Hello and welcome everybody to this webinar in which we're going to look at the complex problem of triaditis in cats. And this is a complex issue to discuss in a relatively short space of time because of course what we're really looking at in this disease is not really one disease at all. What we're actually looking at is a confluence of three separate diseases, all of which are quite common in cats in their own right, but of course also we know, all of which can occur quite frequently.

In combination in cats, so I guess the first question we have to ask ourselves is, really is triadits actually a thing? Is it a disease at all, or are we simply looking at three different conditions which can occur separately? Or can occur in combination.

And as trying to illustrate in this diagram can occur in any pairing or any combination. And I guess that's really the truth of the matter, but it's not quite as beautifully simple as this nice symmetrical diagram. If we think about the individual diseases and their frequency with which they occur, and then we think about how often they occur in combination, we get a rather different and rather skewed diagram.

And it's difficult to give you exact numbers on this, but I think we could probably all recognise that we see many more cats with inflammatory bowel disease enteritis than we do with the other two conditions. And while there is certainly overlap with those other conditions, I think we do see a reasonable proportion of cats who appear at least to have inflammatory bowel disease but without involvement of the bile system or the pancreas. But then we do see those cases that do have those involvements.

And it's interesting, a recent study published relatively small number of cats as you can see, and some of these cats were symptomatic. They had signs consistent with abdominal inflammatory disease. Actually, some of them were completely asymptomatic cats that were undergoing a very hysterectomy.

So these are healthy young cats coming in to be spayed, but during this study, the researchers took biopsies from gut, bile system and, pancreas. And they found a very high proportion of these cats did have inflammation in one or other of those areas, even the asymptomatic cats, which itself raises some interesting questions about these conditions. But what they found in terms of the proportions was, as we might expect, quite a high proportion of cats with enteritis compared to cholangitis.

And perhaps it might surprise you to see how relatively fewer cats had pancreatitis compared to cholangitis. And I wonder if that is something that we would feel is reflected in our diagnostic findings in cats. I do wonder whether actually cholangitis may sometimes go under the radar more often than we realise, and it's perhaps something that we should be looking for more carefully and and having more more paying more attention to, which is one of the reasons why I will dwell a little bit on cholangitis in this session.

But as you can see, at least in this study, more cats had inflammatory bowel disease enteritis than had cholangitis, and more cats had cholangitis than pancreatitis. And interestingly, again, I would suggest very few cats had only pancreatitis with no evidence of inflammation elsewhere. And a high proportion of cats who had pancreatitis also had cholangitis, so that was a common confluence.

Relatively fewer had only enteritis and pancreatitis. So I think just interesting to reflect on that and to consider that when we see a cat with pancreatitis, we really should have a very high index of suspicion that there may also be enteritis and indeed cholangitis. So, those cats with all three do make up a reasonably high proportion of the cats who had pancreatitis.

But we mustn't forget that the cholangitis and enteritis cats also are frequent findings either in isolation or in that combination of enteritis and cholangitis. So it's a complicated situation. I think we can all agree, and I think what it really means is that we need to have a working understanding of all three conditions and an index of suspicion that they may occur in combination and that therefore diagnostic approaches and indeed treatment plans should be designed with that possibility in mind.

So let's have a look at a cat. Let's have a look at a case and see how, how it sometimes looks. And this is a cat called Chip.

He's a 12 year old male neutered Burmese cat. And Chip has around a 2 month history of gradual weight loss. Reasonably significant weight loss.

He's now 4.6 kilogrammes from a healthy weight of 4.9 kilogrammes.

His owner has been aware that he's had periods of not eating so well, but then other periods when he's been fine, so she hadn't really twigged that there was too much of a problem, and she was aware that he was an occasional vomiter, which of course many cats are, and again she had not particularly been concerned about that. What had concerned her and what had triggered her to bring him to the practise was a much more recent and much more severe history of two days of being off his food completely, being very lethargic. And vomiting on a frequent basis over the last two days, so numerous episodes of vomiting per day.

So a marked change in him in the last few days, but when we bear in mind that background history, we can see that as is so common in cats, we can suspect that what we are dealing with is an acute on chronic problem. So we have a look at Chip and we do a physical examination. He had a pyrexia temperature 39.6, so that would certainly help to explain the recent onset of lethargy.

He was a little dehydrated, which is not at all unusual in the cat that's off its food vomiting and pyrexic, so not a great surprise, I would suggest. His abdominal palpation was interesting because there wasn't anything obvious to feel in terms of masses or even areas of discomfort, but when I went to palpate his cranial abdomen, the poor cat actually vomited there and then on the table in front of me, which is a relatively unusual circumstance and certainly I think something that we can say is an abnormality. But really no other significant findings on the physical examination.

So I think this is a cat who is clearly unwell. As I say, we seem to have a chronic, an acute on chronic presentation. I'm sure you, like I would recommend to the owner that we should look into this in a bit more detail and certainly running some blood tests would seem a sensible place to start.

So this was the panel of blood tests that we were able to run on day one, at the time of admission. And I've highlighted the abnormal results in pink for you. So I'll give you a second just to take a look at those and see what you think.

And then we'll talk through some of those abnormalities as to how we can interpret them and and what how much we can rely on them. So I guess the place I would like to start here is with the liver parameters. And we can see that his ALT is actually within reference range, but his alkaline phosphatase is very significantly elevated at 899.

He has a significant increase in his total bilirubin at 22.5 and also a significant elevation in fasting bile acids. So what can we glean from this and what do we learn?

A quick reminder. Bilirubin obviously is an indication of jaundice. And yet I didn't in my clinical examination find any evidence of jaundice.

So why was that? Was I missing something? I think not necessarily.

Because with bilirubin, I think it can be quite helpful to categorise it in terms of the severity of the rays in bilirubin. And to recognise that it's only really when bilirubin goes above 50 that we start to see grossly visible changes in the sclera in the mucosal membranes, in the skin and so on. Below that level, we may still have an elevation on our blood test, but we will not necessarily see external signs of jaundice in the cat.

We certainly will see evidence of increased bilirubin in the urine, if we take a urine sample. So we will see that the urine is bright yellow and we will see bilirubin on our dipstick, and I'm sure that you're aware that because of the relatively high renal threshold that cats have for bilirubin. Any level of bilirubin in their urine does indicate an abnormality.

It does usually indicate that they have raised bilirubin in the blood, although it potentially could be a glomerullar problem, but much more commonly, it's a leader to the fact that we need to be looking at the blood. So Below 50, we will see it in the urine and we will see it in the serum, and we will see it on our blood tests, but we will not see it in the cat. And you may wonder why I'm dwelling on this difference.

Well, I think only because it can be very helpful in when you come to to rank your differential list to consider whether this is whether this is jaundice at the level that you can see, or whether it is what I would term biochemical jaundice, i.e. Below the level of 50.

And if you can actually see jaundice in the cat in the sclera, in the membranes, in the skin, then essentially the most likely differentials are either going to be hemolytic anaemia, which certainly can cause very severe jaundice, but is usually associated with a significant level of anaemia. So generally you would expect to see a PCV below 20%. If the anaemia is acute and severe enough to cause actual jaundice.

So while many of the conditions which will cause jaundice will cause a cat to be mildly anaemic in a generally non-specific anaemia of chronic disease kind of a way, if you are actually looking at a hemolytic anaemia, you should expect to see quite a significant drop in PCV. So that's usually reasonably quickly identifiable. The other category that will cause this level of jaundice to be visible to the naked eye is primary hepatobiliary disease.

Now again, there are a number of conditions in this category, but I think it does help to to focus our thoughts and to. Differential list. So certainly the inflammatory liver and biliary diseases, so acute cholangitis, neutrophilic cholangitis, chronic, chronic chronic neutrophilic cholangitis will cause, Visible jaundice, hepatic lipiddosis is another condition in an overweight cat which you should certainly suspect if you have a cat with acute signs and jaundice.

Certainly FIP can cause inflammation within the liver and the bile system and create a significant level of jaundice. And cholelithiasis will cause jaundice due to obstruction of the bile ducts, but we should be aware that in the cats, if you see choleliths, if you see stones in the gallbladder or the bile system, that is generally in cats, a reliable indicator that they either have now or have had in the past a bacterial infection, so an an acute or neutrophilic cholangitis. And so actually cats with cholelithiasis tend to fall into that category of cats with inflammatory liver and biliary disease.

So really they're all part of the same condition. So in fact, as you can see, if the cat presents to you with physically visible jaundice, your differential list is relatively slim, and I think that helps to focus your further diagnostic tests. Should the cat, as in Chip's case, not look physically jaundiced but have raised bilirubin on your blood tests, then the list of differentials is is really somewhat wider.

It could still be hemolytic anaemia or primary hepatobiliary disease, as in the last slide. But now we have a somewhat wider list of things to think about. So this is the kind of level of raising bilirubin, which we might see with extrahepatic neoplasia putting pressure on the bile duct.

So a mass, you know, a mass in that region. This is the kind of level we will see when there is inflammatory disorders in the region around the bile duct and the bile duct papilla, but not necessarily directly affecting the biliary system itself. And so there we now get into the realms of our friends pancreatitis and inflammatory bowel disease, which can cause a mild level of of of hyperbilirubinemia, even if the bile system is not involved.

And we also in cats will relatively often see small rises in bilirubin when they have general acute or severe inflammatory disease, not necessarily affecting bile duct pancreas or bowel. We can see it in cats with FIP. We can see it in cats with sepsis, Pyothorax will commonly do it, fat necrosis, acute pancreatitis, and of course this nasty corollary to those conditions when they go into a systemic inflammatory response syndrome or SARS.

And those are going to be very, very, very sick cats indeed. So I'm afraid for the mild raises in bilirubin, the list is much longer. But as I say, just thinking about the presence or absence of physical jaundice and the level of bilirubin in the blood can help you to rank your differentials and order your thoughts.

So in Chip's case, we have a total bilirubin of 22.5. So it is certainly significantly elevated, but not up in the, not up in the gross jaundice levels.

What about the liver enzymes? What do we, what can we interpret from from those? Again, I'm sure you're familiar with this, so we can move fairly swiftly through, but we need to remember that alkaline phosphatase and indeed gamma glutamyl transferase GGT if you measure it, these are the cholestatic enzymes.

Alkaline phosphatase in the cat comes from liver and bone. And so it can be elevated where there is cholestasis, whether intra or extrahepatic, or it can be elevated where there is rapid bone growth, and the most common example of that, of course, would be in kittens. Be aware that unlike dogs, cats do not have a corticosteroid induced form of alkaline phosphatase, so liver and bone are the only sources.

You'll be aware that alkaline phosphatase has a much shorter half-life in cats than dogs, and so even relatively smaller increases in alkaline phosphatase can be considered quite significant. But equally that short half life means that any raises in alkaline phosphatase may be cleared quite quickly and so you can actually have normal alkaline phosphatase despite a degree of cholestasis associated with liver disease. So it can be a little misleading.

GGT is only produced in the liver in the cat and again has an extremely short half life. So generally it follows alkaline phosphatase. So generally if alkaline phosphatase is up, GGT will also be up, but to a lesser extent.

And so many times, actually, we don't really get too interested in GGT because alkaline phosphatase gives us just as much information. But the exception to that, and although it's out with the subject of tonight's discussion, I do think it's worth highlighting that in cats with hepatic lipidosis, you will see a relatively unusual pattern in the liver enzymes in that you will have a very high alkaline phosphatase. A really quite high ALT, but generally GGT will be normal or only very marginally raised.

So it's an example. It's the one condition where GGT does not directly mirror alkaline phosphatase. So if you see that pattern, very high ahos.

Really high ALT, but relatively normal GGT you should strongly suspect that there's an element of lipidosis going on, and that of course could be extremely helpful if it if it allows you to move swiftly to appropriate treatment. But as I say, that's kind of out with tonight's discussion. For completeness, just to talk about ALT, which is of course a measure of actual liver cell damage.

Liver is the only source in the cat, but anything which causes compromise or damage to the liver cells will cause a raise in ALT. And so we very commonly see ALT elevated in other diseases which have an impact on the liver. So of course we see very frequently in hyperthyroidism, in diabetes, and indeed in inflammatory bowel disease, we will very commonly see that the ALT is elevated without it necessarily being an indicator of primary liver disease.

The magnitude of any elevation relates to the number of liver cells that are affected, rather than the severity of the damage. And I think really the take home message there is that however high the ALT is, if the disease that's causing it can be identified and is something. That can be treated and managed, then, however high the ALT it can come down quite quickly to more what you might call acceptable levels.

So, so don't use the extent of the elevation of ALT as any kind of prognostic indicator. And again, we have this shorter half-life of ALT in cats compared to dogs, so that again smaller increases in ALT do indicate a significant change going on. So back to Chip who's got his relatively normal, or in fact normal ALT, a very high alkaline phosphatase, so we're suspecting some cholestasis is going on here.

He's got raised bilirubin, which again tends to suggest that in this case there may be some cholestasis going on. And then he's got elevated fasting bile acids. Normal range is less than 5, and his were up at 25.5.

So the ALT being normal was is suggesting to us that we don't have hepatocellular damage. And yet, of course, fasting bile acids we've considered to be an indicator of liver function and elevated fasting bile acids could be an indication of actual liver function failure. So that seems to be a bit of a conundrum, but just bear in mind with serum bile acids, that while certainly they will be elevated when there is reduced liver function, they are, they are managed through enterohepatic circulation in just the same way as bilirubin.

So if you have a cat with elevated bilirubin in which there may be obstruction to bile flow. Then you would expect that bile acids would also be affected and also be elevated. So we cannot rely, we cannot use bile acids as an indication of liver function in cats with.

Obstructive bile duct obstruction or or indeed cholestasis. So that's just a little caveat. If they are on your panel and they come back high in a cap with jaundice, you don't need to be too prognostically gloomy.

Continue to search for the underlying cause, because if it's manageable, like likelihood is that the bile acids will come good as the rest of the disease comes good. OK, so from this we would feel that Chip perhaps does have cholestasis, but he does not at the moment appear to have significant liver cell damage, so we may be thinking cholangitis rather than cholangio hepatitis. Looking through the rest of the panel, he's not anaemic, so therefore we're not concerned about hemolytic anaemia as a cause of his raised bilirubin, but we might have a concern about these white blood cells.

So Chip has neutropenia, quite profound neutropenia. What do we make of that? So neutropenia in cats is a relatively uncommon finding, and it can be an indicator of quite worrisome disease.

But I think the important thing to ask yourself when you see this on a panel, the first thing to ask yourself is, is this an acute problem or a chronic problem? Because certainly if it is a chronic problem, and it is not obviously a drug induced issue from either chemotherapy or methimazole, which hopefully you would know about, then I'm afraid the list of conditions that we get concerned about are all quite significant and quite serious, so retroviral infections, a neoplastic or paraineoplastic change, an immune mediated problem, or myelodysplasia. Saying that it is important to consider, as I say, whether this is indeed a chronic problem or whether actually this may be an acute problem because we also will commonly see a temporary drop in neutrophils prior to development of a neutrophilia.

So a pre-neutrophilic neutropenia may be of much less concern long term than any of those chronic changes. We will also sometimes see neutropenia just as a sample error if there is a clot in the sample, so of course that is worth checking. And Chip is a cat who has recent onset of signs and pyrexia.

So I think we can feel that we may have a focus of bacterial infection somewhere that is drawing the neutrophils into it, using them up from circulation and has not yet had time for the bone marrow to mobilise a response. So in that instance, it's something we will want to keep an eye on. We will want to look for a focus of bacterial infection in our further investigations, and we will certainly want to keep an eye on the neutrophils going forward, perhaps expecting that we might see a rebound effect and a neutrophilia kicking in after a short delay.

OK, so then the final aspect of this panel of blood tests that I wanted to just talk about is this one down here. The snap FPLI on day one on admission came back as abnormal. So of course, FPLI is one of the tests that we can do to try to get an idea of whether there might be pancreatitis.

But we know that there are a number of blood tests we can use, and obviously diagnosis of pancreatitis can be, quite challenging. So what tests are available to us? How do we interpret them?

What do they mean? And I guess the first thing to say is that in cats, and I'm sure you're aware of this, but in cats, amylase is not a a useful assay to run, with regard to pancreatitis. Most cats with pancreatitis will have a normal serum amylase, so please don't, please don't use that as an indicator.

Serum lipase is does have some utility, but again, the standard lipase I say that would be listed on your in-house biochemistry panels and on many standard external panels, again, is not useful for identifying pancreatitis in cats. Lipase, by the standard assay is commonly increased due to dehydration or kidney disease. It does not reliably correlate to pancreatitis.

So we need to do a rather more specific lipase assay, and this is where the feline specific pancreatic lipase or FPL assay, was developed some, some years ago now. And for a long time has been really the mainstay of blood testing for pancreatitis. So we have a reference range between 0.1 and 3.5.

But we have an oddity here because levels above 5.4 are suggestive of pancreatitis, whereas the reference range goes to 3.5.

So we have a grey zone between 3.6 and 5.3, in which we do not know whether the cat may have pancreatitis or not.

And actually even cats who have a SE FPL above 5.4, which is considered suggestive for pancreatitis. Unfortunately, we don't have a lot of data to draw on, but what data we do have suggests that the sensitivity of this essay is really not all that we would like it to be.

So sensitivity is the ability of the test to identify affected cats, and if we have a low sensitivity, as unfortunately we appear to have with this assay. That would imply that quite a lot of cats who have pancreatitis do not show up on this test. Now it certainly seems that there is good correlation for cats with severe or even moderate to severe pancreatitis.

So the higher the level of the assay, the more reliable it is, and the more severe the pancreatitis, the more likely it is that the SE FPL will indeed be elevated. But down at the mild and mild to moderate level, we certainly can see a normal spec FPL in a cat that has pancreatitis. Specificity appears to be quite good.

So published studies have shown a specificity of 100%. In other words, cats that do not have pancreatitis do not appear to show with elevated spec FPL, but again, studies are a little bit limited, so just be a little cautious. If the signs don't fit, I wouldn't rely on it 100%.

You will also be familiar, I'm sure with the test that has become available more recently, which is the feline DGGR lipase assay. And again, this is looking at lipase in a slightly different way and in a way which does appear to correlate to pancreatitis in cats. So it is more reliable than the standard lipase assay and it's not affected by reductions in GFR, so it won't be elevated in cats with kidney disease or dehydration.

Again, we have very limited studies, and most of the studies, indeed all of the studies that I have seen, have, have compared the DGGLGGR lipase to the SEC FPL rather than any studies which actually look at DGGR compared to pancreatic biopsy, which is, of course, the gold standard. But when compared to SE FPL, it does appear to stand up to scrutiny just as well as SE FPL. So the two assays do seem to be equally reliable, or if you are a pessimist, you might argue that they are equally unreliable.

It would have to be said that DGGR is significantly less costly than spec FPL at the moment. And for that reason, I think a lot of people are using that assay, and I don't think that is unreasonable based on the rather limited data that we have so far. The in-house snap FPLI test is interesting because this is, this is, this allows us to get an immediate indication, and so it can be particularly useful in out of hours cases and relatively emergency cases.

And the in-house snap FPLI has similar sensitivity and specificity to the spec FPL assay, but of course it only gives us a normal or an abnormal result. It will not give us an indication of the, if you like, the severity of the elevation. The cut-off point is set such that the vast majority of normal results on the SNA test will have a SE FPL below 3.5.

So that's where the assay cutoff has been set. And the vast majority of abnormal results will indeed prove to have a SE FPL level greater than 5.4, so in that area of suspected suggestive of pancreatitis.

The grey zone cats are always the tricky area, but the way the assay is set up, the cats that are in this grey zone between 3.6 and 5.3, the majority of those will give a normal snap FPL test.

Not all of them, but a majority, round about three quarters. So I guess the take home message here is that if you get an abnormal result, You might have a cat in the grey zone, but most likely you have a cat who has a spec FPL above 5.4.

Beyond that, it has the same limitations in terms of sensitivity and specificity as the quantitative assay. And again, a higher the cats with more severe pancreatitis are more likely to have an abnormal spec FPL and I would suggest by by by that that that in hand in hand with that, sorry. I would suggest that hand in hand with that, cats with a higher level of spec FPL are more likely to have pancreatitis.

So I think if you use the in-house snap test, it could be a really useful immediate indicator of whether you should continue to suspect pancreatitis, but it will not be the be all and end all. And I would certainly advocate where at all possible, if you do get an abnormal snap test, do follow it up with a quantitative assay, whether that's a spec FPL or a DGGR lipase, because that will then give you a number that you can perhaps interpret a little. More clearly, but also a number that you can compare to as time goes on and after treatment to know where, whether things are changing, whether things are improving, or indeed whether the level that you have appears to simply be what is normal for that cat.

So Back to our friendship, just a reminder that he'd had this 2 month history of weight loss, poor appetite, and occasional vomiting, and then a recent history of much more severe vomiting of his food and lethargic. On physical examination, we had pyrexia, dehydration and vomiting when his abdomen was palpated. Our blood test, we had an abnormal snap FPLI and I can tell you that we did send off for a quantitative assay and the SE FPL was 20.4.

So that is quite a significant elevation. And I think would support an involvement of pancreatitis in this cat. But of course we also had raised alkaline phosphatase, raised total bilirubin, and neutropenia in the face of pyrexia, which I would argue may well lead us to suspect that we also have a degree of cholangitis.

So based on all of that, what are we going to do? Where are we going to go from here? We may feel we have enough to go on to start some treatment, and I don't think that would be a wrong decision, and certainly depending on the time of day, it may well be that you would move this cat into treatment pending further investigations.

And indeed, if the client has really very limited. Funds, you may not have the luxury of doing further investigations, and you may need to move into a treatment plan based on your findings and and suspicions when I'll come back to those treatment options in a moment. But I think if you do have the opportunity.

Some further investigations certainly could be useful, and I hope that that you are all feeling that you would like to be, reaching for your ultrasound probe or asking someone else to come in and reach for an ultrasound probe if it's not something that's high in your skill set. And I think these cases can certainly benefit from ultrasound, more so than radiography. Probably x-rays are less likely to provide any strongly useful information, but ultrasound can be highly illuminating.

So what might we see if we are, if we have a cat with acute cholangitis, I think the changes actually are quite recognisable, even if you are not an experienced ultra sonographer. So I hope you can see on the pictures that I've shown got up here that in these cases, the gallbladder, which is here. Here and this one is folded on back on itself, so we're getting it cut twice in cross section and here, and I hope you can see in all cases that the wall of the gallbladder is really quite significantly thickened.

In these two examples, it's quite diffusely thickened. In this example, it's quite sharply defined and has actually developed a striped or striated appearance. And diffuse thickening of the gallbladder wall to greater than 1 millimetre has been shown to be a reliable indicator of gallbladder and bile duct disease.

The other thing that we look for is the the texture, the ecogenicity of the bile here in these top two examples, it is quite black and hypoechoic, and that is normal. Down here, I hope you can see that the bile is actually quite hyperechoic, in a kind of irregular swirly kind of way. And that again is certainly an abnormality and would lead you to suspect that there is perhaps cholangitis going on.

This picture illustrates that what we will very commonly also see is dilation of the common bile duct. So further away from the the gallbladder neck, we should have a a narrowing down and and quite a fine tube. If you can measure this common bile duct and find that it's more than 4 millimetres across, then that is abnormal and that would tend to suggest either present or previous obstruction to the bile duct.

But we do need to be aware that once a cat has had an episode of obstruction. And the bile duct is stretched. It does, it, it, it, it is not an elastic structure, so it doesn't ping back to normality.

That dilation will be a permanent fixture. So you may see this kind of appearance in a cat who is not currently obstructed or does not currently have raised bilirubin. And then we touched on this earlier, but we, we may see cholelith, so here you can see a mineralized density within the gallbladder with shadowing behind it.

But you can also see some mineral densities down here out with the gallbladder again with some shadowing going on behind them. These may be within the bile duct, you will see sometimes choleliths within the bile ducts that are trapped there, or these may actually be within the liver parenchyma but within the intrahepatic bile system. And so you may genuinely see little gallstones dotted around through the liver parencuba sometimes in chains highlighting where the intrahepatic bile ducts are are running.

And cholelis, as I've alluded to, are an indication of previous bacterial infection. So previous cholangitis, which might, if the cat has appropriate signs, might heighten your suspicion for current cholangitis. Be aware that the size of the gallbladder is not particularly relevant, however large it is, if the bile duct is not dilated, a large gallbladder on its own is not an indication of biliary obstruction.

And a small gallbladder is also not an indication of a healthy bile system. We do see cats with jaundice, with obstruction, with very thick, sticky, inspiated bile, but a small gallbladder. So size, I'm afraid is not a good indicator.

Even if you see an enormous gallbladder, don't get too distracted by that. Try and look for these more specific indicators of cholangitis. What about inflammatory bowel disease?

We haven't talked about that very much so far, but inflammatory bowel disease certainly can show some changes on ultrasound. You need a relatively good machine, a high definition probe, and you need a reasonable amount of experience, and you need a fasted cat, which is often . Not a problem, because often these cats are off their food.

That's why they present. But you do need the right, you know, the right equipment and a degree of experience. But what you may see is a diffuse thickening of the small intestinal wall, and that's illustrated up here by these very stripy loops of guts.

So here. We have one cross section through an area of the small intestine with the ingestor in the middle, and then the stripes, black, white, black, white, moving outward from the central lumen and again on this side, black, white, black, white. And we know that we should have maintained striations throughout the gut.

And if we have loss of striations that would suggest neoplasia, but in inflammatory bowel disease, we expect to still see the stripes. Normally this the mucosa is the thickest of the stripes, so that's the the internal layer, the layer closest to the central lumen. If you see a disproportionately thickened muscularis, which is the outer black layer, that that tends to be an indication of either eosinophilic enteritis or of the diffuse form of lymphocytic lymphosarcoma, which is on the differential list for more severely affected cats and often one of the main reasons that we want to try and get a definitive diagnosis.

Generally with diffuse lymphocytic lymphosarcoma, at least in my experience, you will see a significant increase in the size of the lymph nodes throughout the abdomen. Whereas in inflammatory bowel disease they may be mildly increased in size or they may not be increased in size. I wouldn't hold that out as a clear and definitive differentiating factor, but again it will give you a bit of a hint as to whether you should be more concerned about lymphosarcoma or perhaps less concerned.

A biopsy of course is ideal, but not always possible. Other things to look out for with inflammatory bowel disease, we sometimes find that there is an extra stripe. So if we look at this picture, we have in the middle the lumen, so the white stripe in the middle is the gut content, and then we have a black layer of mucosa, a white layer of submucosa, a black layer of muscular.

And at the edge, the serosa. But if you look carefully, and I hope you can see this on your screens, the green arrows are pointing to a very faint, very narrow white line within the mucosa. There's actually another one up here.

So I hope you can see that, actually on this picture. Over here, we've got a similar finding of an extra white stripe within the mucosa. And if you see that, then that does tend to be an indication of quite chronic inflammatory change, and it's probably an area of fibrosis within the mucosa as a consequence of chronic inflammatory change.

So an extra white stripe to look out for. And then perhaps counterintuitively, what we also see in cats that have had chronic inflammatory change is actually a thinning of the small intestinal wall, rather than a thickening, and that's illustrated down here. This cat has walls that are measuring at around 1.5 to 1.7 millimetres where the norm would be somewhere.

Like 2.4 to 2.8 millimetres depending on which bit of bowel you're looking at.

So up here we have a cat who has thickened bowel walls and these are up to 3 millimetres across. Whereas down here we have a cat with thin bowel walls, again, still with stripes, but thin bowel walls, and that tends to be an indication of chronic inflammatory disease. So then we come to pancreatitis.

Now of course the pancreatis in the cat is famously a difficult area for ultrasound and depending on your machine and your level of experience, you may feel that you struggle a bit to find a cat's pancreas. Keep searching, keep looking, they are in there. You can find them, and once you get your eye in and you get your technique good, you will be able to identify them and that can be an incredibly useful skill to develop.

So the sorts of things we might see in pancreatitis, actually in cats with pancreatitis, you might find that you can find their pancreas, even though you perhaps struggle in cats with normal pancreas, because in in pancreatitis, we often see an enlarged pancreas and we often see a pancreas that seems to stand out more and I hope that's illustrated, whoops, sorry. I hope that's illustrated in these two pictures where we have a relatively dark pancreas with a relatively paler surround, because the pancreas is quite hypoechoic, and the surrounding peripancreatic fat is quite hyperechoic, and that would be a classic finding in pancreatitis, but it does make the pancreas stand out for you. What you will also notice in these two pictures is that the outline of the pancreas is really quite irregular.

The pancreas should be a smooth, leaf-like organ. So when you see irregularities like this in the wall, and we've got some here as well, that tends to be an indication of pancreatitis. And then up here, and I appreciate this is difficult to interpret in a in a still image, but what we have here is this is pancreas, and actually what we have here is a relatively hypoechoic pancreas with quite a thickened area in this region.

So you may see a hypoechoic pancreas like here, you may see a hypoechoic pancreas and all of those things can be indicators of pancreatitis. And in the right hands with an experienced operator, those the the pancreat, the ultrasound changes can be quite reliable and possibly with a better sensitivity than the blood tests that we've just discussed, although specificity perhaps not quite so so strong. Again, large studies are lacking and and we don't have really good data and of course, so much with ultrasound depends on the equipment that you have and indeed your experience.

OK. So what did we find with Chip when we did his ultrasound? Looking at these images from his liver and gallbladder, I hope we can agree that there is clear thickening of the gallbladder wall and of the bile duct wall and within the gallbladder, and this is the outline of the gallbladder.

And this is relatively normal bile. We have a large area of hypoechoic material within the bile, so we do have evidence of cholangitis. We also have, I would suggest, evidence of pancreatitis.

This is the view of his, the right limb of the pancreas. Again, I hope you can see that we have a relatively hypoechoic pancreas with relatively hypoechoic tissue around it, and we have a very irregular wall, rather than the normal smooth, leaf-like appearance. So we could certainly suspect a degree of pancreatitis even if we had not seen the elevated spec FPL, and here we have a view of his duodenum with significant thickening of the mucosa, no loss of stripes, but significant thickening of the bowel wall.

So these would be classic findings in a cat with triaditis. So now we have a working diagnosis from our clinical presentation, our blood test findings and our ultrasound to suggest that we do have a combination of pancreatitis, cholangitis, and enteritis. And I would suggest that quite early on in the course of his investigation and management, we would be starting him on a combination of treatments for those diseases.

So we would want him on some intravenous fluids and in our practise we would routinely add into that ranitidine or omeprazole CRI because we commonly see a degree of gastrointestinal ileus in cats with pancreatitis. We would start him on some mropotent, given IV for the nausea and vomiting which could be arising from any of these three conditions. We would have him on buprenorphine because of the likelihood of discomfort from the pancreatitis and cholangitis, even if he's not showing overt signs of pain, we will give him the benefit of the doubt and treat accordingly, and buprenorphine is very safe to use in all three of these conditions.

And if he will take it, we will give him some UDCA subsodiol, to try and start to water down, thin down the bile and encourage bile flow while we try to get to the root of his problems. And then the question arises, should we give him antibiotics? Should we give him corticosteroids?

Let's think about antibiotics first. What would be the rationale for antibiotics in these cases? Well, in acute cholangitis, that is a bacterial infection of the bile duct and gallbladder, usually an ascending infection from the duodenum and usually encompassing one or a combination of.

Type bacteria, so E. Coli, streptococci, enterococci are very common findings. So I would argue that in acute cholangitis, if you have strong suspicion of acute cholangitis, I would argue that antibiotics certainly are indicated.

We'll come back to the choice of which to use in a second. But what about cats with pancreatitis? Is there a rationale for using antibiotics in acute pancreatitis in cats?

Well, it's fair to say that bacteria are rarely cultured from pancreatic tissue in cats, and that would lead us to suggest that perhaps they are not indicated. Having said that, if we look in more detail using a fluoresce in situ hybridization or fish technique, which is a much more sensitive technique, around 35% of cases do in fact have bacteria present in the pancreas. Now that's not quite the same as saying that they have active infection, but the types of bacteria found tend to be again gut bacteria.

And so there is a suspicion at least that some cats with acute pancreatitis may have a bacterial involvement. Furthermore, and as as a a a sort of circumstantial point of view. Withholding antibiotics from cats with acute cholangitis with acute pancreatitis has been shown to be a negative prognostic indicator.

So in other words, cats treated quite aggressively but not given antibiotics appear to have a less good outcome than those. That are given antibiotics, which may be because there is an element of bacterial infection involved. But actually, if we look at our Venn diagram again, and we realise that the vast majority of cats who have pancreatitis also have cholangitis.

But perhaps that cholangitis sometimes goes unnoticed, then we may realise, we may, that may be another reason why many cats with pancreatitis do do better if they're given antibiotics, not because you need antibiotics for pancreatitis, but because they have concurrent cholangitis. So I think there is a rationale for antibiotics in cats like Chip, especially where we have fever, neutropenia, and a strong suspicion of cholangitis. The choice of antibiotic, well, that is gonna need to be empirical if we cannot get a sample for culture and sensitivity.

And so the first line approach would be amoxicillin clavulinate. But given the involvement of gut bacteria, we may consider adding metronidazole either from the outset, or certainly if we do not seem to be getting a rapid improvement in pyrexia, based on from from our first choice antibiotic. But of course, in the ideal world, we would have a specific diagnosis, evidence of bacterial infection to use antibiotics and a culture and sensitivity on which to base the antibiotic choice.

And so I would encourage you to consider getting familiar and confident with the technique of bile aspirate. I know people often find it quite scary to think about doing this, but it is a very straightforward technique, and we have multiple studies now confirming that it is a very well tolerated technique with minimal risk of any adverse consequences. You will of course need to be using ultrasound machine to guide you.

But it is a very straightforward technique. The cat does need to be under either anaesthesia or sedation so that it stays completely still for you. But with that proviso, it is a very straightforward technique.

And essentially what you want to do is get your ultrasound probe in place and get yourself a view in which you have here some liver parenchyma and then a nice area of gallbladder and then we've got more liver the other side. Line it up so that your, so that where your needle is going to go in as you do your ultrasound guided aspirate, you're going to be going through an area of liver and into a reasonable sized area of the gallbladder to give yourself a good chance of hitting it. And then I've just got a little video here which just shows us lining up the needle with the line on the ultrasound machine, which you can just see there.

So we're lining up and going in plane with that into the gallbladder. You can see it's just a blue needle. Oh, it stopped at the key moment and when we draw back.

I'm sorry, that's there we go. You can see the bile flowing in. In this case it's quite watery bile, which is normal, but the colour there is abnormal, it should be a dark, dark bottle green.

But watery bile is normal. Be aware that in cholangitis, the bile may be quite sticky. So if you see that your needle is in place, but you draw back and do not get bile, that can be because the bile is too sticky to come out.

You may use a slight. Wider diameter needle, perhaps a green needle rather than the blue needle, but I would not go too far up that scale if I cannot get a good sample, and I know that my needle is in the right place. I will take that as again circumstantial evidence that the bile is indeed abnormal.

So we need to sedate or anaesthetize the cat to do this, and if the cat does have liver disease, we need to choose our sedation with care. So avoid drugs that are metabolised by the liver if you can. Use the minimum effective dose and use a combination of drugs so that each dose is kept to a minimum.

And just expect that the cat may recover more slowly if there is significant liver disease and significant liver function compromise. So maintain your support and monitoring throughout the entire recovery period and and allow that that may be longer than you otherwise would expect, making sure that you keep the cat warm and on fluids and with its blood pressure controlled and maintained throughout that recovery period. Choice of drugs, benzodiazepines and opioids will be good choices for sedation.

So often a midazolam, butterphenol combination. But if you prefer, then an actual anaesthetic can also be done quite safely, even though perhaps only brief if you're just doing a bi bile aspirate. Propofol is an appropriate agent.

Alfaxolone is an interesting one because it is metabolised by the liver. So you will need to use the minimum effective dose, but then you always would be doing that anyway. You would give a premedication of again, perhaps an opioid and or a benzodiazepine.

And the fact that it is metabolised by the liver means it may be slower to wear off, but alfaxolone wears off so very quickly that even if there is some increase in duration, that is usually not problematic, and it is not hypertensive and does not tend to cause apnea, so it can be a good choice if that's what you are used to using. So in Chip's case, just briefly to, to finish off with Chip, we did take a bile aspirate. You can see we got this kind of turbid yellow viscousy fluid.

And when, when smeared out on a glass slide, we can see that there are neutrophils within the sample. You may see bacteria within the sample if there is a lot of bacteria present, and if you submit. For culture, you may get a positive growth, but it's always worth doing the cytology as well, because in some cases, bile is not, well, in all cases, bile is not a very friendly medium for bacteria.

And so you can get false negatives on culture, but if you see a strong neutrophilic reaction in the cytology, that would still support your diagnosis. So initial treatment for Chip, we got him onto IV fluids and as I say, we would a standard adiranitidine concentrate infusion. IV mropotent, and if we don't get a good early response to that, we will move to Ondansetron, which is not licenced for use in veterinary work, but is a very effective anti-nausea drug if mropotent is not effective.

We started him on intravenous amoxicillin clavulinate for his cholangitis, buprenorphine, and as we discussed, UDCA. Within a couple of days he was much brighter, he was much happier, his temperature had come back to normal and his abdomen was comfortable, but he was still not interested in food, albeit that he was no longer actually vomiting. You can see that his a forces has improved, although he's still very significantly elevated.

His bilirubin is round about the same, and that's not unexpected. It takes a few days for bilirubin to start to drop, even if you're getting on top of. The cholangitis, and that's because of the sticky thick nature of the bile, which takes a while to improve.

And you can see that indeed he has now gone from being neutropenic to neutrophilic as we would perhaps have expected. So at this stage, we have addressed his pancreatitis symptomatically, which is all we can do. We have addressed his cholangitis with the antibiotics and the UDCA.

The area, of course, that we have not yet addressed is the suspected. Enteritis, and I think we have reasonable evidence of that from his poor appetite and vomiting and weight loss over a few months and from the thickened mucosa layer that we saw on our ultrasound. So should we use corticosteroids in this cat?

We would probably not tend to use it right immediately on day one when there is bacterial infection and a compromised cat. But what what point should we introduce it? So at this point with CIP do we continue our current treatment?

Do we investigate for small intestinal disease or do we start him on corticosteroids? So inflammatory bowel disease, the definition of inflammatory bowel disease is a cap that shows gastrointestinal signs of more than 3 weeks' duration, which we have. No response to anthelmintic treatment and no response to dietary trials which we have not yet had an opportunity to do in this case.

Histological evidence of mucosal inflammation, which we do not have unless we have done a biopsy. And clinical improvement on immunomodulatory treatment. And really we need all 5 of those elements to make a definitive diagnosis of inflammatory bowel disease.

But clearly in some circumstances we are not going to be able to fulfil all of those criteria and we are therefore going to have to decide whether we are going to treat regardless based on suspicion because in the real world that sometimes is all that we can do. So if we're going to continue current treatment and, and obviously we're we're certainly at some level going to have to continue with the treatments we've already started, I think at this stage we are thinking about nutritional support and the need for an esophagostomy tube. If we are anaesthetizing him to place an esophagostomy tube, and if you have access to endoscopy for cats and can get into the small intestine to biopsy, then you may well feel that while you have him asleep for esophagostomy tube placement, you will go ahead and do an endoscopy, and I don't think that would be at all unreasonable.

Our other alternative, of course, is surgery to get full thickness biopsies. Can we justify that in this case? Is that a reasonable thing to do?

It's not necessarily unreasonable if he is not responding to treatment as we would expect, and if we feel that we do need perhaps pancreatic biopsies or there are other changes on his ultrasound that worry us. But whether if we have strong suspicion of inflammatory bowel disease and not of any neoplastic process, I guess I would question whether it is a justifiable thing to do. Or do we skip the further investigations, give him nutritional support via the tube, and start corticosteroids, and very often with a strong index of suspicion, that is what we will do.

So Chip was already on the treatment we'd outlined in the in the previous slides, intravenous fluids, ranitidine, buprenorphine, ondansetron, amoxicillin clavalinate UDCA. And we often would then come in with an initial dose of Dexedri and give an IV and then prednisolone to continue. You can see this cat is going to be on quite a combination of medications and at least the antibiotics, anti-nausea and prednisolone are likely to be needed for some time.

And so there is advantage to an esophagostomy tube, if only for the owner to be able to give medication reliably, even once the cat starts. Eating and if we do have the the benefit of a tube, then it becomes more practical to also give liver antioxidant supplements like aiddenyl methionine, sillyinin and so on, which can be quite difficult to dose in in food or manually, but obviously via a tube can be done. So that was the plan with Chip, and you can see that he did respond extremely well.

10 days later, obviously he's back home now with his owner with a tube in place and medications being given that way as well as initially assisted feeding. 10 days on, he's bright and active, eating voluntarily, no vomiting, and you can see that his blood picture is really improving nicely. So we still have some raised globulins reflecting the inflammation.

But a force is continuing to drop. Bilirubin is now on the way down with a concomitant drop in fasting bile acids as we reestablish enterohepatic circulation, and you can see that his white cells have normalised. So at this stage we probably can take him off the anti-nausea treatment, whether it was Marropotent or ondansetron.

But we probably continue with most of the other treatments, although again we're probably phasing out the buprenorphine by now if we have not already done so. A week later he's still doing well, he's still eating well. We could consider taking the tube out once he's eating well, but many owners will opt to keep it while the dosing burden is still quite heavy.

Probably using our antibiotics for a couple of weeks, in this scenario because it can take a little time to really clear out that cholangitis. And then a reducing pattern of prednisolone. We usually would be starting at around 2 milligrammes per kilogramme and then titrating downwards with a long term plan to continue on an appropriate diet and to gradually titrate prednisolone to the lowest effective dose.

And I'm aware that time is running on and I apologise for overrunning somewhat, but I did think I would just take a couple of moments to just talk you through my approach to using prednisolone in inflammatory bowel disease, because I think it is an area that is sometimes not really discussed and can be confused. And if we do not use prednisolone or corticosteroids appropriately, we can get disappointing results, and obviously we want to avoid that. So my initial dose of prednisolone in IBD is a dose of around 2 milligrammes per kilogramme rounded to the nearest half tablet and delivered in a single dose.

You don't need to split the dose. So for a 4 kilogramme cat, I would calculate that 2 milligrammes per kilogramme is 8 milligrammes. We have 5 milligramme tablets, so I would round that to 7.5 milligrammes, and that would be my once a day starting dose.

I would use that no dose until signs are well controlled, whether that's vomiting or diarrhoea or poor appetite. And then for at least 7 more days after I feel that signs have responded. And then I will reduce the dose by half, but again in practical terms, rounding up to the nearest whole or half tablet.

So in our last example, our 4 kilogramme cap that we started on 1.5 tablets once a day, a 50% drop would take us to 3/4 of a tablet. That's not very practical.

It's going to be fiddly for owners, so I would round that up to a whole tablet. And then I'm gonna use that dose for the same amount of time as I needed the initial dose and a bit longer. And therefore, obviously, depending how quickly the signs resolve on the high dose, they will be on the next dose down for a longer or shorter period of time.

But usually it ends up that they're on the first treatment for somewhere around 2 weeks or so and usually once I drop to the 1st 50% drop, I will use it for at least a week or so after, longer. And in in round terms, very often that is going to be around about 2 weeks more or so. But again, it does depend how quickly they respond to treatment.

Then if we make that dose reduction and we do not see any adverse effect in that period, we will reduce by a further 50% again rounded to the nearest whole or half tablet. So in our example, we've gone from 7.5 milligrammes once a day to 5 milligrammes once a day, and now we will reduce to 2.5 milligrammes per day, and again, using it for the same amount of time as the last dose and a bit more.

And usually at least 2 weeks longer. So each time we drop the dose, they stay on that dose for rather longer than they were on the previous dose, and we continue to reduce by 50% increments until we get down to half a tablet every other day. And if they remain good on half a tablet every other day, we will then try the effect of stopping treatment altogether.

So you can see that depending on the size of the cat to start with, it can take really many months to work down the doses, and if at any stage we find that signs are creeping back, we will revert to the previous dose increment and then continue that for longer before we try to reduce again, and we may well find that we just reach a minimum dose below which we cannot go without signs recurring. Always remembering to continue with dietary trials and or dietary management because that is an important part of the treatment of IBD and it will reduce the amount of steroid that is needed. OK, I'm sorry.

I finished it a bit of a cancer there because I am conscious that I have overrun. But I hope that it's been helpful. I hope there's been a few pointers there and maybe a few tips and tricks that you can take back to practise and that you will find useful.

In this complicated arena of three separate diseases, all of which can overlap, and each of which will have their own presenting signs and diagnostic challenges and indeed their own approach to treatment. But as you've seen with Chip, I think these can be increasing incredibly rewarding cases to treat. They can come in really very unwell, very chronically unwell is very acutely as well as very acutely unwell, and yet very often with appropriate treatment, we can turn things around and get a really good long term outcome.

So. Certainly keep it on your radar. Keep cholangitis on your radar perhaps more than it is at the moment, because I think it is sometimes the invisible element and sometimes it's an element of cholangitis which is stopping your cases from responding to treatment the way that you might hope.

So there you are. I hope it's been helpful. Thank you for your attention, and goodnight to everybody.