Well, thank you very much for that introduction. Yes, today I'm going to be talking about laminitis, and obviously the big question is why are we still talking about laminitis really. We all know it exists and we know the problems and pitfalls of treating it and trying to diagnose it.
But with recent research and recent publications looking at some different theories and ideas, I thought it quite important to reiterate some of these different aspects of it. So through this presentation, I'm going to talk about the etiologies behind laminitis from PPID to EMS. I will briefly touch on supporting limb laminitis, as well as some of the causes such as sepsis and SARS, although it is definitely going to mostly be around the PPID and EMS.
Then I'm going to go through some of the recent research protocol of research, sorry, information about the pathological changes seen within the melee and within the hoof capsule. And then talk about some of the treatment protocols that we can undertake, particularly for the endocrineopathic diseases, but also looking at very, very much multimodal pain management, in these cases is I think that's fairly imperative to them. So, why, as I said, why are we talking about this?
Recently, I think there's been quite a fundamental rethink in the pathology and aetiology of laminitis. And this paper, this paradigm shift in laminitis that Karakkowski, and, another whole group did has recently changed a few of our thoughts. Firstly, it's important to consider that laminitis is a clinical syndrome associated with a systemic disease.
Either endocrine, sepsis, systemic inflammatory response syndrome. Rather than it being purely a disease entity in itself. Next, laminitis associated with endocrine disease, whether it's PPID or EMS, is believed to be the predominant form in animals that are presenting for lameness associated with laminitis.
In other words, there's been a fundamental rethink that laminitis is pretty much always due to endocrineopathic disease rather than SARS or sepsis. Third, the designation of laminitis is a primary and severe basement membrane pathology. So a lot of the previous research based on black walnut models and SARS models requires revision.
And we'll go through some of the histopathological pictures associated with that in a moment. Instead, the current data proposes a variable subclinical phase associated with gross changes in the hoof capsule, and that's mostly due to a stretching and elongation of the lamella cells. And this is really important when it comes to looking at the possibility of trying to treat these in the subclinical phase rather than acutely.
And this simple but important shift in the paradigm of laminitis has several big implications. The main one being that any accurate diagnosis of the systemic disease is essential and pivotal for the laminitis management, prognosis and prevention of reoccurrence. And now we also need to look at whether this true disease is laminitis or laminopathy.
I think this is fairly benign in this conversation, as most people continue to call it laminitis. But from a purely scientific point of view, as we'll see a little bit later on, it should really be a laminopathy when it comes to endocrineopathic disease. So I think we all know the clinical signs of laminitis, but it's a very, very brief overview of just one slide.
Most sources are going to present with a single to multi-limb lameness and the vast majority are going to be 2 or 4 limbs. These horses will present in a sawhorse stance with increased digital pulses in any of the affected limbs and a reluctance to move. There should be, or there will be sensitivity to hoof testes, particularly around the tip of the frog associated with the pedal bone.
And the gross hooful alterations that we see talk about the really the the subclinical and the ongoing problems in the vast majority of cases with divergent hoofings, separated white lined and flat or convex souls in the most extreme cases, saying, OK, there has been something going on for a lot longer. But it's important that even though it's a very well recognised disease that we try and add an objective nature to our grading of this to allow for continuation of excellent medical care, irrespective of the clinicians that may well be involved as we go forward in each case. So, Doctor Oel, a good few years ago, created this grading system, with grade 1, including a weight shifting and lameness of trot.
Grade 2, a willingness to move, but a clear lameness to walk and trot. 3, reluctance to move and difficulty in lifting feet, and 4, an absolute marked reluctance or refusal to move and an inability to lift up the feet. Not only does this allow for ongoing medical care to be passed from one clinician to the next, but also allows you to really judge and move forward and tell the client that things are improving.
Other than clinical signs, radiographic radiographic diagnosis is very, very useful. Now, the one thing to obviously state is that there are seldom changes on the radiographs at the onset of clinical disease. And ideally these radiographs should be repeated at multiple time points throughout the the disease progress to monitor the changes.
In the ideal world, you'd be looking at sort of 3 to 4 days for repeat radiographs in the first week and then weekly after that. We're all very aware that that's normally not clinically acceptable or financially viable in the vast majority of the cases. So what are we looking for on the radiographs?
Firstly, we're looking for a divergence and a rotation of that pedal bone away from the dorsal who fall. With the advent of these X-rays with the computer-based X-rays, we can see the dorsal who fall without a marker on there, but always sensible to have a marker anyway. Is there a gas shadow, dorsals to the pedal bone, which really does indicate quite a chronic and severe laminitis.
And is there sinking of the pedal bone, compared to the coronet? When we're looking at these, also, you not only are you trying to assess if there's an acute disease, but also you want to know if there's any chronic changes to that foot. So what we're looking for for chronicity is lack of a gas shadow, dorsal to the pedal bone, but also a ski jump appearance to the tip of P3, as we can see in this radiograph.
And the cadaver limb on the right hand side is actually this foot showing that it slowly prolapsed through the hoo or at a later stage. OK, so we're happy with our diagnosis and now we've got to try and work out what's going on and what the aetiology behind it is. So, the main causes of laminitis, obviously, endocrine disease is our first and foremost, but mechanical and traumatic and toxic also play a role in these.
EMS, PPID, and possibly glucocorticoid steroid administration, although recent, or relatively recent research has shown there seems to be very, very little link between steroids and laminitis. There are two really good studies. This one by Donaldson in 2014 showed that out of 40 laminated horses, 7, 93% of them had some sort of endocrinopathic disease, while 77% of them were not, excuse me, were not tested.
In Karikowski's study, 36 laminitic courses, of which 89% were endocrinopathic and 11% no endocrine disease. In other words, the vast majority of these cases really are endocrinopathic in nature. Obviously, we can have a road founder, or, or excess weight bearing due to support limb laminitis due to fractures or, or similar.
And then the toxic models, infectious, colitis retained placenta, frain retained foetal placentas and pneumonia, or even the black walnut study, although that's pretty much gone out of favour now. So why this change in our knowledge? The one of the first big retrospective studies that was performed on laminitis was by Parsons, and published in 2007.
And this was looking at those cases that were hospital bound. And what we can see is that there's a huge difference in the age groups from 5.8 to 15 years in the second study by Karakkowski.
Also, there's a dramatic difference in the breeds, so from light to ponies and warmbloods. And more importantly, the first group had severe endotoxemia, while the second had no evidence of endotoxemia. And then looking on the other side, you can see that in the latest study looking at the broad spectrum of the population rather than hospital-based horses, the vast majority had hyperinsalemia and previous laminitic episodes.
What does this matter? So Treba in 2006 looked at a comparison of horses that had previously had laminitis versus those that were laminitis naive. So in the left hand graph, the clear white bar graph is the naive ponies versus the hatched.
And what we can see is that there is a marked hyperinsulinemia in these cases, as well as a triglyceride elevation and a body condition score difference. Now they're all the the clinically, sorry, statistically different results. And also looking at this group, which is looking at horses that are fed a grass-based diet versus a non grass-based diet in in horses that are at risk, shows a fivefold increase in the insulin levels in those that are fed grass compared to the naive horses.
So really, these horses are suffering from a severe endocrinopathic disease. So why does this matter in our population in the UK or even in the world? At the moment, obesity is becoming one of the biggest risk factors for human health, and this graph shows the change in body weight, body mass index, sorry, throughout many countries, and that not only stands true for our human population, but also for the equine population and pet population as well.
So over the last 25 years, we've seen an increased obesity due to higher sugar and fat consumption in the humans and that's correlated with a more intensive regime of diet in horses. So, why did these hyperinsulinemic, normally obese ponies, not always obese ponies, what actually causes the laminitis? What we know is that insulin is central to laminitis now.
And as a very, very brief brief and simple overview of insulin, it's released into the circulation after eating. And it normally moves sugars into the cells, and that reduces the blood glucose to a far more normal level. But what we know is that excessive insulin levels can be harmful to both blood flow, cell division and growth, and either or both of these may well be involved in laminitis.
What hyperinsulinemia, excuse me, hyperinsulinemia also does is that it leads to increased cellular apoptosis, cellular elongation and clinical changes in that form. And aspirin, a little while ago, in 2007 showed that aquids that experience sustained high insulin levels develop laminitis, and that's been conclusively shown in multiple different studies. There's a slight difference though in horses versus humans.
And initially this graph is showing us what humans do in diabetes. So with an insulin resistant human, you start to see an increase in your insulin levels. And as that occurs, you get more and more insulin to overcome that insulin resistance and blocking and maintain a normal glucose.
Frustratingly though, the body eventually can't sustain that increased insulin production with a pancreatic insufficiency, and therefore, insulin release is decreased. That therefore leads to a loss of control of blood glucose and type 2 diabetes. This is where you start to see the risk of glucose toxicity, which we don't see in horses, things like ulceration in distal limbs, poor perfusion, and you know, eventually amputation in many of our diabetic patients.
The difference is that in horses this stops at this line where we suddenly have this maintained insulin and a risk of insulin toxicity rather than glucose toxicity. The vast majority of our patients do not have hyper glucosemia. That's not quite a bit, sorry, I hope we'll move on there, but, they have hyperinsulinemia instead.
So what is equine metabolic syndrome? It's a collection of risk factors increasing the risk of laminitis. The vast majority of these patients are obese, although it has to be said there is a subset of horses that are obese on the inside but skinny on the outside, and therefore testing in horses that are perpetually laminitic, even if they phenotypically don't look like an EMS patient is very, very important.
These patients have insulin dysregulation, as I've already mentioned, and they're also likely going to have adipokine dysregulation, which I'll come on to in a second. All of which lead to an insulin resistance and an inability for the cells to respond normally to insulin. And whether this is a failure of the insulin or an excess of pancreatic production doesn't really matter because the end result is the same and actually the vast majority of the control is the same.
So when we look at insulin dysregulation, what is the point in investigating it when we know that 70% of our horses in the UK are classified as overweight? The diagram on the right is actually just for human obesity, but, you know, it just brings to the forefront how much of a problem this really is in our population, how misguided many of our clients are. The investigation into incident dysregulation provides a monitoring baseline, although quite frequently we don't see the improvements we would wish for.
But what it can do is it predicts a laminitis risk in our patients. And that's really important to be able to say to the owner, OK, unless you lose weight and change the insulin dysregulation of this horse, or control the PPID if that is the problem. Then this horse is at a x-fold increase of laminitis.
But in all of these tests, we must be aware of our testing limitations and we'll go through those in a second. So firstly, basal insulin assessment. It's a very easy test.
Obviously we can take the insulin at any time, and we've got some controls, sorry, cut-offs for our fasted when they've been starved overnight and resting as well. The one thing to say with this test is that there is a high risk of false negative in the in the results. In other words, we aren't going to get all the truly insulin dysregulated horses with this test and miss quite a few.
What can be useful though is the resting insulin assessment can allow the the vet and the owner to work out whether that diet is appropriate. Say if you want to turn out a laminitic pony on grass, you can allow them some grass access and then test their insulin and see what it's doing. Now, if it's staying nice and normal, then you're probably at a safer point than you were previously.
More realistically though, the glucose challenge is, is a good way to do it. And there are two tests that we can do. So sorry, first of all, you could, it's ideal to starve or give a small feed at night prior to doing this.
But we can either do a 1 gramme per kilogramme body weight of glucose or dextrose, and then test the blood 2 hours post administration. It's really important to get both a serum and oxalate fluoride, so looking at both your insulin and also your glucose, or run a glucometer at the time of sampling. The reason for that is that we want to know if you've had an adequate absorption of your glucose from the, the administration of the glucose.
The other one is looking at the Caro light test, and it's important it's Caroli with a GH, not LITE, because we don't want less sugar in there. We now recommend a 45 mL per 100 kilogramme, rather than the previously recommended 15 mL per kilogramme because a group run by Jocelyn, Aal at the RBC and here at Lit with Andy showed a much greater differentiation between the laminitic and the non-laminitic ponies, so far, far more useful. And then test that blood again with a glucose, a serum and an oxalate fluoride at about 75 minutes.
Do you need to starve or not? There was a study by Noeletal that found it was acceptable to test direct from pasture, but I think that came with a fairly strong caveat when you actually read the paper, which indicated that the results in those tests were far more variable than those in the starved patients. There was poor repeatability of the sampling.
And also, if you look at the graphs below, although statistically not significant, there's quite a big trend towards a lowering of the insulin in those horses that was fed. And therefore, we do recommend starving prior to these glucose or Caroline testing, whether it be for the whole night or whether you just give them a small feed prior to administration. Adipokines, I mentioned earlier, they are hormones that are produced by fat and are heavily involved in insulin regulation.
What we found is that leptin, one of the adiines, there are many of them, only assesses obesity, and so that's a fairly pointless test because you can do that with your eyes. Adiponectin, on the other hand, particularly high molecular weight adiponectin, is pivotal in increasing insulin sensitivity and also reducing inflammation. So a nice high normal level is what we're looking for.
But in these cases of EMS or suspect EMS, the adiponectin is low. What is its diagnostic use, though? It is, has been shown to be associated with laminitis.
It is an excellent marker, proxy marker for EMS. It is not definitively telling you at all whether this horse has equine metabolic syndrome. And in fact, it's very difficult to do that without a whole combination of tests, including this one, the Carolite, and ideally an insulin administration insulin tolerance test.
The big advantages of adiponectin is it's unaffected by stress or feeding and therefore can be given as an, or sorry, taken as and when it's sensible. Very briefly on two sides, just going to mention PPID I think most of you who know Libook are fairly well versed in the PPID conversation. But obviously PPID is a disease that affects the parts intermediate of the pituitary gland.
And varying changes in that pituitary gland are seen from mild enlargement and proliferation all the way to tumour development. All of these things lead to a pituitary pas intermediate dysfunction. Now, the actual correlation between PPID and laminitis is fairly sketchy, but what we do know is that most PPID cases have an elevated insulin, and therefore this insulin dysregulation is associated with PPID.
And what we've already seen with the insulin is that this is linked with with laminitis. So although it may not be direct, there is a combination and they all work together leading to laminitis. Two easy ways of testing, basal ACTH, the most simple, effective way of doing it and good throughout the year.
If so, you've got very odd or difficult cases, running a TRH stimulation is very sensible. And what we do is give 1 milligramme of TRH to a great horses over 250 kgs or 0.5 in a horse that's less than 250 kgs, and then measure that test at 10 and ideally 30 minutes post administration.
It is important to note that TRH is not licenced in the 1 patients. It is a special and therefore, side effects should be discussed with the owners, which can include muscle fasciculations, licking and yawning, chewing, phlegm and reactions, and coughing. But overall, there's been no significant side effects that have been alerted to either BMD or any of the people using TRH, including ourselves.
Seasonal testing is possible now with with the TRH stimulation. There are result guidelines for the autumnal period. But what is important to say is that range is huge when the grey scale, sorry, the ambiguous area is very large in the autumn.
So for non non autumnal samples, the grey area is 110 to 200 biograms, whereas in autumn it's 200 to 500. So that really does indicate that the results are not all that helpful in the autumn, autumn period. So, looking, we're now looking at the pathological changes of the foot rather than anything to do with PPID.
With further research recently, looking at the hyperinsulinemia model, which thankfully is a more natural model than the black walnut or SERS or sepsis models. We have been able to learn a lot more about the changes within the hoof wall. It's important to note that these research models are still not normal though, because there is an abrupt increase in insulin compared with the insidious onset that you see in the clinical presentation of these cases.
With that said, the changes noted on the histopathological samples occur from about 6 to 48 hours in the hyperinsulinemic models, compared with surge ones occurring near instantly. It's quite a difference between the SARS and endocrine samples, with SARS being an acute precipitous and severe laminitis, normally fatal in nature, whereas the endocrine is protracted subclinical phase and chronic, and that speaks volumes of what probably is happening histopathologically, and so really should change our viewpoint. What's been interesting though in both sets of histopathology samples is that there's a very limited spectrum of lesions that the lamellae show and therefore, there seems to be a relatively limited plasticity of the tissue to trauma.
So when we look at the slides, so this, all the histopathological pictures are from the paper by Patterson Kane in 2018, I think, sorry, earlier I referenced Karakkowski as the paradigm shift, but it was actually Patterson Kane, so sorry about that. But looking at this slide, the dermis is arising axially from the mesenchymal cells overlying the distal phalanx. So in other words, they're going to grow from the phalanx towards the hoo or capsule.
Whilst the epidermis is arising from the overlying ectodermal cells, which develop and then invaginate and create a primary and secondary lamellae. In initial studies, there's quite a big difference in the morphology in the lamellae cells. In other words, they, they saw a lot of what they thought were normal, changes in the lamellae, and they thought, put these all down depending on age, weight, environment, and made it, which made it very, very difficult to assess the differences between those affected with laminitis and those not.
When they then looked back as we've moved forward with our information, what they found was that many of the horses that were presented for histopathology were included in the study had been presented to the hospital for euthanasia for SERS related diseases. In other words, many of these horses probably had subclinical laminitis without actually anyone knowing it. In more recent studies though, there's now been a clear differentiation between those animals with and without laminitis, particularly in the hyperplasia cells.
So now we really are getting a bit more of a handle on the histopathology. So again, these are Patterson and Keynes slides. And what we can see in the first picture is that the secondary lamellae, SEL are sitting at quite an acute angle when compared to the primary lamellae cells.
And they are quite short and wide in nature. When you then look at the second picture, we can see that there is a marked elongation of the secondary lamellae with a more acute angle when compared to the primary lamellae cells. The, there's also, sorry, an acute, a more acute angle, tapering and narrowing of those cells.
Other documented changes can include nuclear rounding, abnormal location of the nucleus, and the stretching. It's thought that these changes occur as a stretching of the lamellae cells as the primary structural event leading to the laminitis. This stretching though, is shortly followed by an increased rate of cellular death and apoptosis.
And it appears that this death occurs in a wave starting axially and spreading abaxi to the who fall, leading to the clinical signs. When we look at these images, we can see that actually is at the bottom of the slide, and it's. The clinical signs of the abnormalities are far more evident abaxially adjacent to the hoof wall.
What we also saw in all of these slides, or they saw in all of these slides, was there was a very limited inflammation in both the chronic and acute changes. And in fact it's all just the lamella tearing and stretching. The big, and this is one of the big differences between these cases and the carbohydrate or black walnut cases, is this leukocyte accumulation within the lamella cells that occurs.
With those cases, the carbohydrate and black walnut, that leukocyte accumulation is, is at its worst when there is lameness and severe laminitis. And therefore, this indicates that those cases are truly laminitis inflammation, whereas the endocrine are a laminopathy and a disease of the lamellae. So When we look historically at all of this, the basement membrane was considered to be integral to the disease process.
But actually, when you look through all this literature, the changes seen within that basement membrane are sporadic and not reproducible in many of the laminitic cases. They are seen in some of the most severe cases though, so they obviously do play some sort of role. There was also a big discussion on whether matrix metallic proteinases were important, and they initially were considered hugely important.
The problem is that only pro MMP 9 was found in the hyperinsulinemia cases, and they were unable to demonstrate any evidence of MMP2 or MMP 9 increases throughout the the cells. And therefore, it probably plays less of a role in laminitis. So what does this mean for us and for the clinician?
I think it means that there's a window of opportunity that we really need to be looking at ensuring we take advantage of. So with chronic endocrine or pathological lesions, they have a pre-clinical stage. So the type and severity of lamella lesions was not correlated to the pain.
In other words, it didn't matter if they were severely painful. It didn't, they didn't mean they had severe histopathological lesions and vice versa as well. And that divergent hoofings were present in nearly all animals in these studies, indicating multiple episodes of laminitics or laminopathy episodes.
So, management of the endocrine disease at these crucial stages early in the horse's life will hopefully prevent or even reverse lamella pathology and allow these horses to do well. Coming back to how does hyperinsulinia affect the lamella structures, the reason I've sort of added this in as a second slide is that this is all slightly newer information. So tensegrity, which is a nice buzzword at the moment, is essentially the cytoskeleton maintaining its cell shape.
The basement membrane acts as an anchor point for these cells and therefore plays an imperative role, but the multiple proteins including kerotene are involved in maintaining the cytoskeleton shape as well as its joining to multiple cells around it. What we see in the laminitic or laminitis cases is that there's an alteration in kerotene in both the basal and suprabasal cells. So what does that mean for our hyperinsulinemia cases?
Insulin-like growth factor one receptors, IGFR IGF1R are seen to be reduced in lamella tissues whilst no other insulin receptors are altered in the lamellae tissue. IGF1R is seen to dynamically interact with integrins and therefore the intracellular signalling cascade in the cells, and the tensegrity of the cells. It's also very closely linked with the production and maintenance of keratin and therefore may well lead to reorgan reorganisation of the cytoskeleton and alteration in the tensetegrity.
So, insulin may well just affect the true structure of the cells, allowing the elongation and eventual tearing of the secondary and primary lamellae cells. OK. So moving on, one last thing is that there does seem to be genetic predisposition.
Now I think we all are fully aware of that when we see the endless cases of ponies with laminitis versus your thoroughbreds with laminitis. But Timson this year, or sorry, last year, took some samples from horses that were laminitis naive and horses that had had laminitis. So he took samples of subcutaneous adipose tissue as well as peripheral blood mononuclear cells.
And what he found was that there was a huge differentiation in the genes presented or active in both the summer and winter, particularly during the summer period. And that the vast majority of these genes were associated with inflammation, excuse me, inflammation. In other words, those that are genetically predisposed are likely to be more inflamed than those that are not.
So looking at treatment of these horses. Lots of this will be very bread and butter to the vast majority of, of clinicians, but I think it's important to talk about a few reasonings behind each of these things as well. So the main aim of initial care is going to be looking at the.
Deep bedding, the management of these horses at the point of care. So deep bedding is essential. Sand is the most appropriate option if we can use it.
The problem is that in the vast majority of cases, most people can't bed their horses down on sand. Therefore, a nice deep bedding, such as shavings or similar is what we'd be looking for. Tranquillizers are obviously very useful.
Now, Aopromazine has a slightly chequered history with this. A lot of people still want to use it to lead to hasodilation within the hoof capsule. But actually, there seems to be limited evidence that that's helpful.
And in fact, when you look at the the surge related horses, particularly, What we try and do with cryotherapy is actually reduce the vasodilation, and that has been clinically proven to, to help improve the clinical presentation of these cases. Therefore, I don't really use aromazine for its vasodilatory effects. I use it more for trying to keep these horses quiet and comfortable and willing to lie down and rest their feet.
Alprazolam Xanax is, has limited known efficacy in the vast majority of cases. It interestingly was used initially for horses or for mares that had aggression towards their foals. And what the big advantages of prazolam is that these horses don't become sleepy.
They, these, they really are just chilled out. I haven't used it for laminitis, but I have used it in multiple different painful situations and very stressed horses here with excellent responses. But One problem with it is that you are going to give the clients a large volume of alprazolam Xanax, which has obviously some degree of risk associated with that for abuse.
All support is essential as well as the deep bedding. So soft rides, these, lovely boots that you can put onto the hoof are fantastic, but do come at a very high cost. So really helpful in horses that have recurrent bouts of laminitis or people who are willing to spend a bit more money.
Furthermore, normal amongst us, we can lean to putty and pants. And it's really important that they are put on in the appropriate way. So looking at this, we use dental impression material here and mix it up as you would 50/50 with the two different components of it.
The putty should then be spread in the caudal third of the foot when the shoe has been removed. And then ideally place a pad and allow them to wait there. That's going to distribute the putty throughout the hoof, the sulky of the feet, and you can make sure that it has reached all the areas you want it to.
And then remove any excess and put a foam pad on there and then tape it all in place. Remember there were some of the Styrofoam pads, you do have to remove the edges of them to ensure that they could press appropriately. But these black foam pads that we have here are absolutely fantastic.
They have very little compression over time, although give a bit of squid for the, the, the comfort of the horse. So when we look at the whole picture, we have to get other teams involved, and I think it's important that from the very beginning a conversation with the farrier is maintained between both the owner and the farrier as well as the vet and the farrier. And what we're looking for is that the fund fundamental aim when considering vary is to consider mechanical support for the laminitic foot.
And what we need to do in the foot is counteract the distractive forces, naturally, namely the upwards ground reaction force on the dorsal hoof wall, especially during the breakover period as that horse walks. And then the caudal pull of the deep digital flexor tendon, causing distraction of the distal phalanx from the dorsal lamina, in other words, that rotation that we see within the X-rays. Now in the acute phase, the goal is to preserve the anatomical location of the distal phalanx within the hoof capsule, and therefore the vascular supply and hopefully the health of the foot.
Now in the normal digit, the net downward force exerted by the weight of the horse on the distal phalanx is counteracted by the upward internal load exerted by the internal lamellae junction, thus supporting the phalanx in the sling of the lamellae. But following disruption to the mallard junction, that net downward force on the distal phalanx may lead to its distal displacement, either sinking or rotation. And the unopposed for the rotation, this is the unopposed cordal pull of the dorsal, DDFT sorry, may result in rotation.
Counteract these structural changes, appropriate trimming and solar support is vitally important. And the radiographic, this is where the radiographs come in because radiographic guidance permits that the toe can be shortened sufficiently to ease that digit that breakover without reducing the forces of the distal interphalangeal joint. Meanwhile, solar support could transfer the load away from the affected lamellae around that tip of the pedal bone at the toe and push it further back.
So in the top left picture, we can see that really reduced toe and therefore reducing the breakover. Now that is quite a severe trim and guided by radiographs. In the upper right picture, we can see that convex look to this soul, which is associated with near prolapse of the pedal bone.
And on the bottom are just a few slide, a few, sorry, . Shoes that have been created by one of our farriers. And what these all allow for is access to different parts of the hoof, so that when there are abscesses, or similarly, you can continue to drain or to to clean those out as required.
I'm sorry about that. . But from my point of view, so, I normally leave our farriers to it.
We're very lucky to have absolutely amazing farriers here, who you can mostly just leave to do the job without too much interaction. But what we need to now advise on is how are we gonna stop this occurring any further. And managing the endocrinopathies is what we need to do.
What we need to look at is a combination of diet, exercise, and pharmaceuticals, obviously with a slight tapering of the exercise in the acute laminitic episodes. But. The most important thing to say is that diet is key to the whole process.
And what we need to be aiming for is a diet of approximately 1.5% of their body weight as forage. Now that includes any hay, haulage, hard feeds, anything else that that horse is given is included in that calculation.
The one thing to say is that it's wise to adjust the the, the diet according to the previous rations. So in some horses when they are being fed excessive amounts of 2.5 upwards of their body weight, dropping to 1.5% is relatively cruel.
So it's more sensible to drop to 2% for a week or two and then drop down further. Soaking is absolutely beneficial, but it's important that it will only remove the water soluble carbohydrates in that hay and therefore won't remove all sugars. About 50% of those structural water soluble carbohydrates will have been lost after about 8 to 16 hours of soaking.
But if warm water is used then they can be shortened quite dramatically. Now, when you soak, it's also important to remember that there is a reduction of about 14% in the dry matter of those of that hay, and therefore you are really going to affect the forage amount total being given to those horses. So you might have to adjust it, the 1.5% up a little bit when soaking.
Now the soaking will have very little effect on the proteins in that hay, but it will reduce the vitamin and mineral content dramatically and therefore a balancer must be given. Now when we look at the slight oddities in the equine population, those that are the skinny fat horses, in other words, skinny on the inside, but metabolically abnormal, we can move away from a carbohydrate rich diet to a fat-based diet, to include things like corn oil. I quite like a product called Copa Coolstances, which is coconut based one and has high fat and protein levels in it.
When we look at the weight loss management in these cases, it's essential to weigh prior to starting the weight loss regime, and that should be done on a we bridge, not with a we tape. That said, I normally use a we tape at the same time and allow the clients to then use it as a guide over the next few months. I normally also tell them when attaching the weight tape around the horse to look away when they join, when they join the two ends together so that they don't try and squeeze an extra few kilos out of that horse.
Ideally reassess the horse in about 2 months from the start of the weight loss programme. And what you're looking to do is to get approximately a 1% body weight per week loss. But obviously that varies between about 0.5 and 2%.
If though we're not achieving the goals that we have deemed appropriate, we need to reassess the food intake. That 1.5% that I talked about in the last slide is a very sensible starting point.
It can in some severe cases, be dropped even down to 1% of the body weight, but I would recommend very, very close monitoring, a weekly vet visits, to ensure that these horses aren't clinically struggling with that, and they may well be going into a hyperlipemic state or becoming very emaciated. And the important thing with these cases is to look at their environment. Are they being kept in a pasture?
Because if so, their intake from grass alone could be as much as 4% of their body weight in the day. And even those horses you've seen them all the, the ponies that just stick their head down and eat from the moment they're put into a pasture to not to being removed, could actually intake 40 to 70% of their requirements in 3 hours alone. Therefore, in a strict weight loss programme, you must stop turnout.
How else can we reduce the intake? Grazing muzzels are fantastic and will reduce the intake by 40 to 83% depending on the type of muzzle given, and also the sward length. And that said, it's very important to ensure that those on a very dry pasture where they're short sword length, are given, supplementary feed if required.
You can also prolong the feeding period by the use of fine weave hay nets, double or triple netting, and also, I quite like doing multiple hay nets half filled in different locations either within the field or within the stable. It's amazing how much horses hate to eat at the back of the stable. Also, we'll take a mouthful and then come to the front of it and keep going back and forwards.
Some of my clients have also created tracks to put their feed on so that they rotate around the whole of the field and keep the horse moving, and the weight loss in those cases is absolutely phenomenal. Another thing that can be done is you can get equine pedometers now, and what you can do is trial different ways of weight loss. In other words, do you put hay nets in places A, B, and C, and then see which ones they move to and from the most, and that can really help give that extra little bit of control of weight loss.
And then diet type is obviously going to be important, let alone with the soaking that we're going to do. So . A group last year looked at comparing Icelandic to standard bred and varying different non-structural carbohydrates.
So they were both assessing the diet as well as the genetics of these horses. In these groups, no history of endocrineopopathic laminitis was seen in either group. And what we could see was that the lower the non-structural carbohydrate, the lower the insulin and glucose response, which is fairly obvious.
And I think what's important, therefore, is to consider what's being fed and maybe even to get an analysis done. Anything less than 12% non-structural carbohydrates is going to be very good. Also, there was a, again coming back to the genetics, there was a lower response in the standard breds compared to the Icelandic, again, indicating gene does play a role in these cases.
So hopefully now with the client on board, we've got all of the management well under control and they're eating a nice diet. How else can we help though? So pharmaceuticals definitely have their place in these cases.
And the most frequently used is metformin. And what we're doing here is we're going to, well, in humans, it reduces weight by reducing sugar absorption. But that doesn't happen in horses.
Part of that is that it has a very poor bioavailability of approximately 4 to 7%. But we do know that it reduces, and inflict to one side and then come back. It does reduce the heat of the insulin following a glucose diet.
So this, the blue line shows horses that were given glucose in a feed, the glucose challenge. And we can see that that peak occurs, whereas those horses given metformin with a glucose in feed had a far more plateaued insulin result, and these horses are all insulin dysregulated horses. Therefore, it definitely plays a role in these cases, but what I have to say is that.
When starting this, there has to be a get out clause. In other words, don't get these horses stuck on metformin forever more, otherwise, you know, these owners are gonna be spending a lot of money on it. The dose is around 30 MB per gig, once, 2 to 3 times a day.
Now levothyroxine could play a role. It's a thyroid hormone, doses 0.1 mg per kg once daily and then gradually reduce.
For me. Why do we use it? I think that's the important question.
There were a couple of studies a little while ago, by Frank over in America that showed there was some weight loss and some improvement to the insulin sensitivity in the small subset of forces that he tested. Also, there seemed to be some help with enterotoxemia induced hyperinsulinemia, so it may well play a role in SERS patients. But for me and my personal experience of levothyroxine is that these horses can become very agitated with it, can become quite aggressive, and therefore, I'm not sure that it's the right thing to do in those that can't be exercised appropriately.
And what I'm showing you, these two pictures are of what can be done with diet alone. So this is a horse that was presented to me for laminitis, and the owners took the diet so seriously that this is in 3 months' time from a 5 body condition score of 5 to a body's condition score of 2.5 with diet alone and no exercise.
That horse is now doing very well and did not need levothyroxine whatsoever. And so it is always the lack of weight loss is always a failure on the owner's part, not on a biological problem. Vella flows in is something that I think could play a really important role in the future, and I really look forward to seeing some more of this.
This was a study that was performed under the funding of Boringer. So obviously we have to take every study that's funded by a drug company with a little pinch of salt. But on the basis of it, ellaioflation is a sodium glucose co-transporter inhibitor, which is going to reduce the renal glucose resorption and promoting a glucose urea.
Therefore, decrease blood glucose and insulin levels. And it has been shown to be very, very effective in humans with diabetes. In this study, they looked at 49 horses that had insulin dysregulation, and split them into a control and a treatment group.
Those in the treatment group had a much, a 22% lower glucose and a 45% lower lower insulin. And more telling was that the treaty group had no laminitis compared with the controlled group. So, as I say, this may well play a role in our future treatment of our EMS patients, but it's a few years from the market.
A brief mention of the SAS cases because I think we can't do the whole talk without doing that. It's really important in the SARS and sepsis cases to reduce the endotoxemia because that is what is going to cause our laminitis. And there are a few things we can do to try and help this.
One drug is polymyin B, which has absolutely amazing endotoxin neutralising properties. We are using this. It is an antibiotic and we're using it at a subtherapeutic antibiotic level.
And it's important to note that it is a quite a nephrotoxic drug, so we have to be cautious with its use, in case of those with endotoxemia that might have, renal perfusion problems. Clinics and melamine may attenuate the cardiovascular effects of ontooxemia at a TID dose. The study looks at Q6 or Q8 hours.
And finally, pentoxihyin on paper looks amazing. It's a methyl xanthine phosphodiestase inhibitor, which is going to be anti-inflammatory by reducing the tumour necrosive factor and MMP action, although, as I've already mentioned, MMPs may not play a role. I rarely use pentoxihy apart from in some of the extreme cases.
Cryotherapy, though, is highly effective as a prophylactic treatment when endotoxemia is suspected. And what you're aiming for is a 5 to 10 degrees temperature for 48 to 72 hours. So all of my cases of colitis or similar, will have cryotherapy for 2 to 3 days, at the very beginning.
And Van Epps in 2016 showed that a fluid bag with wader was the most effective beyond any very special contraption. So finally, analgesia, non-steroidals has multiple licenced products. Now when we look at these, .
I am a big fan of clinicin melamine. I am comfortable with that, but whatever you are comfortable with is what you should use. Just remember, when you are using Clunexin twice a day, you mean using it off licence.
So some care should be taken over its use and advising the owners of that risk. And what are those risks? The biggest risk is the the right dorsal colitis and nephrotoxicity.
And when we're talking about chronic administration, these are very real risks in these patients. So for me, it's really important to run bloods before starting therapy at a minimum for albumin and creatinine, but ideally for a whole basic screen. Some of the more Cox 2 selective products, meloxicam, for example, theoretically have less side effect risks, but in my experience have a much less pain relieving status and therefore I generally don't use them.
But what is important is that we look at a multimodal analgesia. So alongside your nonsteroidals, I pretty much put all of my true laminitic patients on paracetamol. At about 20 migs per kilogramme twice a day, and I interchange it so that every 6 hours, I'll give nonsteroidal paracetamol, non-steroidal paracetamol.
And that gives a much smoother pain relieving status in these patients. Some other species, or many other species suffer liver toxicity, although we haven't seen that in our equine patients but hopefully I'm gonna start looking into that a little bit more, judiciously. Opioids play a fantastic role in our care of these patients as well.
Obviously, we have to be concerned over gastrointestinal stasis in these cases, although the increase in GI stasis versus the increased stasis due to pain has to obviously play a bit of a role. When we look at them, We have morphine, butrophenol, injectables, but I personally lean towards fentanyl patches every single time. I think they're fantastic at giving a really steady pain relief.
One thing is that they are very abusable, so make sure that when you are putting them on, that you write across the elastoplast over many layers to say who put it on and the dose that is under there, so that nobody can take them off. Lots of these other things, looking at ketamine, lidocaine, morphine infusions, all great in a hospital. And we can even reach to a pentofusion, which is a mixture of morphine, Ace, domidine, ketamine, and lidocaine.
All great in the acute cases, but a little bit more difficult in your truly chronic cases due to costs. Really good study by Geddes, that looked at ketamine use for every 6 hours in 24 and tramadol, and he found that that really did improve the outcome in the cases. And so it's something that we really should be trying for in our hospital patients.
And finally, as a treatment, gabapentin. I, I pretty much put every single patient on gabapentin. It's important to note that it has no activity on GABA receptors itself, or of GABA uptake into the brain.
But what it does, it interacts with affinity binding sites in the membrane, which are part of the voltage sensitive calcium channels. But the effect of gabapentin. Remains unclear, and what they have shown in humans and rats is that the gabapentin increases GABA synthesis via these calcium channels.
And therefore, by doing that it increases the production of several other neurotransmitters and prevents a pain response in these patients. Alone, it's not very effective, but when used in conjunction with both paracetamol and non-steroidals, I do find it very helpful. But in some horses, it has absolutely no effect whatsoever.
It does have a relatively low bioavailability of 16%, so there is quite a wide dose range of 5 to 10 milligrammes twice to 3 times a day. Best to start on a slightly lower dose, because some horses can become neurologic on gabapentin as well. In the short term as well, you can use alpha 2 agonists and nerve blocks, but they really are for performing procedures rather than anything else.
So to conclude, obviously we all know this, but laminitis is a highly debilitating disease. And most frequently it is associated with endocrinopathic diseases rather than SARS or sepsis. And the multimodal treatment is essential, and that should include not only the barrier, but man managemental changes, pharmaceuticals, and also multimodal analgesia is absolutely imperative.
And I think we just always need to consider that these are now a syndrome of these endocrineopathic diseases rather than a disease entity by itself. Thank you very much for listening, and if anyone's got any questions, I'll be very happy to take them. Thank you very much for that, Jamie.
I'm sure many of you have taken a lot of useful tips away from that. As Jamie says, we have got a couple of minutes before we hand over to Rachel, so if anyone does have any questions, please do quickly pop them in the Q&A box, or if you've just got any feedback in terms of if you've enjoyed the the presentation, then please do pop it in there so I can read that out. Have we got anyone coming in with any questions or I think you might have been that comprehensive, Jamie, you've er stun them all into silence.
I got lucky there, didn't I? You did. I think we'll just save more to Russell, shall we?
Yeah, no, that's, yeah, it's sound good. No problem. Well, as I say, Russell does work with Jamie closely, and so does Rachel.
So if you do think of any questions, then, you know, I'm sure, . Still posting in the Q&A box, and, I'm sure they'll be able to either answer on Jamie's behalf or get the answer off him, and, we can give it back to you later on if that's OK. But, thank you very much, Jamie.
That's a great way to start this afternoon's session, for the equine stream. Wish you all the best for the rest of the day, and, if Rachel's there, we can start to move over to Rachel. So thank you very much, Jamie.