Good evening everybody, and welcome to this Thursday night members webinar. My name is Bruce Stevenson, and I have the honour and privilege of chairing tonight's webinar. For those of you that are joining us for the first time, if you've got any questions for our speaker, just move your mouse over the screen.

The, control box is normally a black box down the bottom will pop up. You'll see the Q&A box. Click on that and type in all those questions for us, and we will hold those over to the end.

So tonight's speaker is Doctor Bill Saxon, who received his DVM degree from Iowa State University in 1986. He completed his internship at the Animal Medical centre in New York City, followed by a residency at the Animal Medical centre and the University of Pennsylvania. Bill is a board certified by both the American College of Veterinary Internal Medicine and the American College of Veterinary Emergency Medicine and Critical Care.

Bill practised in the San Francisco area and has also owned an intensive care unit in Washington DC. He has published on burn injury, the acute abdomen, feline cardiomyopathy, drug toxicities, and he's also a co-author on the manual of small animal emergency and critical care. Bill has been with IDEX since 1997 as an internal medicine consultant, field medical specialist, and as a speaker at regional, national, and international conferences.

Bill, welcome back to the webinar vet, and it's over to you. Hi, thanks a lot, Bruce. Thanks for the introduction and thanks everybody for joining us.

You know, I'm in California, so it's only 12:30 here, but I know it's getting kind of late there. So we're gonna get through this in about 45 or 50 minutes and just do a review of Preventive care, and kind of why we're talking about it now. And then we're gonna go through 10 kind of surprising or important findings you might stumble across when you're doing preventive care, like in healthy animals and what to do about those findings.

So just to start, one of the reasons that We can talk in more detail about preventive care now is that we actually have sort of standardised definitions of what it is. And our definition is going to be proactive measures taken throughout the life of a pet to prevent disease and promote well-being. That's, you know, pretty broad and obvious definition, but I proactive in italics just because we want to actually do things before pro pre disease occurs and be active institute specific programmes in the practise involving the entire practise team.

So that we can maximise the health and longevity of our patients, and that's the whole goal of preventive care, the why of preventive care would be to basically give pets more birthdays. So we have two recent publications, sort of guidelines in both dogs and cats from to, oh sorry, that my neighbor's dog is just going off there. Anyway, we've got two recently published guidelines, dogs and cats, about what to do throughout their life in terms of preventive care to optimise their longevity and well-being, and we're gonna kind of use these as a jumping off point.

And I've done on this next slide sort of a mash up of the aspects of preventive care to be included in every life stage in dogs and cats. In the dog. Consensus, if you will, 10 aspects are, are indicated, and then in the cat 1, 10 + 111, the elimination habits to be tracked over time, the life of a cat or part of the feline guidelines.

So if we take a look, we can see that by far the majority of what is involved in preventive care is basically taking really good histories and doing good physical examinations. So, In order to institute a preventive care programme in your practise, which, you know, is a new thing to have to consider in these very busy times, it can seem overwhelming. You're already doing a lot of what constitutes good preventive care.

We're gonna pick up some details and on some of these in a minute. And we can absolutely improve the information that we get from history. For example, if we have questionnaires that the owners can fill out perhaps online before they come, specific questions about diet, changes in appetite, etc.

What they've noticed, just to kind of make things efficient and standardised, and then When we get through the history and physical, then we have baseline diagnostic profiles that should be considered throughout the life stage. And that's what we're going to spend sort of the majority of our time on. But if you look at this list, lifestyle effect on patient safety.

So what would that be? Just as you're, you know, coaching your clients if they get, you know, dogs and cats, you know, keeping them safe. So indoor cats and minimise exposure to toxins, minimise exposure to electric cords for young animals, you know, as our job.

As veterinarians in the one health realm of doing our part to ensure that environment, animal and human health are optimal, you know, we need to do a good job on parasite prevention and treatment and also being aware of emerging diseases that might be zoonotic in our area, that sort of thing. It's pretty straightforward. Elimination in cats turns out that something as simple as trending over the lifespan of a cat, defecation habits can be very helpful.

We know that cats with chronic kidney disease, a higher proportion of cats with chronic kidney disease, defecate less than one time per day compared to normal cats. So trending that over the lifespan of the cat, if we see. That we have a decrease in frequency of elimination to less than one time per day.

That might be an early clue that they get is developing chronic kidney disease or some other problem. I think the most likely explanation for why cats with chronic kidney disease would defecate less often is they're probably subclinically dehydrated or frankly dehydrated, overtly dehydrated, and kidney disease may have some effect. Gut motility and other other functions.

Nutrition is super important, with the number of diets we have now to promote health throughout life stages. This is a very useful tool and obviously the goal here is to optimise nutrition and prevent obesity, which can then lead to a host of problems from orthopaedic issues to type 2 diabetes in cats, etc. So, yeah, so those are some things I think that can be helpful just by doing good lifelong preventive care from a history and physical exam perspective.

And now let's talk about what we might see when we have healthy animals that come in for preventive care, unexpected findings that they can be hiding, that we only are gonna Uncover with our thorough examinations and laboratory assessments. So first of all, we've got this cat with decreased frequency of defecation, which means you've trended it from The time the cat was first seen in your clinic throughout life, and now we've just discussed how that could be a sign of chronic kidney disease. A higher proportion of cats with CKD defecate less than once a day compared to normal cats.

OK, this cat you find has lost body weight or muscle mass, and those are two different things. OK, so you can have, you know, an obese cat who has very poor muscle mass, and so different things. We'll talk about the body condition score and the muscle condition score down the line.

So, loss of body weight, you know, cats as they age naturally have sarcopenia, a physiologic weight loss, but if that's accelerated or extreme, clearly it can be due to a number of diseases. And going back to our friend chronic kidney disease again, we know based on a study that was reported in the Journal of Veterinary Internal Medicine in 2016, that weight loss precedes the diagnosis of CKD in a lot of cats. On average, the median weight loss.

In the year prior to a diagnosis of CKD in cancer, 8.9% of their body weight. But weight loss begins as early as 3 years before the diagnosis of CKD and accelerates after.

So it was super important to trend body weight for that and other reasons. And in this study, it looked like a body weight of 4.2 kilogrammes was kind of the cutoff.

Cats at diagnosis of CKD that weighed less than 4.2 kilogrammes had shorter survival, significantly shorter survival times compared to cats that were 4.2 kgs or greater.

Trend body weight, do body condition score and muscle condition score on every exam and we'll talk about the the importance of that and how that works in a in a in a few minutes here. Well right now, for example. So, you know, I think we're all aware that doing body condition score as part of every physical has been important for years and now for the past few years in both dogs and cats muscle condition score is also recommended and the difference is.

You can be obese, have a body condition score of 9, but also have very poor muscle mass. So think about those cats that are fat, but you can see their dorsal spinus processes or the sort of the dorsal aspects of the costal arches, poor muscle condition. It's muscle condition.

That matters, lean body mass that matters when you're interpreting lab results like creatinine, which is a muscle breakdown product. So changes in muscle mass, usually a decrease can affect lower the creatinine value. So important to assess muscle mass and interpreting lab results.

Also, when coming up with drug dosages and nutritional requirements, best to base those calculations, those dosages and calories on lean muscle mass, not total body weight. OK. So, now, #3, the third surprise is you might find high blood pressure, hypertension, and especially in cats.

So what this means is you are measuring blood pressures and we'll talk about when to start doing that, OK? But blood pressure measurement is now part of physical examinations in dogs and cats at various life stages, and we'll talk about when to begin doing that in a minute. So, As we go along, I'm gonna try to point out what I think are useful resources for practising veterinarians and the ACVIM consensus statements are really useful.

These are open source, just Google that ACVIM consensus statement. You'll be taken to a page with a whole raft of state of the art documents that talk about how to diagnose and treat things we commonly see in practise, and they are updated as new information becomes available. So there is a Hypertension consensus statement that was published back in 2018, and that changed how we view high blood pressure.

So the new normal is less than 140. Prior to that, normal blood pressure was considered to be less than 160 millimetres of mercury. Now there's this pre-hypertensive stage in the 140 to 159 range.

This document also tells us how to, what causes blood pressure, how to diagnose it, and how to treat it. So the three causes of hypertension. In small animals are situational, which used to be called white coat hypertension.

Secondary, so high blood pressure is secondary to other disease, mostly kidney disease or endocrine disease, hyperthyroidism, Cushing's, etc. By far the most common form of hypertension is secondary 80% or more. Animals that are hypertensive are hypertensive because of another disease that you need to go looking for, OK?

And then there's this idiopathic. Hypertension, which is up to about 20%, and this is most likely preclinical or early chronic kidney disease, OK? Now, situational.

This is due to excitement, so or stress. This can raise blood pressure on average about 20 millimetres of mercury, but up to 75 millimetres of mercury. So we really do want to get blood pressure measurements in the recommended way, which is a calm, acclimated dog or cat in a quiet environment with the same nurse each time getting the blood pressure from the same limb or tail in the same position, all of that.

So that I think we understand, but there's a couple of things I want to point out. You need to use the right cuff size, and the width of the cuff is 30 to 40% of whatever the circumference of whatever you wrap it around, limb or tail. Now that circumference is gonna be bigger than you think.

Like, it's weird you wrap a tape measure around a skinny leg and a cat and you're surprised at the number you come up with, right? So you got to do the measurement and then multiple. Apply the circumference by 0.3 or 0.4.

And then that is the width of the cup that you will use every other time. We don't want to eyeball it and go, oh, it's a small dog. We'll use this cup, it's a cat, we'll use this cup.

No, just do the measurement, do the math, do it once and you're done. And then when it comes to averaging the serial measurements that you're gonna get in this patient. Even a calm patient, you might notice when you get your first measurements, you'll see that they start to decline.

They sort of do a glide down because the cat is a little bit annoyed that you're, you know, putting pressure around the limbs. So give that those measurements a chance to sort of settle down and plateau, and then you start measuring at that point. And all the measurements that you do that you're gonna average to get the blood pressure should be Reasonably close to each other, less than 28% variation, or less than 20 millimetres of mercury different.

If they're bouncing all over the place, 160, 280, 140, 1929, that's impossible physiologically, that means something is going on technique wise or the animals jerk the limb or the cuff is slit. So wait for the measurements to plateau, average them out if they're consistent. If they're not, or the animals uncooperative, don't try, don't bother.

You will not get an accurate number and that's Information we don't want to use. We don't use bad information. If you can't get a blood pressure, you do really want to know if the animal is hypertensive, and the reason is because of the risk of target organ damage to important organs, eyes, kidneys, brain, heart, right?

So on your physical exam, where will you find evidence of target organ damage most easily by doing a fundic exam. So, my recommendation is Do findings on every patient, part of every physical, you'll get really good at it. It'll take a couple of seconds and you'll know what normal looks like because most will be normal.

Therefore, when a subtle abnormality occurs, you will detect it. All right. So I think all of us could identify retinal detachment or haemorrhage.

That is certainly possible with high blood pressure that's sustained, but the earliest retinal changes due to hypertension are Subtle vessels constrict a little bit. There might be edoema, and that might be hard to identify unless you've done a million fundings and know what normal looks like. So, do fundic exams.

OK. When do we start getting blood pressures? The AAFP feline guidelines recommend getting a baseline blood pressure when cats are young adults, which they define as 1 to 6 years of age.

All right. So, That's young, but that's important. Get that baseline and then you'll detect abnormalities sooner if you can trend that over time and see an increase.

Now, cats less than 6 years of age, they're the ones likeliest to have. Situational hypertension, so you really have to do a good job in those young squirrly cats by making them calm and activating them to get an accurate measure, but this is when to start that young, you know, in dogs we're talking more, you know, adult or senior dogs. Because they have much less, much lower incidence of kidney disease, which is the most common cause of that secondary hypertension that we see in cats.

When we diagnose hypertension that requires therapy, we have two options, good old amlodipine. The dose of amlodipine though is not based on body weight, it's based on blood pressure, as you can see there, with the cutoff being 200. Also, telmisartan, or angiotensin receptor blocker, is a really good antihypertensive.

You can see the dosages there. It's interesting. It's also a really good drug for protonuria.

So in the in North America, in the US elmisartan is approved for hypertension. In Canada, telmisartan is approved for protonuria. So, I would preferentially use telmisartan if I had a cat who was both hypertensive and proteinuric, which is not uncommon because glomerular disease can cause both proteuria and hypertension, but otherwise, take your pick.

OK, between those two drugs. So that's kind of what we might find unexpectedly as part of our physical examination and doing preventive care on our patients. Let's go through some of the changes we might see unexpectedly in healthy animals when we do their lab work.

So we'll start with the CBC and in some animals that look perfectly healthy, we're gonna find a high reticulocyte count when they're not anaemic, and this is unusual that you would even get a reticulocyte count on your CBC if there was no anaemia because most laboratories only release the CBC the reticularcyte count. On the report, if there was anaemia. That's what I used to do up until about 10 years ago when we realised that it's important to have reticulocytes on all CBCs whether there's anaemia or not.

And looking at a million worldwide CBCs over a 3 year period in 2014 to 2017, Doctor Dicola Artif. Clinic pathologist at the time, sadly, he's left Iex, he's retired, I found that it was important to have her t information in 37% of CBC, certainly in the anaemic animals to help determine if you're dealing with regenerative or non-regenerative anaemia, but also in non-anemic patients. Anaemia.

A patient that has a higher retake count that is not anaemic, that could be a clue to some important underlying disease and we have a case example in a minute. There's a relatively new parameter on the CBCs you can get from IEX that's called reticulocyte haemoglobin, and this is a measure of iron availability at the bone marrow level for haemoglobin production, which can also be a really useful tool in identifying iron deficiency from say GI bleeding. Or iron sequestration from inflammation, changes that used to take.

You know, need to, problems that used to in the past have been going on for weeks to months to detect a change, say in the red blood cell indices with external blood loss. But now with this re take haemoglobin, we can identify iron problems within a matter of days, not weeks to months. So let's look at the importance of reticulocytes.

On all CBC is looking at our 10 year old spayed female mixed breed dog, who's coming in, looking pretty good, just in for her wellness exam. And we find when we look at her red cell parameters on the CBC things look great. Nothing to see here.

All right. And this is where it would end in most labs. Off you go, keep looking, you don't know what's going on here with this dog.

Or there's nothing going on. You don't know. With the reticularcyte count though being markedly elevated, 189,000, now we have a whole different Animal to contend with here.

Why would there be high reticulocytes when there's no anaemia? Well first, is it just a lab error? Did the machine misidentify those cells?

How can you prove that the report is accurate? This is where the graphics that your machine spits out can be really helpful. This is, these are called dot plots, where each cell type has its own colour and lives in its own little area, and we can see normal on the right here.

It's normal for all animals to have reticulocytes in their circulation because there's about a 1% turnover of red blood cell mass on a daily basis due to old cells dying off, etc. So the bone marrow is continually replacing those with a low number of reticular cys, so. The purple dots, reticulocytes are normal, but look at our dog on the right.

The report said she had a high number of reticulocytes, higher than normal. Does she have more purple dots than normal? Yes.

So we can say, yeah, she's got a high reticulocyte count. What does that mean? Well, that means you better go looking for splenic disease, number one, because Any, what I like to think about is where do reticulocytes live.

They are born in the bone marrow, they circulate in the blood, and they mature into mature red blood cells in the spleen. So if I've got a high reticulocyte count, especially without anaemia, I'm thinking about damage to organs like the spleen, where reticulocytes live. So having retics on all CBCs will allow you to identify sort of important underlying disease in your patients.

And you're gonna find this in about 5 to 10% of dogs without anaemia. If you see mostly healthy patients, you'll be toward the low end. If you see a significant portion of critical or emergency patients, it'll be toward the high end.

This can be a physiologic change simply due to excitement. Epinephrine levels go up, cause splenic contraction, and that squeezes out those maturing reticulate those reticular cytes there that are maturing to red blood cells. When this happens, it's only a mild elevation in reticular cys.

So look at the actual number of reticular cytes. If it's low, if it's increased by less than 120,000, less than 100. 30,000, it's potentially just due to excitement, young healthy animal.

If the particular cyte count is over 120 or certainly 130, then you've got something significant going on a tumour, spleen, liver, inflammatory disease. You could have a cult bleeding or heyolysis where there is no anaemia because the bone marrow can keep up with the loss by producing higher tics, and reticular cytosis, so. Those are things to consider, and having that ret count will be a tip off, preventing, say, a more significant problem like this mass rupturing.

We're talking about establishing baseline parameters, not only history of physical, but laboratory parameters in young adult animals, so we can trend them over time and detect problems sooner. Let's say we had done so in our patient here, and we noticed looking back that yes, today her her hematocrit is 43, which is normal for all dogs, but let's say she in the past, historically has a hematocrit that's in the 50s, 52, 53, 51, 55, like that. So, Even though today, when she comes in, her hematocrit is normal for all dogs, not normal for her.

So her decrease in hematocrit, in addition to the irratics really points us toward doing more of a workup in this patient to find some underlying disease as part of preventive care. OK. So, CBC, another thing that we want to talk about is finding incidental meaning, unexpected thrombocytopenia in dogs or cats that have no peticia ecchymosis or any other signs of a bleeding disorder.

So this is an important thing to keep in mind. In the animal, platelet's job is to, when there's a stimulus like endothelial damage, platelets who circulate in that resting sort of spherical form, activate, send out pseudopods, and they aggravate to form this clump, the first line of defence and haemorrhage. And that is great when it occurs in the patient.

That's what platelets are supposed to do. It's not so great when it occurs in the blood tube because what that does, those platelet clumps in the blood sample. Lower all automated platelet counts to an unpredictable degree.

Now, there's not a lot we can do about this. It is the job of platelets to clump and cat platelets in particular are big and active, and about 70% of feline blood samples have clumps. So it's not your fault if there are clumps, it's not the lab's fault, it's what platelets do.

The point here is when you get a low platelet count from a lab in clinic reference lab, always verify by determining if clumps are present. Can your machine tell you whether there are clumps, either by looking at the dot plot or giving you a warning? Do you need to look at.

Blood film to see if clumps are present because we don't want to treat thrombocytopenia that are due to clumping, and we don't want to ignore thrombocytopenias thinking, well, it's just due to clumping because I don't see any evidence of a bleeding disorder in my patients. All right. You can't tell how many platelets a dog or cat has by looking at the dog, meaning you could have a dog with ITP, immune thermocytopenia, with a platelet count of 10,000, and that dog certainly could come in bleeding for sure.

That platelet count is below the bleeding threshold of about 3000 to 50,000. But many of those dogs look like a million bucks. No petechia, no ecchymosis, no anything.

So if you get blood work back on that dog and you find a platelet count of 8000. It's that incidental unexpected thrombocytopenia, we don't want to ignore it, thinking the machine clumps, there's a platelet clumps and the machine just gave us an artificially low count. Verify all low counts.

What diseases do we expect to cause thrombocytopenia? Well, by far the majority are infectious disease, neoplasia, and other forms of inflammation. And in those situations, the platelet count is only mildly to moderately decreased, not low enough to cause bleeding.

Therefore, you treat the underlying disease and the platelet count returns to normal. The least common but most severe cause of thrombocytopenia is immune mediated thrombocytopenia. And these dogs, platelet count is below the bleeding threshold in a lot of them.

So if you have a dog or a cat with a platelet count of 12,000, 18,000, even 2000. Immune thrombocytopenia. Nothing else drops the platelet count to that degree.

Now, that could be secondary to vector-borne disease or neoplasia. But in those dogs, the platelet count is the problem. We need to increase it quickly to get the platelet count above the bleeding threshold to minimise ongoing haemorrhage or the risk of developing haemorrhage.

It's important, vector-borne diseases in dogs is a really common cause of thrombocytopenia. It may be the only evidence of disease, the importance of screening healthy patients for vector-borne disease versus only testing for effective borne disease in sick patients who you suspect might have Erlichia or anaplasma, is that most doctors. Infective borne disease have no clinical signs.

And so they can be infected. You can have a positive test result and no signs. So finding a positive result during preventive care, the next step would be to get your baseline lab work.

Do you have evidence of thrombocytopenia that would support infection versus just exposure? Do you have high globulins, proteinuria, thrombocytopenia? Anaemia, that sort of thing.

And this can also help determine who we need to treat. A dog who's not clinical, that tests positive for a vector borne disease that has normal lab work, just needs better fleet and tick control, right? A dog who is not clinical tests positive for vector borne disease and has a low platelet count or protonuria, that dog needs to be treated for the vector borne disease, OK.

All right, so immune thrombocytopenia, again, this is the most severe form of thrombocytopenia, the dogs that could come in actively bleeding or bleed at any moment if they're not. And if they're stable, we just start them on immunosuppressive prednisone. We want to give no more than 2 mixs per cake once a day.

We want to give that in the morning to minimise nighttime PUBD so the owners don't go crazy. If we have a dog who's over 25 kilogrammes, we don't base it on body weight, we base it on surface areas, so the dose for larger dogs. So 50 mg per metre square per day.

There's no point in going higher than that. You don't get any more immunosuppression. You just get more side effects.

Doxycycline for sure in animals that could possibly be harbouring tick-borne disease. If the ITP dog is bleeding, all right. Then in addition to prednisone and doxycycline, to get that.

That count above the bleeding threshold faster. We want to give themcristine once IV or immune human intravenous immunoglobulin, which you would get from, you know, the nearest hospital pharmacy. It's not as easy as it used to be to get that, but it, it's both fincristine and A human intravenous immunoglobulin, when given with prednisone, have been shown in prospective studies to get the platelet count above above the bleeding threshold quicker than just using prednisone alone.

So you shorten hospital stays, patients do better, less expense to the owner. If they're bleeding to the point where they're anaemic and need haemoglobin, oxygen carrying capacity, I give these dogs packed red blood cells. It's kind of hard to give enough platelets.

And dogs that are actively destroying platelets to stop bleeding, but, you know, threshold blood has platelets, platelet rich plasma has platelets. You might get. Enough of an increase for long enough to stop severe haemorrhage, but I tend to just reach for pack of red blood cells.

These dogs tend to have a pretty good prognosis. That prognosis isn't quite as good if they've got GI bleeding, but I don't give up on these dogs. They seem to respond better and faster than dogs I have had that have immediate hemolytic anaemia.

OK. So that's kind of what you might see on the CBC in preventive care, unexpected findings. Let's talk about the biochemical panel, where you might have a perfectly healthy dog or cat that comes in for preventive care, and you see the SGMA has increased and the other GFR biomarkers are normal.

And this makes sense because STMA is the most sensitive marker of GFR that we currently have. It will increase when we've lost on average 40%, as little as 25% of our GFR and that's much sooner than. When we see PUPD in order for urine specific gravity to be affected by kidney disease, we need to have lost 2/3 of our kidney function and for creatinine increase, 3/4 of our kidney function.

So yes, you will see dogs and cats who come in looking great. The only indication of decreased GFR is an elevated STMA and that is what an increased STA means that GFR is decreased. It doesn't mean chronic kidney disease.

It doesn't even mean kidney disease. I think we should train ourselves to think whenever. We see an elevation in the GFR biomarker like BUN creatinine are estimate to say, why is my patient's GFR decreased?

Not, why are my patient's kidneys not functioning. And if we remember back to vet school, there are 3 main causes of a decrease in GFR pre-renal, renal and post renal causes. And in the same animal, that could be any combination or all three of these.

So it's important to do a really thorough assessment for potential causes of GFR because some of them are reversible. You've got a dehydrated shoy patient. Fix it.

If we do that in time and the damage hasn't been so severe, we might prevent renal disease. If we have post renal azotemia either from urethral or more commonly or with increasing prevalence these days, ureteral obstruction, if we address the post renal cause, we might therefore minimise the renal azotemia where if we've got significant enough decrease in GFR due to renal causes for long enough, that becomes an irreversible self-propagating process. So, If we are still in that.

Realm of not being sure what to do when we see an estimate elevation. I think the best resource is the algorithm, that you can get online and it, I've never seen this not work. If the question is what do I do now when I see this estimate elevation, this always answers the question.

The first thing if you don't already have it is get a complete urinalysis and if you have any evidence. The estimate has increased and your urinalysis reveals any other evidence of a kidney issue, decrease specific gravity proteuria of renal origin, then you work that patient up. OK?

If you have a mild elevation in STMA 15 to 19, these dogs and cats look really great. If their urinalysis is completely normal, all you do is recheck. The STA in a month or so, all right?

If your estimate is greater than or equal to 20, that is a significant enough decrease in GFR that we want to investigate those dogs right now. OK? The algorithm is kind of where to go until we're kind of Us to how to deal with these SGMAs.

And we tend to, you know, really be questioning those, the significance of the results in that mild increase range from 15 to 19. It is true. The higher the SGMA, the more likely it is that it represents true decrease in GFR.

But dogs or cats that have those values in the 15 to 19 range. 72% of those will have persistent elevations in a year, so we don't want to ignore those mild elevations because that's the sweet spot. We there's no other way, nothing else is abnormal.

The creatinines are normal, their specific gra gravities are normal. This is the sweet spot where estimate is our. Flu to continue monitoring those patients.

OK. So, very common, especially in older dogs, when you have no clinical signs to get lab work back, that shows increases in liver enzymes and this is complicated cause nobody knows how to deal with this. Do we in this asymptomatic dog.

Monitor only? Do we get bile acids? Do we get an ultrasound?

Do we get a biopsy? How far do we go? Well, in order to answer the question, there really is no answer.

It's sort of clinicians intuition and looking at things. The the some information you can use to answer the question how far do we go in this dog or cat is considered the magnitude of the increase, the trend. Over time, the pattern, the relationship of those enzymes to each other and breed.

So, obviously we're more concerned when we have moderate to severe increases in these liver enzymes. So what is that? How do you define that?

Most of us would say that value in the dog anyway, an increase of 3 to 4 times normal range or more gets your attention. Now, the most recent edition of Ettinger's internal medicine textbook says that one up to 5 times. Normal is a mild increase.

5 to 10 times normal is a moderate increase, and over 10 times normal is a severe increase in liver enzymes. That seems kind of high to me. I think 5 times is like a moderate to, you know, 5 times is a severe elevation or, you know, you know, it's, it's variable.

So you, you can go by the book, 0 to 5 times is mild, 5 to 10 is moderate, over 10 is. Severe or in that 3 to 4 times range, it should get your attention. Now, cats, we don't tolerate increases at all because they have far less liver enzymes per gramme of liver tissue than dogs and have shorter half-life of liver enzymes versus dogs.

So any increase should get our attention there, especially if it's a new finding, or we have trends that are increasing. Now, a decreasing trend. It is interesting.

That could be good. That could be liver insult that has resolved, or if we're developing cirrhosis, that could be bad, right? The liver mass is not there to produce these enzymes, but so trending can be another way to determine whether we need to work these guys up.

I also look at the pattern of LOS to ALT. I'm way more concerned if The ALT is as high or higher than the APOs, because that means we have on ALT means we have ongoing hepatocellular leakage from something, toxin inflammation, neoplasia. Those dogs get worked up.

If it's a dog that has a mild elevation in L phosp, no other signs. It's not increasing over time. I'm maybe more conservative.

There. The ALT is the one that gets my attention because it means active hepato cellular leakage. If I got a Scotty though, I'm a little concerned about even mild to moderate increases in a hos.

Scotty's have a 21 hydroxylase enzyme deficiency, that's part of the cortisol pathway, meaning that precursors to cortisol increase. Namely, Andronstein dion, and this might be part of why they developed their predistribution to vacuoar hepatopathy, and some of these dogs go on to transform to adenocarcinoma, and that's kind of related maybe to that Andronstein dione, to that enzyme deficiency, right? So I'm more concerned about an isolated mild or so outfas in Scotty's for this reason.

And also in Scotty if I do diagnose Cushing's disease in Scotty, where in most breeds I would be using rilesta these days as my initial treatment for Cushing's and Scotty's, I'm gonna go with Lysedrin Y. Trilita is also a drug that blocks 2 hydroxylase enzymes in the cortisol pathway. Therefore, it might further increase precursoress like Androstein dion which could increase the risk of Adenocarcinoma.

So maybe in cage we want to use Lysodrin instead of Trilota when we confirm Cushing's disease. In a Labrador, I'm way more concerned about modest elevations in ALT than in other breeds, especially these days. Labs have a genetic predisposition to hepatic disease.

They lack some enzymes that are part of copper metabolism excretion, and then in the states anyway, since 1997, they changed the form of copper and dog foods to make it a more bioavailable form, meaning dogs are walking around with higher copper levels in their blood. So you add that to the Labrador's risk for liver disease, and now we're seeing copper associated hepatopathy more often in Labradors and other breeds, including Scotties. So.

If I got a lab who comes in with a modest elevation of ALT, I'm gonna be more concerned about that dog and work it up sooner than other breeds because of this issue, and then Or cholestatic enzymes, EAS and GGT, they can be helpful to have both of those because they might help us localise where in the liver cholestasis is. And this is because they're produced in two different areas. Elkhos is produced by the patocytes primarily that line the bile canliculate in the parenchyma, whereas GDT primarily is produced by the epithelial cells that line the bile ducts.

So if we have A dog, for example, who's got a GDT that is much higher than the Alfos, where is the problem? Biliary tree. Why is that important to identify?

Some biliary problems are obstructive and can cause leakage in bioperitonites, which is a horrendous. You'd have to contend with. So looking at both might help you localise cholestasis.

So here's an example of a dog who comes in, looks pretty good. We've got an outfas that's 3 times normal and a GGT that's 12 times normal. So this is a dog who has that pattern.

There is a higher GGT relative to its normal than Alfos. What are we gonna do in this dog sooner than later, we're gonna get this dog image. So that's the key.

If we have that pattern, we're gonna image these dogs for some obstructive surgical disease and here we have a gallbladder mucous cele. Could be a pancreatic mass, could be choleli, any number of things, but finding that elevation primarily. And GGT gets you to image these guys sooner than later.

If we don't have the GGT, let's ignore the bilirubin and the lipase in this dog. And let's just look at the cholestatic enzymes. If we don't have GGT here, then we've got this dog who's in for preventive care and he looks pretty good.

And we see an out costs of 600, and that's only 3 times normal. That's that, huh? What do you do with that?

If it's a Scotty, we're gonna work it up, right? Look at ultrasound doesn't have adenocarcinoma, right? But in other breeds, it might be, especially if it's not been.

You know, if it's you know, sort of continually in that range, we might just continue to monitor, right? In, in that case, this patient that would be a big risk because we're missing identification of the surgical disease. So useful to have both Alphos and GGT and in cats, if we see a high outhos in a cat with a normal GGT, what does that cat have?

Libidosis. Until proven otherwise. Reason being with lipiddosis, if pale cytes are swollen with fat, right?

And glycogen, and they compress the biliuli and that induces alkhosp production. There's not much going on in the biliary epithelial cells with lipiddosis unless they have concurrent cholangitis or cholangio hepatitis. So high alk phosp with normal GGT in a cat means lipiddosis.

Useful to have both. All right. This is another thing that we're gonna find, especially in some older cats as we see the incidence of idiopathic hypercalcemia increase.

All right. So you look at an animal looks great and for preventive care, and you see a modest increase in total calcium. What do you do?

Well, You don't really have a problem with calcium unless you have a problem with ionised calcium because the total calcium isn't really predictive of what the ionised calcium is doing, and it's the ionised calcium that matters. It's, it's usually an issue where we've got a total calcium that's only mildly above or below the reference interval and the ionised calcium is normal, right? You can have though, animals with total calciums 1415, 16 that have normal ionised calciums, and it kind of depends on which agent the the reference lab uses to determine total calcium.

The point is If you have especially a mild increase in or decrease in total calcium before you do an expensive or extensive workup, get an ionised calcium, OK? And if the ionised calcium is normal, you don't have a problem. Now, this should be done in the clinic with fresh blood because things can change, pH can change, and that can alter the ionised calcium.

As the sample goes to the lab, you know, exposure to air, time sent to the lab, time to send to the lab, all of that can change the calcium, so it is important to get this done pet side whenever you can. We, that's difficult in some instances. So we have these surrogates and there are these correction formulas that we've learned, and they don't really work well in cats at all, and they don't work that great in dogs either, but that's something that you can do.

But a better thing to do to. If you can't get an actual ionised calcium to determine the likelihood of your patient's total calcium being real or not, you know, is get what's called a predicted ionised calcium a pikeup. This is something you can get online and you just plug into this formula, parameters that you already have from your lab work, and then it spits out your patient's predicted likely ionised calcium, and you'll get a range for your patient, and then there's a normal range.

So you just compare the two and that there it explains how to do this on the website. So, My recommendation is to follow these guidelines in terms of when to run an ionised calcium, not routinely because if your calcium is normal, you could still have an ionised calcium problem if your total calcium is normal, but that's, we can just probably for now say we don't need to run ionised calciums as part of a routine screening, but you should, if you can, with higher low total calciums, especially if they are mild changes or if your patient shows any signs that could be related to a calcium disorder. It's required to make the diagnosis of idiopathic hypercalcemia in cats, right?

These are the cats that come in with only mild increases in total calciums and you can't find any other cause and you wanna make the diagnosis of idiopathic, you can't unless your ionised calcium is also high, and we also use ionised calcium whenever possible to monitor treatment. When we have post-op parathyroidectomy patients. So it's not that common that we deal with hypercalcemia or hypocalcemia these days other than in cats.

Well, it's not that common that we Encounter it, and therefore we don't have a lot of practise, I think, interpreting these panels. If we've got a dog like our dog here, who's got a total calcium of 14.6, now that to me is likely true hypercalistemia, but it isn't until we get an IS calcium that confirms it.

So in this dog, we want to know, does it have primary hyperthyroidism or neoplasia, the two primary ruleouts for calciums that are that high. So this is when we send in the sample for a PTH level, parathyroid hormone level, and ionised calcium. It's hard to interpret these.

So I just want to review it so we can be really good at making our diagnosis. The way to interpret these panels is the first thing you look at and the only thing. You look at initially is the ionised calcium.

Don't look at anything else. Go to the ionised calcium. It's high so that confirms that we truly have a hypercalcieic patient.

And then we don't look at anything else yet. We just think, OK, the calcium is high. What should the PTH level be?

It should be zero, right? The job of PTH is to raise calcium. If calcium is already high, there should be by negative feedback, the parathyroid gland should be shut down, not producing PTH.

So then we look at the PTH and we go, well, It's not zero, it's in the normal range. So what does that mean? Well, it's normal for all dogs, but that's inappropriately elevated with hypercalcemia.

The diagnosis here is a slam dunk. This dog has primary hyperparathyroidism, OK? Most dogs with primary hyperparathyroidism have PTH levels in the lower half of the normal range.

But that's not appropriate when the calcium is high, OK, so like 45% will have PTH levels in the lower half of the normal range, another 25 or so will have PTH levels in the upper half of the normal range, and only about a quarter have high PTH levels, right? So a PTH level in the normal reference interval with a calcium that is elevated is not normal. It's diagnostic for primary hyperparathyroidism.

If you had started by looking at the PTH level and gone, OK, PTH level is normal, great, calcium is high. Oh, that must be due to neoplasia. You would have made the total wrong assessment.

OK, so start with the calcium, think what should the PTH level be, then look at the PTH level. It does not have to be high. For the dog to have primary hyperparathyroidism, it just has to be in the normal range.

OK, so now let's look at the urinalysis. We're gonna finish up by looking at two important parameters that we might find incidentally in normal animals to preventive care that we should not ignore. And one is normal glycemic glucose urea.

You've got glucose in the urine, blood sugar is normal. This means tubular damage until proven otherwise. OK, obviously.

If there was diabetes, you would have high blood sugar as well. So you'd have hyperglycemia and glucose urea. When you have a normal blood sugar, but glucose in the urine is high, something going on with the tubules.

It's their job to reabsorb filtered glucose. Now, sometimes there's just an inborn area of metabolism. You can have renal tubular glucose era or Fanconi syndrome.

All right. So obviously, if it's a young, healthy animal, we wanna consider possible. Congenital or genetic problems.

But if it's an older animal and a new finding, we have to think about tubular disease. The kidney tubules are the most active part of the nephron. They have the highest energy requirements, so they're most vulnerable to toxin, ischemia, and other problems, infection.

So when you have glucose in the urine and normal blood sugar, we want to think about toxin, infection, leptop, yelo and others. And there's a clue here based on the urine. Of copper associate hepatopathy, and that is finding glucose uri in the urine.

Why is that? Copper is a heavy metal can cause tubular injury and lead to glucoseura. So let's go back to our Labrador.

Comes in with this ALT that's not really high, not scary high. It's just 2 to 3 times normal and we don't know what to do. Well, we were concerned about it because it's a lab anyway, but still, what, how far do we go?

Do we just monitor it? What do we do? Well, if that dog has glucose in the urine, it has copper associated hepatopathy until proven otherwise.

OK, so now we know we need to evaluate that dog more completely. The point here is, without a urinalysis, you would have missed this very important finding. So here is the pitch for making sure whenever you send in blood on a patient you sent in urine.

Sometimes the only abnormalities the patient will display on the lab can be found in the urine or the earliest ones will be found there, and you can't really interpret GFR biomarkers without specific gravity. The key here is get urine. The only time it needs to be a systo is if you're gonna culture it for purposes of complete.

The database on any other patient, in any other situation, any urine sample will do free catch, catheter, tabletop, carrier, floor, food bowl, you name it. Just use the urine that the patient gives you. OK, to start with.

Now, if you find something that doesn't make sense in urine, like some cleaning solutions from A tabletop sample or, you know, a food bowl sample. Some cleaning solutions cross react with glucose on the urine dipstick. So if you have a sample obtained in that method and you find glucose in the urine, well, first get a blood glucose, cause you might have just diagnosed diabetes in about 30 seconds, but if the blood glucose is normal and the sample is contaminated, if you will, just get a clean sample, but you get the picture, just get urine.

So much useful information. And this one I think we're gonna finish with protonuria because of its importance. It's increasingly recognised that protonuria is damaging to the kidneys, can cause and exacerbate kidney disease, as well as being an indication of systemic disease, inflammatory, infectious, that.

Borne neoplasia. So we don't want to ignore what I'm gonna call incidental proteinuria, meaning you've got a perfectly healthy animal. This is preventive care we're doing here.

And you find protein in the urine. We don't want to ignore it. How often will that occur?

Up to about 25% of normal dogs and cats have protein in the urine. And the reason it's important is what we just talked about, it's damaging to the kidneys, is the bottom line. With chronic kidney disease, I want to just point to the low, the last bullet point here.

Per the iris per a study that was done years ago, cats with stage one non-oemic chronic kidney disease. You could predict their survival by looking at their urine protein creatinine ratio. So cats that had a normal urine protein creatinine ratio less than 0.2, that's really low, by the way.

The new normal is less than 0.2 with chronic kidney disease. The median survival is about 1000 days.

If the your protein ratio is in the borderline range, this is for the iris guidelines, 0.2 to 0.4, median survival drops by half.

And we don't recommend or I doesn't, I, iris doesn't recommend treating proteinuria with CKD in cats until the UPC is greater than 0.4, that would be 0.5 in dogs.

Now, if you look at the difference in survival, the biggest improvement is or the biggest drop off is when dogs, cats go from having a normal UPC to the borderline UPC range. So in my view, It makes sense to treat cats that have borderline porttonuria if they're in stage one non-naotenic CKD rather than wait until they're above that 0.4.

So it will be interesting to see if the guidelines are modified down the line to account for this. In other words, it seems to me like you get a big, big drop off in survival in that borderline range. Why not treat those?

OK. So clinical clinicians preference at this point, I think. All right.

Because of this increased awareness of how damaging proteinuria can be, the Irish guidelines around proteinuria were updated in 2015. The new normal became 0.2, super, super low compared to prior normals or point of one or two.

In years past, borderline as we talked about is 0.2 to 0.4 in cats, up to 0.5 in dogs.

We treat with persistent renal proteinuria of with the UPC above 0.4 in cats and above 0.5 in a dog.

What does this mean? Persistent renal. Well, just like with GFR, there are pre-renal, renal, and post renal causes of proteinuria.

So pre-renal, that's really rare. Myeloma. Something like shock or heat stroke or seizures, you would know looking at the blood work and the patient if the protein that you see in the urine is prerenal.

Post renal is most common, and that's due to inflammation or haemorrhage in the lower urinary tract. So we've ruled out pre, we've ruled out post by looking at our urinalysis, sediment exam, and now we've identified renal proteinuria persistent is 3 or more increased amounts of protein in the urine, at least 2 weeks apart. So once you've got persistent renal proteinuria, then we have reasons to go to the Irish site and plug into their proteinuria guidelines.

Now prior to 2015, if you found Persistent renal protonuria and non-azotemic stage 1 CKD treatment was not recommended. We waited until they were in stage 2 azotemic CKD, not anymore. Now we treat them in stage 1.

So that's chronic kidney disease. If the animal doesn't have chronic kidney disease, we investigate for underlying diseases that would cause protonuria, tick-borne infectious, other infectious, inflammatory, neoplastic, immune mediated, when the UPC is above 1 and we treat if it's above 2. That's a dramatic amount of protein in the urine when when we have a UPC above 2.

So how do we detect protein in the urine? Usually we start with our good old dipstick and that's not going anywhere. We just need to recognise that in order for the dipstick protein to be positive, there needs to be 30 mg per DL or more of protein in the urine.

It's not very sensitive. Therefore, any amount of protein in the urine should be considered significant regardless of specific gravity. So, Not very quantitative.

We can't predict the UPC which is all we care about in terms of treatment decisions by looking at the dipstick, even if we have tracer one plus protein in a highly concentrated sample, where in the past we might have thought not doing a UPC because that's not a lot of protein. And that part is true. It's not a lot of protein, but these days it doesn't take a lot of protein for the UPC to be above that 0.2 normal range that we're worried about, and above, you know, 0.4 or 5 where we might want to treat them, so the.

It's important to follow up any protein in the urine on the dipstick regardless of specific gravity and base all treatment decisions on the UPC only. We don't want to say we've got 4 + protein in a 10/10 specific gravity from the dipstick. Therefore, I'm gonna get this dog treated for protonuria.

No, there's nothing quantitative really about the dipstick protein in relation to this. Of gravity, the protein ratio is more sensitive. It detects 5 perd of protein or more.

The only time you do not need to follow to get a urine proteinatinine ratio is when you have a negative dipstick protein with a concentrated urine sample. Chances of that UPC being above 0.2 super slim.

All right. You need to get that UPC if we've got persistent protonuria, OK, minimum of 3 samples with inactive sediment, no blood, no inflammation, at least 2 weeks apart. If the animal's hypoalbuinemic, then we're getting a UPC right off the bat.

Because that would potentially indicate severe glomerular disease, and with every animal with chronic kidney disease, part of the staging is primarily staging based on both creatinine and the IDEX SDA. Now it's the IDEX STMA that is part of the current staging guidelines for CKD in cats, right? And then we substage all dogs and cats, or iris staging for dogs and cats for CKD.

It's the combination of the creatinine and the IDESGMA. Every animal that gets staged for chronic kidney disease, first primarily staged with creatinine and STMA substage based on proteinuria and blood pressure. So regardless of whether there's protein on the dipstick or not, even if there is no protein on the dipstick, every CKD patient gets a UPC to substage.

Now, again, you know, in order for there to be protein on the dipstick, there has to be 30s per DL of protein in that sample. So a negative. Protein on the dipstick doesn't mean no protein in the urine, just means less than 30s per DL.

Now that is not a lot of protein, but it doesn't take a lot of protein to kick those UPCs up into the levels that we're concerned about in chronic kidney disease patients. All right. So what is the best sample to get your protein creatinine ratio?

We get this question a lot. It doesn't matter. You know, similar, it does not matter whether you do a cysto or voided sample as long as you look at a sentiment exam and make sure there's no blood or inflammation.

All right. Sys may be slightly preferred to minimise contamination of the from the lower urinary tract, but it can cause arogenic haemorrhage and it can also cause problems if And animals have bladder masses or coagulopathies, right? So just use the same pick the method, use the same one in your patient because there's a difference between cystos in the clinic.

UPCs are slightly higher enough to change your classification versus home samples. Use the same method compare apples to apples. How much blood does it take to affect the UPC microscopic hematuria that discolours the urine to any degree.

Can affect the UPC and change it from normal to borderline or borderline to elevated. So the only time That we really want to. Get a UPC on a sample that has hematuria would be microscopic only.

Certainly any sample of gross hematuria, that's too much blood, that's going to affect the UPC. If you have microscopic hematuria and the urine is clear or pale yellow, submit the urine for UBC. If it's dark yellow, pink or red, get another sample.

That does not have microscopic hematuria to assess your UPC. And then finally, we also often get the question, should we use a spot sample, pool samples, average of 3 samples? How do we get a valid UPC?

It really doesn't matter at all, unless you have a high UPC or are monitoring a patient. Who's being treated for protonuria. The higher the UPCs, the more they vary from day to day.

In those animals, you do want to get 3 consecutive daily morning urine samples, have their own refrigerate, then bring those samples in, you get an equal aliqua from each, mix it together, and that is what you send in for a UPC. And then I think by now we're all familiar with how to treat protonaria, OK? Same old stuff.

You can use thalmisartan as first line therapy or ACE inhibitors, either one is fine. If you have low albumin and your concerns would be you, it'd be 2020 of your units, 20 whatever milligrammes per DL would be your units or grammes per litre. Anyway, yours would be 20, less than 20 for you guys.

Wherever you would use aspirin in the past for its antithrombotic effects, whether it's this disease or cast with cardiomyopathy, who you're worried about your thromboembolism or have already thrown one, wherever you would have used aspirin. In the past, now use clopidogrel, Plavix. It has been shown in controlled studies, randomised control studies to be more effective as an anti-thrombotic agent than aspirin.

Now, I don't know if you see Lyme disease in your area yet. You're likely going to at some point. We see that here it forms a, it causes an immunoglomulonephritis, .

Severe form of Lyme disease and in those animals, in addition to the standard therapy above, you want to give anti or immunosuppressive therapy, Mycophenolate if you have it, prednisolone if you don't. OK. So that's just the importance of getting urine, looking for changes, and not ignoring incidental protonuria.

So we made it to our list of 10 surprising findings that you might see on your preventive care from both your history, physical, and the lab work. So I, I'm happy to stick around and answer any questions. I know it's getting late, so if you guys got to take off, that's fine.

And then let us know what other topics you'd like to hear going forward and we'll be happy to do what we can to bring those to you. So thanks very much. Bill, thank you.

That was absolutely fascinating. And it's always great to have the old memory cells jogged a little bit about routine stuff. We all think, oh, here's another vaccine, catch up time and You know, you, you, you tend to, to slip away from this great thought process that you've given us now in, in, the routine workups of these patients.

So, thank you for stimulating that grey matter again. Well, there's just, there's just so much there. Like, if we know what to look for, and especially if we know what to do when we find surprises, then I think it can really, really benefit our patients and that's the whole goal.

Yeah, I think, I think the thing is, is that we probably all know what to do. It's just a question of actually getting in and thinking about it, you know. We're we're so busy these days and there's just so much demand on our time.

I totally get it. And I just think that I, you know, kudos to to practising veterinarians these days are in the trenches dealing with what these times are, are like. And that's why if we can do anything to make it easier by bringing you this kind of content, let us know.

And then, . Also, just get urine. I mean, literally the thing, I think the, the missing link to really helping a lot of our patients and getting as much diagnostic utility out of their lab work as possible as we just don't have the urine.

And so I hope, you know, that we ended up with a couple of important findings that you see in the urine. Just get a sample and and include that, and I think we'll do a much better job of helping our patients. Yeah, I think, I think that is, that's really good advice.

And I must say what struck me, As well as is consistent type of urine. That's not something I must be honest and put my hand up to say that I've ever paid much attention to. You know, this time it might be a free flow, and next time it might be a cisto and that.

So, that was really good advice. Yeah, listen. So I'm, I'm all I'm all down with get whatever sample they give you.

And, and as long as you're looking at a sentiment exam, and you, you can determine that it's clean. Then I think you can get a pretty accurate assessment of the urine, including UPC, but the consistent thing was specifically important with urine protein creatinine ratio because that's where you'll see a difference between Cysto and clinic and free catch at home. But to complete the minimum database on sample they get, I, I literally dragged the dipstick through urine on the tabletop.

That's all I can do out of your shoe, pretty much, you name it. Yeah, I'm sure we've all had that situation where we've been standing in the wrong place where they've urinated, but anyway. Bill, thank you so much for your time.

It has always has been fantastic to listen to you and we really do appreciate it. To all of those of you that have attended tonight, thank you also for your time. We do appreciate it and Bill was right.

Guys, this is our channel. You know, if you don't tell us And I'm one of you telling the webinar vet what it is we want. They're not gonna be bringing us the stuff that we want.

So drop Dawn an email, the fantastic team at the webinar vet. Let them know the subjects you want. And, between you and I, let's get Bill back again.

He's fantastic to listen to. So thanks, Bill, and thanks everybody for attending. Have a great night.

And to my controller Dawn in the background, as always, thank you for everything you've done. And until the next time, it's Bruce Stevenson saying good night.