hello and welcome to part three of chapter 14 on the liver we had just finished up part two uh looking at late stage cirrhosis and we are moving into other manifestations of uh chronic liver diseases I'm going to show you a laundry list of different manifestations and this is just so that you can have it all in one place I have a separate slide devoted to each one of these things hopefully with what we have talked about so far with normal liver function it will become easier to see where all of these symptoms are coming from in fact we've already discussed where some of those are coming from so we won't spend a lot of time on it and then we'll wrap up the end of this lecture with a couple of other causes we talked about hepsi or the the different viral hepatitises um and then we'll we'll wrap up with a couple of other causes of chronic liver disease um so I'm not even going to read these here I'm just going to go one at a time jaundice that yellowing of the skin the cause of it is as you will remember decreased conjugation of bilirubin the bilirubin comes from the recycling uh well of the the breakdown of red blood cells and the hemoglobin um the iron of the heme gets taken out and then the other part is the so-called unconjugated bilirubin in the liver it's supposed to get conjugated and become more water-soluble and it can be eliminated um much of it coming out in the bile some of it going out in the urine but whoops oh my goodness but in the case of liver failure this isn't happening and so the the um unconjugated Billy or indirect Billy Rubin builds up in the blood uh so we see the yellowing of the skin and the increase in um indirect abilirubin on the blood test another consequence of liver failure is bruising and bleeding and we've talked about why this happens too um a reduction in the clotting factors oh what we had said before was um on a PT test the the clotting time the Prothrombin time is going to be increased it's going to take longer to clot what you can see on your patient is uh things that would ordinarily not have caused a bruise or wouldn't have caused bleeding out of the body is now causing bruising and bleeding out of the body because we don't have enough of these clotting factors to get down to make the fibrin to make the blood clots another consequence is edema throughout the entire body this one is tied to a decrease in the production of albumin the famous protein that the liver makes largely what albumin is about okay so this cartoon here is this little tube thing is supposed to represent a capillary and here are some cells of the tissue of I don't know whatever tissue you want to talk about um Let's Pretend We're in uh muscle in the leg the um blood flow through the capillary clearly some stuff is going to leave the capillaries that's the way capillaries are supposed to work um but then stuff is supposed to come back into the capillary um and continue on its way in the vein and you know back towards the heart what happens here is because the oncotic pressure of the blood and again oncotic is um the specific term that's used it's like it's the osmotic pressure that's due to the presence of proteins and so if we don't have a lot of protein in the blood we're missing a lot of this albumin that's ordinarily here that draws the water back from the tissues back into the capillaries that water is going to come out of the capillaries and not come back in that's what we call edema and that's going to happen everywhere as I said specifically in the leg but it's going to happen in the lungs it's going to happen all over the body all right more consequences another set of proteins that is in short supply due to liver failure is the complement proteins those are needed for infection management that's part of the innate immunity and I'll remind you um one of the things when one complement proteins attach onto the outside of virus particles or or bacteria or toxins it oxidizes them that makes them tasty makes it more attractive to the neutrophils and the macrophages to take that stuff in complement proteins also act as chemotactic factors they bring they signal to the white blood cells that are circulating through the circulatory system it draws them out of the of those vessels and into the tissues um and we don't have those complement proteins so we don't have that signaling system happen and then finally that membrane attack complex the you know grand finale of the complement Cascade that's not happening either and so we have a difficult time fighting off bacterial infections for example all right aside these um this one's a little bit trickier to understand um it it can be traced back to the portal hypertension and I will remind you let's see here's the liver and these structures represent for example the stomach it's been cut open here the spleen this is the pancreas the duodenum the blood vessels that recollect blood that that's coming from those organs that blood all of it before it goes back to the heart has to pass through the liver through the so-called hepatic portal vein but if this the liver is becoming fibrotic those blood vessels are getting narrower not as much material can or not as much fluid can pass easily through those tubes this is going to slow down transport through this organ and we're going to start having a buildup of fluid and that just backs up into the tributaries okay as this backs up remember pressure the hydrostatic pressure the push out of the blood vessels is going to be stronger than the pull in especially because we have low albumin and we're not able to draw that fluid back in so we have high pressure pushing out we have decreased oncotic pressure pulling back in directly a result of this increase in pressure in the blood vessels flowing through the liver let's see so yes it's physically uncomfortable um the patient this is a man looks like you know nine months pregnant um and you know you've heard patients talking about you know they have this huge belly it's pushing up on the abdomen is pushing up into the thoracic cavity the lungs can expand as well one of the things that our patients report is not being able to catch their breath they're not able to breathe enough um and again and then there's also a demon going on um in the in the lungs as well I mean so this is going to be a difficult situation for the patients all right another uh problem that again can be traced back to the hepatic uh the portal hypertension are esophageal varices and uh hematism I know I I have trouble saying that word uh vomiting blood in other words so what's happening here is again we have you know a slowed blood flow I have it here like it's blocked completely it's it's just significantly restricted and so there's this increase in pressure um in these blood vessels and so all of this pressure backs up and backs up and backs up into um the the vessels that are draining this distal part of the esophagus those veins increased pressure that's going to swell um this is the inside of an esophagus and this is a varicosity um in the blood vessels on the inside of the esophagus these can rupture and the patient may start to vomit blood this is an emergency um this is also something to consider for example if one is placing an NG Tube um this is a a risk of rupturing uh these vessels and again traced back to the portal hypertension yeah I'll mention it in passing um we're draining the blood from the colon as well and back up the pressure this can also lead to hemorrhoids development of varicosities in the rectum okay and then finally confusion for the patients um What on earth does that does the brain have to do with the liver why on Earth would we have this confusion happening well it comes back to the liver no longer being able to do something with the the amino groups um oh okay back up um so the proteins are made of amino acids and amino acids are called that because they have an amino group which is a nitrogen and a couple of hydrogens and so if we break down the amino acid because we're going to use that protein for something else we have to do something with those nitrogens in the absence of any cooking the kitchen of the liver um no in if the liver is working right and we get to cook and we get to make something we can put a couple of those ammonias together along with some other atoms and make urea which is waste but not completely toxic if the liver is not functioning well enough to do that then we get this buildup of ammonia and that ammonia is really damaging to our tissues especially in the central nervous system where it interferes with neurotransmitter function and has some other effects um this condition where we have the elevated ammonia and the confusion this is known as hepatic encephalopathy and let me see oh I should have been walking through this here so uh the amino acid metabolism so um uh break off that amino group what's supposed to happen is a couple of ammonias and some carbon dioxide get put together into urea so here's one of the ammonia groups and there's the amino groups here's the other one and this urea is eliminated through the uh through the kidneys but if this isn't working if we can't do this reaction because the liver is not functioning well enough then we just get more and more and more of ammonia in the blood and eventually it finds its way into the brain and um that leads to the confusion the current treatment is not great but it is the treatment that we have and that is to provide lactulose uh you may recognize the OS ending this is a sugar this is a it's a disaccharide it's like the lactose and a glucose I think and anyway we don't have the enzyme to digest this lactulose into those two monosaccharides so lactulose stays in the digestive tract and through mechanisms that I cannot describe um ends up decreasing the amount of ammonia in the bloodstream a little bit it's not perfect and it has significant consequences or side effects and that is again we've talked about this before because we talked about it with with lactose and people who don't have lactase they don't have the enzyme to break that apart if you have a sugar in the digestive tract and it stays in the digestive tract and doesn't get absorbed that draws more water into the digestive tract and causes diarrhea because you have more fluid coming into the digestive tract and so although we're treating the patients with the lactulose to address the ammonia or creating this other problem where they're dehydrating where they are making they have severe diarrhea and um often we're not controlling the amount of ammonia enough to completely eliminate the confusion so you have this confused patient with severe diarrhea it can be a mess okay that's enough about that and this will be I think our final slide um additional causes of chronic liver disease we had talked about the hepatitis causes let's talk a little bit about alcoholic liver disease this is one of the most common causes of liver disease around the world and why it happens is ethanol is a toxin I know we enjoy it and ingest it on purpose but our liver wants to get rid of it and when our liver metabolizes it it breaks it into something called acetaldehyde which is really toxic to the liver liver is just such a good organ I mean it's like throwing itself on the grenade you know it's like oh I'm taking one for the team um yeah so it's it's trying to detoxify this ethanol for us and it breaks into these acetaldehyde which is damaging to the liver um and so this leads to some altered metabolic pathways that are going to cause the liver to make more lipids the fats but it so it increases the fats that are being made but it decreases the fats that can leave the liver and so that promotes the fatty liver so one of the consequences of having too much alcohol is the liver becomes enlarged with fat additionally because of the damage that we're doing with the acetyl acetaldehyde we end up with inflammation the the stellate cells of the fibroblasts they make vibrant and they promote fibrosis this can progress um if the exposure to the alcohol continues it you can go from steatohepatitis um so uh fatty liver through fibrosis all the way to cirrhosis and then in extreme cases this can develop all the way to hepatocellular carcinoma about a quarter of liver transplants are due to this and and why not more is in order to be a candidate for a liver transplant one has to be considered um a good Steward of the liver that's being donated and somebody who has a chronic problem with alcohol consumption uh it's hard for them to to become candidates for a liver transplant okay and then finally the final topic is non-alcoholic fatty liver disease so we see some of the same symptoms that we see with alcoholic liver diseases this fatty liver you know the deposition of fat in the liver and the person might not touch alcohol at all it's highly associated with obesity diabetes and metabolic syndrome and what we're finding a lot is although it's fat that's being built up it's not fat in the diet that's creating the problem it's the excess energy that's uh being consumed largely in the form of carbohydrate and that's leading to the fatty liver disease um so the fatty acids are made in the liver but the secretion is inhibited and so this the the fat stays in the liver um as with the alcohol uh if the alcohol can be eliminated from the diet um some of the the damage may be reversible if it's reverse if it's stopped early enough the same goes for uh non-alcoholic fatty liver disease um if the person's uh can successfully make some lifestyle adjustments so that um they can maybe help reverse their type 2 diabetes help reverse the Obesity um some medications um bariatric surgery can help this significantly they can help reverse this process and again if it's caught early enough then the damage can be reversed and the person does not have to live with the cirrhosis for the rest of their lives and that brings us to the end of the chapter on the liver have a great week