hello and welcome to part two of chapter 14 on the liver where we had left off with part one was the end of this is what happens in normal liver function and now for the rest of the uh lecture we're going to be talking about when things go wrong with the liver fortunately uh the liver has fantastic regenerative capacity now it's not infinite um but the liver is really pretty good at uh fixing itself um acute damage to the liver because of uh drug exposure or uh he hepatitis infection uh especially hepatitis A this can be followed by recovery and regrowth we can make more hepatocytes in fact um this is the reason that we can have uh living liver donors now you know you know kidney donors basically most people are born with two kidneys and uh one can elect to donate one of those kidneys to somebody else we don't have two livers we have one liver but it's and people don't donate the entire liver they take part of the liver um and Transplant that to somebody else and then the the the donor um it takes some time but that liver the cells of that liver can regrow um and come back to full liver functioning just really really impressive organ again I know it's brown and Blobby looking but oh my gosh that's amazing yeah brain can't do that kidneys can't do that uh so yeah big fan of liver we have ways of assessing how the liver is doing um because as we've said the liver can get damaged uh similar to the tropinin test um that we did we were checking somebody for damage to cardiac muscle cells remember cardiac muscle cells when they die they split open and there's something that a bunch of stuff gets released into the bloodstream but there particular markers that are unique to cardiac muscle cells and that's what we look for In The Blood same goes for the liver um if there's damage to the liver to the point that some of the liver cells die and we have necrosis some stuff's going to spill into the bloodstream and uh these are liver enzymes what we call them these blood tests uh the two that we hear about the most are alt and a there's this is the full name I'm not going to test you on the actual names of these things things because we always just call them alt and a um alt is the most specific liver marker um but you'll see both of these reported then um ggt another enzyme and in case you don't believe me about the enzymes uh Ace remember like lactase um th those are uh the names of enzymes end in ASE what did I want to tell you about that okay um different enzymes will be elevated uh that might give us some insight into what is causing the problem so for example ggt tends to be uh elevated um when the damage is due to excessive alcohol intake Alp can reflect uh chasis all right so so that's uh liver cells dying and and uh we're looking in the blood for evidence of stuff spilling into the blood these others are um looking for evidence of the liver not quite doing its job anymore and so we look for um markers based on the fact that we expect the liver to make a bunch of proteins for us so one of the things that the liver makes as I've said repeatedly is albumin and albumin is the most common protein in the blood and um when the liver is not functioning well it doesn't make as much albumin and so we look for exactly how much albumin is in the blood and that's going to decrease with liver damage the other proteins that decrease uh with liver damage are the coagulation proteins uh those are the ones for clot the clotting factors they're also going to decrease but instead of counting like how how much coagulation factors do we have we actually look at the other look at it the other way we say Okay Co coagulation factors are there to help us clot so if we have less coagulation factors that's going to take us longer to clot and so that's what we look at is um how long does it take to clot or the prothombin time the PT and that's going to get longer if it's just indicative that we don't have as many clotting factors as we had before for and then the third um another way of uh assessing uh liver function is uh assessing the the kitchen capacity um specifically with Billy Rubin remember we talked about the how the unconjugated Billy Rubin or indirect Billy Rubin um gets conjugated or made into direct to Billy Rubin if the liver is not functioning well we actually get a buildup of this indirect or unconjugated Billy root and this other number goes so the direct or conjugated goes down and indirect unconjugated go up this is looking at the blood um ah when uh liver damage goes on chronically um the the the liver becomes fibrotic um and so we assess how much fibrosis there is the nonin noninvasive ways of assessing in is with ultrasound MRI CT scans um now the gold standard like the most detailed um is actually taking a biopsy of the liver but that's a really invasive procedure and so mostly we rely on ultrasound M CT scan to changing topics a little bit um let's talk about specific acute liver injuries um more than half of the cases in this country are can be traced back to a drug induced liver injury and acetaminophen is absolutely the most common Culp the most common culprit um it is however predictably D dose dependent uh so you know patients aren't supposed to get too much acetominophen every day um and if they do most of us most patients are going to respond in this pretty predictable way that liver gets overwhelmed um by trying to manage all of this acetaminophen and so there's there's damage the the more overdosed the acetominophen is the worse the damage is so that's not surprising um it how can I say this it's not that it's not important um it it's very important especially given how uh useful acetominophen is and how common it is uh to in in this country um the the trickier thing though is is other drugs uh including some antibiotics that some patients will not have any problems their livers will have no problem processing this or processing this uh molecule no damage will will occur and then other patients end up with severe liver injury this is referred to as idiosyncratic meaning it's Unique to the individual and so there are certain drugs that can cause liver damage even though most patients won't get liver damage from it and so we're on the lookout for when we're giving patients medications be on the lookout for um signs of liver damage and so some of the the milder cases uh the symptoms are pretty vague uh they don't the patient doesn't feel well they might have some nausea um but then if it's mild enough it's going to resolve spontaneously doesn't you know no intervention is needed however in acute cases one of the clearest signs right away is um patients appearing jaist because of that elevated Billy Rubin and that's I mean before you even do a blood test you can start seeing the change in the color of the patient especially in the Scara um okay so more liver damage or Kinds of liing Kinds of liver damage of problems with liver acute chasis um that means that the bile is not flowing it's being made but it's not making it into the digestive tract uh so there's blockage and this can be due to gall stones this could be due to a cancer uh or pancreatic inflammation uh it can happen in response to certain medications uh again can be unique to the patient um and uh something that happens in pregnancy for some patients as we've mentioned jaundice is one of the clear signs uh that you see quickly uh remember much of the Billy ruin is going to go out in the bile it has and has that intense yellow to green color um if it doesn't get out in the bile it's going to spill into the blood and that's where that yellowing color of the skin comes from um addition additional U signs uh will look uh at blood tests elevated ggt Alp um ah increasing in the the circulating bile salts so remember going out in the bile is both trash and recycling um so trash is Billy Rubin but the stuff that is needed in the digestive system and it's going to get recycled is the bio salts some of the bile salts even though they're supposed to get recycled some of that goes out in the stool and so the amount of that that gets recycled gets back in the bloodstream is manageable if none of it's going out in the stool it ends up being deposited in the skin and it can cause intense it itching for the patients and then finally um again as we've said the um the Billy ruin is provide that really dark brown color to the stool and so the the stool doesn't get dark uh looks paler than usual but because there's more Billy Rubin in the blood and more of it's coming out through the kidneys the urine is going to get darker and again it's due to the failure in bile secretion all right now let's talk about hepatitis uh that's a general term itis of course means inflammation and HEPA having to do with the or having to do with the liver it can be acute or chronic chronic meaning more than six months in duration and it lots of different causes it could be chronic alcohol exposure um obesity some of the viruses the three that we're going to talk about and that's coming up next hepatitis A uh this one is the one that's best known for fecal oral route of infection this one um there can be outbreaks daycare centers and restaurants um somebody doesn't wash their hands completely and it can get passed from one person to another uh it's an it's an acute infection It generally resolves uh there is a vaccine available for this um how it's diagnosed is looking for immunoglobulins against it so remember IGM and IGG those are the two um immunoglobulins that uh we have in you know the Primary Response first we see IGM come up and then IGG comes later um mostly once people have had hepatitis A they're immune and um they generally don't get sick from it a second time Hepatitis B um it can have acute and chronic infections U or possible The Chronic part is it's a DNA virus and the DNA actually gets integrated into the host's DNA um and so then the patient has it for life it's treatable um but we cannot clear we don't have a way yet to clear this infection uh this one is bloodborne and is sexually transmissible there is a vaccine available for it you have to take it three doses um some people even after taking it in three doses they're they don't they're called non-converters they don't become immune um and so they go through the series a second time and again if they don't become immune the second time then we just say okay that's the best we can do for you uh so yeah vaccine development isn't perfect but there is a vaccine um it's just a little bit tricky to get uh immune to this thing and then finally uh hepatitis C this one is bloodborne also sexually transmissible this one is so tricky because it can be asymptomatic for years somebody can have slowly developing therosis we don't know it until they're they have severe uh liver problems um this is what contributes to you know it being transmitted so readily because people don't know that they're infected if uh hepsi goes untreated it can progress to therosis and beyond that in a small percentage of cases can lead all the way to hipat Cellular cancer this is in fact heepsy um is the most common reason for liver transplantation think three qus of liver transplants are are due to uh having had a chronic hepsy infection that went untreated testing for hepsy is available uh the recommended screening weirdly enough um that there's one time screening recommended for the Baby Boomers people born between 1945 and 1965 turns out that most of these undiagnosed cases are in Baby Boomers they had no idea that they had contracted um heepsy and they've been living with it for decades uh it is screening more routine screening is recommended for people with high risk behaviors people who for example share needles um who are uh sexually active with multiple partners um so yeah screening is recommended unfortunately there is no vaccine for heepsy yet uh fortunately there is a treatment regimen that can completely clear uh infections for many patients uh it's expensive and it's long but it's coming AA able all right let's talk some more about chronic liver disease um and some of the vascular changes that we see so when when a patient has chronic liver inflammation this can actually lead to hepatocyte death um that it activates some of the fibro blasts that are in the liver called stellate cells um this results in fibrosis that is you're putting down scar tissue in uh in the liver tissue that's going to have some consequences um one is the capillaries get more narrow that's going to increase the pressure in the the capillaries um but the cell the endothelial cells get less leaky so less stuff can pass out of um the those capillaries so have less permeability so less stuff can get passed through and that's what the is all about it's passing stuff uh from the blood from from the blood into the liver cells and from the liver cells back into the blood and that gets harder and harder to do so as we lose the permeability as we increase the resistance um what develops is increased pressure in through the liver and that backs up just like it did with the heart failure and you know the pressure is backed up follow it backwards um the if the blood is having a difficult time flowing through the liver because of all of this fibrotic tissue that's going to back up into the the portal vein um and that's what we call portal hypertension and that's got a bunch of consequences as we'll see now uh liver curosis in the early stages um can be asymptomatic but um if if the liver damage is sustained um it can proceed all the way to um decompensation in in other words when patients are showing symptoms uh and that's again due to the extensive fibrosis and then the development of the portal hypertension in the early stages it can be reversible because the liver is so awesome at repairing itself the hepat sites can reproduce and um so if it's caught early enough and so if the the cause can be identified and addressed so for example if the cause is excessive exposure to alcohol and the person is able to abstain from alcohol and I know that that is a lot easier said than done um but if they can they may be able to recoup um most if not all of their liver function uh if the damage is due to a Heep SE infection and it's identified and treated again if it's caught early enough then that damage can be reversed but if it goes on um after a certain point the the damage is irreversible you just don't have enough cells uh that can replace themselves and the fibrosis is in there and can't undo that um and then in that case if somebody is in this stage then normal function at least at present um can only be achieved by transplant either from a living donor or um uh somebody who died uh in late stage uh therosis the liver becomes hard gets smaller it becomes nodular in appearance a healthy liver is kind of smooth on the outside and this is not that okay and that is the end of part two and I will see you in part three