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with a particular focus with a particular focus on some surgical causes of June days. So just to walk you through what we're going to, um, talk about Magdalena said these session is going to be split in two parts. We're going to have a presentation and then some clinical scenarios following After, uh, during this presentation, I'm going to talk to you about the different ideologies and pathophysiology of jaundice. We're going to see that Jones can be divided into prehepatic. So before the liver intrahepatic inside the liver and posthepatic after the liver and we're going to look at the different diagnostic tools that can be used to differentiate between these three types of Joan days and finally I'm going to pass the ball over to you so that you can apply to try and applied above two some clinical scenarios. So, Joan, these, um, it was quite a very easy definition. It's called a sort of yellowish discoloration of the skin and so clearer, um, mucus membranes more in general. And during this presentation, I'm going to split Joan this into three different into three categories. Join these death got causes before the liver joined is caused by problems within the liver and joined this related to problems after deliver. Just give you briefly a brief, brief explanation or a brief definition, I should say of what Joan is is. But just so you've got something written down, uh, Jones is that yellowish discoloration of the skin is clear, which is the white part around the eyes and mucous membranes more in general and is due to the deposition of builder been inside these membranes. Uh, John is only becomes a visible if the bilirubin levels in the blood stream are at least two or three times greater than after reference value. Uh, this is in the eyes. And then if the levels become four or five times greater than the upper reference value, then you also have something skin more generally. So again, this is to underline that John this becomes visible firstly in the eyes. And then if the values rise even further, it becomes visible in the skin. John Doe's can only take place. As I said, if bilirubin is raised and there is a technical term for these, which is hyperbilirubinemia. So essentially you've got two different terms that are sort of linked together, you've got a raised Philippine level that's called hyperbilirubinemia, which is a laboratory definition. And then if the levels are a place two or three times, you've got also some clinical definition, which is in this case June days. And if the levels are even further higher from the eyes, you also get discoloration of the skin more in general. So let's talk a bit about, um, why we get jaundice and what's the sort of, uh, physiological processes behind bilirubin metabolism? We can see that if you look at the left part of, um of these lights, you've got the spleen, bones and him and sort of blood system more in general. So essentially you can realize that bilirubin is a metabolic product from, uh, hemoglobin. So you've got the hemoglobin inside the red blood cells. In any case, is when there is breakdown of red blood cells, you've got release of hemoglobin within the bloodstream, and then the hemoglobin becomes sort of metabolized to bilirubin, and then it's processed into deliver, where you've got all these four steps. So you've got a breakdown of rebel cells. You've got these hemoglobin that becomes metabolized from hemoglobin to bilirubin. and then bilirubin Mex its way to deliver where it's up taken. So essentially bilirubin will move from the bloodstream into the path. Insight into the liver cells and the liver cells Will will work on this bill. Urbane. We'll try to make it easier for them to secrete these into into the bile. So essentially, this is a process called conjugation, where bilirubin is linked to something called Blue Chronic asset Not important to remember, but just just so that you know that inside the liver cells, bilirubin becomes linked to something else. And once this has happened, one step too, has happened. We move to step three secretion, so these conjugated blurb in when you get because the liver been is now linked to something else. These secreted into the bile ducts into the small Can Alec wide, are between the, uh, sinusoids in the liver and then will make its way into the bigger pile Dax and then reach their colon through all the all the small bubble first and then the colon and inside the colon. You can see that there are farther modifications related to, uh, bacteria present inside uh, the bowel and because of these transformation from something that's yellow yellowish. First, it then becomes brown. Call sir Kable in, and that's why the feces have a brownish color. That's because there is circa ballin in the stools. At some 0.20% of these could actually escape the colon, get back into the bloodstream, and it's created into the urine, something called your Oberlin. So you can see it's quite a fairly complicated process. And many things can go wrong throughout these, uh, these pathway. And when looking at the three different cause of June, geez, uh, we can see that in the pipe, a thick coz it's if anything goes wrong. It's mainly related to these portions up here where you've got, uh, the breakdown of red blood cells and the uptake of unconjugated bilirubin, uh, Hepatocytes, in case it's something wrong in the liver. The problem will be around here, and it will be mainly with the conjugation. So the bilirubin becoming linked to these blue chronic assets or the excretion of these Can you get a little bit into the bile in case of posthepatic jump. This is something happening after the liver. The problem will be mainly with drainage so there may possibly There is some something causing a mechanical obstruction and preventing uh, vial from flowing from the liver into, uh, into the bowel. This is seems a fairly complex slide, but it's just to prove a point. Some some of you may have heard the terms of direct Blur being an indirect blur being, and I've I think I've realized that these can sort of quote some confusion. So this is just as like to clarify why the terms direct and indirect blur being can be used as well. If you have a look at how the laboratory is going to test is going to check for bilirubin in blood samples, you see that on the left they're going to, uh, add a dye to the block and see whether when you get the blurb in, reacts or not. So that's why it's called direct, because can you get the blurb in? Will directly react with the dye indirect blurb in instead does not react with the dye, and the only way of calculating the UN conjugated blurb in is to work out. First, the conjugated blurb in and then the total bilirubin and then so and then taking away the conjugated blurb in from the total amount. So that's why it's called indirect bilirubin. Because it's measured indirectly. It's not something to keep in mind. It's just if you come across to the terms direct, but it has been an indirect little bit so that, you know, that can be used as synonyms for conjugated and unconjugated a little bit. So now we're going to have a look in more details about the three different causes of, uh, the three different, uh, groups of jaundice. Uh, let's start with the prep a tick. Jaundice. So we said it's something related to an increased breakdown of, uh, red blood cells. Uh, so we're talking up here in the top left corner. Or it could be a problem in the Epatha sites, where they're not really able to uptake as much better vein as they would like to. And there are some very fairly common causes of increased hemoglobin breakdown, and the first common one will be, uh, hemolytic anemia. Essentially, that means that red blood cells, instead of, uh, having a lifespan of three months, they usually die, uh, much sooner due to several causes. For example, it could be a problem in the shape of the red blood cells. Instead of having a normal disc odd shape, they may have something very spherical that struggles to go through capillaries. And so it breaks down. It could be something autoimmune, Some, uh, antibodies attacking the red blood cell and causing it to break to break down. Um, there are other other causes, but the main the main one is this Humility Kanae Miya that will cause an increased release of hemoglobin, Indian bloodstream and hence an increased amount of unconjugated blur being and the liver is not able to keep up with increased amounts. All the receptors are going to be saturated and and then and that's why we've got an increased amount of and can you get a little bit in the bloodstream? Uh, there is also something called Gilbert syndrome. Uh, some people pronounce it Gilbert syndrome syndrome, and the guy was French. So perhaps Gilbert is most appropriate. Essentially, it's, uh, it's a congenital disorder where the liver does not have as many enzymes as it should have. An uptake is a bit impaired. So essentially, it's all about this step. One of the four steps. It's believer it's not able to, uh, uptake as much blurb in as it will like. And there is an increased amount of and can you get the blurb it in the blood stream? Usually you're going to have a patient with John Days, but not many other signs and symptoms apart from those related to, uh, anemia. So that could be, uh, power. So whites can, uh, big tachycardia short of breath. Um, low BP, that kind of stuff, If we move on and have a look at John is due to, I mean, a labor problem. So intrahepatic jaundice. We're going to talk about mainly conjugation and secretion. So those are the steps that take place within the patio. Sites that that can become impaired in case of a liver disease the most common liver disease that are going to affect these, uh, pathway are essentially, uh, an inflammation of the liver, hepatitis or a chronic disease of the liver such as cirrhosis. So what happens is we're going to have both, uh, unconjugated little bit and can you get a little been increasing the bloodstream? And the reason for that is, uh, first because uh, because the path to sites are not really able to perform the congregation. Uh, they're not really able to uptake color. Been as well. So all the all the blurb in that is waiting to be processed by the liver is just going to increase and waiting for its turn at the same time. Uh, the path asides. The liver cells are not really able to get rid of all the blurb in that has already been processed. And that's the Kona get blurry. They're not really able to excrete that into the bile duct into the kind of like like, and so we're going to have a mixed picture here. Here's the key word. There is going to be a mixed picture, and you're going to have raised unconjugated and corn negated, glittering both. As we said, hepatitis and cirrhosis are the main causes, and the reasons for the are two folds. The first, the path A. Sites are going to be increasingly impaired because of the infection inflammation, and then secondly, because the path sites are going to be swollen, all the candle equalize. All these small biotechs within delivery are going to be abstracted, so it's going to be a degree of intrahepatic biliary obstruction as well. And finally, if we look, um, what happens after liver, we're going to see that posthepatic joined. This is mainly due to an increase in congregate pillar been and posthepatic. Jaundice is also known as surgical jaundice because his debt jaundice, that surgeons can deal with that can I can actually fix. What happens is if you look at step number four. What happens? Sorry. What happens is due to some sort of obstruction, which could be due, for example, a stone, uh, getting stuck in the common bile duct. Or, for example, it could be a tumor such as a head of the pancreas tumor or a tumor of the, uh, biliary tree or other sources of of, uh, stenosis, which means stricturing of the Common Bite act and essentially, the liver is working. Okay, there are no problems before deliver. All the bile that is processed into the liver is not able to make its way down into the column and will, uh, start accumulating uh, up here in into into the bloodstream again. So well, there are other symptoms and signs that associated with with obstructive Gandhi's. We saw that obstruct obstructive joint disease merely posthepatic happens mainly after the liver, but there is some degree of obstruction also inside the liver as well. Uh, during intraoperative, Jundi is due to this swelling of the liver cells obstructing the canal decline. Essentially, what happens is the liver is able to process, uh, bilirubin. OK, is able to congregate blurb in. But can you get the bilirubin is not able to get down to the column because there is an obstruction into the common bile duct. So what happens is, uh, bilirubin is going to find another way. He's going to escape from the liver, is going to go back into the bloodstream, and it's going to essentially be is created into into urine. So it's going to get excreted through the kidneys. And we if you remember the first, Like we said, that, uh, bile bilirubin after, uh, getting metabolized to Circleville and is going to give that brown color to stools. If bilirubin is not able to reach the colon, um, it's not going to get metabolized to circle billing, and so stools are not going to be brown anymore. So in this case, if there is an obstruction. And you, if there is an obstruction in the clearance pathway of pillar, be stools are going to be pale. And on the heavy side, uh, bilirubin is going to get straight it through the kidneys. So urine from yellow is going to become dark brown, dark orange, dark brown. And then what you can also get is due to the increased amount of bile cells and blurb in, uh, in the bloodstream. They may get deposited under the skin and cause a lot of h A lot of creators, and in some circumstances, uh, joined is if it's due to an obstruction could be associated with abdominal pain as well. Uh, this is not always the case. It can and cannot be present. It depends on the cause of the obstruction. But if the obstruction is, for example due to a stone, uh, in the common backpacked, then there is definitely going to be abdominal pain. And then we're going to have a look at other cases where there is no pain at all, and why you should be aware of that as well. In the case of a painless of obstructive Gandhi's, there is something known as Corpus Year Low. Essentially, what these law says is when, if you've got a patient with painless John D's and you could feel perhaps an enlarged mass in the right proponent of the abdomen, the cause of these journeys and palpable mass is unlikely to be Goldstone's. And you should. You should suspect and abstracting pancreatic or Hillary cancer. In this case, you can see the cartoon that there is, uh, on the left. There is quite an enlarged gallbladder, uh, which is nontender. So here is the key word. It's painless, and then you can see that there is a tumor in the head of the pancreas. And if you look at the cartoon on the right and you can see why the tumor in the head of the pancreas is going to close jaundice, the common bagged act, um, will travel for a portion of its tract within the pancreas. So if there is an allergic mass in the head of the pancreas, it's going to engulf is going to wrap grounds, uh, common back, back Then it's going to compress it, causing an upstream delegation and joined this. So this is something very important to keep in mind that you can differentiate Postobstructive joined is into painless jaundice. So joined is that it's not associated with any pain or joint is that is associated with some pain in case there is joined is and no pain, then always keep in mind that it could be an underlying malignancy. And here are some a laboratory tests and imaging techniques that we can use to try and differentiate these three different types of Gandhi's three hepatic intrahepatic and posthepatic. We can always start with something called liver function Tests. Um, we've got bilirubin. We've got outlined phospho teas. We've got Gamma GT, and then we've got transaminases. So these are going to let us know whether it's a problem in secretion. Uh, the bilirubin. Uh, it's going to be a call, a static picture whether, for example, it's a problem within deliver. And if that's the case, I'm going to expect the liver enzymes. So the transaminases to be raised other things we can check for. If if we think it's a pre hepatic jaundice, it could be some markers of Kim Alexis. So we're going to have a look at the hemoglobin ldh haptoglobin reticular site count. Uh, if you suspect it's something due to hepatitis, then you can always do the potatoes theology. So looking for hepatitis A, B, C, D or E, and then, in case of a chronic labour picture, it may be useful to look for, uh, some liver markers such as iron are albumen and platelets, and then to have a better look at what, uh, what could be the cause of the obstruction? If you suspect that there is an obstructive jaundice, uh, we can. We can also do some sort of imaging. And the two most common used imaging tools are abdominal ultrasound, which is always the best initial test. If if you suspect, it's it's gold from disease, or you can always go for a CT scan. And that's fairly useful. If you think that the Joan disease due to suspect malignancy and we mentioned a couple of them to choose head of the pancreas malignancy, you can see that we've got a few, uh, tools that we can use. Um, I would I would recommend always starting weight liver function tests to try and have an idea of whether it's inside the liver before the liver or half to deliver. And, uh, I'm going to walk you through a nice summary to have a better idea of how to differentiate between three types of journeys. So we've got here at table just putting together all the different. Asked all different features and and laboratory, uh, tests that we talked about. You can see that there is a column for a hepatic. Joined is one for interp, a thick Lundy's and one for post hepatic. Join these when we've got a mixture of, um, clinical picture features and laboratory, um, results. If you look at the color of the stools, um, they're always, um, dark in case of prep a tick. Dundee's so bilirubin is getting excreted normally, Uh, and it's not going to affect the normal, uh, post hepatic metabolism. But if in case of intrahepatic and posthepatic Dundee's, uh, it may be the case that you've got an obstruction, uh, so we're talking about the column two and column three. And because you've got obstruction, um, the bacteria inside the colon Roybal to metabolize bilirubin. And so the stools are lacking the ingredient they make, and they make them dark and so stools are ready pale. And then easiest way to differentiate between the three different types of jaundice is to look at the Unconjugated versus Kong. You get a little bit and you can see that in case of prep a tick. Jaundice is very easy to find a very raised. And can you get a blurb in which is not present in the case of post hepatic jaundice and is just minimally raised or somehow raised in case of intrahepatic jaundice? And in case of prehepatic during this, that's the only thing that's going to be raised. So if you see the only abnormal thing you're going to find is just an increase increase, and can you get the color bit? All the other tests that you're going to run? All the other things that we're going to check on this table are absolutely normal. In the case of intra, Patrick Jones is, you can see that more or less everything is affected. It is because we said in Compatic, Jonesy's gives a sort of mixed picture, so stools are going to be affected, and can you get the blurb in? Is going to be raised when you get the blurb in Is going to be raised because both the making both the pathway before deliver it and in the liver are affected. Um, some excretory function of the liver is good to be affected as well, so cholestatic enzymes are going to be raised. And because it's a problem of deliver, it's an intrinsic program of the liver. The liver enzymes are going to be are going to be raised transaminases the yard enzymes showing that there is some necrosis, some death of the liver cells, and you can see that these point is only present in case of impropriety. Just these. And so that's a fairly valid point that you can use to differentiate between the three types of journeys. Looking at post hepatic journeys, you can see that it's merely a post, um, liver picture. So the liver was able to congregate the blurb in, and you're going to have a very, uh, raised when you get the bilirubin in the bloodstream. And because there is an obstruction. All the enzymes related to bile drainage, such as our client was raising Gamma GT are going to be very raised. I understand he's going to be, uh, a bit overwhelming, but we're going to go through, uh, hepatic intrahepatic and post it back at Johns is through the scenarios as well. And hopefully they will make things clearer. I'm not going to go through the different treatments, uh, into much detail for the simple reason that different treatment of joint is is going to be dependent on the underlying cause. And there are several causes. And, uh, I think it's, uh it's outside the scope of these session to cover all of them. Um, something perhaps you can keep in mind is some initial treatment could be symptomatic in the first place. Um, in case of obstructive Jones is we said that by all souls and blur, being can deposit under the skin and cause a lot of it. And if that's the case, people may need some, uh, anti itch medications such as some anti estimates, for example. So here's the summary. We said that job This is something defined as a yellowish discoloration of the skin. It's clear submitting the eyes and mucous membranes due to the the position of pillar been and blurb in is something produced by the breakdown of, uh, red blood cells. We divided Jonas into before the liver causes problems within deliver itself. So interp a tick journeys and problems related to the secretion, um, and drainage of, uh, bilirubin meaning, uh, posthepatic journeys. We had a quick look at different liver function. Tests can be used and and those can help identify the different cause of Jonas. And we mentioned a bit about what imaging tools we can use. And I have stressed the importance of going straight for a CT, uh, to look for cancer. In case you've got someone presented with painless obstructive joint ease. Treatment depends on the underlying etiology. And sometimes you may need to, uh, use some symptomatic treatment to treat each those by bile salts. So we're not going to move on to some clinical scenarios before we do that. Um