July 23, 2024

🔓 Demystifying Those D$&@ Liver Enzymes. With Prof Jill Maddison.

🔓 Demystifying Those D$&@ Liver Enzymes. With Prof Jill Maddison.
Apple Podcasts podcast player icon Spotify podcast player icon RSS Feed podcast player icon
Apple Podcasts podcast player icon Spotify podcast player icon RSS Feed podcast player icon
Season 1

Ah, those liver enzymes... sometimes they are up when you don't expect them to be. Sometimes they're up a bit... but not that much, so you don't know if it's actually significant. Or sometimes they're way out of whack, but you're not sure what that means exactly, or what to do next.

In this episode, Small Animal Medicine Specialist, RCVS Course Director and clinical reasoning guru Prof Jill Maddison helps us take a fresh look at  liver enzymes. We review what each enzyme tells us in dogs and in cats, how to interpret changes in both the 'well' patient with the surprise finding on bloods, and in the sick patient, and Prof Jill clears up common misconceptions and pitfalls around ALP, ALT, GGT, and bile acids.

This clinical episode has been unlocked for you by Vetnostics Pathology, one of the largest veterinary pathology groups in Australia with the most veterinary pathologists and veterinary medicine consultants. Vetnostics is the new nationally aligned name of what used to the SVS Pathology Network ( (Vetnostics NSW/ACT, Vetpath Laboratory Services WA/NT, ASAP Laboratory Vic , QMLVetnostics Qld/NNSW and TML Vetnostics Tas), with a new consolidated website (www.vetnostics.com), but the same exceptional quality diagnostics, same extensive courier network and same veterinary pathologists and veterinary medicine consultants on other the end of the phone or email to talk you through any tricky results and cases. 

Join our community of Vet Vault Nerds to lift your clinical game and get your groove back with our up-to-date, easy-to-consume clinical episodes at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vvn.supercast.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠.

Get help with your tricky cases in our ⁠⁠⁠⁠⁠⁠⁠⁠Specialist Support Space.⁠⁠⁠⁠⁠⁠⁠⁠

⁠Subscribe to our weekly newsletter⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠here⁠⁠⁠⁠⁠⁠ ⁠for Hubert's favourite clinical and non-clinical learnings from the week.

 

Episode Topics and Timestamps

05:01 ALT and ALP: Detailed Analysis

05:40 Challenges in Diagnosing Liver Disease

06:40 Liver Enzymes in Cats vs. Dogs

20:44 Bile Acids and Liver Function

26:51 Pre-Anaesthetic Liver Checks

36:35 Understanding Cholangitis in Cats

36:53 The Complexity of Diagnosing Liver Disease

37:45 The Role of Blood Tests in Wellness Checks

38:11 Interpreting Reference Ranges

40:53 Case Studies: Real-World Examples

42:05 The Challenges of Wellness Screening

44:21 The Importance of Biopsies

55:14 Biases in Diagnosis

This episode from our clinical podcast series is brought to you by Vet Gnostics Pathology, one of the largest veterinary pathology groups in Australia with the most veterinary pathologists and veterinary medicine consultants.You'd have heard other sponsored episodes on here by the SVS Pathology Network.
Well, same group, but now all under the brand Vet Gnostics.Which makes me, as someone whose job it is to tell you about our sponsor, very, very happy.Because previously I always had to say this episode is brought to you by the SVS Pathology Network, which depending where you are in Australia, is Vetnostics or QML Vetnostics or Vetpath or ASAP Labs or, or, or or.
Well, no more, they've just rebranded into a single brand.So it's nice and simple.Just vetnostics, one website, vetgnostics.com dot AU.Same exceptional quality diagnostics though, same extensive Courier network and same veteran pathologist and veterinary medicine consultants on the end of the phone or e-mail to talk you through those tricky results and tricky cases.
Which when it comes to the topic for this episode is super useful because man, those liver enzymes can get confusing.But we're going to try and help you with that in this episode.So picture this.You've run those pre GA bloods or the health screen and you're apparently healthy dog and you get the results back and guess what?
One of those frigging liver enzymes are up now what you all your sick patients liver enzymes are up a bit, but not that much.What does that mean and what's next?Never fear, we have the Queen of Medicine with us.To clarify, Professor Jill Madison has lived and breathed Clint Path and medicine for her entire career.
She's published more articles than many of us have read and given more talks and taught more students than anyone I know.And she's even written a few textbooks about it, including her phenomenal book on clinical reasoning.And you're going to need your clinical reasoning for this one.In this episode, we'll take a fresh look at the liver enzymes first in the sick animal to decide whether the liver is the main problem or just an innocent bystander or actually more like a noisy commentator.
Like we're sick.I'm fine though, but I'm very upset.Look at me, someone.And then we look at abnormal liver results in the supposedly healthy animal.You know, that Spay or that dental Jill helps us understand what each of the enzymes mean, and she clears up common misconceptions and pitfalls.
If you love this episode with Prof Jill, which you will, we have a bunch of other episodes with her on our razor proof subscriber clinical podcasts like Making Sensible Antibiotic Decisions, Interpreting Pancreatitis, Blood Tests and How to Work Up the Jaundiced Cat.In addition to our roughly 500 other episodes and counting in small animal medicine, surgery and emergency and critical care, all of them backed up by our very popular show notes.
So just to be clear, the bulk of our clinical episodes are on the subscriber only podcast, which you won't find on your podcast player until you subscribe at vvn.supercast.com.And to help motivate you to go check it out, I have to share this lovely heart warming e-mail testimonial that we received a while ago about our episodes around, I think it was calcium metabolism.
It comes from Sam, and Sam says it's the first time I've ever actually understood this shit.Isn't that just beautiful?Go and check it out for free for two weeks or ask your boss to contact us at info@theredfall.com to organize a discounted practice subscription for the entire team.
The link is in the show description right here on your podcast player.OK, onward with those damn liver enzymes with Professor Joel Madison.Welcome back to the Vet Vault.
I'm so excited to have you back.And we are going to tackle liver enzymes, which is huge and cause of much consternation and confusion.I've got two hats that I wear when I do this conversation.One is the last decade plus something of my career, which is the emergency clinician where I get sick animals and I run bloods and look for what's abnormal.
Occasionally I'll do some pre GI stuff, but it's mostly you're sick, you're vomiting, your unwell, you're here, let me dig and I'll do bloods and then I'll see oh, liver enzymes up.I'll put this in here now, but maybe we'll come back to it.But I'll often I'll often want to look at Lt. for example, to see have I got as evidence of hypoxemia or shock or something like that.
There's a few things that I use it for practically.Now I'm looking for very specific things versus the first decade of my career when I would do lots of pre GI bloods or, you know, health screens and those sort of things.That's a whole different scenario where I'm not really expecting disease.My patients are healthy, maybe it's a bit fat or you know, there's a few things.
But then I go, oh, there's that high LP or Lt. or some liver enzyme change where I go bugger.Now what do I do with this?Yeah.So and that's what that's a really great summary of what everybody's facing.And I think we need to look at the situations where we do liver enzymes.
Let's just first say just as a recap, everybody knows this, but if we look at ALT, it's the enzyme that leaks out of the hepatic paranchymal cells when they're damaged.But the damage doesn't have to be very much.We look at alkaline phosphatase ALP, which is the enzyme that its production is induced and it's released when there's Cholestasis, so slowing of bile flow or increased bile flow.
And then particularly for cats, we look at GGT, which is similarly induced enzymes.So if we're just sticking with the enzymes that we use, that's where they come from, but that's also what creates some real confusions about it.So I think the first thing to say, let let's take the sick animal first.
If we have an animal that is unwell and because liver disease can create practically any clinical sign you can think of, it's totally appropriate to be looking at liver parameters when you have a vomiting animal, diarrhoea, whatever, unless it's very clear that it's primary GI disease.
But that's another lecture.And then we scratch our heads because it can go both ways.So we could say, well, the liver enzymes are all normal.They're all in the reference range.This animal can't have liver disease.But actually that's not true because you can have some liver disorders where for various reasons, they don't result in an increased level of enzymes.
You know, examples would be proticable.Shunts often don't.Minimal and numb.Sometimes if you've got very extensive infiltrative neoplasia of the liver or if you've got cirrhosis, the liver has just hardly got any cells to leak out.And the other thing we have to be really careful of is that cats are even worse.
So cats can have that half life of their enzymes is much shorter than it is in dogs.So they can have a similar level of damage to their liver, but will have a lower level of enzyme increase.And with alkaline phosphatasing cats, it's particularly marked because there's a even bigger difference in the half life.
So it's something like six hours in the cat and 72 hours in the dog.But also the cat doesn't produce as much ALP, it's not induced as much by Cholestasis.So you can have and can have a jaundiced cat because it's got a paterbillary disease, who will have and can have a normal alkaline phosphatase.
So you usually have an increased ALT, but they can have a normal alkaline phosphatase and that just would never happen in a dog pretty much.So you've got that issue that first of all, you can have serious liver disease and have normal enzymes.And that is absolutely the case and particularly the case in cats.
If you then flip it around and say, OK, I've got an unwell animal and I'm hunting whether the clinical signs this animal is showing is due to liver disease.And I do my liver enzymes and they are increased, they're above the reference range.
The problem for ALT and ALP except in in cats is that just because it's above the reference range doesn't mean that we have significant pathology.So if we take ALT, so ALT is the leakage enzyme.
It leaks out of hepatic paranchimal cells and it definitely will leak, but it doesn't take much of an insult.So you saying for example, that you check ALT because there's a measure of hypoxia, for example, is quite true.
So if the liver is subjected to hypoxia because of cardiac disease or respiratory disease or profound anemia, ALT will will go up a bit.But it also of course can go up if there's direct damage to the liver parenchyma itself.And so if we're hunting in an unwell animal and we have changes in liver enzymes, if we just take the dog, what I usually say is that if the number is 10 times the reference range, so you've got in a dog, the reference range is usually less than 60 for ALT.
If it's 600 or more than you've got pretty good evidence that you've got some hepatobiliary pathology going on.There are some non hepatic diseases that might do that.So sometimes in diabetes we see it because of getting hepatic lipidosis.
Sometimes we see it in Cushing's disease because they get a sort of steroid hepatitis.Sometimes we'll see it in pancreatitis because of the secondary effects.But in those scenarios that you just described, the app still the liver is sad.Like it's not fake eye, it is still liver sad, but it's not a primary liver condition.
Is that correct?Well, it's sad.In that it's leaking, but you don't, you don't need to treat it.So it doesn't need any liver supplements or anything like that.You treat the underlying disease and it will be fine.You know, the liver's got a huge reserve.So the liver's going leaky.What I call ALT is a drama queen.
So it just, it just leaks out when anything goes wrong, basically anything pretty much come in the body.We talked about snowflakes.Snowflakes before the podcast is the liver.Exactly.Well, one of my one of my one of my analogies and this might, this might offend some people, but I hope not is that it's a like it's the the liver is a bit like an organiser for the Australian Workers Union in that it goes, oh, oh, the guts a bit inflamed, right.
Everybody out and he goes, oh, I feel sick too.I'm not going to or the heart's a bit wrong.Yep, everybody up.So that's what I use as an analogy.It kind of is a sympathy organ.So it it goes out in sympathy.It doesn't go out function wise.
It just goes out with ALT.It just goes out a bit.So when it's greater than than 10 times, you certainly look at it and it might be you go, yeah, that's fine, you know, and and there'll be question marks, you know, you might have a diabetic that's got an ALT of, you know, 607 hundred 800 and you go, does this mean there is important paranchinal disease there I need to worry about?
You say, well, I've got to manage the diabetes and see what happens.Pancreatitis, same deal.You know, pancreatitis, you can get quite a significant increase in ALT and in the vast majority of cases, the management of the pancreatitis will resolve that liver enzyme problem.
But if it persists, then that's telling you you've got an UN underlying problem.So one of the things to remember is that it's a dynamic system.So if you're thinking you've got a secondary change that's causing the increase in ALT, then you need to monitor the ALT after that primary problem that you're dealing with has been resolved because there could be something sort of oozing along there.
So that's the 10 times above the reference range.You know that there's something going on in that liver and sometimes it can be outside of the liver, but you need to, once you've resolved that the diabetes or the pancreatitis or whatever, you still need to check because it doesn't rule out there being an underlying liver problem.
But usually in those situations, you don't need to do anything specific for the liver.And if there's nothing, there's none of those secondary problems like diabetes, like Cushing's, like pancreatitis, then when the enzyme is about 10 times the reference range, you're looking at hepatibiliary pathology.
It doesn't tell you for sure that it's the liver parenchyma.It still could be the post hepatic structures, the, the biliary tract and the gallbladder, but you can focus on that area.So then the next group that I talk about are the ones that are about 5 times.
So they're, you know, they're 300 to 600, something like that.And they're probably the most head scratching because they could be either they, they could be, and particularly in a cat, particularly in a cat that could be primary hepatibiliary disease, but it could also be secondary to all those diseases we said.
And in the cat, for example, hyperthyroidism.And that's where you, you just can't, with that sort of level, you can't diagnose liver disease just based on those enzymes and you can't rule it out.So you need something else.So they're the animals that unless they're jaundiced, they, you would do bile acids on, for example.
And it's really important, you know, there are a lot of animals that have significant liver disease and they're not jaundiced.It really depends on how the pathology lies within the liver and whether it affects the biliary ductules, whether or not they'll be jaundiced.So those that sort of 5 * 5 to 10 times, they're really quite head scratching.
And then you've got the ones you've just mentioned.So you've got the ones that are less than five times.So they're two to three times the reference range and they're head scratching as well because it could be liver disease, particularly in a cap, it could be one of the, if you like, semi silent liver pathologies, but they're often not.
So it's often not.So it's often the secondary things like hypoxia, like inflammatory mediators floating around, like old age, just a bit of fatty liver.And then it becomes in what we're talking about at the moment is that we're hunting the cause of an unwell animal.
So it will depend on what else pops up.So if there's nothing else to explain why the animal's unwell, Although if there's no other clinical pathology, then you've got to consider the fact that if your animal's got vomiting or diarrhoea or weight loss, then it could be primary gastrointestinal disease with some minor changes in liver enzymes.
And you have to keep that in mind.And if you were still hunting liver disease, this again where you would do bile acids, which I'll talk about separately.So that's your that's your ALT.And that's where I guess the take home message is that in the dog you can have quite a range.
In the cat you take more note of minor changes and you've got to remember, but you've got to remember diseases like hyperthyroidism in the cat, which will increase ALT.If you look at ALP, So alkaline phosphatase, it has a different genesis.
It is produced by induction and which is stimulated by cholostasis.As everybody knows, it poses a challenge because it has ISO enzymes.So it has enzymes of ALP which derive from other places other than being increased by cholostasis.
And so you can have bone enzyme which can be in young animals because I'll have a reference range up to three times the adult reference range in the first six months of life.We've got osteomyelitis or osteosarcoma.We can have an increase in ALP and interestingly in cats who frequently it's the only non hepatibiliary disease that will cause an increase in ALP in cats is hyperthyroidism.
And what's been discussed recently is that that in fact is bone isoenzyme.It's about bone turnover rather than relating to the liver.You can have breed related increases in ALP.So in Siberian Huskies, for example, they can have really big increases in ALP, which means nothing.
I'll ask a malamute to have a increase in ALP that is just familial and means nothing.Like it's literally means nothing.And it can be quite high around 1000 when they're six months old, but still around 700 when they're a year old.
Scotty Terriers can have a similar situation as well.We know that in dogs steroids will induce ALP, but not in cats.And phenobarb, am I right?Does phenobarb also induce it?Phenobarb will do it as well in dogs, but not in cats.
Cats.Interestingly, hemolysis can sometimes increase ALP.Don't really know why and it's interesting the bone ALP or the the bone ISO enzyme is both in cats and dogs.And we just recently did a study looking at liver enzyme changes in cats with different sorts of liver diseases and the ALP was often not increased.
And that's because as discussed before, it can have a very short, it does have a very short half life in cats and they don't produce as much.But when we analyze the data and compared it with controls at the same age, there was no increase.So in cats with shunts, for example, they will have an increase in ALP, but it's a bone change, not a liver change.
Whereas cats with other types of liver pathology may or may not have an increase in ALP.It's very insensitive in detecting sort of paraclimal disease.So interpreting that, does it mean for us looking at cat bloods don't Can't ignore ALP but don't put too much stake in what you see on ALP up or down doesn't really tell you that much.
Well, I think if it's up you do like if it's up you go, that's, that's abnormal.If it's in the reference range, then no, it doesn't mean I've had too many vets say to me, well, it can't have liver disease because the ALP was normal.And I think as I said before, you can absolutely have a cat with cholangitis for example, who's jaundiced, has an increased ALT, which they usually will, but have AALP within the reference range.
And that would never happen with a dog.That would just never happen with a dog because in the dog the ALP is a more sensitive marker than of Cholestasis.Then it will go up before bilirubin goes up significantly.So they're very different that way.And so in cats, what we do, the enzyme that helps in cats is that gamma GT is more sensitive to Cholestasis in cats than it is in dogs.
It can be useful in dogs if you're scratching your head about that young dog, whether the ALP is an increase indicating liver disease or bone growth.So gamma GT is something to do there because it's not doesn't have a bone isoenzyme, but in cats it is more sensitive to Cholestasis than ALP.
It's much.You can't compare the numbers because it's a much lower reference range, but it will go up more, Gamma GT will go up more.The only time that's not the case in the cat is that it appears that in many cases of cats with hepatic lipidosis, which is not a very common disorder at all, despite if you read American textbooks you think it is.
But it's actually not in Australasia and in the UK and in Asia.But in those cats for I don't know why, they will often have AALP that is increased to a greater proportion proportionality than their gamma GT, which is the reverse of what happens in liver diseases.
And we've another study we've just done looked at that as well.And we definitely found that in that the group of cats that we had that had the most common was that they had cholingitis of some sort or they had shunts.But we did have some that had hepatic lipidosis and they were the ones where their ALP was higher than the gamma GT from a proportional point of view, not an absolute number because it's got a different reference range.
OK so so let me rephrase my take away from earlier.When you are considering liver disease and a cat have low expectations of ALP.If ALP is significantly up and it's a fat cat then you go Oh well you may be an hepatic lipidosis case.
Does that make sense?Well, if you've got a cat that fits the hepatic lipidosis profile, which is an overweight cat that hasn't eaten for a while.So if it fits that profiles, then yes.And for all of those situations where you're scratching your head and I might as well go sort of do a little side into bile acids, this is where you would do bile acids unless it was jaundiced, because we don't do bile acids in jaundiced animals because it doesn't tell us anything that we don't already know.
So the thing to say about bile acids is it doesn't tell you about function.People say that they're a liver function test.It's not.It is produced by the liver.So it is part of liver function.But the bile acids will increase for three reasons.One is if there's biliary obstruction either within the liver or outside of the liver in the common bile duct. 2 is if there's vascular problems, so shunting, porticable, shunting, intrapathetic, extrapathetic, partial, whatever.
And the third is if there's paranchinal disease.But, and this is what This is why I refuse to call him a function test, because albumin, for example, tests the function of the liver.So if you have an animal that's got liver disease and it has a low albumin, you know that that animal has only got 20% or less of its liver function.
With bile acids, they go up if liver function is decreased.And the reason why they go up is because what happens is that the liver can't extract the bile acid from the portal vein.So bile acids per SE don't tell you about, don't quantify the dysfunction of the liver that's present, but they're really useful for when you're scratching your head saying are these enzymes, do they mean something?
But I'll then say that you've got to be careful with bile acids as well because again, another study that we've done fairly recently showed that you still can have a proportion of both cats and dogs that have absolutely car carrying liver disease and will have normal bile acids within the reference range.
In dogs, you can have a bile acid level above the reference range.And so usually people don't really take that much notice of it until it gets to be about 40 to 60, the reference range being nought to 25 or 5 to 25 or something like that.
But we've shown absolutely that and particularly in cats.We had, I think our study, haven't got the figures right in front of me, but I think the study that we had showed that almost half of the cats that had card carrying liver disease had a fasting bile acids less than the reference range.And about a third of them, and I think maybe it was 1/4 of them had a postprandial bile acid when it was done less than the reference range.
So the take home message about bile acids is that they can be really useful in adding to your information stockpile if you like, when you're chasing liver disease, but you also can't rule out liver disease based on normal bile acids, which makes it all very frustrating.
So I have, I have a grey zone.My liver enzymes are up, but I think, well, I think you might actually be a liver disease.I can't find another reason for it.You don't have a pancreatitis, you're unwell.Let me do a biased system.If biased system comes back as raised has increased, which always I have to always have to stop and think about that.
Then we go, OK, liver function does seem no, no, not function.You just said not function, but liver seems to be a problem.If I have increased liver enzymes plus a bile acid that is raised but but normal bile acid still doesn't mean you're off the hook.
It's definitely not liver.You can't put liver aside, OK?You can't put liver aside.And you've also got to remember that there are still those diseases like Cushing's, like diabetes, like pancreatitis, who will increase both liver enzymes and bile acids.So you've got to, you know, now Cushing should be easy because it's not going to present as a sick animal.
It's got a different cluster of clinical signs.But pancreatitis is more of a challenge because obviously they can present, but you know, they've got their other challenges as well.So, So hang on.So pancreatitis can also increase bile acids.Did I understand that correctly?How does that work, Jill?
Because it's the same old thing in that it's causing anything that causes Cholestasis because it can increase bile acids.Yeah.So, you know, if you've got any change in flow to bile, the bilirubin and bile acids are excreted separately.But still, if you have any intrahepatic or extra hepatic change to bile flow, that can increase ALP and also can increase bile acids.
OK.And because the pancreas just loves hanging out with the liver when it gets inflamed and swollen, then those inflammatory mediators are going to impact on the liver and the swelling is going to impact on bile flow in the in the bile ducts.So usually the clinical sign cluster is probably a bit different.
But of course, you can have both going on.I mean, you can have both pancreatitis and liver disease.So they're the ones and that and that's the same in cats as well.OK, that's where we're hunting.We're hunting a diagnosis of liver disease.So it has its challenges.
Quick interruption to remind you about a way that we can help you in clinical practice.So one of the perks of making the clinical podcasts is that I gradually developed a long list of e-mail addresses and phone numbers for some of the world's best specialists.And every now and again I would abuse this privilege with a sneaky text message for some case help like I have this case.
What do you think?Or can you have a quick look at these breads or bloods or whatever?Priceless.Well, not priceless actually, because I've gathered some of these smart people in an online space where you can do exactly the same for about 15 bucks a month.
We've created our specialist support space with specialists in medicine, surgery, emergency and critical care, dermatology, a diabetes specialist, and an oncologist where you can send a quick SOS for those tricky cases where you need just a little bit of extra brain power.You can sign up with the link in the show description.
Then we have, and this probably comes up more, I am doing a liver profile or I'm doing liver enzymes as a check before I do something that potentially might damage the liver or might influence how I do something.
So that would be your pre anaesthetic check and it would be your pre, you know, prescribing non steroidal check for an example, you know, you might say, right, I'm doing that.Now the first thing to say about your pre anaesthetic check is that now I'm not an anaesthetist and I can't quote the figures at you, but I'm pretty sure that there's some pretty good studies out there that have shown that the mere fact of the clean path changes in a pre anaesthetic profile rarely changes the status of that anaesthesia.
You know, in the ASA grading, it rarely changes it.And that when it's a surprise, there's two possibilities.So when you have an animal that's, that seems perfectly well and they have, you know, quite a change in enzymes, then either there's been a very poor history taken, the animal's been dropped off without any really good history being taken about how it's been, etcetera, etcetera.
So it is in fact unwell.And that applies to when, you know, the argument is, Oh well, I picked up hypercalcemia and I wouldn't have picked it up.But actually when that dog was properly assessed, it turned out it wasn't particularly well and it had been drinking more water, et cetera, et cetera.Now the thing that gets quite tricky here is that we're probably more likely to do a pre anaesthetic check and or a pre non steroidal check in older animals.
And in older dogs they just very confusingly and very annoyingly can have some changes in their liver which are benign but change enzymes.So they can have vacuola hepatopathy, which really doesn't do anything much clinically if anything, but can really push up the liver enzymes, push up bile acids and they can have hepatomas that will push up the enzymes and nodular hyperplasia.
So the older dogs, we've got to be really careful because they can have benign pathology.It is pathology in their liver that doesn't influence anything.It doesn't influence how they metabolize drugs or do anything, but can have quite marked change in liver enzymes or bile acids, and we've got to be aware of that for those dogs.
Now, it doesn't mean some of those dogs turn out that, you know, that they're having a pre anaesthetic check before they're dental and they're ALP sky high that turns out they've got Cushings.But again, you know, there hasn't been a great history, but still.But sometimes, you know, they just sneak up on you and, and not saying that you can't that you don't evaluate them because you probably do evaluate them.
Although you know, you can do ultrasound on their livers and you can find some proxy looking stuff, but it's still not, it's not pathological.So they're, they're really my own dog.Years ago, buddy, being a vet's dog, absolutely shocking mouth.
And so was going to have a dental at at Sydney Uni and had some pre anesthetic bloods and his ALP was sky high.So we did a lot of those decks on him or an ACH stem at the time, I can't remember.He didn't have Cushing.Someone did a, that Gray melon did a ultrasound of his liver and it looked a bit proxy, but he was perfectly, perfectly, perfectly well.
Like perfectly well.And this was before it was recognized about vacuola, hepatopathy and nodular hyperplasia and stuff.And we and I just went, oh, you know, he's perfectly well.And also his mouth was so bad.It could easily be not so much for ALP, but well, it could be for ALPI guess, but also ALT, you know, just inflammatory mediators floating around in the body can do things.
Anyway, we went ahead and cleaned his teeth to with no problems at all.And he lived until he was 18.And of course with the anesthesia that we use these days, that was that was in the very old days where you used pedophile, but this was, you couldn't be doing that now where you would worry if you had.
But you know, if you do have an animal where it seems, well, the liver enzymes are up a bit, it doesn't mean you don't anaesthetize it.You just make sure that that liver is supported, that it's well perfused, that they're on fluids, that you maintain the blood pressure, you know, etcetera, etcetera, etcetera.
So you say up a bit.So where those bloods are up a bit, so vacuole or hepatopathy those things, what range are we gonna fall in?And again are they, is this ALP specific because I often find the old dogs with the ALP is that ALT as well?Will they both go up?
Yeah, Alt can be up as well.I would think probably, you know, it's one of those things that's so hard because to prove all of this, you have to then have biopsies from these dogs that proves what their diagnosis was.And so often they don't get biopsied if they are really well.
But ALP can be very high, ALP can be very high, ALT probably moderate.I would say I wouldn't expect it to be 10 times higher.I would it's that it's the maybe five times the reference range.But ALP can be very high, as can bile acids, as can bile acids.
And bile acids as well.So you do this and then you go, well, let me check bile acids and then they come back abnormal and then you can still go, but it might be nothing.Yeah, exactly.And then you then you, you know, you've got an ultrasound, but then just to make life really difficult, ultrasound is very good at assessing postopatic disorders.
So you know, identifying whether you've got a mucosal, whether you've got Cholecystitis, whether you've got stones there, whatever.But we have to remember with parenchymal disorders.And again we've done a recent study and there's another study at RVC that the sensitivity of ultrasound in detecting pathology in the liver parenchyma is variable depending on the type of pathology and particularly for inflammatory paranchimal disease.
In the most recent study we did in another in cats and one that was done in dogs a few years ago showed that round about 40% of cats that had card carrying biopsy proved inflammatory liver disease.And same as the dogs had ultrasounds that were read out as normal by board certified, appropriately skilled ultrasonographers.
So you, you have to be careful there as well.And sometimes with these animals, the only time you detect that liver disease is based on a biopsy.And you know, I've got a, I've got a great example of a dog, a whippet that the only, the only sign she showed was inappetant.
She didn't have vomiting, she didn't have diarrhea, she didn't have anything.She lost a bit of weight.She had absolutely normal liver enzymes.She had absolutely normal ultrasound, but a biopsy because there was nothing, there was just nothing else.A biopsy.She had neopleasure.
So but neopleasure.To be fair, usually with neopleasure of the liver, it's more obvious, but it's the one that's actually more likely to get false positives.So I have, you know, people doing ultrasounds and they'll say, well, here's a bump or here's a whatever, it must be neoplastic.
It doesn't have to be.It might be one of the benign and nomas and the other disease that causes a problem.And this is more in young dogs.So this is when young dogs get might have a pre anesthetic check and suddenly they've got an increase in liver enzymes or and then they have a bile acids done and their bile acids are sky high is dogs that have portal vein hyperplasia.
So those dogs are often breeds that are very similar to dogs that get shunts.They're usually not clinical.Occasionally they are, but usually they're not clinical.But they can have changes as well that would be sorted out by an appropriate ultrasound.
As long as it had, what's it called?I'm having a having a mental block, you know, colour things, Doppler.Doppler, yeah.So those we're going to differentiate with lack of clinical signs, but bloods are going to tell you, Yep, that this could definitely be a shunt, refer it to an ultrasonographer and they're going to say, no, not a shunt.
Portal vein hyperplasia?Never heard of that.So they're the ones where you're doing it because you want to reassure yourself there was not a problem to start with before you did something.Sometimes it's defensive and there's just no black and white rule.
With those.You've got to really look at the animal.You've got to really look at why you're doing the anaesthetic.I think the blanket, oh, the liver enzymes are up.We shouldn't do an anaesthetic is wrong.It doesn't make any sense really.The blanket, oh, let's send it home for a month with Sami or whatever is just silly in my opinion.
I mean, there's no, you know, those Sami and whether or not they do something, they're not doing anything for if that animal did have underlying liver disease that those products are not doing anything.They're just kind of supporting the liver if you like, if it is damaged.And so you've got to, you've got to make a judgement.
It's a, if you've got an animal that's got an absolutely disgusting mouth and for its welfare, it needs to have its teeth cleaned.It should have its teeth cleaned and you should take precautions with the anaesthetic.Of course, you should make sure that it's on fluids.You should make sure its blood pressure is maintained.I would avoid using non steroidals in those dogs just because they are heavily hepatically metabolized, you know, and you'd look at and you'd maybe discuss with a, with an anesthetist, a specialist anesthetist, you know, what they would recommend and how to anesthetize them.
But if we didn't anesthetize animals and have liver disease, we'd never get any biopsies, you know, which is one of the reasons why they don't get biopsy people.Oh, it's got liver disease.I can't anesthetize it.Well, you know, that's just a vicious cycle because until often with some of these animals with paranchinal disease, until you get a biopsy, you don't know what you're dealing with.
You don't know whether it needs antibiotics.Now, sometimes with cats, for example, with cholangitis, often you can get, if you aspirate the bile from the the common bile duct, you can get inflammatory cells and you can grow stuff and things like that.And that can really help sort out whether it's neutrophilic or lymphocytic.
But it's just, there is no absolute black and white answer.Some years ago, a lot of years ago, I was asked to give a lecture and I can't remember for who it might have been for WSA.And they wanted me to give a lecture on drugs and liver disease or liver disease and drugs.
And I thought, oh, this is good.This will be a good opportunity to really dive into the literature and find out what's there.Well, it didn't help at all.It still ended up you've just got to say you've got to take it each individual case.You've got to use, you know what I call, I call it a dossier of evidence.
You need a dossier of evidence.You need to accumulate evidence on your patient.You need to use common sense.You need to the history and physical exam are just as important as the, as the blood results.And then I think here's the third one.And this one is the one that I, I guess I philosophically object, object to, although I appreciate that financially it's probably makes money for practices.
But I'm doing bloods as a Wellness check there.It's not like, I mean, I've already said that, you know, the evidence that actually the anaesthetic status rarely changes as a result of bloods alone.You know, it might, it changes because of physically and findings or historical findings, but rarely as a result of bloods alone.
When you do a Wellness check, what are you doing?So the first thing to say, and I probably should have said this right at the beginning and this is what people forget, is that a reference range, if you remember back to your undergraduate days and maths is the main ±2 standard deviations in a normal population, in a world population.
So it's supposed to be, you know, a bell curve and it's the main ±2 standard deviations.So that means that 5% of normal animals will be outside the reference range anyway.So 2.5% will be below the reference range, which matters for some tests and not for others.
Doesn't matter for liver enzymes, matters for albumin for example, or calcium. 2.5% will be above the reference range.And the more tests you do in a biochemical profile, the more likely you are to find something that's out of the reference range.
So that's why we don't call it, we don't call it a normal range because for two reasons.One is you can be a normal animal and outside the reference range because you're one of that 5%.Or you can be an abnormal animal but within the reference range because you've got a shunt and your liver enzymes aren't up or you've got cirrhosis and your liver enzymes aren't up.
So that's why we call it a reference range, not a normal range, because it doesn't say that the animal's normal and it doesn't necessarily say that the animal's abnormal.So going back to the Wellness check, you go, well, what is it that you're doing now?
Always the argument is that the bloods may pick up something that's just grumbling along that hasn't been detected in this perfectly well animal.Like, perfectly well animal.And that's probably true in a tiny proportion of cases.
And liver disease can do it where Because one of the things I should have said about the sort of two to three times the reference range, one of the things that you may say is, look, I really don't think this is a problem in this animal, but you always should follow it up unless you've got a reason for it.
You know, you always should follow it up because there is the occasional dog, that maybe cat, where something's grumbling away.You know, we've got to admit they can't say to us.Do you know what?I just feel a bit weird around my upper abdomen.Or they're a Labrador, which means nothing's going to put them off their food until you know.
They're dead sick.You know, they've, they've got a real drive for food.So there's, you know, there's no doubt.But I'll, I'll use another example of another dog of mine, which was a border terrier Oscar.So he, he was 10 and he had an acute onset, acute onset of vomiting and abdominal pain.
And so I just patent recognized that oh, he's got pancreatitis and he turned out to have it was absolutely riddled with him angiosarcoma.Now he was part of, he was a control dog in one of our studies here, mitral valve study where there are dogs that you know, they're the control dogs.
So he had every six months his liver enzymes done and they were absolutely, perfectly normal.And he'd had them done probably a month before and they were absolutely normal.So that's a dog where he was cooking something.
But a Wellness check, which he was getting as part of being part of the trial, didn't pick up a thing.Not a thing.And you know, in retrospect, he probably, he got it, got a bit of decreased exercise tolerance and he'd get some funny anxiety, which was probably little bleeds happening.
And he probably, if he could have, would have said to us, my tummy feels funny, but he couldn't.Yeah, I often think if you if you're going to do Wellness screening and had the questions, how far do you go with it then?Because I was going to say a scan, an annual ultrasound or a six month, the ultrasound or an old animal would probably be at least add something to go.
So let's go look for those sort of things.But again, how far do you take it?Do you go for your annual CT, whole body CT or?And also, it increases, and it's been shown in human medicine, it increases what's called chasing the clinically inconsequential.
There's one paper where they talk about an old lady, I can't even remember why she had a scan, but it was sort of a general checkup and they discovered a nodule.And then they chase it and chase it and chase it.Now, you know, I'm not saying you shouldn't chase it, but they kept on chasing it and it turned out to be nothing.But you know, the reality is, and this is, and I think this is the problem.
If when you did a Wellness screen or even a pre GA screen and you found increased enzymes, ALT and ALP and then you had one more test you could do which would say yes or no, worry about it, you'd go, OK, fair enough.
I'll do this.You know, just like if you have a screening test when they check your poo for blood, you know, as a screening test for bowel cancer, they're not saying when you've got blood in your poo you've got bowel cancer.But it triggers, OK, now we will do proctoscopy or whatever we'll do.But the problem for the liver is that it's layers of it.
So you say, OK, my liver enzymes are up, what will I do?I'll do bile acids if they're normal and I've got a really well animal and I've got some moderately increased liver enzymes and normal bile acids, I'm probably OK.If the bile acids are up in a dog, it may not mean anything.
If they're up in a cat, it probably does.We've our studies showed far fewer false positives.Or you say I've got increased liver enzymes.I look at that.I do some bile acids, they're up a bit.I go into ultrasound and then you, you're caught in two ways because the false negatives are there.
So this dog could have paracrinal disease, but you're not picking up on ultrasound or it may not have paraclinal disease, but it's got a few funny looking proxy nodules which are perfectly benign.And then the next step is biopsy.And that's a very, and I'm not saying it shouldn't be done, but it's a very invasive step.
So you have to recognize that there's these layers, layers of assessment and at all of them, they've got false positives and false negatives.Now if they all line up and someone's got a really good analogy of of medical errors that I was listening to a lecture at Singapore Vet a couple of weeks ago that Arthur House was doing with Al Taylor.
And they have a really great analogy of Swiss cheese.And if you have slices of Swiss cheese, right, that's got holes in it.If those slices are overlapping, something going through 1 hole doesn't go through the rest of the cheese because it's whatever.But if they all line up, all the holes line up, then you've got multiple errors that then turns into a really big error.
And that's kind of like that with the liver.And it can go both ways.You know, it can be that everything's normal.So enzymes are normal, bio acids are normal, ultrasound's normal.And then most of the time that will mean there's no problem with the liver.But occasionally, occasionally.
So it's, it's frustrating.It's in the pancreas is almost no better.Although yeah, that's another story, isn't it?See these sort of episodes, on the one hand, like I always come into them thinking, well, we're going to, we're going to sort this out.Like we're going to get clarity.And then it's always a little bit of like, well, that's not going to give us clarity.
But in a way it's good because I think some of the frustration that we feel in GP practice is I, I don't get this.It's must be a problem with me.I, I'm stupid or I don't know enough, but I listen to you and I go there.It is just complicated.
It's just not a simple solution.But anyway, it's nice for me to hear it to go, well, you know, everybody struggles with it.And the, the downside is that you have to think about it.There's not a, a recipe of going, well, this is absurd.This means this, and this means this problem down.It's like, well, there's some evidence, here's some other evidence, but consider XY and Z and now you have to think about it.
It's just tricky, isn't?It if I had to give particular take home messages, I think where if you look at the danger, if you like the danger to the animal by what the vet may or may not interpret the danger of over interpreting moderate changes in liver enzymes when that animal really does need an anaesthetic to have its teeth done or to whatever it needs for its welfare.
So I think there's that over interpretation of, of moderate changes in liver enzymes, which may or may not indicate that animal's got underlying liver disease.But one of the things about underlying liver disease is you can't, you cannot predict to what degree that liver disease, even if there is liver disease there is going to affect drug metabolism.
I've just come up with a great analogy as I was giving a lecture the other day in Drugs and Cats and it came into liver disease stuff.And I've come up with a great analogy is that the enzymes, what we know is that the enzymes in the liver in relation to metabolizing drugs, they decline at different rates as the liver function declines.
And some of them declined very quickly, some of them declined steadily, and some of them just really hang on in there.And because it's autumn here in the UK, it really made me think about, it's like autumn leaves, you know, if you look at lovely pictures of a wood in autumn, there's a whole range of colours.
And the reason why it's so lovely is not just that there's a range of autumnal colours, you know, yellow, orange, red.But there's also some trees there, not just the ones that are not deciduous, where they hang on for a long time and they don't drop their leaves until quite at the end.
So that's my analogy that I'm now going to use.So even if you did have liver disease, it doesn't mean that animal can't have an anaesthetic.It does mean you need to be careful.If it really does have liver disease, you need to be careful about some drugs.And I probably would avoid non steroidals, for example.
But it doesn't mean it can't have propofol.It doesn't mean it can't have opioids or benzos.They might have a slower recovery, but it's not going to damage them.Whereas non steroidals can be, can be an issue.So that's one.The other danger I think is where ultrasonographers, the specialist ultrasonographers wouldn't say this, but the those who have developed their expertise through CPD training and things like that, but are not specialists might do it.
More likely is to say this animal doesn't have liver disease based on this liver ultrasound.And that's dangerous because we've got pretty good evidence that that is just not true, particularly in certain types of liver disease, particularly inflammatory disease, which of course is the major form of liver disease in cancer.
So that's dangerous to the patient to rule out liver disease based on based on ultrasound.It's similarly to rule out liver disease based on normal bile acids, particularly in cats, but also in dogs.So it's more the ruling out that's the worry.
And just the recognition that, and I say this all the time, is that you might have clinical signs consistent with liver disease, which of course can be anything.You might have clean path that's consistent.You're not scratching your head.You go this animal's got liver disease, this animal has compatibility disease, but you don't know what type it is.
And that's the problem.Because then to know what type it is usually means a biopsy of some sort.Yeah, yeah.So I've been screwing down my takeaways from the session and I I started with the same.My take away #1 is don't over interpret but conversely don't count on liver enzymes to tell you the full truth.
They can be your guide but they can also deceive you so don't don't trust them completely the same I do.I'm exactly that.I'm the GP ultra sonographer who's done some extra stuff, but I, I know that unless it's screaming obvious, unless I have large tumors or a, as you say, a mucosal or, or I can see well, there's a screaming pancreatitis.
I don't make a call on what I can see on a liver ultrasound.So don't trust the ultrasound to tell you the full, the whole truth and the full truth either.And probably if you really think liver, my take away from this is do more biopsies.And as you say, we don't really do that because it's a big thing and now you've got a sick animal.
But if you really want to know, then that's what you're going to have to do.Does that does that sound fair?Yeah, I think that sounds fair.And I think also just going back to what you call as an ultrasonographer, in the study that we just did on cats, what we did was we noted down what the ultrasonographer, if they had made a call, you know, if they'd said it could be AB or C, you know, most of the time they would give the range of what the pathologies could be.
And 40% of the time they were wrong.These are specialist ultrasonographers 40% of the time.And the biopsy thing, there are liver diseases which are perfectly treatable with a real prognosis.There are those that are treatable with a reasonable prognosis.There are those that are untreatable and you just can't know.
And even when you look and say, oh, look at this proxy looking liver, it must be a tumor, can be bacterial disease, it can be nodular benign tumors.It, you know, really, really challenging.I think what you, what you said, she was right in that it's not so much that there's an easy answer because there isn't.
And a lot of experienced vets will know that.They'll know, they'll go, you know, these enzymes are up, but it just doesn't fit, you know, and then they find another reason for whites unwell or whatever it is.My one other take away is vacuohilar hepatopathy.
I think I'm going to use that one a lot.Well, it could just be like a Hillary at the top with it.At least I can give it a name.Yeah, yeah, yeah.Because that is the the one tricky aspect of this that I still struggle with a little bit is that, oh, no conversation.So I do Bloods and I see Lavaine sums up and I don't think for, you know, the algorithm goes with my head and I go, I don't think it's a big issue.
But when I report blood results to owners, I, I can't leave stuff out.But I always find that really hard to say, well, we've got this and this on bloods.We have high liver enzymes.And then to try and summarize it without just saying, but I'm not that worried about it.It's to say, well, it, it could be a range of things.
I don't know.How do you discuss that with an owner when you think it's not really a big deal?I personally think that one of the things you say is that we should monitor it, that, you know, we've got a moderate increase in liver enzymes, we've got other explanations for why Fluffy is unwell.This has been a bit unexpected.
We'll still go ahead with the anaesthetic to do the teeth or whatever and we should monitor it.So we should let's check them again, you know, not the next day, although they can.So ALT in particular can come down really quickly.And I've got a great case of a dog that, for example, had episodes of vomiting, had had previous pancreatitis, had its bloods.
It's it's ALT and ALP were probably about been under 10 times reference range.It's SNAP was positive.It turned out to have an intestinal foreign body, a corncob.But basically the bloods I've got that were taken the next day after he was rehydrated showed a really dramatic decrease in ALT.
Going back to your comment that you see in emergency practice of the impact of dehydration or hypoxia or whatever on enzymes.But but I think when you've got moderately increased enzymes that you have made a clinical judgement that you think it's not part of the clinical picture or it's not going to stop you doing what you were going to do.
I think you say to the owner, we need to keep an eye on it.It may or may not be a problem.And so we need to monitor it and check them again in the month.And then if there is something underlying there, they'll usually be going up.So I think that's the conversation you have.OK, that makes so much sense.
Can I give you one more case example?At least do it recently.So this was a dog, this was a Lakeland terrier, I think, and elderly, about 13.She had had episodes of kind of bit of vomiting, bit of diarrhea, bit of bloating, et cetera, et cetera.
And she had bloods done and they were all absolutely normal.And she had an ultrasound done and the ultrasonographer, who wasn't a specialist, said, oh, there's some stuff I can see in the gallbladder and I think there's something going on there.And there's a bit of sludge and there's a bit of this, that and the other.And so they put this dog on Demarin and various things.
And anyway, this went on for probably nine months, and she had bloods done probably three times in that time.And they're absolutely normal.And then I was asked to look at the case and she still had a diagnosis of Cholecystitis or something.And I said, well, I absolutely appreciate that liver enzymes can be normal in liver disease.
There is no way that this dog has biliary disease and has had perfectly normal enzymes, no changes in albumin.It wasn't like she was getting liver failure or anything like that.They weren't going up.They weren't going down.And I said there is no way that this dog.So what had happened there was it's what's called a framing bias and also a anchoring bias where the bits that didn't fit the diagnosis that had been made were just ignored.
And she turned out to have, even though the owner had her on a hypoallergenic diet, it turned out that she was also giving her goat's milk and some other stuff as well.And she turned out to have chronic diet related entropathy.And that is the flip where you just cannot look at any of the tests in isolation, be it ultrasound, be it bloods, be it whatever you have to put it all together.
Which bit was the framing bias?They took the changes that they'd seen in the biliary tract, the gallbladder, and I can't quite remember what it was, but it was all a bit vague and a bit, there's sludge there.And they had made a diagnosis based on what their ultrasound interpretation of biliary disease of some sort.
And yet everything else didn't fit, Nothing fitted.I mean, of course, in in biliary disease, they can have intermittent vomiting, intermittent diarrhea.So that wasn't the bit that didn't fit.The bloating didn't fit.She bloated up, but the fact that she had absolutely unremarkable, absolutely unremarkable bloods on several occasions.
And while we've said yes, you can have liver disease and have normal bloods, it is really unusual and it's very unusual.And it would not happen in biliary disease.You know, you have your normal bloods, your normal enzymes in paranchinal disease when that liver is not, you know, the cells aren't just been wiped out or the tumor like in Pearl Oscar just ooze between the the cells but hadn't damaged them.
Or you've got a shunt where you've just bypassing the liver or you've got cirrhosis where you've basically wiped it out.And in the in those cirrhosis and the sort of really advanced neoplasia other than Hemangiosar, you'll have other changes.You'll start to get hyperlvinemia, blah, blah, blah.
Same with the shunt.So an anchoring bias is where you hang onto a diagnosis that you won't let go of despite evidence to the contrary.Framing bias is where you ignore the bits of your of the animal that don't fit your diagnosis.
And then confirmation bias, which is you know they all blend.But confirmation bias is where you actively seek information to confirm your assumption and ignore any information that doesn't confirm.You know, you can use social media, social issues to as an example for very easily, very easily.
And so that's an example where that animal does not have liver disease.So she was referred, she had everything done, but she did not have biliary tract disease.And so biliary disease is a whole lot easier in lots of ways than paranchinal disease.
It's paranchinal disease that really poses the challenge.So biliary is biliary disease easier because you're going to have very likely going to have changes in bloods and bile acids and it's going to be more in your face.Jill, there was magic.Thank you so, so much.
Before you disappear, I wanted to tell you about my weekly newsletter.I speak to so many interesting people and learn so many new things while making the clinical podcast.So I thought I'd create a little summary each week of the stuff that stood out for me.We call it the Vet Vault 321, and it consists of three clinical pills.
These are three things that I've taken away from making the clinical podcast episodes, my light bulb moments.Two other things.These could be quotes, links, movies, books, a podcast highlight, maybe even from my own podcast.Anything that I've come across outside of clinical vetting that I think that you might find interesting.
And then one thing to think about, which is usually something that I'm pondering this week and that I'd like you to ponder with me.If you'd like to get these in your inbox each week, then follow the newsletter link in the show description wherever you're listening.It's free and I'd like to think it's useful.OK, we'll see you next time.

Prof Jill Maddison