Good evening everybody and welcome to tonight's webinar. My name is Bruce Stevenson and I have the honour and privilege of chairing tonight's webinar, which is proudly sponsored by IEX. So a huge big thank you to IDEX for their sponsorship of tonight's webinar.

Just a little bit of housekeeping. If you have any questions during the presentation, just move your mouse over the screen. You'll see a little black control bar pops up normally at the bottom.

And there's a little Q&A box on there. Click on that, pop your questions into it and we will hold all of those over to the end and time permitting, we will go through as many as what we can. So tonight, we are very privileged to have with us Doctor Bill Saxon, and he received his DBM degree at Iowa State University in 1986.

He completed his internship at the Animal Medical centre in New York, followed by his residency at the Animal Medical centre and at the University of Pennsylvania. He is board certified by the American College of Veterinary Internal Medicine and the American College of Veterinary Emergency Medicine and Critical Care. He practised in the San Francisco area and has owned an intensive care unit in Washington DC.

Bill has published on burn injury, the acute abdomen, feline cardiomyopathy, drug toxicities, and he's also the co-author of the manual of Small Animal Emergency and Critical Care. He has been an IDEX employee since 1997 and is currently a field medical specialist and as a speaker and regional, national, and international conference appearances. Bill, welcome to the webinar vet and it's over to you.

I really appreciate the intro, Bruce and welcome everyone. Thank you for Spending some time with us. We're all, well, you guys in practise are crazy busy these days, I'm sure.

So it's nice, we really do appreciate your time. I'm gonna turn off my video for the rest cause nobody of this and come back on the Q&A cause nobody needs to be looking at me for the rest of this talk. OK.

What we're gonna cover here is, basically, How to get the most information we can from our patients and their lab work, and we're gonna focus on a patient with liver disease who will sort of be our starting point. And we don't have to talk about these because we're gonna cover them all, don't worry about that. Abigail here is gonna be our starting point and then we're gonna branch off and cover other types of cases as we get through her workup just to kind of get more.

Of a rounded discussion and kind of focused on liver disease because that's something that we see all the time, you know, in dogs and cats, as well, and there's just some information I wanted to share with you about how to deal with it. So let's go. OK, back to Abby.

So she's a seven year old spayed female lab mix, who comes in with an acute presentation. She's just not doing well. She's lethargic, she's anorectic and I'm questioning of the owner, which, you know, we always ask about.

You know, coughing, sneezing, vomiting, diarrhoea, PUPD, you know, cover the main organ systems. There is some question about whether or not she's PUPD, you know, the husband and wife can never quite agree on this. But anyway, that's what she's coming in for, basically just a sudden onset of, of clinical science.

Nothing that crazy in her history in the You know, a month or two prior to this presentation, she was treated with ciprofloxacin for pyoderma, would not be my choice. I hope they used a really high dose because it has a really poor bio ability in, in, dogs and cats, as you know. She's current on all of her vaccines.

She's good with her preventive care, appropriate diet, and no travel history. So we look at Abby on our physical exam, and she's lethargic. Her heart rate's 160 now.

You know, for a large dog, this is tachycardia, OK? If you were a young lad who was bouncing around the room and excited, I could give her 160 just from excitement. But, you know, in a dog who's not well, a large dog breed dog over 120, certainly over 140, I'm starting to get a little concerned about something going on hemodynamically.

Her temp and respiratory rate are normal. She's icteric, so right away we know we've got a big expensive problem on our hands. And we're gonna have to have a really lengthy chat with the owner, so she's yellow, and now we have a serious issue on our hands.

We're gonna have to deal with. She's a little bit tacky on her mucous membrane, suggesting some mild dehydration, not surprising given her anorexia. Her capillary refill time is normal.

She's got a pretty good body condition score and surprisingly nothing really significant on her chest or auscultation or her abdominal palpation. OK, so, you know this, it's great that Abigail had a body condition score done, but I just wanna make sure we all are aware that we should also be doing. Muscle condition score, in addition to the body condition score on all of our patients, both canine and feline this first came out in cats a few years back and then they added dogs a year or so after that, but this is now recommended by Wasava World Small Animal Ven Association and AHA and other groups to include in every physical along with the body condition score, because you can have obesity.

You know, a high body condition score and have poor muscle condition. So, muscle condition is really what matters when we're talking about calculating drug dosages, nutritional requirements, evaluating lab parameters because creatinine, for example, which is a muscle breakdown product, can be affected by changes in muscle mass either increases if you're a heavily muscled dog like a roti or a greyhound or More commonly with a decrease in muscle mass, which would lower the creatinines and think about those skinny older cats with chronic kidney disease or hyperthyroidism. So the muscle condition score, just want to push, you know, make a point about having this be part of every physical if we can do that.

OK. So Abigail then, when we look at her history and her physical make a problem list, and I always like to put these as a critical list like we put these in. The a decreasing order of severity, right?

We want to fix the most serious problem. First, we have a patient left to deal with the other problems and even though Itaru is are like gonna be what we kinda hang our differential diagnosis on, her most significant problem is her tachycardia, which indicates she's either hypovolemic, painful, or perhaps dehydrated or a combination of all those. So you always want to stabilise the cardiovascular system and the respiratory system before anything else if your patient presents with those signs.

Irus is our big concern here and then the other problems you can see are just in, you know, decreasing order of severity. So, when we're making a differential diagnosis, we always, I always recommend pick the most unusual abnormality, OK, because that's narrows the differential list the most and it gets you efficiently toward the right further diagnostic path. So let's say you have Abigail, for sure, it's Itaru.

That is exactly what we're gonna hone in on. If we made a differential diagnosis list, for example, for anorexia, we would be here for 2 days, right? But Icarus is pretty straightforward.

This would be the same thing if we had, say, a dog or a cat with hypercalcemia. That's unusual, and that has a manageable, I short differential list, and that's really going to make it more efficient in the workup. So whenever we see it, we want to think about prehepatic, intrahepatic, and post-hepatic causes.

And it's pretty easy to eliminate prehepatic icterus. You just look for anaemia because prepatic icterus is due to hemolysis, whether that's immune mediated or, you know, anything that's causing red cell rupture, you know, parasites like hemotrophic mycoplasma, heavy metal toxicities, and then you can have these inherited RBC enzyme deficiencies in say springer spaniels. And other breeds.

And then if you've got sort of your diabetic, classic diabetic who's hypophosphateemic, that can also cause hemolysis. So we look at the CBC and if there's no anaemia, we can exclude preapatois. OK.

Post-topatic icteris is the next easiest thing to exclude. You just look at the liver enzymes and we'll be doing this, but, you know, if you have a postopathic condition. Biliary duct, gallbladder, you know, proximal intestinal neoplasia, pancreatitis.

At least acutely, which Abigail is an acute patient, you're gonna see primarily those cholestatic enzymes elevated, OK? So if you have an animal that's icteric and you have a high bilirubin and you have an ahos and a GGT that are markedly elevated, but your ALT is not, that's post paddock. Intrapado, this is the one that is the least preferred because it has, it's the most vague, it has the highest number of potential ruleouts, and you identify this by having ruled out pre.

And ruled out post and like the call mark here with intropatic is you have high levels of both leakage enzymes and cholestatic enzymes. So that's what we're gonna do with Abigail. We're gonna work through her minimum database CDC chem panel urinalysis to try to determine what is the cause of her icterus and see what else we can find.

Along the way. Now I will tell you that Abigail's work up here was complete, but the information we have is kind of ragtag. So her CBC vet just kind of wrote normal platelet count 62,000.

So the only abnormality on Abigail's CBC was for sort of moderate to marked thrombocytopenia. This is just a look at what a complete CBC would look like. Including the red cells, white cells, and platelets, and we're just going to cover some of the key things here that will help us with not only some a case like Abigail, but all of our other animals that we look at CBC's on.

So, I'm just gonna point out what I use to kind of guide me when I look at the red cell parameters. So if we have a trauma patient present, OK, we, we never know. Dog gets hit by a car, comes in looking pretty stable.

Great. Is he just a stable hit by car? No internal injuries, a couple of hours of hospitalisation, maybe some IV fluids.

Good to go, or is there something lurking like a splenic laceration that might cause hemo peritoneum and complicate things. What I always look at when I get my initial quick assessment test, which always in a trauma patient include a pack cell volume and total solids is Look at the total solids, OK? If I have an acute trauma patient who's got a normal PCV but total solids are low, like 5.5 or 5.4, 5.2, that to me is a sign of potential internal haemorrhage.

If I'm not Any external cause. Why is that? Well, when you bleed, both the red cells and the proteins in the blood, the total solids, decrease.

But you have splendid contraction if you're stressed and that can cause the PCV to rise into the normal range. So you look at that. Total solids along with your PCV and if it's low, you gotta watch that dog for evidence of anaemia as you give them fluid.

So 2 hours later after you give aggressive fluid therapy to that dog who comes in. Normal PCV low total solids, you may find the PCV after fluid shifts and rehydration is now like 22, like super low and the solids even lower. So anyway, that's a clue for your trauma patients.

Now, when we're looking at any kind of patient with anaemia, all we need to do to classify it as regenerative or non-regenerative, and that's the first thing we wanna do is look at the absolute reticulocyte count. The red blood cell indices that we're kind of taught can help us determine if we have regeneration or not, often don't, OK? And only about 10% of the cases where you see those anaemic animals, when you see those classic.

Indexy changes, the increase in the MCV mean corpuscular volume and a decrease in the MCHC mean corpuscular haemoglobin concentration. It's all about the absolute reticulocyte count and here's an example of that. So I don't think anybody would argue that this patient is profoundly anaemic.

We have a hematocrit of 16. By the way, The definition of anaemia for the World Health organisation is really a low haemoglobin concentration. We focus on the haemoglobin because that's what matters.

That's what carries oxygen. You can think of the red cells as just bags that carry haemoglobin, and that's why when we get a CBC they just look at our haemoglobin. So, this animal has a marked anaemia.

All of her red cell parameters are count inadequate and most importantly, the haemoglobin are low and look at her, her Reticulocyte count is sky high, 413,000. There's no doubt in anybody's mind that this is a regenerative anaemia, yet her indices are normal. All to say focus on the ret count PS.

You can also look at the magnitude of the reticulocyte count to get some idea of what's causing the regeneration. So the highest reticulocyte counts above, say 200,000, are seen with hemolytic disease, OK? Immune hemolytic anaemia, for example.

Lower reticulocyte counts, certainly you could still have immune mediated hemolytic anaemia, but that would be seen also with haemorrhage. So, below 200,000 rets that could be haemorrhage or hemolysis, the two causes of regenerative anemias, above 200,000, you're thinking more of immune mediated hemolytic anaemia. OK.

Look at the count. In the past, we only got retake counts on the lab results when there was an anaemia present because we thought that the only reason you needed a retake count was to help classify the anaemia, but that's not true. All right, we now know that it's important to have reticular cys whenever you get a CBC because they're elevated in a fairly significant percentage of dogs that aren't anaemic.

Now, depending on what kind of practise you are in, if you're seeing mostly stable patients, you'll have a 2 to 4% incidence of this. If you see more critical patients, up to a 10% incidence of reticular cytosis without anaemia. And what causes this?

Two basic Pathophysiologies, one is just physiologic where you have an excited animal whose spleen contracts, those red cells being stored there that are maturing there into the bloodstream, and the reticulocytes also are in the spleen because they are the immature forms that turn into red, mature red cells there. So splenic contraction will increase the reticulocyte count and possibly the red cell count, right? So healthy animal could just be physiologic.

If it's a young puppy, for example, you, you still could have something causing anaemia that's mild enough where there's blood loss, excuse me, where there's mild enough blood loss, say a mild hookworm infestation. What, so there's no anaemia because the bone marrow is kicking out more red cells can keep up with that mild blood loss, hence the reticular cytosis. So even though that happy healthy puppy could just have splenic contraction causing that tick count to increase, make sure you deworm and make sure there's no hookworms too because there might be some mild bleeding.

That the bone marrow could keep up with by producing increased reticulocytes, OK? In older animals though, when you see this reticular cytosis without anaemia, then you've got a problem with an organ where the reticular cytes live. And I'm always thinking first and foremost about the spleen, and if we have retics on all CBCs, we're gonna find these splenic masses.

Before they rupture. OK. So that's we'd much rather find this now and be able to schedule an elective procedure on a stable patient than have this explode, rupture and have the dog come in collapsed with hemoperitoneum and that whole emergency that we're kind of classically trained to deal with.

So super helpful to have her ticks on all CBCs. Because you might identify in a non-anemic animal with a higher tick count, a problem either with mild blood loss from parasites, fleas, you know, earlier mild hetic anaemia or damage to liver, spleen, or bone marrow. Super helpful.

And then we have, 01 other thing, just as with reticulocyte counts, you can use the magnitude with an anaemic patient with regeneration, you know, to determine whether you've got hemolysis, super high retic count, or haemorrhage maybe a lower retic count. Similarly, in animals that are not anaemic, you can use the degree. Of increase in the reticulocyte count to help you determine whether you have a physiologic change, not to worry, or something more bothersome, like a splenic tumour.

OK. So, reticulocyte counts up to about 120 to 130,000, you know, consistent with excitement, splenic contraction. Above that, 150, 180, that animal needs to be imaged to see if it has an issue with splenic or hepatic neoplasia.

OK, new parameter on the CBC would be the reticulocy haemoglobin, and this is an early marker of iron deficiency. It goes down when you have decreased iron availability in the bone marrow. And this is interesting because we were also taught that red cell indices could help identify, say, iron deficient anaemia, and they do eventually the MCD and the MCHC will decrease.

But those are mean values, average values of size and haemoglobin concentration in the red cells. There's 35 trillion of them in the circulation, 25 trillion of them in the circulation, and so it takes a while for the mean to change, weeks to months, whereas anything associated with the reticulocytes gives you sort of a real-time what's happening at the bone marrow now assessment because reticulocytes only circulate in the blood for 2 to 3 days versus say 100 days for a mature red cell in a dog. So, iron is required for haemoglobin production in the bone marrow, and it's the bone marrow macrophages that sort of store the iron and release it to the developing red cells.

OK? There are two reasons why you might have a decrease in reticulocyte haemoglobin. One is you've got external blood loss, so there's just no iron in the body.

Most of the Iron in the bodies in blood. So if you have external bleeding, you will have a true iron deficiency, less iron present. And on the left, you see, there's a couple of bone marrow macrophages that have no iron in them, and so those surrounding developing red cells, not getting any iron.

The other cause of the decrease retic haemoglobin is inflammation, where it's not that we don't have enough iron, there's iron there. It's just trapped and sequestered in the macrophages and so that would be a central macrophage there and those green black clouds are just precipitated haemoglobin not being released. And when this occurs, There can be a decrease in the the verticulocyte haemoglobin.

So inflammation causes release of those cytokines, and they cause the liver to produce something called hepyin, and that hepyin is what causes the haemoglobin to be the iron to be trapped in the macrophages in the bone marrow. So what do we do as clinicians? We look first, if we have a decrease inmatic haemoglobin and that's the abnormality, we don't care if it's increased.

If it's decreased, we have decreased iron availability for haemoglobin production in the bone marrow. And that can be due to external blood loss. So first we rule out external bleeding from a GI issue or a bladder tumour, severe internal or external parasites.

All these remove blood from the body, take iron with it, and can drop the retic haemoglobin, OK? Luckily, fortunately, external bleeding is less common than inflammation as a cause of decreased iron decreased iron availability and a decreased haemoglobin. So, If we have no external bleeding, we always evaluate for that first because it's way more severe.

We would have to address that right away. If we find no evidence of external bleeding, then by default, we have inflammation and if we don't know which kind. It just tells us we need to go looking for a source of systemic inflammation in our patients.

So pay attention to the retic haemoglobin. When it's low, something's affecting iron availability for haemoglobin production in the reticular cys, rule out external blood loss. If you don't find it, find a source of inflammation.

OK. So then moving from the red cell picture to the white cells, remember, really important to have At least a 5-part differential, so neutrophils, lymphocytes, monocytes, basophils, and neosinophils. If you can get it a six-part differential to include band neutrophils, immature neutrophils at present, super important to have a differential because we can't use the total number.

Of white cells and neutrophils to determine if our patients have inflammation or infection because half of them with severe inflammation or infection have normal total white cell and neutrophil counts, and some of the more severe patients actually have decreased counts if you have an early, say, septic process. So what we really want to do when we're trying to assess for inflammation or infection is identify immature band neutrophils or neutrophils that have a toxic change, OK? The count doesn't matter, band neutrophils and toxic change in neutrophils does matter.

And if those are present, mortality doubles in patients with inflammation or infection. So really important to be able to identify those. If we see a sick animal that has a normal lymphocyte count, we would expect a sick patient to have a lymphoenia from the stress lephogram that's mediated by cortisol.

Disease causes stress. Cortisol levels increase. Those increased cortisol levels drop the lymphocyte count causing lympheenia.

That's sort of the hallmark characteristic change of the stress leukogram. You might also see other changes in the stress leukogram like a neutrophilia, monocytosis, but it's the lympopenia that characterises stress leukogram. If you have a sick animal that doesn't have a lympopenia, what should you be thinking about?

Well, where's the cortisol in that animal? Maybe it's Addisonian. So I always look at the lymphocyte count, and even if it's in the normal range, it shouldn't be in a sick patient.

It shouldn't be. Above, it shouldn't be a sick animal should not have a lymphocyte count above 1500. OK, so normal in a sick patient, that can be consistent with stress.

It doesn't have to be below normal, but above 1500 in a sick animal, I worry about Addison's disease and I would consider getting a resting cortisol, OK? So, we've talked about sort of the inflammatory leukogram, which is characterised by the left shifter toxic change, the stress leukogram, which is characterised by the lympopenia. I always like to mention that third type of leukogram that we often forget, and that's physiologic leukogram, and that one is just an excited animal, epinephrine level goes up and that causes lymphocytosis.

So, A lymphocytosis in a healthy animal may be a normal finding, OK, just due to excitement. It's really helpful to have had previous lab work and have trended the values in the patient over time because if you look back and, and notice, yeah, that animal always has a mild lymphocytosis, that's fine. If, however, you see looking back that you have a new finding of lymphocytosis or progressively increasing lymphocyte count.

They might be concerned about some sort of chronic inflammatory disease. And remember too that the neutrophil count can be up to 2 times normal just due to stress. So finding say if you're upper upper normal for neutrophils is 12,000, up to 24,000 could simply be due to stress.

So we don't want to put animals on antibiotics who have high neutrophil counts, say 16,000, 18,000. And use that as the sole justification for using antibiotics, right? We would need to, before we gave antibiotics to that animal, determine if there were signs of inflammation looking at left shifter toxic change.

By the way, it's been reported that dogs can have a stress leukogram that will drive the neutrophil count up to 35,000. Now, that's kind of crazy high in my book, and I never want it to be above 30. If it's above 30,000, I'm thinking about inflammation or infection regardless of what else I'm seeing, but up to 2.

Normal may just be stress. We don't want to pull the trigger too quickly to give antibiotics based solely on an elevated neutrophil count. OK, back to Abigail.

OK, so we're finally back to our victoric dog, and this is her biochemical profile, and we're not surprised to see her bilirubin's elevated. Because she's yellow. And when you have clinical jaundice, you know, your jaundice, you know your total bilirubin is above 1.5 or 2.

You can't really detect bilirubin clinically when it's below that value, but we know from the fact that Abigail is yellow, that your bilirubin is up there and it is 18.4. And remember, our job here is to determine if she's pre.

Hepatic, intrahepatic, or post-hepatic as a cause of her bilirubin, we know from her CBC being normal in terms of a red count, that it's not preapatic. We look at her liver enzymes and we see that both her leakage enzymes, ALT and cholestatic enzymes are sky high, so she is intrahepatic. Now this is Kind of a double-edged sword.

It's bad news because these guys are often severe, they might be the sickest. They're the hardest to diagnose because there are so many possible rule outs, and therefore, sometimes we can't really even do specific therapy because we're just having to support them without a diagnosis or at least until we get one. The good news though is that these guys don't give up on them because as bad as these initial blood values look, if we do a really appropriate aggressive therapy and supportive care for Abigail, regardless of what's causing her liver disease, she has a chance of a complete recovery, OK?

Now, what I also like to remind people of this it's kind of helpful to look at the EPOS and GGT together because if they Show certain patterns they can help us localise our liver problem. And it has to do with where these enzymes are primarily produced in the liver. The alkaline phosphatase is produced by the patocytes within the parenchyma that line those bileannuliuli, OK.

And the GGT on the other hand, is primarily produced by the epithelial cells lining the bile duct. So if you have an animal that has GDT that is much more elevated than the alkaline phosphatase, where is the problem? Biliary tree, and that's super helpful to know because sometimes those are surgical diseases if they're obstructive diseases.

So let's take an example of that. This is a 10 year old Maltese who comes in with vague cranial abdominal issues, pain, discomfort, and we get his chem panel and we see that Paulie has elevations in both the outhos and GGT. By the way, this is also a patient who's icorate and CBC normal, so we've ruled out preapatic, and then this animal, you know, how would we classify this icterus?

We probably could see it because it's 1.9. It'd be subtle, wouldn't be as bright yellow as Abigail.

This is clinical jaundice, but is it intrahepatic or postopathic? This is a posterpatic. Iter poster child look of a postopathic icterate patient because the leakage enzymes ALT high, a little bit high there, but it's the, the cholestatic enzymes that really grab our attention, OK?

And the GGT here relative to its normal range is much higher than the Alphos. So the alkhos 3 times its normal range, the GGT about 11 or 12 times above its normal range. So this puts us in that we're concerned now about a problem in the biliary tree, and we're gonna image these dogs.

But the point here is if you find this pattern where the it's the. CGT that's primarily elevated, image these animals with an abdominal ultrasound to make sure they don't have surgical disease because we don't want the bile biliary tract to rupture and cause bile peritonitis. That's never fun.

So we promptly ultrasounded Polly's abdomen and identified a gallbladder and mucous seal with that classic steator or cut Tro pattern, and here, this is a surgical patient if The owners can do it. We can treat these stable patients with gallbladder mucous cells that have no evidence of per gallbladder fluid indicating mild leakage with activeol and maybe antibiotics and careful monitoring, but ideally get these out. OK.

So use the GTT and the elk hos together to help localise. In cats, you know, there's a condition where we'll see elevated elk hos and the normal GGT. When we see that pattern in the cat, what does that cat have?

Lipidosis, hepatic lipiddosis, and knowing where these enzymes come from, explains that. So with lippidosis, the hepatocytes are swollen with fat. Which compresses those bolican liuli and induce a phosp production.

Nothing's happening in the biliary tree in those cats unless they have a separate issue, right? So there would be no reason that simple fat accumulation in the liver would affect the epithelial cells of the bile duct, right? So when you see highho normal GGT in the cat.

It's not hepatoclipidosis, at least that's one of its problems. Let's look at Abigail's leakage GDT and Alc foss. They're both elevated to about the same degree.

So here she just has broad. Cholestasis, we can't determine whether it's permeal or biliary tree. It's all over the place, basically.

So she's got this pan-hepatic problem as we can see here with her intrahepaticist. Urinalysis, we never want to leave that out of any patients workup, certainly the sick ones and, you know, obviously when she comes in, we would expect her to have a lot of bilirubin in her urine, right? It's normal for male dogs only.

To have bilirubin in their urine. OK. Female dogs and cats should not have bilirubin in their urine, and we certainly would expect an icic animal to have a lot of bilirubin in the urine because bilirubin Nuria precedes bilirubinemia.

So by the time we see increased bilirubin in the blood, there is bilirubin in the urine. I just wanted to show you where. Series of your analysis here just to kind of give you a heads up.

So when she comes in, obviously she's critical in it, but I just wanted to say, remember how we mentioned that in spite of that, with her introstatic interest, those animals can do better. Months later, she's doing better, she's normalised. So there's this good news is we have to worry about Abe.

I don't want to worry about her the whole time. She's gonna do fine because we know how to deal with her. So.

What are her likely rule outs? Let's just run the list here. So something that's causing dramatic intrapaicists running the list here, I think the only thing that doesn't make sense is congenital portalymic shunt.

I think Abigail could have any of these other problems, but not congenital portal systemic shunt. Why is that? In those animals, it's not because she's 7, you know, it's, you know, portal systemsmic shunts don't have to present.

When our animals are young, right? It depends on the degree of shunting and other factors, but they can present as adults up to 10 years of age sometimes as first presentation from problems with the portal systemic shunt. What makes this not a portal systemic shunt is that she's icric and she has elevated liver enzymes and those portal systemic shunts, dogs usually.

They are not icic, and their enzymes are usually normal. What you might find obviously on the panel would be indications of decreased liver function. So the albumen and the BUN might be low, glucose might be low, cholesterol might be low, but they don't have elevated liver enzymes.

So we are now going to have to sort of proceed with determining which of these possible causes of her inopathic icterus we're dealing with. And now is where we're gonna kind of, kinda cover some disease categories that will help you with all of your patients that present with liver disease or otherwise, right? So obviously, leptospirosis, just a, a quick update here, it's everywhere.

Let's just admit it. Nobody's immune from having to consider leptospirosis in a given practise area anymore. But what I think it is important to remember is we all Know that we should be thinking about lepto in a patient like Abigail, and especially a patient that has liver and kidney issues, but there are atypical forms of leptospirosis, which we should have a high index of suspicion for the disease when we see animals that have just respiratory signs, OK, or just hepatic signs without kidney involvement or even healthy animals that are just PUPD.

That may be the only abnormality in a lepto patient. Nothing going on in the panel or the CBC clinically, good appetite, active, just PUPD and that's because lepto can affect. ADH action in the kidney and can cause a nephrogenic diabetes incipidus with varying specific gravities including hypotheuric ones.

So here is a big plug to consider atypical lepto when you're working up a dog with hyposheuria, specific gravity less than 1007. All right. We know that the rule out list is pretty short for hypothinuric dogs.

It's Cushing's, pyelonephritis, diabetes incipidus, psychogenic polydipsia, OK. Add lepto to the list, especially in a non-vaccinated dog. Dogs should be vaccinated for lepto.

It's not considered a core vaccine in the United States yet, but it's highly recommended to use those, you know, quadrivalent forerovar vaccines because they are really effective. To diagnose leptospirosis, we have serology or PCR testing. PCR testing is not affected by vaccines.

Serology is, so in a vaccinated animal, we want to do PCR for lepto on urine and hold blood. To treat lepto, it's way easier than it used to be. We used to have to give 3 weeks of the penicillin and then 3 to 6 weeks of a tetracycline.

Now it's just give them doxycycline at the tick dose, 10 mg per gig per day for 14 days, you're good to go. OK? If the animal's too sick to get oral medication on presentation, and you don't have injectable.

Give ampicillin or give a penicillin. As soon as the dog is taking orals, get him on doxy and count that as day one, treat all dogs in the house, even if they're asymptomatic because they can shed lepto without signs. Cats do get lepto, can shed lepto.

They don't often get sick from lepto. So it's kind of Clinicians preference, whether or not to treat cats, I probably would not. They're not as likely to, they're not as likely to get exposed by drinking dog urine or being exposed that way.

They're more fastidious, OK? But treat all household dogs, . And there might be lifelong immunity to lepto.

There's not been a reported case of a dog getting lepto twice. However, nobody, never say never, but you don't have to vaccinate a dog quickly after recovery from lepto. You can wait 1 year from recovery and then start vaccinating again.

The vaccine is good for 15 months, so be it yearly, the the newer for Seroar vaccines. OK. That mushroom toxicity is another thing on Abigail's differential list, and I wanted to give you an update about that as well.

This is horrible. Nobody likes to see this. It happens when we're have wet weather, so it can be a seasonal spring and fall sort of.

Incidents. We know that the, the mushrooms that have Amanitotoxins are the most toxic, and it doesn't take much for dog or cat to ingest a potentially lethal dose, and the organs affected primarily are liver, GI tract, and kidney because this these amineins, these toxins basically cause cell death. They inhibit RNA function.

OK. This is garter prognosis still. I think we might be able to improve on that with a couple of new, new tools at our disposition.

One of them actually is that there is now a test for it, a urine test for the most toxic principle in mushrooms, which is the amineotoxins, right? And, and so. There's the website there.

This is something that we can do to sort of make a diagnosis and if we have a positive result, institute some pretty aggressive therapy, and we'll talk about that in a little while. But the The clue clinically for us that we, our dog with severe liver disease might have a mushroom toxicity is the combination of those crazy liver enzymes that Abigail has and hypoglycemia. OK.

So if you see that combo, put mushroom toxicity higher on the list and consider maybe running that test for the toxin, OK? Now, we're all seeing more of this. We might not know we're seeing it, but we're seeing copper associated hepatopathy.

The main reason is because of a change in commercial dog foods that happened in the late 90s, where they changed to a more bioavailable form of copper, more absorbable form, so the amount of copper in the diet might not have changed, but the absorption in the dogs have changed. And copper can accumulate for a couple of reasons. It can be associated with just a hereditary genetic defect that impairs copper elimination or it can accumulate secondary to inflammatory diseases, and this is going to be exacerbated by these more bioavailable forms of copper in current diets.

Labradors are the poster child of this problem, and the clue here is if you see especially a Labrador. With an increase in in ALT and this is, this is kind of that scenario where often we've got asymptomatic animals, older dogs that come in with elevated liver enzymes, and we're not sure how aggressive to be with those dogs. Do we simply monitor?

Do we do bile acids? Do we do an ultrasound? Do we get a biopsy?

It's kind of hard in an individual patient to know what to do. So it's helpful to know signs of OK, this is a problem we need to pursue. And when it comes to this copper associated hepatopathy, the clue to pursue it is a lab poster child with an ALT elevation, especially if it's increasing.

Again, really helpful to have baseline parameters established for all of our patients when they're young and healthy so we can trend them over time. And if we've got a lab whose ALT is either newly elevated or progressively increased and has glucose urea. With a normal blood glucose, that is a real red flag for copper associated hepatopathy.

And why would you have glucose urea with copper associated hepatopathy because copper is toxic basically to the proximal tubular cells and it impairs glucose reabsorption and can cause actually glucose leakage as well. So, the clue that you're dealing with copper hepatopathy is Primarily ALT increase and it may be mild with glucose and a normal blood glucose. Work those dogs up if you can by getting copper qualification.

The trigger for treating these guys used to be above 1000 and now it's above 600 only, because we know if we intervene early, we can actually have a full recovery, all right, if they're related to diet or liver disease and not the the hereditary copper storage issues that say Bedlington's have. Treat them all with diet, minimising copper content in diet, and you can see a couple of options there, and then chelate them with penicillamine, and this is lifelong in dogs that have hereditary issues with copper excretion, 4 to 6 months in in other breeds with sort of inflammatory conditions causing secondary cop accumulation. It's a 10 to 15 MB per kg BID dose.

Give it on an empty stomach if you can. If side effects occur, which they're not uncommon, a couple of options would be just to decrease the dose and ramp up again if you can, divide into smaller doses, or you can give with a small amount of food, it won't completely eliminate absorption. And then, in addition to diet and chelation with the penicillamine.

Your typical hepatic support your antioxidant, vitamins E, Sami, and, you know, psilocybin basically. OK, so remember though, labs, ALT with normal glycemic glucosea think copper, OK, can cause aanconi-like syndrome and cause glucose to occur in the urine. All right.

So those are some little side streets to go down just to, you know, help us with other types of patients that could present with liver pathology, OK? All right, so now we've got Abigail again, and we've got to rule out the conditions we suspect she has and consider additional diagnostics. So I think we should absolutely screen her for lepto.

She's a dog, right? Coagulation panel, if we're thinking about biopsying her for sure. If she were anaemic or we found that she had excessive bleeding on vene puncture 100% because we know that patients with severe liver disease can develop coagulopathy, that's where most coagulation factors are performed, are formed.

Bbile acids, we are not doing bile acids in Abigail because she's icteric. We don't run bile acids on icic patients because basically, The bile acids and bilirubin kind of share an expiratory pathway. So if the bile acids are increased, there's no way we can use that.

If the bilirubin is increased, we can't use the bile acids to determine anything about function. They may just be increased in the blood because of regurgitation and not not helping us identify if the liver is capable of re uptaking those bile acids with enteropathic circulation. So don't do bile acids in curate patients.

If Abigail were neurologic, obtunded, and we worried about hepatoencephalopathy, we would absolutely consider resting ammonia level and to work her up, does she have a mass? Are we gonna need to get, you know, biopsies or aspirs? We're absolutely gonna want to get an ultrasound on her and consider tissue if she's not responding to our treatment.

So Abigail has a series of lepto titers run and they're all negative. Does this rule out lepto? No, because she's an acute presentation, right?

So she may not have had time for to serial convert. In this case, Abigail came in actually before PCR was available. So in this case, we would treat her for lepto if we were worried that she had it.

And then we would do convalescent titers 2 weeks later and look for that 4-fold increase to determine retrospectively, if she had acute lepto. So, If you can't get PCR then, and your initial titers for infectious disease are negative in an acute patient, 2 to 3 week convalescent titers, look for a 4-fold increase, treat in the meantime, treatment will not affect the convalescent titers. This is not Abigail's PCR but I just wanted to show you what they look like.

So PCR is done on blood and urine, and another, another advantage of PCR testing for lepto is. Leptose circulates in the blood for the 1st 5 to 7 days after exposure, and then it's eliminated in the urine. So we can get a diagnosis of lepto before serro conversion during that first week of therapy using PCR.

So here we have positive on blood and urine. So she's an acute patient, probably at that weak threshold where she still has some circulating organisms and is starting to shed in the urine. Try to get both blood and urine to be able to catch those acute patients.

Now we're not doing bile acids in Abigail, right, cause she's Iri. They're not helpful in icic patients, but I did want to point out that according to Doctor Sharon centre, who's sort of our hepatic guru, and she said this multiple times and it is in print in the proceedings of the ACCVM Congress in 2017, fasting for bile acids is not necessary, OK? No, no problem fasting, but fasting is not necessary, and those caps.

Those bold are not mine. That's exactly how it appears in proceedings. She had bolded those letters.

There is no need to fast for paired bile acids. We want to get paired bile acids when we run it pre and to our post samples, but fasting is not necessary. Why that's helpful is, it's possible to run bile acids in the clinic now, and that is really helpful for us because Especially without having to fast, if we get a patient in for lab work, whether it's sick or for pre-anesthetic, or for wellness testing and we identify something on the chemistry panel that would want us to consider bile acids.

In the past, the animal and the client would have to come back another time after being fasted to get bile acids. Not anymore. You can just get those bile acids while they're still there, one and done.

Or another advantage to not having to fast is you have an animal that comes and say an 8 week old say teacup poodle that's seizuring and hypoglycemic, and you want to rule out portal systemic shunt, which can cause seizures and hypoglycemia. You don't want to fast that animal who's already hypoglycemic to get para bile acids, you don't have to, OK? .

So that animal that comes in again, neurologic, that you're concerned about liver function, bile acids are fine to do in those patients. Paired bile acids are fine. They will give you a good assessment of liver function as the potential cause of those neurologic signs.

If you are able to run an ammonia level in the clinic, and that can be done on the catalyst machine. That is actually a better test to run, say, undid young animal comes in, you're worried about portosystemic shunt. If it's me, I'm getting an in-house ammonia level because that's more sensitive of fasting ammonia is more sensitive than resting bile acids at identifying portsystemic shunts.

For bile acids, you need to do that 0 and 2 hour post, the pre might be normal in a shunt animal. It's the post elevation that you're looking for, and you don't want to wait 2 hours necessarily, and if you have a severely neurologic patient, they might not it might not be safe to feed them. So think about ammonia levels, resting, if you can run them in the clinic, when you have an animal with liver signs and neurologic disease, especially if they're icteric when you can't run bile acids anyway.

OK, so back to Abgail, we're definitely gonna image your liver. Does she have anything specific? We're trying to find a specific.

Diagnosis that we can aim our therapy at and as usual with the picture that we see in Abigail's blood work, the liver is just generally enlarged, homogeneously hyperchoic. Nothing to really hang our hats on there. We definitely want to think about getting a piece of that liver and before we do, we need to evaluate her for bleeding risk.

And so we do PT and PTT as a coagulation assessment on Abigail and both are Sky high. We don't get an endpoint. So let's look at coagulation panels and and and sort of just review how they can help us.

There's only two conditions that I know of that cause both the PT and PTT to never clot, those sky-high values, and that's either what Abigail has likely which is acute severe hepatic necrosis or amicoagonodenocy toxicity. Those are the two you have to be thinking of, OK? Now And they can both cause eventually both PT and PTT to be elevated.

Let's look at the results, these hypotheticals that I have on the slide here. We have an animal who comes in with a normal prothrombin time and an abnormal partial thromboplast in time. Could that possibly possibly be an anticoagulantodenoide?

The answer is no, and the reason is with anticoagulant adenocide, the PT always goes up first because it assesses factor 7, which has the shortest half-life of the factors that are affected by anticoagulant adenoides. So, You always see the PT elevate first with anticoagulantrodenoide. So if you see that the PTT elevated without a PT increase, it's liver disease, it's a factor abnormality, say, haemophilia A or B, it is not.

So this is, let's say this is a puppy, and it's got some bleeding, excessive bleeding, and you run your coags and the owners swore that the dog could not have gotten into warfarin toxicity and a cragnant adenocy toxicity. You're like, hmm, sometimes they do and we don't know it. Let's hope it's that because we can treat that, right?

This would tell you, no, now we have to assess this guy for haemophilia and submit factor analysis. OK. So, can we use the results of Abigail's abnormal coaggs to predict bleeding and the answer is not really, OK, because it's very complicated.

With liver disease, both procoagulants and anticoagulants are affected and the balance determines whether they're gonna bleed or not. You can't just look at the PT and PTT. Probably better to assess coagulation overall, doing something like thromboelastography that we mostly can't do in practise.

So what do we do? If we need to get a biopsy on Abigail or or a fine needle aspirate, and we have those scary COAG times, we're going to give her, we're gonna do the procedure. If we think we're gonna get, you know, we're gonna weigh the risk-benefit ratio.

If we think the benefit outweighs the risk, we're going for it. And we're just gonna monitor really carefully for bleeding after. There's no way to predict whether she will or not.

She might not bleed, but I'm certainly gonna have blood products on hand. I might not give them prior to surgery because there, that hasn't been shown either and our patients are on the human side to prevent bleeding again because it may not be just the lack of clotting factors, but I'm gonna have blood on hand to give if I develop anaemia post-procedure, I'm gonna give her vitamin K cause she's totally static and bile is not being delivered probably to the intestines, therefore not absorbing fat soluble vitamins. We're gonna give her vitamin K sub Q, but if we have, say, a stable patient, say with warfarin toxicity or anticoagulant organicide toxicity, if you can give the drug PO because it works faster, believe it or not, PO because it has a first high first pass effect on the liver, which is where it's needed.

The bottom line is, get your coaggs to be aware of the potential for bleeding, have blood products on hand, give them prior to surgery if you feel like you'd have a lower blood pressure, or certainly if they're anaemic, and just what whatever you do, whether you give blood products or not, whether the COAG times are increased or not, it's all about monitoring the PC and total solids. Hourly, every 2 hours, every 4 hours for the 1st 12 to 24 hours after the procedure to see if haemorrhage has developed. We get Abigail's fine needle aspirate, and lo and behold, it's just that sort of non-specific hepatocellular necrosis that we were thinking was her problem, and this is the list.

Of possibilities, right? She certainly could have lepto with those titers being negative acutely doesn't rule it out. Could the ciprofloxacin that she was exposed to, could she have some idiosyncratic toxic reaction to that possibly?

Is there some drug she got into we didn't know about? All these other issues you see here. She certainly doesn't have heat stroke, you know, and probably not severe hypoxia, but this is again the scenario we find also is that we don't have a definitive diagnosis.

We can run the toxin test to see if there's Mine need in toxins that might help us, but at this, at this point, it's all about. Supportive care. This is the point.

We're gonna end with how to get these patients where we don't have definitive diagnosis supported so that their liver can regenerate and they can have a good outcome. And these are the cornerstones of therapy and there's no surprise here, and let's just go through them. We're gonna want to start with intravenous fluids and basically you guys, it's super simple these days.

Just pick whatever balanced crystalloid you have on your shelf if it's lactated ringers or normalsol R or whatever you have, regardless of the disease you're dealing with, that's a good start. OK. If you have severely low albumin and you're worried about third spacing of those fluids, you can give head of starch, might be some concerns about platelet dysfunction.

But we've given it to a lot of these patients and we've had good success, but start with crystalloids, and then, you know, these animals might need potassium, B vitamins, and because some, some severe hepatic patients are hypoglycemic, you might need to add dextrose to the fluids as well. When we're trying to decide if we're Actually restoring volume and profusion to these patients, the lactate, blood lactate can be a really useful parameter and you can run that on your machine as well. The concern here is with liver disease, it doesn't work that great because liver functions required for lactate to be metabolised, so an increase in lactate in the liver patient could just be liver dysfunction, not an indication of perfusion.

A better indication of perfusion than lactate would be based excess on a venous blood gas. So if you're really concerned and and wanna do a assure yourself in the most secure way possible that you're restoring normal fluid volume and profusion. Base excess is probably the way to go.

You can use your all your other markers, blood pressure, pulse quality, pulse strength, all of those things are certainly helpful, but they can be normal. And you can still have at the cellular level, an oxygen deficit. So it's helpful to have something that's a little closer to the cells telling you what's going on there and lactate works great in, in patients that don't have liver disease, so severe shock, GDVs, etc.

Base excess works in all of them because it's not affected by as many things as lactate. And then with fluids, as always, just get as much as you need, as long as you need based on your monitoring. We don't need at this point to give Abigail any blood products because she's not bleeding, all right?

If she had bleeding occur, then I would reach for whole blood because If I, if I didn't have what I'm always reaching for first is component therapy. Give just what they need. If she's bleeding, it's probably because, at least partly, she doesn't have clotting factors because of her liver dysfunction.

So I'm giving her frozen, fresh rosen plasma to replace clotting factors. If she's anaemic. I'm giving her either whole blood or packed red cells to restore the red cells.

There's nothing we can do. There's no blood product we can give that is effective at raising the platelet count significantly. So if we're bleeding because of a low platelet count, and she's not likely to bleed at this count, but let's say you had a dog that had immune thrombocytopenia with a platelet count of say 12,000 or 8000, don't give that dog.

There's no way to give that dog enough platelets in any blood product to Raise that platelet count to a level above the bleeding threshold because the dog's immune system will just destroy the transfused platelets. So in those dogs with ITP that are bleeding and anaemic, just give them packed red cells. They need oxygen carrying until you get that platelet count up by giving prednisone or vincristine, that sort of thing.

And the dose for all blood products is pretty straightforward. You can see it there. Got to cover her with broad spectrum antibiotics, no surprise there because she's at risk for sepsis.

Support with antioxidant therapy, and I'd always like to point out, you guys, if you have severe liver disease, severe shock, severe respiratory disease, sepsis. A really good antioxidant overall is a acetylcysteine or that mucus. The same thing you would use as the antidote for Tylenol or acetaminophen, acetaminophen toxicity.

I would absolutely give a dog like Abigail with fulminant acute hepatic necrosis, this drug, acetylcysteine, following the same protocol you would use if you had a treated cat, for example, with Tylenol toxicity. OK. Support with you know, with Aagol or ursodeoxycholic acid, many beneficial properties if she can take oral medication.

She's at risk for gastrointestinal haemorrhage or oesophageal haemorrhage, so support with omeprazole or panprotozole and H proton pump inhibitor. Cover her with sucrofate and give it as a suspension, it coats better. Then giving by, you know, pill in pill form.

If we need anti-nausea, anti-medicine, and appetite stimulating effects, you know, mirroetine can do all of those and this drug can be given orally injectably long term at a make per kid 24, you know, every per day. And then if she is neurologic. Any hepatic patient that's neurologic, we want to address that by giving lactulose to minimise the absorption from the colon of ammonia and other encephalopathic toxins.

And then if they're really severe obtunded or comatose, we want to give them either warm water or lactulose enemas. I have seen. Puppies come in Basically undid comatose due to portal systemic shunts who in blind, who after a warm water or lactulose enema, just sit upright or can see it's a very effective treatment in these acute patients.

Fortunately, most of them aren't severe enough to to warrant that. We want to support these guys nutritionally, OK, because they need that to heal, and with any acute disease, so any acute liver disease, acute kidney disease, no time to restrict protein. Protein limited diets are only to be used in chronic disease states to restore positive protein balance and acute diseases, you gotta give them basically normal protein levels.

You don't need to add protein levels, just don't restrict. OK. If we're dealing with any kind of toxin, OK, that can be absorbed or it undergoes enteropathic circulation, mushrooms included, do all the normal toxic things you're gonna do, induce emesis, etc.

With mushrooms in particular, OK? We want to give them syllabin because it has a direct protective effect on the most toxic principle in mushrooms. OK, so more specific therapy here.

And then we want to keep giving them activated charcoal. It can be given every 6 hours, can be given as a slow infusion through a nasal gastric tube, OK? If you're gonna be giving it intermittently, you know, spread it out, give the medications 2 to 4 hours before you give the activated charcoal.

We don't often do biliary drainage. I mean, you can do it, it works great just to eliminate the toxin accumulating there. But here is another specific treatment you can use when you have these toxins that are reabsorbable, excuse me, and that is cholestyramine.

It's a resin that binds bile acids. Then prevents, therefore, that enteropathic recirculation that allows these toxins to pass through the liver multiple times, causing more damage and sometimes even systemic damage as they occur. So the conditions you might well consider that are listed here from vitamin D toxicosis to all the various toxicities we see.

And the dose there is, you know, listed there for you. So this is something that I think we should be thinking more about. You know, probably we're not gonna stock it in our clinics.

Maybe a nearby emergency clinic would have it, human hospital might have it. So think about that to try to get these dogs to have a better prognosis. And then when it comes to monitoring any critical patient, you guys know what to do.

Just vital signs, physical exams, nothing's more important than getting your hands on your patients as often as possible. Look at your lab work on a daily basis. More important things that can change quickly, more often than that.

So PCD solids, blood glucose electrolytes, depending on severity of anywhere from every 2 hours to every 6 to 12 hours, obviously spread out the interval as they stabilise. And then, you know, you can have what happened in Abigail happen, even as severe as she was on presentation with really good supportive care, a dedicated staff and client, Abigail had a really good outcome. With that, I'm gonna stop.

Oh, I think we went full hours, I think I went a little longer than usual. I hope we still have time for questions. I'm happy to stay and answer them as long as, you know, there are any.

And I think that the webinar will be up on a site for you guys to refer to for dosages or anything else that might have been kind of passed by too quickly. So thank you so much for your attention and, and I'll be happy to take any questions. Bill, thank you so much for an absolute, absolutely spellbinding.

Webinar. It was just fantastic. I don't worry about the time I hanging on every word you've said, so, not a problem and we will be taking some questions.

Just a big thank you to IEX for their sponsorship of tonight. It's, it's really fascinating for us to sit and listen. To somebody like you talking and, and, there've been a couple of comments coming through, saying things like, he makes it sound so simple.

I wish I had that encyclopaedic knowledge. And it, it is, it's, it's, you know, when we listen to somebody with your immense knowledge and that, you sort of think, wow, yeah, that makes a lot of sense that I, I, yeah, I know that. And then you get next to the patient and you think, hell, what was it that Bill was saying again?

So that's why I'm always like, that's why I'm, especially when it comes to, like, what are you gonna make your differential diagnosis based on? Pick the weirdest problem. So, when I get a patient, my first thing is, oh boy, this is gonna be expensive.

And then my second thing is, well, great. It's gonna be super easy to narrow it down to one of those three categories. And once I'm in the category, that's gonna help me decide what to do next.

So, so same thing, like if you have an anaemic patient. Once you know it's PCD is 12, you're like, oh boy, this is gonna be complicated. Well, I just have to determine, is it regenerative or non-regenerative.

Once I know that, it's very straightforward. So I, I, I panic for a minute, like everybody does, like, oh. Then I go, hold on, what's, how do I break this down?

So, yeah, it can be helpful. Yeah, step by step. You know, it reminds me of the old saying of, how do you eat an elephant one mouthful at a time.

So we've got some very interesting questions that are coming through. Before I get to those, I'd just like to remind all the attendees, please. In the chat box, Dawn has just popped in the link to the survey monkey.

Folks, the webinar vet is, is a fantastic invention and we, I will always be grateful to Anthony for coming up with the idea. But we need to remember that This is our channel, this is your channel. So if you do those survey monkeys for us, it gives us feedback, it lets us know what you want, and it, we can then go out and source and look for those topics.

So spend a little bit of time after we've finished and just complete that survey monkey for us. Well, the first question comes from Jackie, who says, why do we see bilirubin in urine of normal male dogs? OK.

That, thank you, Jackie. The the answer is male dogs can actually conjugate bilirubin in their kidney tubules of all things, and they might also have a lower threshold than other than female dogs or cats. So that's why.

Now, I thought the question was gonna be, why do we see bilirubin in the urine in some normal animals like cats, female dogs. The rule is you shouldn't, but the reality is sometimes you do. OK.

So my rule of thumb is Got a healthy animal, Prian, wellness, brand of care. Get him in, get the urinalysis. I always get urine.

There's no excuse for not getting urine if you get blood. If I see trace bilirubin or 1 plus bilirubin in a concentrated urine sample, specific gravity 1040, 1050, I don't care what the animal is. If there's nothing else on my history of physical and blood work, I'm like, probably shouldn't be there.

I'm not concerned. If it's a cat, I'm a little more concerned and I might want to get that animal back in, or at least get more questions like ask more questions to the owner about art, is there anything going on like any days where the cat doesn't need it, does it sit around more? OK, so male dogs, you can live with it for the reasons we just discussed.

I can live with it. It is a small amount of bilirubin in a highly concentrated sample in anybody. If I've convinced myself looking at the patient and the blood work that I've got no concerns.

Excellent. Bill, you opened the door on cats and we have another question which says, is there a concern if a cat has only elevated GGT? Yeah, yeah, because in cats that may be the very first sign of a cholestatic problem, so, so.

If I see that change, again, it's like, look at, I never really wanna treat numbers. I don't want to ignore them, but I also don't wanna just treat a number. But if I've got an elevated GGT only in a cat, and I've seen nothing on that cat, and it looks perfectly healthy.

And I've dug into the history, nothing, and there's no bilirubin in the urine, and in that cat there should, if there's bilirubin in the urine in that cat, that's a problem, right? Cause now you have two indicators of chole stasis potentially. But I also look, so then I, I would say this, if it's just the GGG mild elevation, nothing else, just recheck sooner than, you know, maybe a couple of months unless science develops sooner.

If it's also check to see if there's hemolysis in the sample because there's a lot of GGT in red blood cells, so when they burst, if you have a hemolyzed sample, that can cause the GGT to increase. OK. So rule out hemolysis, we're talking healthy cat here with just a GG.

Rule out hemolysis. Make sure there's no bilirubin in the urine. We check, OK.

But just keep in mind, cats, that can be the first indication of pancreatitis, cholangitis, chole you know, cholecystitis, all of those things, so. And sensitive marker in cats for, for choostasis for sure. Yeah, great.

Folks, before we carry on with other questions, we're getting a lot of questions coming through about access to the information that Bill has so kindly shared with us. Just a reminder that all of our webinars are recorded and it will be up on the webinar. Vets website within the next couple of days.

And then you can go back and you can watch it and you can pause it and rewind it and everything else, which we are not able to do in the live webinar. So, we can't go back to slides, but you can go back and watch the recording. So watch the website.

It will be up shortly. Another question we have from Anonymous. They didn't give a name.

As I learned in university, the lymphocytosis is when inflammation is chronic and neutrophilia is when the inflammation is acute. But you said that lymphocytosis may be always in sick animals. So what could you comment information, what I learned about the acute and chronic inflammation.

OK, so what you learned, that's true, and there's more. There wait, there's more. So we talked about that physiologic leukogram, where the lymphocytosis can be transient and just due to epinephrine release due to excitement.

So that can be an acute. It can be over in that, that, that whole thing that that stress that, sorry, that physiologic luhogram is a matter of a couple of hours and it's over. Even 30 minutes, the lymphocyte count can be back to normal after the stress is resolved.

So look at the patient, but you're right. If you do have a lymphocyte count that is in a mellow, calm, or an ill animal, it takes a while for those cells to gear up, you know, in response to some antigenic. You know, exposure to some antigen or some illness.

So yeah, chronic disease, 100% will raise lymphocyte count. But just remember, my point was that not all lymphocytetosis are Worth pursuing. They can just be a transient result of excitement.

Neutrophils will go up sooner for sure, because they have a really fast, short half-life in the blood and their high, high turnover rate, and there's marginating pools that can be recruited. So you're right, acute. Infection, let's just say inf inflammation happens now.

Neutrophil is gonna go up for lymphocytes. Lymphocytes might go down due to stress. OK, in that scenario, but lymphocytes can go up quickly and transiently just due to excitement.

I hope that answers, whoever that is, anonymous, if that didn't answer your question, please type it in again because we really want to make sure that this is clear. Fantastic. Bill, here's a real hot potato for you and I.

I apologise beforehand. A question has come through saying, you mentioned copper toxicity due to certain formulations of commercial food. You opened this door on your own, Bill.

Are the companies aware of this issue and is it a problem in foods in the UK? Well, I believe that it is a worldwide problem. I'm Only because I've never been to a lecture or read an article where it's mentioned anything geo-specific, OK?

How can we figure that out? Well, That's a good question. You could contact whatever diet companies you deal with and ask them what form of copper they Use Copper, Oxide was the old form, which was less bioavailable.

I'm going back to this slide, copper sulphate. Is the newer form since 1997, which is more bioavailable. So, This is what is causing the concern these days, so that would be one suggestion I have.

Also, I meant to apologise that the units in the blood work were our units, sorry about that. But yeah, so as far as, as far as whether it's worldwide, I, my hunch is, yes, one way to know would be to just find out what form of the copper, what form the copper is in in the diets you're feeding. Fantastic.

We have run very far over, but we've still got a couple of questions. I'm gonna give you apologise. It's always a good sign for me attendees are the numbers are static on my counter.

That shows that it's a good thing and that's happening, so that's a good thing. Last question for you for tonight. Ruth wants to know, do you trust the dipsticks for bilirubin in urine?

Unless the urine is really, really discoloured, yes, right? So if you've got, you know, a marked hemolysis or dark, you know, from, from either bright red to sort of that brown red urine you might see and severe illness with, you know, either hematuria or myoglobinuria or hemoglobinuria. If the urine is not severely discoloured, I trust it.

If it's severely discoloured, brown, red, then it's really hard to assess. There are those, there's those you strip readers that have a way of eliminating that background colour that can give you a more active result in discoloured urine, but yeah, trust it, especially if the urine is clear, through dark yellow is fine. If it's red, red brown, then that can discolour all the pads basically.

Harder to assess, yeah. OK, let's let's do one more question. Let's do one more one because I don't want to leave.

You got time for one more? There are so many comments coming through here about what a fantastic webinar and how much people have enjoyed it. And it's hard to philtre through for questions.

I don't feel bad. There's there's so much appreciation. Thank you.

That was fantastic. I, I understand. I hope to hear more of your lectures, so much information.

Thank you for joining us this evening. Thank you very much for all the information, watching you from Germany. So it's, it's truly a global audience and the appreciation across the board.

And if we were in an audit you would be hearing thunderous applause. That aside, I was, I was just gonna go there like, I can't wait till we can be in person because then this would be more of a discussion and we could, we could stop along the way and clarify things and it would just, we'll get back to it. So stay safe everybody.

Thank you so much. Have a great plan. Bill, thank you for your time.

Much appreciated. Everybody that's attended tonight, thank you so much for your time. I hope you enjoyed it as much as I did.

And to dawn my controller in the background for making everything happen seamlessly, as always, much appreciated. From myself, Bruce Stevenson, it's goodnight.