Acute Liver Failure | Clinical Medicine

what's up Ninja nerds in this video today we're going to be talking about AC cute liver failure this is a part of our clinical medicine section and if you guys like this video please support us and the ways that you can do that is by hitting that like button commenting down the comment section and please subscribe also if you guys get an opportunity I highly suggest you guys do this please go down the description box below there's a link to our website on our website we have a lot of really cool things offer there some great notes some great illustrations we're developing quiz questions as well as a lot of exam prep courses a lot of things that are coming there so please go check that out if you have the opportunity let's talk a little bit about acute liver failure so what is it acute liver failure is when the liver decides to fail it takes a crap and it decides okay I'm not going to long no longer produce things I'm no longer going to filter things as I should be doing but it develops acutely abruptly usually we use this like term on a time frame that's you know ambiguous but less than kind of like 26 weeks um and then on top of that the most important point is that acute liver failures the liver fails acutely without an history of underlying liver disease that's really the big thing and that's what's really important to kind of differentiate between something like therosis so therosis is a liver has chronic liver injury it's repeated liver injury usually underlying liver disease that progresses over time it's more than 26 weeks and that's one of the big differences here now with that being said what's really causing the liver to become injured and lose its synthetic and filtering function that's a great question and I think one of the best ways to kind of phenotype that is based upon this concept is it a direct perinal HPA toite injury or is it a indirect in other words it's vascular related pingal injury so let's talk about that a little bit more here's the liver we take a piece of the liver one little cell called a hocy and zoom in on it when I injure this liver so a patient experiences some some type of liver injury generally when there's massive liver death liver cell death aasy death it causes a massive inflammatory reaction and usually the liver if it has enough time it compensates and regenerates that's one of the beautiful things about the liver but if it occurs massively acutely without the time for it to be able to compensate and regenerate that's what will precipitate the terrible findings that we see in aiber Failure but the question is what's causing the injury itself so what's directly hitting these liver cells causing them to become damaged and you know what's one of the cool things is that whenever a liver cell is damaged it really signals that there's something wrong via particular lab markers and some of those lab markers that leak out of the cell as a result they'll be elevated on laboratory studies that we'll talk about a little bit later and some of you guys will probably know these what are some of these things this could be things like as this could be things like alt and this could be things like your Billy Ruben and this could be various types this could be actually a mixt it could be unconjugated and conjugated Billy ribin but either way they're all going to be elevated now this is a marker of liver injury right but we'll talk a little bit later about things that actually are more indicative of liver function like albumin production and more other things like coagulation protein production or filtering of things like ammonia and other kind of like bacterian toxins but if there's an injury to the liver what's the causes and really it comes down to a couple different things here one is drug induced and I don't want to go too crazy and list every single CA I want you to focus on the biggest ones and usually the most common one is going to be Tylenol or acetaminophen so Tylenol toxicity is going to be something that you'll see whenever a patient is taking more than four grams of Tylenol per day generally if you take less than four grams per day where you're within that kind of at least four grams per day you're within that normal recommended daily allowance but if you go way above that higher chance of causing a lot of Tylenol toxicity and thus drug induced lury liver injury we call Dailly second one is it could be viral induced and there's a bunch of different viruses hepatotropic viruses there's so many I think the biggest ones to be able to remember is your hepatitis A virus your Hepatitis B virus your hepatitis C virus your Hepatitis E virus usually these hepatotropic viruses are going to be by far the most common I'd say out of these I'd say Hepatitis A and hepatitis E are probably more of the acute type whereas Hepatitis B and hepatitis C they can cause acute liver failure but they're more likely to cause more of the therosis type of picture you can also see these in patients who of hepatitis I'm sorry uh herpes simplex virus and potentially CMV but this is more in like imuno compromised patients so think about this this is a potential if a patient is having things like this they've had potential uh dirty needle or blood exposure or seminal fluid exposure something like that or they've had some dirty food they had some food from like a food truck that probably wasn't cooked properly or they were traveling uh these are potential things that could be more of a source especially in the clinical vignette that would suggest hepatitis viruses all right what's another one another one this one's actually really difficult to differentiate it's called antibody mediate we also call this autoimmune hepatitis so autoimmune so autoimmune hepatitis is kind of tough to diagnose it's usually kind of lower in the food chain so when you think about this when you'll see a patient who have massively elevated ests and alts they won't all the time present with this classic like joint pain or rashes or anything like that often times they'll have massively elevated ests alts and Billy ruin and you'll send off antibodies that are the source of this cause and generally there's so many of them but I think the biggest ones that you'll send generally are going to be things like Ana so anti-nuclear antibody anti smooth muscle antibody I G G usually the soluble type and there is another one called anti- liver kidney microma one antibodies but I'd say these are going to be by far the most important ones and they're indicative of antibody mediated damage okay okay so you'll send off viral panels you'll send off a Tylenol level you'll send off antibody levels the last one's a little bit more tough but it's when I say it's tough It's not really a lab value it's more of a clinical history that you're going to be picking this up on a patient is usually pregnant usually third trimester they're showing features of preeclampsia hypertension protein Uria and if they also show signs of acute liver failure such as well we'll talk about a little bit later white upper quadrant pain jaundice ptic conopy coagulopathy Etc then you want to think about what's called we usually use the kind of the abbreviation your acute fatty um infiltration of the liver during pregnancy this is usually something that will happen again in patients who exhibit features of preeclampsia so you really want to look for that within the history third trimester hypertension protein Uria and then Now features of liver dysfunction usually the pathophysiology behind this is that they don't break down fatty acid so they don't undergo beta oxidation and those fats build up within the liver and cause massive steatosis all right that's this concept of direct liver injury that causes these levels to fly off the handle but what if it's not direct injury to the prinkl cells by drugs by viruses by antibodies or by fatty infiltration from beta oxidation dysfunction what if it's the vessels that in some way shape or form are diseased are not delivering what they're supposed to this is the artery the TIC artery so we'll say this is the TIC artery its design is to deliver son of a gun its design is to deliver oxygen-rich blood to the actual liver cells that's his job it'll drop off oxygen this is the TIC vein it's supposed to be able to remove waste products uh generally well anything that comes through the liver it actually gets cleansed but it'll take blood from the liver that's gotten cleansed removed of toxins remove the bacteria and then it'll put it back into the systemic circulation if there's disease disase of these and you're not allowing for these arterial or venous systems to work properly the liver can either not get oxygen or it can become congested if that happens the liver will then become injured if it becomes injured one of the things that is usually a sign of liver injury is elevated ests ALT and Billy Rubin and then the downstream negative consequences of having acute liver failure which we'll talk about is the complications of the loss of synthetic function and filtering function but this is what we'll potentially see here with respect to the lab values that suggest liver injury now if you think about it here's the aorta here's the TIC artery what's the problem here that could be causing oxygen not be delivered to the liver cells and the concept behind this is the patient is developing something called es schic hepatitis and it is literally what the name says a patient is developing inflammation of the liver because of aeia what could be the cause it's usually shock and the primary way that you identify this is that the patient will have profoundly low blood pressures so blood pressures will be in the turd they'll be in the tank they're not going to be good and because of that if my heart let's say have cardiogenic shock is not generating good good cardiac output obstructive shock can't get blood out of the heart hypmic shock don't have the volume to deliver the blood to the tissues or septic shock my blood vessels are dilated and there's no resistance and again I'm not generating a pressure I'm not profusing the tissues that's the concept here is that the blood that's supposed to be circulating through here and dropping it off to the tissue cells let's say here is going to be a couple hepatocytes they're supposed to be receiving oxygen which is dependent upon the blood pressure if the blood pressure is in the tank you're not going to peruse these tissues if you don't give them oxygen they will become es schic and they'll start to die and that's that's what you're going to see as a result okay the other concept is what if it's actually from the vein so the Venus one is twofold it could either be due to one is if you get really really deep down here and you look at this look there's a clot within the atic veins right so if you have hepatic vein clots all right so hepatic vein clots this is usually due to a disease called Bud kiari Sy syndrome and this is when you have a bunch of clots of the TIC veins if there's clots within the TIC veins what's supposed to happen is I'm supposed to take blood that's coming from these liver cells move it through these hepatic veins into the inferior vena and then into the systemic circulation eventually but if this is being impeded at this point am I going to get blood through there no the liver cells will then become congested injured we got the point so think about this usually in a patient who has liver cancer hepatocellular carcinoma they have malignancy anything that makes them hypercoagulable so underlying like hypercoagulable condition like gene mutations like Factor five lien prothombin genes or antiphospholipid or anything to that effect that makes them hypercoaguable polycythemia these are really big things to see in the vignette that would suggest this lastly is that maybe it's a little bit further more dist where the inferior vena is being congested because this process where blood is supposed to be entering into the right heart is impaired if that's impaired it's because the right heart sucks and it's not doing its job so this would be what we call hepatic vein congestion so what if the hepatic vein is congested with blood because it can't allow for that blood to go to the inferior V cave into the right heart because the right heart is all jacked up this would be in the scenario of right heart failure if a patient has right heart heart failure like terrible constrictive pericarditis it could potentially cause their liver to become super congested and can cause acute liver failure often times with these it's about looking for the history of right heart failure doing an echocardiogram considering doing an ultrasound or or Doppler ultrasound of the actual liver veins and looking for the actual clots there and then looking in the context that a patient just have terrible blood pressure these are ways that we can use just to think about a patient having some type of acute liver failure I think one of the biggest things to remember is when a patient comes in with acute liver failure they don't say hey my liver's jacked up dude it's they're going to come in with some very subtle signs and I think one of those big ones to think about is when the liver is really inflamed because of injury it stretches on that glein capsule which is actually kind of inated and creates this pain where the liver sits the right upper quadrant so look for right upper quadrant pain but you know it's a really big sign it's related to this Billy here I'll as it for you if the Billy is elevated you know where this likes to go and deposit it loves to deposit in the Scara and when it deposits into the Scara it actually causes a yellowish discoloration ioris it can also deposit into the skin all over the place and it can cause jaon disappearance so in a patient who comes in jaist you really want to think about acute liver failure especially if they have no underlying history of liver disease and it's developed acutely or abruptly less than 26 weeks now let's talk about the complications all right my friends so now we have a patient comes in acute liver failure they're showing signs of right upper quadrant pain maybe they're showing shines of ioris or yellowish discoloration that would suggest jaundice we're thinking oh maybe something's wrong with the liver we think okay what could be the causes it could be tanol toxicity it could be viral it could be autoimmune could be pregnancy related I got to think through my clinical history in the scenario could be vascular related are they in shock do they have right heart failure is their suggestion of hypercoaguable state and Bug kiari syndrome those all those thoughts are going on in my mind but the thing that you should also be understanding is that yes okay I'm going to work up the patient see if they do fit the acute liver failure category work up the cause which one's the likely cause but but you want to be watching out for other complications because acute liver failure is not just defined as the liver is failing you have markers of liver injury we really Define it off of a liver that's actually again failing without underlying history of liver disease very abruptly and we use two other very specific categories they have inyopools solutely necessary in the nosis these are the two big hitters that you have to remember for acute liver failure you can have big elevated liver enzymes but you need these things as well to call it acute liver failure so what the heck is hepatic and cyop the concept behind this and we'll go over what the patient will look like in a second is they have to have underlying liver dysfunction you can see this in curosis and you can see this in acute liver failure but the liver is injured in some way shape or form and there is dis function normally let's say here's the gut coming via the gut you have the portal vein right so this is going to be coming from the gut coming from the gut you're going to have a bunch of different things but often sometimes one of these molecules that we love to use is what's is the example of encylopedic now ammonia when it comes from the gut it goes via the portal vein When It Go goes via the portal vein it goes into the liver and it's supposed to be metabolized it'll be metabolized by the liver you can also have it coming from other ways too it can be coming from muscle tissue via the arterial system to the liver either way ammonia is supposed to be metabolized by the liver but if the liver has injury or dysfunction is it going to be able to clear that ammonia very well no and so what happens is this clearance of ammonia doesn't occur very well and so what ends up happening is whenever the blood leaves the liver goes via hepatic veins and enters into the systemic circulation guess what happens it doesn't get cleared it's supposed to be broken down into Ura that doesn't happen and so these ammonia levels as a result build and build right because this process here where you're supposed to clear it is not occurring there's damage there's dysfunction and so ammonia will not be cleared it'll build up within the systemic circulation now what we know is that ammonia loves the brain it loves like the astrocytes of the brain and what happens is it goes and it actually gets taken up by these astrocytes in the brain when they get taken up by the asites they actually specifically they'll bind onto an amino acid called it'll bind on to like glutamate and convert into glutamine and glutamine is really kind of like osmotic and it'll pull water into the cells this will also kind of like alter some of the activity of the neurons just in general and so what can happen is two particular things as a result of this ammonia building up in the actual brain cells one is it can cause cerebral edema and this is the terrifying super scary sphincter pinching kind of thing that you just don't want to see in these patients is cerebral edema why what is cerebral edema do it'll cause the brain to start swelling the skulls a fixed space the mon Kelly Doctrine tells us that so because of that what happens to the intracranial pressure as a result it can increase and so what we could see as a result is that we could see these patients developing elevated intracranial pressures and sometimes we actually use monitors to do that in patients with severe acute liver failure and elevated intracranial pressures secondary to cerebral edema because that's the ammonia that's causing this problem the ammonia will really lead to this situation here now the other thing here is when you cause dysfunction in these neurons not only will they swell but you could also lead to two other particular findings one is these patients can develop what's called a altered mental status we often use the kind of abbreviation AMS that's one you know what else here's the key term asterixis it's kind of like this weird flapping trimor if you will so if a patient presents with confusion hallucinations insomnia lethargy stuper coma agitation uh all of these particular things we can consider that altered mental status and if they have a flapping trimmer you extend their hands and it kind of flaps back that's indicative of asteris and then if you by some way got a CT scan or used particular measurements of being able to quantify inur cranial pressure it would be elevated because of the edema Factor all of this is due to the liver not being able to metabolize the ammonia not being able to filter and clear it properly so this is really where the issue arises is that the ammonia will then cause brain dysfunction leading to this incopy Factor so when a patient comes in with acute liver failure look at their degree of mental status are they confused Delirious are they not making sense are they agitated are they sleepy lethargic comos look for all of those findings do they have asterixis these are big things to look out for now incopy and acute liver failure sure can happen on its own but often times there's precipitants that kind of increase the ammonia in general whether it's increasing the absorption decreasing the clearance so not only is it in the setting of acute liver failure by itself but it can be let's say agitated or precipitated so we can say that this can be precipitated by a couple other factors such as what sometimes it could be precipitated by infections like s so what called spontaneous bacterial peritonitis it can be exacerbated by GI bleeds it can be exacerbated by renal failure where you can't clear the ammonia and so I think it's important to realize that or dehydration these are important things to consider as a trigger so this can be precipitated by infections like SP GI bleed renal failure hypovolemia in the setting of liver dysfunction acute liver failure okay we have a patient confused altered asterixis potentially cerebral edema elevated inal pressure that's one finding the second one is they have to have coagulopathy as well so coagulopathy is again the liver is jacked up it's not working and if it's all messed up one of the other functions of the liver not just to clear is clear ammonia you know what else it does it makes clotting proteins so it's supposed to synthesize these clotting proteins it puts it into the bloodstream and these will circulate through the bloodstream and they're very important clotting proteins there's so many of them that it makes it makes things like Factor 2 Factor 7 Factor 9 and Factor 10 and all of these are important because these are procoagulants meaning they want to induce clotting it'll also make some other ones like protein C and protein s but those are anti-coagulants they want to prevent clotting here's the problem whenever your liver fails you fail to produce these procoagulants into a degree yes the anti-coagulants but these are the ones I want you to focus on if I can't produce these procoagulants let's write that down Pro coagulant can I induce clotting no and as a result I'll have decreased clotting that occurs if I have decreased clotting obviously as a result there's increased risk of bleeding and how can bleeding present well in these patients it can look a lot of different ways but often times it can be from let's say from most terrifying to least terrifying one way is you can literally bleed into the brain I see this a lot working in a neurocritical care you see this as intracranial hemorrhages this is a really really terrifying one the probably the one with the highest mortality rate you can see bleeds from the GI tract so GI bleeds would be another particular one that you want to watch out for so watch out for I watch out for GI bleeds and the ones that I think would be the least scary but they still can occur is like epistaxis gingival bleeding or anything around the skin so lots of bruising and petii so look for mucocutaneous bleeding we call this mucco cutaneous bleeding and this could literally be as simple as like them having multiple multiple bruises and pular Lead iian so that's a really important one but here's the other thing Factor s is the really big one because what's interesting is it's one of those procoagulant that gives us an idea of what we call the INR the international normalized ratio which is a lab value that we use a lot so ammonia is one of those that we use as a lab value we can look for that but we really prefer the exam and the setting of acute liver failure but off this one it's hard to like measure all of these so what we do is we use one of those which is a better measurement and so you'll have decreased clotting and so what we do is is we can actually say that if there's less of these very specifically though very specifically Factor seven it will actually do what it'll increase the bleeding time and one of those is via the Inon R so the Inon R sometimes we also say PT let's actually write that down PT R so the pton r will be elevated and this is indicative very specifically that there's something going on with Factor 7 which is a product that is produced by the liver that's really really important okay and the patient who has failing liver massively elevated liver markers they also have jaundice right upper quadrant pain confusion asteris and an elevated INR usually greater than 1.5 some will say 1.6 then I'm really thinking it's a cute liver failure other things that would add to the supporting nature that it's acute liver failure is obviously going through the diagnostic tests and finding the cause but other things would be hypoglycemia so the concept behind this is that the liver is failing it's losing its ability to perform its natural functions one of them is to perform something called glycogenolysis and gluconeogenesis if the liver jacked up can you do that do you have enzymes that are capable of helping that process no so gluconeogenesis is impaired and glycogenolysis is impaired if that's the case this is supposed to form new glucose from non-carbohydrate and break down glycogen into glucose putting it into the bloodstream so it's supposed to take from the liver and put which I'll represent as these kind of like black dots here glucose molecules but if you can't do this process here what's going to happen to the glucose MO ules within the bloodstream it's not going to go into the bloodstream because I can't do these and so you'll have a patient with hypoglycemia very low blood glucose levels so look for hypoglycemia and elevated INR generally like greater than 1.5 and elevated ammonia or usually evidence of confusion or incopy with asterixis all right so the last thing that I want you guys to watch out for is infection risk is really high in patients with acute liver failure it's it's a couple reasons why one is inside the liver so the liver is all jacked up and so that means that not only is the liver cells injured but some of the other cells that are associated with the liver cells around it such as these cells here are also injured and dysfunctional and this includes these like little liver cells um these macras that sit within a liver and they're called cuper cells they're like little macras and so what happens is Imagine bacteria here's some bacteria or some fungi or different things like that they're coming from the gut and naturally what happens is is if it does make it to the liver the liver will have cup for cells that will destroy these little suckers prevent them from getting into the bloodstream the other concept is that you have these other molecules that your liver releases and so it makes these other molecules here called complement proteins so we'll put here I'm just going to say that there's these molecules here called complement proteins and these are really helpful in breaking down or at least in increasing inflammation and helping to break down bacteria and patients who have acute liver failure they have decreased complement proteins and decreased cup for cells which means that they have a decreased ability to clear bacteria so that means that tons and tons of bacteria that should not generally be me making it through the liver and getting into the systemic circulation do if this happens and I get lots of these bacteria into the bloodstream what are they going to do they're going to go to your respiratory tract this is the three sites that they love the respiratory tract the urinary tract and they like to stay in the blood and if this happens it can cause pneumonia it can cause a UTI or it can cause sepsis and so that's the concept here you can get a patient Who develops pneumonia they can develop a urinary tract infection or they can potentially develop sepsis and even high risk of septic shock that's the scary thing about this one all right that covers the complications of acute liver failure now if I have a patient who comes in abrupt failure of the liver massively elevated lfts ALT Billy Rubin jaundice right up a quadrant pain work up the causes then think do they have encylopedic of acute liver failure think about these two to watch out for scary scary complications and to add to the diagnosis now let's talk about the Diagnostics I think a patient has acute liver failure I need to have what well first I need to have liver injuries severe liver injuries I'm going to get some lfts I'm going look at those a and ALT molecules are they super elevated at least greater than a thousand yeah that definitely supports hepatocellular injury and then I would think about some of the causes here in a second but let's at least a diagnose acute liver failure do do they have features of encylopedia edema well I can obtain a pneumonia but I don't need a pneumonia so if pneumonia is elevated okay cool that definitely helps me suspect that they may have acute liver failure with producing an adequate amount of factor 27 9 10 what does that actually help me with the PTINR this is the lab value if they have less procoagulant they'll take a longer time to clot so their PT their prothombin time will be very long or high if you will and so if their PT is elevated at least greater than 1.5 that suggests a coagulopathy so if they have a paracellular injury in combination with definitely have a c Li failure then you have to start thinking about what are the causes do they have an accidental ingestion or a purposeful ingestion maybe check a Tylenol level to rule out Dilly do they have any potential risk of having hepatitis check the viral serologies hepatitis A B uh e and I wouldn't really waste your time potentially on C but you can if you'd like the other one is get a liver ultrasound with Doppler to look to see if they have any bud kiari syndrome and then also you could do an Ana and anti-smooth muscle antibody to rule out any type of autoimmune hepatitis you could also get an echocardiogram to rule out right heart failure and then also look at their history to see if they have any recent events of a profound hypotension shock or Cardiac Arrest which may suggest es schic hepatitis all right we've talked about liver failure and acute liver failure how do we treat it well unfortunately the damage has already been done to the liver your job is trying to at least prevent complications such as them continuing to have profound and fulminant hepatic failure so you can try your best to try to reverse the underlying cause but a lot of the times that maybe be very difficult because you're trying to find the cause when this patient is very very sick so a lot of the times one of the first things that's usually mentioned is do they have any Tylenol toxicity if there is there is a drug that has been shown to reduce mortality in Tylenol toxicity related acute liver failure and that drug is called IV in acetal cysteine also referred to as Knack the mechanism by how this works is not completely clear but it's been shown to really reduce a lot of the inflammation and potentially reduce the risk of profound fulma hepatic failure and the need for transplant and that's a really significant mortality benefit there is some data suggest that even if it is not related to Tylen Tylenol toxicity you should still use uh this drug either way in any other cause of Al aul failure even if it's not Tylenol toxicity but do remember that it's more beneficial and the studies suggested it to be more mortality benefit related for tyol toxicity often times unfortunately with these patients you're going to support them the best that you can to allow the liver to heal but often times they may you know progress to needing a liver transplant encylopedia and so a couple different ways that we can do that is by giving them something called lactose and potentially refaim if they need it and then if they have really high in cranial pressure often times you'll try to treat them with things like hypertonic saline and mantol but we'll talk about that more in the neurology section let's focus a little bit on the lacos of the refaim more particularly because these are common agents that are used in acute liver failure and therosis lactose being the first one what we do is we give this drug it's ingested and what it does is it acts on these bacteria particularly in the colon and helps by specifically do something really interesting it increases like this lacos it leads to like a lot of lactic acid and acetic acid production from the bacteria the bacteria break down the lactose make a lot of lactic acid acetic acid why is that helpful what happens is these guys release a proton off of them that proton binds with the amonia that may be present within the actual bowels converts it into ammonium which is not really going to be absorbed as easily it's less toxic and allow for it to be excreted into the feces and so that's one way that we can drop the ammonia levels and reduce the actual trigger which we believe is ammonia that's causing the encylopedia raaen has just been shown to destroy some of the bacteria in the colon and if you destroy some of the bacteria in the colon you may reduce a little bit of that ammonia production in general so that's the concept there what about the quag apathy often times it's usually going to be giving something like ffp and sometimes vitamin K the concept behind this is that your liver is pretty damaged but maybe you have some residual liver cells that are actually healthy the vitamin K will stimulate those remaining residual healthy liver cells to produce lots of factors 2 7 9 and 10 so you get more procoagulants ffp or PCC will literally repete the actual factors 2 7 n and 10 so either you're making more or you're just replacing them in a in a solution when I get more of these I get more procoagulants and I allow for me if I have a hole or tear in a blood for me to repair that hole and lead to a clot there which reduces the risk of bleeding this is often times can be give usually before procedures or if they have any complications such as an intracranial hemorrhage maybe a GI bleed or lots of mucocutaneous bleeding hypoglycemia it's actually relatively simple you're just going to give them dextrose the other thing is reducing infection risk you do not start these patients on antibiotics but have a low threshold to start them on antibiotics if they develop a fever a profound [Music] oh

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Length: 35min 33sec (2133 seconds)

Published: Mon Mar 11 2024