Hello everyone, my name's James McMurra. Welcome to this session on the investigation of jaundice in small animals. So we're going to talk through a few things today.

We're going to start out with the physiology of bilirubin metabolism, then moving on to measuring bilirubin in practise. The big three, which is sort of the way that I remember my differentials for patients that present with jaundice, and the approach to the investigation of these guys, and then at the end there's a few cases I'm just going to quickly present and talk through sort of my train of thought as we're investigating these jaundiced patients at our clinic. So there's a brief introduction, jaundice or icterus, those terms are obviously interchangeable, is the yellow discoloration of the sclera mucous membranes and skin, and it's caused by hyperbilirubinemia, so high bilirubin pigment levels in the blood.

You typically don't see jaundice clinically until the bilirubin level is above 30 millimoles per litre. So note that you can be hyperbilirubinemic and not be jaundiced. And also conversely, As your bilirubin level normalises or drops below 30, you can still remain jaundiced for several days because the bilirubin is a pigment and it just sort of stains some of the peripheral tissues like the sclera, so you can remain jaundiced even potentially with normal bilirubin levels.

Jaundice is a manifestation of many different diseases, so it's sort of a presenting sign really, rather than a disease itself. Hence our interest in the investigation of these patients. With respect to the physiology, we just need to briefly understand how bilirubin is, metabolised in the body and excreted, and, and that can help us understand when things go wrong.

So the majority of bilirubin, about 80%, is produced from the degradation of haemoglobin, during red blood cell breakdown by the mononuclear phagocytic system. A minority of the bilirubin is derived from metabolism of myoglobin, cytocrim P450. An excess heme production for an ineffective bone marrow, erythropoiesis.

Essentially, macrophages oxidise the heme group from the haemoglobin into biliverdin, and biliverdin is then converted to unconjugated bilirubin by, biliverdin reductase. When conjugated bilirubin is released into the plasma, and it binds to albumin, obviously the, the plasma protein, . And unconjugated bilirubin in the blood is the most dominant form of bilirubin with much smaller levels of conjugated bilirubin present in the blood.

Unconjugated bilirubin has strong hydrogen bonds between the hydrophilic groups, making it water insoluble or lipophilic. Protein transports of the sinusoidal membrane of the hepatocytes transports the unconjugated bilirubin bound to albumin, from the blood into the hepatocytes, and then the mitochondria within the hepatocyte conjugates the bilirubin to glucuronic acid. This conjugation process causes bilirubin to now become water soluble, which is really important to allow it to be excreted in the bile.

Conjugation also prevents bilirubin from binding, albumin or any other, intracellular proteins as well. So this is the rate limiting step in the physiology of bilirubin metabolism, and it's this that often becomes quite quickly overwhelmed when we've got very high levels of bilirubin production in the blood or issues with cellular function within the liver. Conjugated bilirubin is excreted across the canocular membrane into the biliary tree, and it is stored obviously in the gallbladder.

The gallbladder then ejects the bile into the small intestine through the common bile duct and then the duodenal papula, and this occurs with the bile salts, and at this point then, the bilirubin is not absorbed through the intestine, as the conjugated bilirubin as it now is, remains hydrophilic, so it can't be absorbed through the wall by itself. And the bacteria and intestinal enzymes then reduce conjugated bilirubin to urobilinnogen. And the vast majority of this Eurobilinnogen is broken down into euro billing, and sterco billing, which is then passed in the faeces.

And it's actually the stercobi in itself that produces this sort of orangey brownie colour, to the faeces. A very small amount of the urbainnogen is resorbed by the liver and undergoes enteropathic circulation. And a very small amount is, bypasses the liver, sorry, and is then excreted in the urine, so sort of very, very small amounts of eurobalingin.

So let's move on just then to talking about bilirubin and its measurements in clinical practise. So total bilirubin is tends to be what we measure on our chemistry analyzers, and it is made up of both conjugated and unconjugated bilirubin in the plasma or serum. Be aware when we're handling these samples that we don't want to leave, the blood tube for too long in direct sunlight, as the UV, will cause bilirubin to oxidise and can affect the level of our measurement.

And also bear in mind as well that lipemia, which is that sort of whitish discoloration of the serum because of high cholesterol and triglyceride levels, or homolysis, which is a red discoloration. Because of, hemolytic anemias, both can interfere, with the assay results as well. So when we're looking at measuring bilirubin, the normal reference range is 0 to 15 millimo per litre, and once we get above that, we've got hyperbilirubinemia, and it's worth noting that hyperbilirubinemia always is abnormal.

OK, if the bilirubin level is actually high enough, we might see the discoloration. Of the, plasma itself, within the tube as you can see on this sample, just to the left of the screen, on a cap that presented just this week, with really severe hemolytic anaemia, and as you can tell from this image, a precipitously low, PCV. When measuring the magnitude of elevation of bilirubin, it can sometimes be useful in helping us determine the cause.

We'll touch on this later when we discuss the different causes of jaundice. But there are certain diseases where bilirubin tends to be, you know, often quite high, such as hemolytic anemias, and cholestatic, sorry, postopathic cholestatic diseases, whereas there's other disorders where bilirubin levels don't tend to be quite as high. Patients with things such as, chronic hepatitis, for instance.

So it can sometimes be a bit useful to, to bear in mind the magnitude of, of bilirubin elevation in context of the possible causes. When we're measuring bilirubin in the urine, we're gonna be using urine dipsticks, and this reacts with conjugated bilirubin, which, as we said earlier, is the only form that we tend to see in the urine. Increased conjugated bilirubin in the blood produces bilirubin urea, and it does so before we get hyperbilirubinemia.

So that's interesting because we can certainly then use it in patients that aren't yet hyperbilirubinemic to screen them for evidence of developing cholestatic disease or hepatic dysfunction by checking their urine bilirubin levels. Now when we do this, it's really important to remember a couple of things. One is that a small amount of bilirubin is normal in the urine of dogs, so a trace to even one plus bilirubin should be considered normal in dogs.

Particularly if the urine is, is quite concentrated. However, bilirubin is never normal in the urine of a cat. So whenever we see any level of bilirubin in the urine of a cat, it certainly warrants, further investigation.

OK, so now we're on to sort of the meat of the presentation, really thinking about the causes of jaundice. The best way for me to remember the causes is to group them in one of these three groups, which I referred to at the beginning of the talk is the big 3. So these are pre-hepatic diseases, i.e., diseases that occur before the liver.

That can lead to increased bilirubin within the blood. We then have hepatic diseases, so diseases within the liver that affect the way that the liver is able to metabolise and excrete bilirubin. And then we've got post-hepatic diseases, diseases that sort of functionally or structurally cause cholestasis essentially and reduced bile flow into the intestine.

So this is a really nice way to sort of group things in your head when you've got a draw on this case in front of you and you want to quickly think about your differentials. So we're gonna go through each of them now in a little bit more detail. So within the patients with pre-hepatic disease, we've said it's markedly increased levels of bilirubin caused by the breakdown of red blood cells.

And hemolytic anaemia really is the most classic example of this, where we get rapid and severe hemolysis which essentially overwhelms the liver's capacity. To excrete that bilirubin. And what happens in these patients as well is that not only do we have significant increase in the amount of circulating bilirubin in the blood, but we also get problems with liver function because the liver is an organ that requires a lot of oxygen.

To work normally and in a severely anaemic patient, the liver starts to become quite unhappy, and we get a degree of hepatic dysfunction with cholestasis, secondary to the hypoxic damage. So this in combination with the markedly increased levels of bilirubin in the blood, causes the patients to remain hyperbilirubinemic and the liver's capacity to deal with that is very much overwhelmed. Within the preapatic causes, and we've said that sort of primary or autoimmune immune-mediated hemolytic anaemia is the classic example we'd think of certainly in dogs.

But there are other causes as well that we have to be aware of. So we have infectious diseases as well. Babeia canis is, is an important differential in in dogs with haemolysis, and something we can quite easily screen for, with a PCR and an EDTA sample.

And we've got other infectious diseases as well, which actually in cats, are a more common cause of haemolysis than than primary immune-mediated hemolytic anaemia. And some of the classics include mycoplasma hemophilus. That, you know, intra, erythrocytic, parasite that's transmitted by, flea bites, feline infectious peritonitis amongst others.

We also have metabolic causes as well, and a good example of this would be hypophosphateemia. So this is something, that we can see in the context of DKA treatment. Patients who present with DKA can often become really quite profoundly hypophosphatemic.

Within the first day or so of therapy, and a really severe, and rapid hypophosphatemia does itself, lead to red cell hemolysis. So it's something that we have to monitor for our DK patients, that are developing hypophosphateemia. And we also have some inherited causes of haemolysis as well.

So we've got pyruva chinase deficiency in cats and phosphofructoyase deficiency, in dogs. So these are inherited disorders that we have to sort of be aware of. In certain breeds, so PFK typically affecting, Abyssinian and Somali cats, sorry, PK deficiency affecting Aabssinian and Somali cats, whereas PFK deficiency often affects, .

West Highland white terriers. So these are diseases that you have to be aware of and we can, you know, test, do genetic testing for these diseases in our patients quite easily actually. We then have microangiopathic hemolytic anaemia, so these are disorders basically whereby the red cells are sort of physically damaged when passing through small vessels, and they develop schistocytes and, and, and cells get lysed and release a lot of, haemoglobin.

And a good example of disease that can cause this is DIC. Disseminated intraocular coagulopathy. We also have toxins as well.

Of course we know about paracetamol, you know, in cats, for instance, as well as, other toxins that can cause perhaps oxidative damage to red cells in cats, such as, you know, onion garlic. So the prehepatic causes are are a relatively short list of disorders with primary IMHA in dogs being by far the most common thing that we probably see in primary care practise. But then we have a much larger group of diseases within the hepatic group.

So these are patients that have defective uptake or conjugation of bilirubin in the hepatocyte, with decreased excretion of conjugated bilirubin into the bile, and these are typically caused by, as the name suggests, primary liver disease, with abnormal function. So a good example would be a fulminant, you know, acute hepatitis, for instance. But any disease essentially of the liver tissue itself, you know, can cause a hepatic jaundice.

So hepatic neoplasia, copper storage disease, chronic hepatitis, toxic, you know, infectious causes, so long, long list. And then we have the post-hepatic patients as well. So these are the patients that have cholestatic disease, essentially, and that cholestasis, as the name post-hepatic suggests, is after the hepatocytes, so it can either occur still within the liver.

So intrahepatic, because of changes to the liver tissue itself, affecting bile flow through the cannoliculae. So for instance, feline lipidosis, we get marked hepatocyte swelling, because of vacuation, and the swelling of the cells actually causes, problems of bile throat flow through the liver. And even though it is a primary liver disease itself, it's actually not a hepatic cause of the jaundice because it's not so much the cellular dysfunction that's always the cause of the jaundice, but more the cholestatic implications of the primary liver disease, if that sort of makes sense.

But actually most post-hepatic disorders do occur outside of the liver and, you know, probably easiest to remember that way. And these are the diseases that are extrahepatic, so they essentially reduce bile flow. Within the biliary tree, typically the gallbladder common bile duct at the level of the Judeal papula, and these can be sort of functional diseases, you know, where there's ter function versus structural diseases where there is sort of an anatomical, you know, physical blockage of flow.

And some things, some good examples really of these, would be cholelithiasis, so gallstones stuck within the common bile ducts, for instance, . Or the other diseases that are in the area of the the biliary tree, such as pancreatitis, for instance, not a disease of the bili tree itself, but pancreatitis, the inflammation that comes along with it, certainly, . It's quite sort of a profound stimulator of cholestasis within the biliary tree.

Fab. So we've sort of talked about bilirubin metabolism and how we're going to just start to arrange the differential diagnoses in our head for these patients. It's now time to start working through that list of differentials, and this is the diagnostic pathway, as it were.

And the first step of which certainly in my head, is to try and exclude pre-hepatic jaundice as a cause of that patient's jaundice. So this is nice and easy to do because essentially you're saying is the patient anaemic? And if the patient is not anaemic, they are not going to have a pre-hepatic cause of their jaundice, and we can get rid of all of those differentials.

So we're essentially going to do. A hematocrit or a manual PCV which is you know, arguably more accurate and preferable to assess whether the patient is anaemic or not. If of course the patient is anaemic, then they certainly could have a pre-hepatic cause to their jaundice.

But bear in mind it doesn't mean they have to have only a pre-hepatic cause to their jaundice, OK? And that actually there's a lot of patients who have hepatic or post-hepatic disease, which also have an anaemia. But it's not because of hemolysis.

So a good example of that would be the patient with chronic hepatitis that has a mild non-regenerative anaemia, secondary to its chronic disease. So essentially having an anaemia doesn't mean it is preopathic, but not having one does help us rule it out. So if we do find a degree of anaemia in one of our patients with jaundice, the next thing that we have to do is a full hemogram with a smear analysis.

Now it's always recommended that that's sent out to an external pathologist for . Wet lab analysis and, you know, pathologist smear review, but depending on how confident you are with your smear analysis, that that could be done in-house as well. And what we're really looking for is to try and decide, OK, if this patient is anaemic, does their anaemia look like it is a hemolytic one or not?

And to do this in dogs, there's a few things that we can sort of look for because we've we've already said that dogs really are the the the sort of the main species that's affected primarily by the autoimmune hemolytic anaemia, . So the things that we typically look for are evidence of spirocytosis. So these are these very small, circular red cells that lack the central pallor, and they've had their, membrane chewed essentially by macrophages that damages the shape of the cells and they lose that biconcave disc shape and become spherical.

So they're classic really, patients with immune-mediated hemolytic anaemia. And we may see evidence as well of autoagglutination. So that's a test whereby we mix EDTA blood from the patient with saline and look for evidence of macroscopic agglutination on a glass slide.

I'll show you an image of that in a second. But also, if you even don't have macroscopic agglutination, we want to pop that slide under the microscope on a on a lowish magnification and have a look for micro agglutination, which can be positive as well in these IMHA patients. Ghost cells as well, will be significantly increased in patients with hemolytic anaemia.

And also we might end up testing our patients for, anti erythrocyte antibodies, so, you know, a Coombs test to help support, the probability of them having a hemolytic anaemia. So when we're thinking about the diagnosis of IMHA, probably the best resource, is this ACVIM consensus statement on the diagnosis of the disease in cats and dogs, which you can see, just referenced down here. So this is an open access paper, that, that anybody can, can have a little look at and a read through, you know, some really useful information there and flow charts that help you in the diagnosis of IMHA in your patients.

And on the left of the screen here, we've just got a classic sort of smear from a patient with IMHA in which you've got a massive variation in not only the size but also the hue or colour of all of these red cells. So we've got a lot of anisocy anisocytosis and polychromasia. With also evidence of plenty of spherocytes as well, so these very small spherical red cells here as well.

So this is a really very markedly regenerative anaemia, typical of what we see in IMHA in dogs, certainly not always what we're seeing with IMHA in cats because they're sort of weird little creatures really and don't seem to read the textbooks. But essentially the pre-hepatic patients should be the most easy to diagnose. Once we have documented anaemia and we've decided this homolysis based on the results of a hemogram and a smear analysis, then we can sort of investigate the different causes of that homolysis further.

Sort of a standard really, which, you know, to be honest, is kind of a bit beyond the scope of this talk today. Moving on, once we've got rid of pre-hepatic causes, we're then left with the patients with hepatic disease and post-hepatic disease. And the way that we really differentiate these patients is the use of abdominal imaging.

Sonography should be considered the method of choice in these patients, although advanced imaging may have its place as well. So with the imaging, what we're doing is we're really very much looking at the liver and the whole of the biliary tree, the duodenum and the surrounding structures such as the pancreas, to look for evidence of disease in those areas, and correlate that with our blood test results. Obviously if we're expecting hepatic disease, we typically should see elevations in our, liver enzyme activity.

To help support the idea that there's a primary hepatic disease going on. And if we're looking at post hepatic disease, our liver enzymes actually might sort of give us an idea that the patient has posthepatic disease because we'll actually have more a greater magnitude of elevation of our cholestatic markers, such as ALP than we will of our hepatocellular markers such as ALT. So essentially patients with primary liver disease, typically both hepatocellular and cholestatic markers, increase roughly in the same proportion, unless it's a toxic or a traumatic injury to the liver, in which case often the ALT goes up quite a lot higher than the cholestatic markers, whereas patients with the post-hepatic disease typically have more significant elevations in their cholestatic markers, .

And cholesterol, hypercholesterolemia, than, than their hepatocellular markers. So on the imaging what we're going to look at is All of the structures that we've mentioned there and also help decide whether or not we need to take any samples whilst we're imaging the patient. So some individuals might benefit from hepatic aspirates and or cholecystocentesis, which is sampling the bile from the gallbladder.

Now hepatic aspirates can be useful, primarily in dogs for diagnosing vacular hepatopathy. And lymphoma and in cats for diagnosing lippidosis and lymphoma, they are really quite sort of sensitive for both of those diseases in both species. However, hepatic aspirates are not so good at diagnosing other diseases such as hepatitis.

You know, that's a disorder that we really do need a biopsy to be able to diagnose, and aspirates can't be used. To diagnose your form of, of hepatitis. So I think it's important to bear that in mind, as aspirs are really useful and very regularly performed, but they're only really able to rule in or out.

Vacular hepatopathy, lymphoma in dogs and lymphoma or lipidosis in cats really, . Collecystocentesis, done ultrasonographic, you know, under ultrasonographic guidance is generally, pretty safe. There was one retrospective, study, as sort of mentioned below here from the Journal of Small Animal practise, looking at patients who underwent cholecystocentesis, and the complication rate was really quite low, .

In the order of about 2.5% for major complications, but within that only a very, very small amount of the major complications were actually bile leakage and bile peritonitis, with haemorrhage and anaesthetic complications being equally, you know, as likely. So generally with an experienced operator, coldyesis can be really useful for sampling, sampling the biome.

Particularly when you're looking for evidence of infection in the gallbladder or bacterilia, allowing you to perform cytology and cultures on the bile fluid itself. Patients, who undergo imaging as well, we sort of want to look for those that really need to bypass, initial medical management really and go straight to surgery. So typically we want to think about the changes that we'd see in patients with biliary obstruction.

So marked dilation of the common bile duct with a colelith, you know, found in the common bile ducts, for instance. Bear in mind that the size of the gallbladder in cats and dogs really doesn't tell us much about whether or not they're likely to have an obstruction. And actually large gallbladders are commonly seen in patients that have been fasted, which really all of our patients should have been for an ultrasound study, so it really doesn't help us very much in whether or not the patient's got an obstruction based on the size of their gallbladder.

But we also need to consider going to surgery for patients as well that need further sampling. So as we'll talk later on, cats, for instance, with suspected cholangitis, dogs with suspected chronic hepatitis, in which the diagnosis can only be made on a biopsy, you know, they may warrant the next step in their investigations being surgery. To get those biopsies, instead of medical management, depending on the, initial, depending on the case and its presentation.

We also need to be aware of the patients that are a surgical emergency. So typically we're thinking about patients that for instance have bile peritonitis, so ruptured gallbladder and bile within their peritoneum. These patients are generally really quite systemically unwell because bile peritonitis is really very painful and makes patients particularly unwell, often presenting with, with acute abdomens.

In these individuals, we'll see, generally an anechoic peritoneal effusion. It can often be really quite small and obviously centred more around the cranial abdomen, but when we do see it, we want to take a sample of that effusion to test it, to screen for a bile peritonitis, and we can put that fluid through a chemistry analyzer and measure the total bilirubin on the effusion. What we typically see is that if you've got a bile peritonitis, the bilirubin on the effusion will be over twice the bilirubin level in the blood, and that can help us reach a diagnosis.

It may grossly look like bilibile as well, sort of bright green fluid that we draw out. We also want to perform cytology and cultures on this fluid to see if it's a septic or a non-septic bile peritonitis, . Depending on the sort of specific cause of the gallbladder rupture in the first instance, so these patients are surgical emergencies and generally have a really guarded prognosis with a good 50% of patients not surviving.

Do bear in mind as well, that there have been some reports of patients with very acute, gallbladder ruptures that aren't yet hyperbilirubinemic or jaundiced. So whilst hyperbilirubinemia and our jaundiced patients, we have to have bowel peritonitis on the list of possible differentials, don't take bowel peritonitis off your list of differentials in a patient that is not jaundiced because it, they can still be. They can still have bowel peritonitis and just not yet be jaundiced, from it.

So these are just some images of different patients with hepatic and post-hepatic diseases. I just to very quickly go through them. I'm not a diagnostic imager by trade, but I've seen a lot of these studies being done in my patients, and these are all some of my patients from the clinic.

So this was a cat here who had a very thick and abnormal gallbladder wall with multiple coleliths within the gallbladder. So you can see these. Very hyperchoic structures with distal acoustic shadowing here, within the gallbladder.

This same cat as well has a lot of mineralized inspeated material at the level of the duodenal papula. So this is the Judeanum papilla here adjacent to the duodenum, and this is something that in a recent study has been found to be much sort of underrepresented on imaging studies and at surgery patients who have relatively normal imaging of their duodenal papula at surgery can be found to have lots of mineralized and inspeated material stuck within there when a duodenotomy is performed to cannulate and flush the duodenal papilla. .

This here is a patient of course with a gallbladder mucous sele, so this one is a very sort of mature mucous cele, and we have this classic steellate or cut kiwi appearance. These are one of the few things that certainly with respect to liver and gallbladder ultra sonography, it's one of the things that actually you can definitively diagnose based on sonography alone, almost all of the. Disorders need, you know, a combination of imaging and clin path and, and biopsies, but a gallbladder mucousyle is something you can definitely diagnose on an ultrasound.

This is a patient with hepatic neoplasia and some very heterogeneous, unhappy, looking hepatic parenchyma with some very hyperchoic patches interspersed with more hypoechoic and even cystic regions. This was a hepatic apatocellular carcinoma. Another patient again, with hepatic neoplasia, you can really appreciate these various hypoechoic, mass-like lesions throughout the parenchyma and around the liver here, we've got a, a small peritoneal effusion as well.

And then this is a patient with a dilated common bile duct. This is the common bile duct here, dilated and actually has some ecogenic material within the common bile duct as well. This is a patient with extrahepatic, you know, cholestasis, expatic, extrahepatic, extrahepatic, hepatic, hepatic causes, OK?

So at this point, I thought it'd be worth briefly mentioning erectus. Erectus, also known as bilirubin encephalopathy, is something that's really quite uncommon but important to be aware of because when it happens, it is pretty bad for our patient. So essentially this is a disorder where the unconjugated bilirubin that's in the blood.

When it's at very, very high levels, it passes across the blood brain barrier because it is in fact a lipophilic, as we said earlier, and this causes the pigment to build up within the brain tissues and discolour regions of the brain itself, and this intracellular increase in bilirubin is damaging to the cells of the brain and leads to neural necrosis and impaired function. So ultimately what we end up seeing is that patients with really very high bilirubin levels. Often in the fold of several 100 millimoles per litre, can start to develop neurological signs.

Typically these signs are altered mentation, ataxia, but can also lead, you know, to seizure-like behaviour as well. These patients require a lot of supportive care. Once they start to develop neurological signs, the prognosis is very, very guarded because the damage, whilst may be reversible, in other cases, might be permanent.

Seizures can be treated with anti-epileptics. Fluid therapy can help, to increase, you know, bilirubin loss through the urine, but ultimately patients, with the most severe disease, may actually benefit from treatment with therapeutic, plasma exchange, something that we refer to as apheresis and it's performed by an apheresis machine where we basically remove the patient's plasma, OK, from their body. And then replace it with a different fluid, so we're getting rid of all these really high levels of the bilirubin pigments to protect the brain from the damage caused by that.

So there's only, you know, a small number of places in the UK that will be able to perform this and it might be something that's worth considering in a patient that has a very high bilirubin levels just prior to the onset of, of neurological symptoms. We'll touch on this a little bit later on in, in one of our cases as well. Oh, and just to mention, of course, this is very similar to what can actually occur in newborn babies that develop jaundice within the first couple of weeks of life, and often in, in the human medical profession are treated with UV light therapy quite successfully.

But if bilirubin levels are high enough in children, there's poor little poor little guys undergo therapeutic plasma exchange as well to protect their brains from the damaging effects of the bilirubin pigment. So what about treatment and prognosis? Well, when we look at the investigation of the jaundice, the treatment and prognosis entirely depends on what the final diagnosis is.

The treatment plan itself is to treat the underlying disease, to reduce bilirubin, you know, accumulation within the blood, and we can use the bilirubin levels to monitor our patients to make sure that they're heading in the right direction, but we don't tend to treat the actual high bilirubin level itself unless the risk of this Cicus. So the prognosis can really vary in our patients. Depending on the underlying, diagnosis and the severity of their presentation, but generally, we do know that prognosis is at least as bad as sort of guarded, in most individuals.

Looking at patients that present with jaundice, there is a paper. From, July 2022, which there's an image of below, which is a retrospective study looking at, a number of canines, that presented. Jaundiced, or hyperbilirubinemic, to clinics in, in Australia, and they looked at all the different diagnoses and outcomes and essentially, most common were the hepatic and post-hepatic causes.

Of jaundice, with the prehepatic causes being less common. And what they found is that the prognosis was significantly worse in patients regardless of their diagnosis, who had a bilirubin level over 60 millimoles per litre. And in patients with, pre-hepatic, and post-hepatic causes, of their jaundice.

So I think ultimately, the prognosis just depends on what the underlying disease is and the individual case, but it is generally very varied. So we said we'd talk about a few cases, and this is where I thought it would really help sort of cement and solidify what I've been through already by talking through these cases, they were all real cases that are dealt with in the clinic, sort of explaining my thought process along the way, and my approach to the investigation as well as a little bit on treatment as well. So the first case is Kou.

COD was a really sweet, 1 year, 8 month old male neutered domestic short hair, and he presented to the clinic as a referral with a 2 week history of hypoorexia, so lack of appetite, associated weight loss, which is not too surprising. Progressive lethargy, as you see, he sort of here looks sort of a bit quiet and tucked up, and he wasn't moving around much during the consultation and hadn't been at home. He'd been doing a lot of sleeping and just hiding under the bed in the spare room as cats typically do when they're unwell.

And of course the owner had noticed jaundice. Now, this is certainly not always common for the owner to notice jaundice, even in the really very jaundiced patients. So even when you don't get jaundice described by owners, it's always something that we look for in our physical examination by having a look at the colour of the sclera and the mucous membranes once we're performing the full physical examination.

Sometimes the only sign of jaundice that the owners' report is marked discoloration of the urine, which can be quite sort of brown or orange in colour. They may not actually spot the jaundice, on the sclera or or mucous membranes of their pet, but, but only the discoloration of the urine. So, already with this cat, we want to start thinking about the signalment.

So this is a young cat, that's presenting with hypoorexia and weight loss, typical of really any disease in a cat, and it's jaundiced. So we're already starting to think about, OK, could this patient have pre-hepatic, hepatic, post-hepatic causes? So the physical examination can be helpful.

And in this cat, there were really quite pale mucous membranes that were a little bit jaundiced and of course the sclera were jaundiced. And as soon as we saw these pale mucous membranes, you know, it should start to ring alarm bells in your head. OK, perhaps we've got pale mucous membranes here because of an anaemia and that perhaps pre-hepatic causes of the jaundice should go to the top of our list of differentials, OK?

So we're already sort of refining the differential list in our head before we've even seen any blood work. Then on the physical examination, the abdomen was really quite acidic, so there was a fluid thrill on the allotment of the abdomen, indicating a large volume of fluid within there and of course that immediately rings. Some alarm bells in our head for a few different diseases, but in particular, I think, effusive feline infectious peritonitis, as well as various liver diseases of young cats, particularly lymphocytic cholangitis, being a disease of young cats that can cause effusions.

As well as neoplasia or septic peritonitis, essentially just think when you see an ascites, what are the types of fluid that could be in there, i.e., blood, septic exudate, transudate, and then roughly, you know, for each of those, think of a few of your top differentials in light of the case.

So the patient's bodily condition score was reduced to a 2 out of 9, as sort of described by the owners. So, so far with the CIs in combination with the pale mucous membranes, I'm sort of thinking, OK, wow, this could actually be pre-hepatic and all hepatic and or post-hepatic, so I think all. You know, cards are still on the table at this point.

So we decided to perform biochemistry with haematology to help investigate whether or not there's an anaemia and to look for evidence of changes in the bloods that would indicate hepatic or postopathic disease. And what we see in the clin path is that there is a marked hyperglobulinemia, so very high levels of the globulin. Now this is something that typically is seen with chronic inflammatory, infectious or neoplastic disease.

And We can help differentiate the inflammatory or neoplastic diseases sometimes by performing a serum protein electrophoresis. So we're gonna look at the immunoglobulins. And see whether it's a single immunoglobulin class that's elevated, which we call a monoclonal gammopathy, which is typically something we see more commonly with neoplasia.

And bear in mind lymphoma is one of those neoplasms that can affect quite young animals. Or do we have a, polyclonal gammopathy where several immunoglobulin spikes, are increased on the blood work, and that's something we'd see more commonly with chronic, inflammatory infectious diseases. So we didn't actually perform an SPE in this patient because we kind of made the diagnosis without the need for that, but it's something that we could have considered at this point.

Of course, out of all of those sort of causes of hyperglobulinemia that I've mentioned, concerningly high on the list, had to be FIP given the fact that the globulins were so high, the count is so young and it has a larger fusion. But do bear in mind that again, lymphocytic cholangitis, which is a primary sort of autoimmune liver disease of cats, can cause hyperglobu anaemia in young cats and it can cause quite high protein peritoneal effusions and is one of the sort of primary differentials for a patient that you think has got FIP. Of course there was a moderate hyperbilirubinemia.

We knew this was going to be the case because we'd seen the patient was jaundiced, fine. And then we had, also on the chemistry profile, mildly elevated prepranial bile acids. Now it's at this point, I have to mention to you a really important thing to remember, and that is that we cannot interpret bile acids in patients that have high bilirubin levels.

Bile acids are typically performed to tell us about liver function. But when a patient's got elevated bilirubin and could have cholestatic disease, the bile acids will go up because of the cholestasis and actually not then tell us anything about liver function. So do not perform bile acid stim tests in jaundiced patients.

They don't help us. Otherwise the liver enzymes were normal, so I was a bit less convinced that this was, you know, a primary sort of hepatic, cause or even, necessarily a post-hepatic cause. And when we looked at the patient's hemogram, we realised that they had a normocytic normochromic anaemia.

So this means that the patient had a non-regenerative, anaemia, which, you know, is quite common to see in lots of systemically, certainly chronic systemically unwell cats. Now it was mild, the hematocrit was something in the order of low 20s with above 27, and the reference interval being normal. So we sort of looked at this and said, OK, what's the probability that this is a pre-hepatic sort of primary immune-mediated hemolytic anaemia?

And we thought it would probably be pretty low, given that there wasn't really a severe anaemia, moderate to severe anaemia. And this patient tested sort of coups negative, had no evidence of, in saline agglutination, and therefore we thought perhaps the anaemia, whilst obviously can be seen with prehepatic causes, probably. Wasn't a primary IMHA in this individual.

It also wouldn't explain the, the peritoneal effusion unless it was a secondary AMHA secondary to something like a neoplastic process. Mildlympopenia was also seen as well, something that we can see in FIP in cats. We then performed imaging, obviously we've got this large fusion, we want to have a look at the liver.

And the surrounding structures, and also allow sampling of the effusion itself. So there was a large anechoic peritoneal effusion which was sampled, and there was also a moderate jujunal lymphadenomegaly. So enlargement of these lymph nodes is a really common reactive change in many different diseases that can affect the intestinal tract and potentially other parts of the abdomen as well.

And we considered sampling the lymph nodes with aspirates, but based on the fact they were, they were just moderately enlarged, and we had this sample of peritoneal effusion to analyse which we really hoped would sort of, You know, be the key to unlock the diagnosis, we decided not to perform the aspirates. In this individual to to sort of keep costs as as low as possible really. But certainly enlarged lymph nodes are something in the abdomen you can see also in cases of FIP because of the granulomatous disease that can affect many of the organs in the abdomen.

So the fluid that we yielded from the abdominal centesis was a really viscous, translucent, straw colour diffusion as you can see in these images that when shaken, frothed up, . And have this yellowy colour to it. So the best thing to do in a patient that you've just taken abdominal effusion from in your clinic and you have the sort of suspicion that this patient could have FIP, the best thing to do is to test the protein levels there and then on that effusion because patients with FIP have very protein rich effusions.

So we popped this. On the refractometer, and had a look, and the total solids were sort of in the order of, 67 grammes per deciliter or 6070 grammes per litre, which is really very high and consistent with the protein richer fusion. We had a little look under the microscope at the effusion as well, did some cytology and saw some sort of rare macrophages, but certainly no evidence of a septic process.

There were no bacteria, and there were no significantly increased numbers of, of degenerate neutrophils or neutrophils at all. So having had a look at this fluid in-house, before we've even sent it off, we've got a really high index of suspicion this cat has effusive FIP. Based on, really the whole picture and putting all the pieces, together.

So at which point we decided to submit, the effusion to the external lab, for them to have a look at it and yes, it was certainly a protein, rich effusion, that was non-septic, and we asked for a feline coronavirus PCR to be run on that. And that was of course, high positive on a QPCR, for feline coronavirus. An alpha one AGP, which is an inflammatory marker.

Inflammatory protein in cats that we can use, was markedly elevated, and this is often seen in our FIP cats. Note that an elevated alpha one AGP is not specific to FIP, it's just a marker of inflammation, and it is often very high in, in these FIP cats, and can just help. You know, the piece of the puzzle to support the diagnosis, and it's in fact something where we can monitor throughout treatment to check that the alpha and AGP is decreasing that our patient is heading in the right direction.

So at this point, we had enough pieces of the puzzle, to give the patient a presumptive diagnosis of FIP. Bear in mind, FIP can be really quite hard to definitively diagnose. But we had enough here to say, OK, let's discuss treatment options with the owners, and of course, as you will all know, we have some new treatment options for FIP.

With, the use of novel human antiviral drugs including remdezair and GS 441524. So in this individual, actually whilst we were waiting the FOV PCRs, we decided to start, GS therapy, as a lot of these patients can start to improve really quite quickly on these antivirals and sometimes by the time you actually get back the FOV PCR or other further testing that's pending at the lab. The patient is already well on its way to recovery, and that real positive response to therapy as well helps to reinforce your diagnosis of FIP.

So the cap was started on a 12 week oral course of GS and we didn't use an initial injectable course, for a few reasons really, primarily, money, perhaps a lack of robust evidence to say that. Patients will do better with an initial injectable course, you know, and, and sort of the patient was well enough to be managed as an outpatient after having had the investigations. So the patient showed a really quite profound response to GS therapy, and with marked improvements in in all of the clinical signs within the first two weeks of therapy.

And we monitored the patient, serially throughout the 12 weeks of therapy, and saw resolution of the anaemia, the hyperglobu anaemia, the hyperbilirubinemia, and normalisation of the alpha 1 AGP, as well as all biochemical and haematological parameters by the end of the 12 week mark. Which allowed us to then sign this patient off as having had a a complete response to therapy. Obviously with the caveat that a small number of these guys can, can relapse further on down the line.

So this is a really nice case that successfully, you know, was investigated and responded to therapy. Now this moves us on to case number 2. So case number 2 was Toby, he was a 9 year old, male neutered old English sheepdog, and he presented to the hospital as an emergency, with collapse.

The owners reported, he's also been a little bit hyperexic and lethargic running up to this episode of collapse, and that the owners themselves as well had noted that he was quite profoundly jaundiced. Now Toby's a case that I'd managed previously. About a year prior for immune-mediated thrombocytopenia, and he was treated initially with azathioprine and prednisolone.

And his ITP responded really nicely to therapy, but he actually did develop a significant hepatopathy associated with the azathioprine use. So this is something to be aware of when we're selecting our immunosuppressive agents for our patients, the side effect profile of each of these drugs. It's one of the things that we should always monitor for.

So, he was started on azathioprine therapy, but at follow up monitoring blood tests, progressive elevations in the liver enzymes were noted. Necessitating discontinuation of this drug, and then the liver enzymes did normalise thereafter. He responded really nicely, to prednisolone therapy, even though he's a big dog, and he did get some pretty significant steroid side effects.

He ended up being on prednisolone for about 6 months, and then had been off prednisolone for about 4 or 5 months and in clinical remission before he presented to the clinic, . In his collapsed state. So it's important to always bear our, our patient's previous, medical history in mind when he presents to the clinics that can help us with the investigation and certainly was pertinent in his case.

So on physical examination of very pale mucous membranes with a rapid capillary refill time, high heart rate, and bounding pulses. Now these findings altogether are highly suggestive of anaemia and really quite a profound anaemia. So right at the top of our list of differentials, we were thinking about pre-hepatic causes of this dog's jaundice.

Now we also had a history of IMTP as well, and what we know is that patients who have immune mediated disease can relapse and it's not impossible for a patient with one immune-mediated disease to sort of develop another one. So we had to bear in mind the possibility of IMHA in his case. His jaundiced, sclera were noted on physical examination, as had been noted by the odours, and he was a bit overconditioned 7 out of 9.

He never really lost the bodily fat that he gained from his steroid therapy, the year prior. Biochem and haematology was performed because we had the suspicion of this anaemia in order to confirm, a reduced PCV, and have a look at, a hemogram to see if there was evidence of homolysis, but we also wanted to check, of course, for hepatic and post-hepatic causes, particularly because we know this patient has a history of a hepatopathy. Even though he's not on azathioprine therapy anymore, we do have to sort of bear it in mind.

So, as I was working through this patient. You know, I had preapatic causes in my head. I had hepatic causes in my head, and also, he was, you know, an older, overweight dog that that also could have plenty of reasons to have postapatic disease as well, you know, he would be at increased risk of pancreatitis, given his weight and age, but also, other postapatic diseases such as, cholecystitis or cholelithiasis as well.

So on the Le blood tests, a mildly elevated urea was noted. Quite a few different reasons why the patient could have had this, including gastrointestinal, blood loss if he had a hepatic or or post-hepatic cause, of his jaundice. Could be some dehydration.

And if he has got IMHA in at least one study, an elevated urea has been found to be a negative prognostic indicator for these patients. He had mildly elevated ALT and ALP enzyme activity. So, in the face of marked hyperbilirubinemia, so his bilirubin level was over 350 millimo per litre, it was through the roof, as you can tell from this picture of his gums, he was really, really jaundiced.

Now looking at those elevated liver enzymes, OK, they're up, so could he have, A hepatic or post-hepatic cause of his jaundice. Yes, it's certainly possible. Typically though, you would expect the liver enzymes to be higher than this.

We do know, however, that the magnitude of elevation of your liver enzymes doesn't actually tell anything about. Necessarily the possible cause of those liver enzyme elevations and it certainly doesn't tell you about prognosis. But typically with severe primary liver disease, or postopathic, disease that's bad enough to cause this degree of hyperbilirubinemia, you would expect generally markedly elevated liver enzymes.

Now the caveat to that is a patient with very end stage liver disease, so cirrhotic liver disease in which their hepatic mass is massively reduced and it's just been replaced by. Fibrosis, and in those guys actually a significant lack of remaining functional hepatocytes does mean that liver enzymes can actually be only very mildly increased, normal, or even low in patients with very end-stage liver disease. So we did sort of bear that in mind.

Otherwise there was a mild hypercholesterolemia, so that is something that can be seen in patients with, you know, some primary liver diseases, but particularly common in patients with post-hepatic disease as well. So we thought, OK, we'll bear that in mind. He had a marked inflammatory leukogram.

Which is probably not too surprising in this individual, and he had a moderate to marked regenerative anaemia. So on his smear analysis, we saw that there was marked polychromasia and anisocytosis and as well as evidence of a hemolytic process because he had a lot of ghost cells. He was in saline agglutination positive.

And there are a lot of spherocytes on his smear as well. So at this point, really, I'm being pushed towards pre-hepatic causes of his jaundice and particularly immune mediated hemolytic anaemia, and that perhaps these liver enzyme elevations are just secondary to hypoxemic liver damage associated with the severe anaemia. Nonetheless, I wanted to just be sure about the liver and surrounding areas, so he did perform imaging.

He had mild hepatomegaly, and the liver was a little bit hyperrechoic throughout, but reasonably homogeneous. So a big bright liver, essentially, which is something that we can quite commonly see in patients with, well, dogs at least, with vacular hepatopathies to build up of fat within the liver, and that's not too surprising, you know, in an overweight older dog. So we did consider the possibility of primary liver disease, that could be more sinister, particularly, lymphoma, and did decide to perform hepatic aspirates.

We also identified a hypoechoic splenic mass. So, having seen that, we obviously did consider, well, if we think this patient's got IMHA, is it possible that he's got a neoplastic process that's triggering that, and perhaps we should aspirate this mass just to see what it is. Now do bear in mind that, the ACVIM consensus, on, the diagnosis of IMHA in patients that I showed you earlier, just talk about the association between IMHA and neoplasia, and really did found, did find, negligible to very weak evidence that actually neoplasia does cause IMHA.

So it's something that we always think about in our hemolytic anaemia patients screening for neoplasia, but I suppose the likelihood that we're going to find clinically significant neoplasia, that is the cause of the MHA is probably very, very low, but nonetheless for completeness we aspirated the mass. Ecogenic material was seen in the gallbladder. Nothing more than that, and of course whilst we do have postopathic causes on our list still potentially, as contributing factors to his jaundice, and we felt that ecogenic material in the John's gallbladder is very much normal, and, you know, likely wasn't clinically significant in his case, so we didn't perform cholecystocentesis.

We did thoracic radiographs as well, to screen for any evidence. Of thoracic disease, and they were normal. So the results came back from the aspirates, hepatic aspirates were consistent with possible neutrophilic inflammation and vacuoar change.

Now again, as I said earlier, we can use aspirates to diagnose vacular hepatopathies, great, that makes sense with what we were thinking and what we were seeing on the imaging of this patient. That's generally nothing to worry about. They said possible neutrophilic inflammation.

This we take with a big pinch of salt. Sure, there could be neutrophilic inflammation in this patient's liver. Can we diagnose them with a neutrophilic hepatitis off the back of this?

I don't think so. We'd really need a biopsy to be able to do that. So we sort of said to ourselves, you know, is it likely this patient has neutrophilic inflammation in its liver, possibly?

Is it likely that it's infectious, really quite highly unlikely, given everything else that we're seeing, and that probably the neutrophilic inflammation that's in the liver is just secondary to the hypoxemic damage that's occurring there because of the anaemia. So the splenic aspirates came back and they were consistent with extrabadillary hematopoieis and lymphoid hyperplasia, both of which are really common. Processes to occur in the spleen in an anaemic patient and actually splenic masses are something we see really quite frequently in our anaemic patients and when we aspirate them very commonly are these sort of reactive processes within the spleen and actually not anything sinister.

So it's important to have that in the back of your head and and not write off an IMHA patient with a mass in its spleen as simply having, you know, a cancerous process and and having a a a poor outcome. The patient's loan and beholders Cooms positive, consistent with everything else that we've seen supporting your diagnosis of IMHA. And at this point we also requested Babezia PCR as I said earlier, it's an uncommon but, you know, reasonably, important, infectious cause of IMHA in dogs, and those, and those were negative.

So we had a diagnosis of non-associative, which is the new term for primary immune-mediated hemolytic anaemia. Toby was medically managed in the ICU for 7 days. During that time, he received two packed red blood cell transfusions because of, continuous decreases in his PCV despite therapy.

He required very supportive treatments including, Intravenous fluid therapy as he developed some diarrhoea and wasn't drinking very well, and, assisted enteral nutrition with the placement of a nasal gastric tube. He was treated with prednisolone, for his IMHA, but also with a second agent for two reasons really. One, his, presentation was so severe, and his PCV decreases were so rapid that we felt we needed a second agent on board as early as possible, to try and help.

Combat, the the remediated destruction of the red cells. Although bear in mind there is no evidence that two agents are better than one, currently. But we also selected a second agent because again he's a really big dog, and on steroids long term he's going to get really significant steroid side effects.

And by using a second agent in combination with our steroids, we're able to taper the dose of steroids more quickly than if we're using them as the lone agent. So we selected mycophenolate mofatil alongside the prednisolone in his case. It doesn't tend to cause the significant hepatic changes that we can associate with azathioprine.

Generally it's pretty quick in its onset of action, as well, and is nowhere near as expensive as cyclosporin in these patients. We of course started him on antithrombotics because of the significantly increased risk of thromboembolism in patients with IMHA and we started him on. A combination of, of an anticoagulant with rivaroxaban, and an antiplatelet, therapy with clopidogrel.

Throughout his stay in the hospital, and most of the time he was discharged on, on high doses of prednisolone. He was also started on hepato protective therapy because he had obviously a history of hepatopathy whilst on immunosuppressive drugs and had, currently got elevated liver enzyme activities as well. So that was with adenosyl methionine, and syamine.

During therapy in the hospital, poor Toby started to develop pretty significant neurological signs. And those symptoms were primarily, reduced mentation, and ataxia. And we were really worried about him developing Cicarus given his bilirubin level of 350.

So we did discuss with the owners, therapeutic plasma exchange, however, it wasn't a treatment option for him on cost grounds. And instead, we sort of had to roll the dice really and see how well he would do with simply supportive therapy and hope that the, in neurological signs, you know, were reversible. So the good news for Toby is that after one week in the ICU his PCV stabilised and whilst his bilirubin levels were still markedly elevated, the neurological signs did resolve, and he was able to eat well and ambulate, at which point he was discharged, from the hospital.

The bad news for Portobi bless him, is that, he'd been doing really well for about 4 months as an outpatient with normal PCV. Only very mild elevations of liver enzymes and we were down citrating the dose of his prednisolone, when all of a sudden, 4 months later, he dropped dead, bless him, as an outpatient at home, unsure of cause of death, however, in his case. But nonetheless, he was a very interesting case and a very challenging case to manage with, you know, very significant pre-hepatic cause of this jaundice.

So then finally on to case number 3, and this is Daisy, 1213 year old, male neutered, bless him, he's obviously got a bit of a gender crisis going on, domestic short haired cat, who presented to the clinic with a two-week history of vomiting, hyperexia, and jaundice. On his physical examination, he had cranial organomegaly so at the very front of his abdomen. You couldn't be sure it was exactly the liver, but it just felt very full, whether it was the stomach, the gallbladder, lymph nodes, it was a bit hard to say.

He was perhaps a little bit painful, but obviously in cats it can be very hard to assess in some individuals. Had a bit of a loss of lean muscle mass, with the bodily conditions score of 3 out of 9, and jaundiced sclera. So just based on what we know about him so far, when we've got evidence of jaundice in a patient that doesn't have evidence of anaemia, he's not got, you know, tachycardia, pale mucous membranes, we probably then are going to be pushed more towards hepatic and post-hepatic causes, and this really fits quite nicely with the fact that he's vomiting because cats with primary liver disease or post-hepatic causes of jaundice can quite, quite often vomit.

So we did buy a cam to look . At the liver and we also did haematology to see if there was an anaemia or not, and what we saw were moderately elevated liver enzyme activities. So even though they were only moderately elevated, that's really significant in a cat because cats have much shorter half lives for their liver enzymes, and even mild elevations in liver enzymes are significant, much more so than they may be in a dog with elevations of the same magnitude.

So we immediately thought, OK, this patient probably has a degree of hepatic and or post-hepatic disease, of course, was markedly hyperbilirubinemic but also had a marked hypercholesterolemia. So that's something that we certainly can see in patients with cholestasis and post-hepatic liver disease. An inflammatory leukogram as well was found.

Consistent with potentially an infectious, disease process because it was left shifted, or at least a markedly inflammatory disease. Given the possibility of us having, post-traumatic disease based on what we knew about the case so far, we did, . Pancreatic, lipase testing, with the SEC, PLI, and this is markedly elevated, suggestive of, an active pancreatitis.

FIV and FELV snap testing, were negative, so we decided to proceed with abdominal imaging with sonography to try and sort of look at the liver and surrounding area. And what was found is that there was a really hyperrechoic and thickened gallbladder wall. And these are types of changes what we typically see with disease of the gallbladder in cats and dogs, this bright increased ecogenicity of the gallbladder wall that's thickened and irregular and sometimes a bit polyploid in its appearance.

And there was also multiple choleliths within the gallbladder. The common bile duct itself was also markedly distended and had echogenic material within it. Although we didn't see an actual cholelith within the common bile duct or within the duodenal papula itself.

So we didn't know if there was a colith there potentially we couldn't see, because we needed a coalesce in the gallbladder, or whether the choleliths were just sort of innocent bystanders really, and there was other disease within the liver, gallbladder and pancreas area, you know, actually that were causing the jaundice. So the liver parenchyma looks very normal, so bear in mind that with cats, their livers can look completely normal when they have cholangitis. So we can't use that to sort of exclude significant liver disease in our cats.

It would be unlikely that they had lipidosis if they had a grossly normal looking liver, but we couldn't use it to exclude other disease processes, so do, do bear that in mind. On the ultrasound there were changes of the pancreas that certainly were consistent, with acute pancreatitis, which we expected anyway from the PLI testing. So we saw a scant peritoneal effusion, very hyperchoic peri pancreatic fat, markedly enlarged pancreas, but we also saw a markedly enlarged duodenal papillae.

So this image here to the left is is what we saw with Daisy, a really enlarged sort of. Duodenal papula here on the duodenum, and it almost looks very much like granulomatous change or or potentially even neoplastic change. So with his case, we were concerned that firstly there was evidence of biliary tract obstruction, given what we'd seen on the imaging and on the clinical pathology.

So that was one reason to potentially take him to surgery at this point, to try and see if there was an obstruction, if there was, see what we could do for it to relieve the obstruction. But also we wanted to sample the gallbladder, take some liver biopsies as well, so. Daisy was taken to laparotomy, and what was found is that there was an enlarged but expressible gallbladder.

So that meant that probably there wasn't any biliary tract obstruction. There was a really dilated common bile duct. So a duodenotomy was performed to allow flushing of the duodealpaya, and actually the duodenal papila did flush, indicating that there wasn't complete obstruction at that level.

There are of course changes consistent with pancreatitis that that we knew about, and, once we were happy that the, common bile duct wasn't completely obstructed. We decided that, we would take some liver biopsies, and perform cholecystocentesis to have a look at the, the bile itself and the liver tissue. And essentially what we're seeing on the results once they've come back, is that the liver biopsies were consistent with the neutrophilic cholangitis.

So this is one of the most common forms of, of sort of . Primary liver disease in cats, and it's due to bacterial infection within the biliary tree and and the inflammation spilling over into the hepatic parenchyma causing essentially a a cholangio hepatitis. And the bioaspirates came back with evidence of bacteria on cytology, and the culture was positive for E.

Coli with sensitivity to multiple different antibiotics. Great. So this confirmed our suspicions from the histopathology that we had bacterial infection within the gallbladder.

So that's a cholecystitis and also cholangitis found on the liver biopsies. Now note here that the liver cultures were negative. So this is quite often seen in neutral the cholangitis patients that the bile aspirates are more likely to be positive than the liver biopsies on culture.

So whenever we're performing liver biopsies and cats, we really should always perform cholecystocentesis as well to send some of the bile off for analysis to help us with our diagnosis. So, Daisy was diagnosed with an acute pancreatitis and a neutrophilic cholangitis. It is possible that this could have been a triaditis and that there could be concurrent chronic enteropathy, you know, with small intestinal inflammatory bowel disease.

However, there wasn't really any previous chronic history of GI disease and the intestines did look largely normal on sonography and at surgery, but nonetheless, we did consider the possibility of concurrent IBD, you know, and the option of future, . Sort of further investigation, you know, of that potential problem as well. So for the, the acute presentation with the the jaundice and vomiting, the patient was, managed with a 4 week course of amoxicclavulanic acid, for which the E.

Coli was sensitive to, although E. Coli can often have inherent resistance, this class of antibiotics. Hepato protective therapy, an ursodeoxycholic acid as well as as a choleratic amongst the many other things that it does.

An initial short course of sublingual buprenorphine was also prescribed as an analgesia because of the acute, pancreatitis, and assisted enteral nutrition with an esophagostomy tube as well, because we felt this patient probably wouldn't be eating normally for a good period of time, and that no tube would allow us to send this patient home to the owners, to be able to feed appropriately. So Daisy did pretty well really. There was a return of appetite with one week allowing us to remove the feeding tube.

There was resolution of the jaundice, and normalisation of the liver enzymes as well, by the 4 week, recheck, at which point, pretty much all of the therapy was discontinued. And then we simply advised the owner. Long term on on the sort of possibility of a hydrolysed diet, in case there was an underlying chronic enteropathy as part of this patient's disease and it truly was sort of a triaditis.

So, so Daisy did pretty well, but we did obviously make the owners aware of the possibility of future relapse, potentially of both the pancreatitis and or neutrophilic cholangitis, which, you know, we do sometimes see in these cases. So that was it. Thank you very much for listening.

I hope there are some top tips that you can take away with you to help in the investigation of these patients in general practise. Some of these cases can be quite tricky, but pretty much always these cases are often very, you know, rewarding to investigate and medically manage. Well, thank you again, and you all take care.