclear lucaites you have to have a certain number if you will and we use this arbitrary number of greater than 250 per millimeter cubed of blood I'm sorry per millimeter cubed of acidic fluid so if I had tap into that fluid and it was less than 250 then it's just a normal AES but if I tapped into it and there's greater than 250 pmns It's actually an AES that's infected with bacteria and we call this now SBP spontaneous bacterial paratis so look for fever right increasing fever acidic pmns and increasing abdominal pain often times this may be very ambiguous and sometimes the only way that they present is that SP is one of the biggest triggers for a patic andal opathy and so patients will have S kind of be insu you won't know it and then they'll start becoming way way way more confused and you're like oh what was the trigger for their ptic and Cal opathy that's probably s and then you have to do a parentesis so that's a really big thing to watch out for in a patient who has SBP watch out for any kind of recent things that they have again prior history GI bleed these are really really big ones to watch out for last one that I want to talk about that's related to portal hypertension is very confusing it's it frustrates a lot of people because there's still a lot of kind of like questions about it but when you have a high P portal blood pressure all this pressure inside of the Venus system is so high and so what your your liver kind of like hepatic uh vessels will actually try to do in the hopes that it'll help is they'll release a lot of what's called um vasod dilators and then there's a lot of these that are released um just an example it could be things like nitric oxide or prostacyclin many different things but there's a lot of these vasod dilators that are released their goal is is to try to work here on your your splank niic blood vessels so what it wants to do is it wants to cause the splenic vessels to kind of like dilate so that's the the the the process that actually happens here it causes do what we call splank niic vasod dilation and that may sound like oh that's a great thing because now you dilate the actual kind of the portal veins and Etc problem is that you dilate not just the portal veins on this side you dilate some of the actual splank neck blood vessels the arteries the superior mesenteric artery inferior mesenteric artery ciac artery and what that does is it pulls a ton of blood unfortunately in the actual the actual portal circulation and so what happens is if you pull blood here I'm going to just use that term that you're pulling the blood you're keeping blood away from your actual like your systemic vascular system and so your body goes into like this thing of where it's like geez I don't have enough blood actually going to other organs it's all just staying in my git and so what it does it ramps up your renin otens and aldosterone system your sympathetic nervous system all get kind of kicked up and when they do that what it does is it leads to this unfortunate event cuz you know whenever your your vessels is actually vasoconstrict one of the vessels that's the first one to get vasoconstricted is the renal vessels and so often times this leads to what's called renal artery Vaso constriction and that renal artery vasal constriction my friends is what leads to this kidney injury because now you're kind of affecting the profusion of the kidneys and if you lead to increased renal artery vasal constriction as a result of this kind of like Cascade you're trying to just increase your blood pressure you so you squeeze blood away from nonvital organs and in this case the kidneys is the first one it leads to reduced renal profusion and this will precipitate an acute kidney injury and usually this is characterized by a urine output that goes down and a creatinine that kind of kicks up and so I think these are really really big things to watch out for here and a patient who has ceros is is watch out for did they develop an acute kidney injury that's actually associated with their portal hypertension okay so now from this we have a patient who has portal hypertension they've developed hepatic and cyop ferraes aites SBP or aadal renal syndrome these are all related to the high portal blood pressure the next concept that I want to talk about here is whenever the patient's not just having portal hypertension but their liver is actually not doing its job in functioning in the way that it should so what if the liver is starting to fail right so it's not related to portal blood pressure it's the actual hepatocytes that aren't doing a good job anymore and they're not actually synthesizing things so in this scenario let's say that we have a patient here that one of the problems that's really interesting here is that they're not synthesizing a protein called albumin you know albumin is really really important it helps to kind of maintain osmotic pressure and keep things in the blood vessels but if alumin is really really low you know what it can actually precipitate especially in this scenario it can help to stimulate AES because it also kind of like you have high hydrostatic pressure and if you have less of this alumin to keep things in the bloodstream uh that's also going to precipitate aides another interesting thing is that often times a penal syndrome also can uh kind of stimulate or worse in aites as well uh interestingly but we won't go too far down that rabbit hole all right so the other concept I think is really helpful here is that the liver also makes a lot of clotting proteins so one of the things that it does it makes clotting proteins like factors two I think this is the big one factor 7 uh factor nine and another one called Factor 10 but it's also forgotten that not only does it make these it also makes anti-coagulants like antithrombin 3 and protein C and protein s and so there's often times an imbalance between these now the issue though is that we often like to make it easier on ourselves and remember that often times these are the ones that get affected more significantly and so these are what's called your procoagulants all right so procoagulants they want to induce clotting if I have less of these the problem then leads to that I have an increased risk of coagulopathy and this could be bleeding and so in this patient they may develop like a big old intracranial hemorrhage they may develop an epistaxis they may develop like mucocutaneous bleeding of some part or maybe they develop ptii or bruises or maybe they even develop a GI bleed so I think it's important to remember that coagulopathies can present in various different ways such as I's mucocutaneous bleeding and GI bleeds so watch out for that if a patient comes in they have an altered mental status or they they have some type of epistaxis or tons and tons of these nasty like petic lesions or they come in with a profound GI bleed all right another concept I don't want to get too crazy here is that these actual procoagulants one of the big ones here is um Factor 7 and when factor 7even is actually low it really Alters the extrinsic pathway which is a really important measure of what's called your INR International normalized ratio and often times this will be elevated at least greater than 1.5 so in a patient who has an elevated INR with underlying liver disease you really want to think about this coagulopathy Factor there a higher risk of bleeding potentially another thing that can also happen is that platelets you know the liver does make a molecule called TPO it does make a molecule called TPO and if you have less liver function you don't make TPO you're going to end up with decreasing platelets and decreasing platelets also lends to the fact that these are supposed to plug up holes in blood vessels that are broken and now if you have less of these platelets what are you going to increase the risk of bleeding and so again it kind of propagates the same process we already talked a little bit about this but whenever the liver is failing it decreases ammonia clearance so it's supposed to clear ammonia in this way because it's supposed to run through the liver but if you're developing a shunt or just the liver is not doing its job so there's decreased um ammonia clearance in other words you're not going through What's called the Ura cycle properly and you're not taking converting ammonia into Ura then the ammonia will build and if ammonia builds again we already know how that will present altered mental status asterixis cerebral edema another one here is that when the liver starts to fail this is really interesting uh you have the part of the liver it's supposed to take and metabolize estrogen right and whenever you don't do that you end up with super super high levels of estrogen and this estrogen that's in high levels can cause various clinical manifestations so some of the ones that I want you guys to remember is going to be things like testicular atrophy also could be things like gynecomastia so enlargement of the tissue in the in the actual male it also could be like this redness appearance of the hands called Palmer Emma and then these weird little kind of like blood vessels that look like spiders it's called spider angomas those are classic skin findings for the Stigmata of CHR chronic liver disease last and not and but not least least is when the liver fails and I think this is one of the really big ones to remember is the liver is supposed to do two things it's supposed to take and conjugate Billy Rubin but if the liver is destroyed and it's not working well there's decrease conjugation of Billy Rubin and if you guys need to go back to your kind of Step One Concepts here your basic kind of pathophysiology is just taking your Billy ruin and adding on glucuronate and so it can be excreted but on top of that it's also not good at excreting because that dependent upon a pis cellular function so if there's decreased conjugation and excretion of Billy Rubin then what happens is Billy Ruben won't get eliminated and if it won't get eliminated then the Billy Ruben levels within your bloodstream will be super high and the unfortunate consequence of having super high Billy Rubin levels is that it deposits in very specific areas such as the Scara where it can cause ioris and other areas of the skin where it may cause this overall yellowish discoloration which we refer to as jaundice so we can see how therosis can cause so many different problems I think the last thing to remember here is that therosis can really increase your risk of a very specific type of cancer and that cancer is called hpat cellular carcinoma so it's often times the most important risk factor significant risk factor for uh pyoc carcinom osis you have chronic inflammation over time this will just cause dysplasia and these cells will start to actually start to become a little bit more cancerous and so these can start to develop these cancerous tumors I think one of the biggest things that's actually relevant here is that you should be doing serial ultrasounds to look for tumors every couple months six months generally but the other thing is trending a molecule that's often secreted by these tumors and it's called um Alpha fetal protein and so often times when these tumors are present they'll pump out this molecule called Alpha fetal protein that may be super elevated in patients who have then converted from therosis to Ayo carcinoma so watch out for that all right tons of complications here now let's talk about the Diagnostics of curosis all right we talked a lot about sorosis the pathophys the causes and the complications I think the next thing is how do I really diagnose therosis it's relatively tough I think often times you should have labs and imaging that are suggestive of curosis but the only true definitive way to diagnose it because you need to biopsy and find evidence of significant nodular fibrosis let's talk a little bit about some of the labs one of the first thing is you should get a CBC you should get lfts a PT INR and an abum and I'll explain why when the lfts come up it'll show that they have maybe some degree of increased a alt that's not always true because as you have more fibrous tissue that is replacing aasy tissue you don't have as many tissue areas that you're holding on to these enzymes but in a perfect world increased as and ALT may be a potential uh thing that you see in curosis what's a little bit more helpful is that they will definitely have a degree of increased Billy rupin this is because their liver cells are struggling to be able to excrete the Billy rupin and conjugate the Billy ribbon so it may build up in the bloodstream and contribute to jaundice the other thing that's really helpful is that they'll have an elevated pt/inr that'll be at least greater than 1.5 and that'll suggest an underlying coagulopathy the albumin level will be low suggesting that their liver is struggling to be able to produce albumin which is a natural protein that the liver makes and the last thing is that in patients with severe curosis they may struggle to release a hormone called thrombo poetin which is a hormone that's supposed to be able to stimulate the bone marrow to make platelets and these will be low if you do see at least most of these kind of like labed derangements it's somewhat supportive of therosis but that's only one part of the pie I need further Imaging to support therosis such as an abdominal ultrasound with elastography this looks like the stiffness of the liver as you replace normal liver tissue with fibrous tissue the stiffness of the liver will significantly increase and so what I want to see is I want to see nodular fibrosis of the liver and then when I test El listography on them I'll see a significant amount of liver stiffness and that's definitely diagnostic of ceros but it's not definitively diagnostic if I have both of these it really helps but in order to definitively confirm therosis or at least say hey I worked them up for therosis and I couldn't figure out the cause and I want to definitely know what the cause is I can actually do a liver biopsy and the beautiful thing about a liver biopsy is that it'll show you all these areas of nodular fibrosis that is occurring here in this blue tissue but on top of that if I'm confused if they have you know autoimmune hepatitis or maybe I think that they could have hemocromatosis Wilson's disease Etc this will definitively diagnose that and be very helpful in that scenario so from this point I have a definitive diagnosis of therosis the next question that comes up is how do I determine if it's a decompensated cerotic patient or a compensated cerotic patient often times compensated patients are usually asymptomatic patients who are decompensated we look for a couple things one is I want to know do they have acies do do they have spontaneous bacterial peritonitis do they have esophageal vyses hepatorenal syndrome or hepatic andoperational lied and they have aites you should definitely do a paracentesis the reason why is you want to see if they have SB and it's been shown that if you identify this this can reduce mortality so so how do we determine if it's actually first off their aites is serotic related well first we test something called a sag ratio which is a serum alumin acidic gradient and if it's greater than 1.1 which we'll talk about this in another lecture that suggests it's portal hypertension related and then I want to see is there lots of nutrifil or pmn if there's less than 250 it's not SBP which tells me okay this is Portal hypertension related most commonly it's therosis and that's probably going to be therosis related AES but if I'm like ah I want to see if they have SB well the SAG should still be greater than 1.1 because that will be their trigger to form an AIC fluid but if I have greater than 250 PM pmn that means that I have bacteria that translocated triggered inflammation and caused neutrophils or pmn to come into the acidic fluid and I need at least greater than or equal to 250 if I have greater than 250 I got the diagnosis of SB I don't even need to wait for the cultures to come back to tell me if I have a bacteria I have the diagn nosis that's what the benefit of the parentesis is if I have a patient who's actively having hematemesis or having molinaa or anemia then I should definitely work them up for verical bleeding because they could have esophagal vyses that ruptured and I should do an EGD and the EGD will help me to find and also treat the veral bleeding I should also check an ammonia level now it's important to remember that a normal ammonia level does not exclude the actual presence of curosis what I'm looking for I'm sorry in cyop if I have an elevated amonia level cool but if I have a patient who has therosis and their mental status is different from their Baseline I should be definitely having a high degree of Suspicion for hepatic incopy again therosis and sephy apathy with a normal ammonia could still be atic and cyop therosis and then confusion with a elevated pneumonia definitely helps with diagnosing aaic and cyop again confusion asterixis decline mental status and even cerebral edema definitely makes me think that they have hepatic Andy apathy especially in the scenario of underlying curosis and even better in elevated pneumonia level lastly if I check the BMP and they have a super elevated creatinine and very poor urine production I'm definitely thinking they have an acute kidney injury and I'll send off more studies like a you know the urinary sodium and the uranos molality and the urine creatinine and see what their phena is because usually that'll be a pre-renal type uh but if it looks like it's this I probably have a patient who has a penal syndrome especially if they have therosis all right so we talked a lot about the diagnosis of therosis now especially if it's a decompensated state or a compensated State I think the important thing to remember for sosis is how do we really treat these patients it's really about treating the complications the first one is aites and patients who have aites you really have to think about this in a couple mechanistic typ type of way one is sodium restriction that's going to be helpful but the other one is feride and spirolactone with spirolactone being the more helpful one here so think about this portal hypertension the body releases vasod dilators to try to be able to dilate the splenic vessels and by doing that the thought is that it'll reduce the portal pressures right that's the thought the concept behind this though is that splenic Vaso dilation leads to that reflexive renal artery vasil constriction and that increases the Ren and angot tens ostrin system and what happens here is that will then increase sodium and water retention which can worsen the aites so what if at this point here I add a mechanistic drug here like spirolactone which is an aldosterone antagonist it'll block aldosterone here and if I block aldosterone I'll block sodium and water retention and block the aites and if I give them feros amide and they have excess amounts of sodium and water within their blood system I'll be able to remove that from the body via the kidneys and again reduce the atis this is the first thing that you should start on a patient to as thees is restrict their sodium to at least less than two grams per day start them on a combination of spaone and feros amide and usually it's pretty high doses of spaone and low doses of fosite if they have tons and I mean a very very large amount of aites that is refractory to medical management as we just talked about and you have the capability to do a parentesis test that fluid to make sure they don't have SP if you remove more than five liters we call it a large volume parentesis it is of utmost importance that after you give take off five liters you give them back albumin because if not you can make them hypotensive you can actually increase the risk of them developing hpat renal syndrome and that can be a very terrible thing that could put them into acute renal failure so it's always important that if you pull off greater than five liters you give them albumin now the next thing here is if a patient has a cides that is refractory to medical management they're requiring frequent large volume Paris Andes with abum replacement you should start looking into getting them a tips a trans jugular intop patic phto systemic shunt it's basically a bypass so here we have like the portal vein and then here we're going to have like the TIC veins that empty into the inferior venne Cava if I could create like this little connection that goes straight from the portal vein right to the TIC vein I can bypass all these other circuits where there's lots of resistance to blood flow and this is a way of me being able to reduce the portal pressure and reduce some of the complications such as aites usually a tips is a way of just kind of like bridging a patient to eventually seeing if they're a candidate for transplant for especially in a cerotic patient the next uh thing complication that we want to manage is spontaneous bacterial peritonitis oftentimes is an infection that can be treated by giving them antibiotics usually seph triaxone is the first first line uh but sometimes cylin can also be another drug that we give the TIC andyl opathy is another really big one that we have to be able to recognize if a patient has curosis and they come in with an altered mental status they come in with asterixis they come in with any features of cerebral edema it's important to get that ammonia down so often times we'll treat them with lactose because that gets converted by bacteria into lactic acid and acetic acid which gives up protons binds the ammonia up in the gut and excretes it out of the body in the form of ammonium which is a way of dropping the ammonia and potentially reducing the incop mechanisms refaim may help to kind of really chew up some of the bacteria that are also generating a lot of ammonia as well the next one's aat renal syndrome this one's actually a really interesting type of thing hepatorenal syndrome is a complication we talked about the you see and portal hypertension but there's often times triggers like for example in atic andyl apathy there's lots of triggers usually a tips is a really common trigger uh another one is if they have a GI bleed that can also be a pretty bad trigger with a padal renal syndrome the common triggers here is a patient develops SB or they get a large volume parentesis and they pull off T tons of that volume they don't replace their albumin or a patient who has therosis they get severely dehydrated Um this can definitely put a patient into a Pinal syndrome so it's important to think about this one mechanistically it's all about that Ren and Angiotensin aldosterone system right so portal hypertension splenic Vaso dilation it's supposed to cause renal artery vasil constriction but you want to reduce that that's your goal you want to reduce spanic vasal constriction Vaso dilation that'll reduce renal artery Vaso constriction and then you won't be causing as much of a problem with poor renal profusion so again portal hypertension naturally causes spanking phas of dilation which causes renal artery vaser constriction reduce renal profusion and increases the risk of heaal renal syndrome what my goal is is to decrease the splenic phaso dilation decrease the renal artery Vaso constriction so I have more more renal profusion and I don't cause them to have aat renal syndrome how do I do that I give them octreotide or madrine otide and madrine are basically splenic Vaso constrictors and if you vasoconstrict the splenic vessels they will not dilate they will not pull blood in the splenic vessels and so you'll have more effective arterial blood volume in your systemic circulation that means I won't activate the sympathetic nervous system I won't activate the renin Angiotensin aldosterone system and I won't vasoconstrict my renal arteries and reduce renal profusion that's the mechanism but there's another thing that we should also consider in these patients they have declined liver function so they don't make as much albumin albumin is supposed to regulate their oncotic pressure if there's less albumin they're going to have less oncotic pressure less ability to hold on to the fluid inside of their actual circulation and so because of that they'll leak a lot of that fluid into their interstitial spaces and cause edema which will reduce their effect of arterial blood volume that'll then do what says Hey kidneys I'm going to increase the renal vase or constriction to retain more fluid which then causes an Aki so what if I give these patients albumin if I give them albumin I'll naturally increase their oncotic pressure keep more fluid in their circulation increase their effec of arterial blood volume and that I won't renally Vaso contract their arteries and I'll maintain good profusion through their glami and not cause an Aki this is the Triad that we often give to these patients the next thing is veril bleeding Verso bleeding is really important to think about with this patient again they have varices there portal hypertension that gastric uh those gastric veins are under high pressure so the concept behind this is that your body again releases vasodilators they splenic vasodilate and it causes changes in your portal pressure hopefully trying to drop the portal pressure and we see these patients develop a lot of veril bleeding what we need to do is think about how can I change this what I'm going to do is I'm going to give this patient octreotide now octreotide causes splenic Vaso constriction we already talked about that if I splenic vas or constrict what happens is I'm going to reduce the blood flow kind of going into the portal circulation right I'm going to try to reduce blood flow going in through the splank niic arteries across the splank niic kind of capillary system and through the splenic veins so I'm going to cause splenic vaser constriction what that's going to do is that's going to decrease the splenic vasor dilation that's going to then drop your portal pressure and that's going to then help to reduce your veral bleeding because your whole goal is to really constrict these spanic vessels drop the portal pressure so that I'm not going to cause as much blood flow going across those portal veins and then I won't bleed as much the other thing is that you naturally prophylactically will give these patients sefri aome it used to be thought that it reduces the risk of s uh but it's just something that they see a mortality benefit in and then you're going to as soon as you can if they're hemodynamically stable send them to endoscopy so that when they do the EGD they can go down there and they can actually take a little rubber band and kind of wrap it around these varices and ligate that off and that's the ways that we would treat this so it's going to be octreotide to spenic Vaso constrict them and reduce the portal pressure seph trioxin to reduce mortality related to infection endoscopy EGD to go and ligate off these vares and then eventually you should try to get them a tips to prevent this from happening in the future now the last thing that we can do as a way of being able to prevent them from developing veral bleeds if we don't go to a tips is we can use something called propanolol or natalo and the concept behind that is it helps to be able to again reduce the splank niic circulation because it causes splank vasil constriction all right the last thing that we should should watch out for therosis is a pular carcinoma this is a big one you generally do this by doing an abdominal ultrasound every 6 months to look for any kind of weird Echo densities that could suggest a mass in the liver and also check those Alpha fetal proteins in combination because if the AFP levels are really high and you have a mass inside of the liver there's a very high chance that the patient could have a pular carcinoma so that's an important thing to be able to pick up at this point the patient has been treated for therosis we've helped to minimize the actual complications primarily the next thing is with most patients who are serotic if they continue to advance and progress through their disease they will ultimately end up requiring a transplant and so the patients who we have to look at here we have to prognosticate and use different tools to gain that ability to determine their need for transplant so how do we do that well one way that we can kind of determine this is we can predict their risk of survival over a one-year period and the likelihood of complications based upon some lab values one is we use something called the child Pew score we don't often use this as much as we used to in the past um and I think that this maybe helps you to remember it so remember know your ABCDE by one year else in other words these factors that I'm going to tell you determines the one-ear survival rate and complications so it's a for albumin is it low B for Billy Rubin is it high C for coagulation is their ion are elevated D for distin abdomen other words do they have lots of aites and E for is htic and cyop ay this is the more commonly utilized scoring system that we utilize to determine the need for transplant uh because it predicts their three-month mortality rate which is very helpful and this is called the meld sodium score this one it's a little bit of a a you know stretch but I think it helps me to remember it which is boy I need this transplant come on and with this it may help you to identify some of the factors that determines their need for a transplant such as what well B4 Billy Rubin is it elevated I for INR is it elevated n for sodium do they have a padal syndrome or hyponatremia because hyponatremia can actually occur commonly that a pat renal syndrome patient D for dialysis have they had dialysis related to hpat renal syndrome and C for creatinine do they have any evidence of again hpat renal syndrome so you can see here that it's more related to coagulopathy hyperbar rubinia hyponatremia and then a padal renal syndrome and that'll determine the patient's really quick need for do they need to get a transplant we need to get them on the transplant list all right my friends that's sosis it was a monster I hope it made sense I hope that you guys enjoyed it and as always until next [Music] time [Music]

Channel: Ninja Nerd

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

Id: R1f1gWCyutA

Length: 60min 59sec (3659 seconds)

Published: Mon Mar 11 2024