Good evening everybody, and welcome, to the webinar vet. My name is Andy Mee from Veterinary Management Consulting. And tonight it's my pleasure to introduce you to Jonathan Lidbury, who's going to talk to us about approaches to gastrointestinal bleeding.
Just to remind everybody, if you have any questions as we're going through the presentation, please, do put those in the chat box, and then we can come to them at the end. So, Jonathan received his veterinary degree from the University of Glasgow back in 2002, and after working in general and referral practises in the UK, he completed an internship in small animal medicine and surgery at the California Animal Hospital in LA. In 2007, he joined the GI lab as a PhD student student and then started a residency in small animal internal medicine in 2008.
He achieved board certification with the American College of Veterinary Internal Medicine in 2011, and he's interested in all areas of small animal gastroenterology, and he's working to develop new non-invasive tests for liver disease in dogs. He currently serves as an assistant professor with the Department of Veterinary Small Animal Clinical Sciences at Texas A&M University. So without further ado, I'll hand you over.
Thank you very much, Jonathan. Well, thank you very much for the introduction and, welcome, good evening, and good afternoon to everybody. So, I'm going to be talking about, gastrointestinal bleeding, this afternoon, this evening and how to approach it.
So we'll go through, diagnostic approach to this, important problem. I do have one disclosure about the presentation, and that's that I've acted as a paid speaker and I've received some research support from Infinity Medical and going to mention that Alicam capsule endoscopy system. So just bear that in mind during the presentation.
So, we'll start by talking a little bit about background, to the problem of, GI bleeding, and what causes it, things like that. So, the image here shows, a kind of gross surgical picture, of an ulcer, and hey, we've got on the right, we've got, a microscopic image of the same ulcer, which was, in this, dog's stomach. So, when we're talking about gastrointestinal bleeding, it's a problem that seems to be more common in dogs than cats.
Cats definitely can get it, it's just that the, the, the dogs tend to get it more often. It's quite variable in, in how severe and how, quickly it kind of presents. So you can have life-threatening, gastrointestinal blood loss.
And obviously, it's really important to kind of address that in an aggressive way, with supportive treatment to save that patient's life. Sometimes it presents in a, a much more kind of chronic, and insidious way. And sometimes then it's actually hard to recognise that the patient even has GI bleeding.
So very variable kind of, onset of this problem. So let's review, gastric acid secretion, and, we'll kind of come back to this a bit when we talk about therapeutics. So the, the figure on the left shows, an oxytic cell in the stomach, which is obviously the main producer of hydrochloric acids, so gastric acid.
And if we think back to physiology, there's 3 big stimulators for gastric acid production. One of those is acetylcholine. Histamine is another one of those, and that works via histamine 2 receptors on that eintic cell.
And then lastly, gastrin, is also a, a, a potent stimulator, of gastric acid secretion. And it's a proton pump, that actually causes, the secretion of the acid. So it's this, pump which exchanges hydrogen ions for potassium ions, on the apical surface of this genic cell.
So, the stomach pH and naturally in, animals is really down quite low, you know, PH1, PH2, pH3 after a meal. And that's a very acidic pH which potentially could cause all kinds of damage to the, the animal's tissues. But luckily, the body has several ways in which it protects the gastric mucosa, from that acid injury.
The first and outer layer labelled A, is a kind of thick mucous gel layer, which, are produced by cells of the, the gastric epithelium. And that mucus, also contains, bicarbonate layers, or bicarbonate ions, which, neutral, help neutralise the acid. Then, labelled C, we have this, tight, epithelial layers, with tight junctions between the cells.
And that really stops, paracellular transports of those protons to the acid, between the cells, back to the, the tissues beneath them. And then lastly, we have prostaglandins, which stimulates, mucosal blood flow, and also tissue repair. So they have a very important protective mechanism as well.
Unfortunately, even given all these protective mechanisms, sometimes they become overwhelmed. So, we can divide gastrointestinal bleeding down into different categories, and, firstly, you can get overt GI bleeding when there's visible GI blood loss. And so that could be hematosis.
It could be melana where there's altered blood in their faeces or it could be hematochezia when there's fresh blood. And again, that's called overt GI bleeding. Other cases, I, as I mentioned before, they're a lot more insidious and harder to diagnose, and those ones may not have, visible GI blood loss.
And usually, if it's possible, the next step with those ones would be, especially in human medicine would be to do endoscopy. And if you can find the source, after doing an upper and lower GI endoscopy, then those ones would be categorised as having obscure GI bleeding. Now, sometimes it's really tricky and you do an endoscopy, or you're not able to do one, as the case may be, and you're still not able to find the source of that bleeding.
In those cases in human medicine, I tend to have occult GI bleeding. So those are the hardest to, to really pin down and find out what's going on. And sometimes those occur in, animals as well.
So next, we'll talk a little bit about causes of GI bleeding and just recap those and suddenly there are quite a few different things that can cause GI bleeding. So, in very kind of general terms, I guess there's three possible things. The first would be gastrointestinal ulceration, and that's probably the, the most common, and oftentimes, that's, the ulcers are most commonly either in the stomach or the duodenum.
And obviously, the reason for that is that those are the areas of the GI tract that are exposed to, low pHs and gastric acid, the, the most, often. Hemostatic abnormalities, so generalised bleeding disorders could also cause GI bleeding. They tend to cause bleeding elsewhere as well, of course, and these tend to be a bit less common.
And then the least common cause would be vascular disorders, and for example, vascular actasia is a, a blood vessel abnormality, in the intestinal mucosa and that can lead to bleeding. That's really quite uncommon. So GI ulceration is the, the leading cause of GI bleeding.
So if we break things down a little bit more, then, drugs are an important cause of GI bleeding. Non-steroidals being, one of the, the most likely, class of drugs to cause, GI bleeding. Ibuprofen, tends to be particularly bad for doing that, but, other agents can do it, even agents that we think is being safe.
Glucocorticoids also can cause GI bleeding. Now, prednisone and prednisolone, in my experience, can cause GI bleeding, but they, it doesn't tend to happen that often. But you get the odd dog that is very sensitive to those agents, and it can sometimes cause GI bleeding.
Dexamethasone, is, a much worse culprit for causing GI bleeding. So given a high enough dose, a lot of dogs, and cats on dexamethasone will develop really quite significant and clinically important GI bleeding. Antithrombotic drugs like aspirin and clopidogrel have the, potential to cause GI bleeding.
We tend to use low dose aspirin for as an antithrombotic, and that can help alleviate that. Anticoagulants like warfarin or heparin, occasionally used in dogs, to inhibit coagulation, and those naturally could cause GI bleeding and bleeding elsewhere too. Next, we have systemic and metabolic disease.
So, a lot of time in textbooks, Emia is cited as, an important cause of GI bleeding, and so animals with advanced kidney disease, can have GI bleeding. In actual fact, there's a study in cats, fairly recently with chronic kidney disease and actually found that GI ulceration wasn't actually as common as we thought in, in those cats, but certainly there is a, a possibility for that to happen with the urethia. Hepatic disease, so, potentially portal hypertension could contribute to GI bleeding.
Certainly it's a problem in people. Also, it's interesting that dogs with intrahepatic congenital portal systemic shunts seem to have quite a high tendency to have GI bleeding. Also dogs with pancreatitis, and cats with pancreatitis can have GI bleeding, and also animals with Addison's disease as well.
Neoplasia. So, a variety of neoplasia could cause GI bleeding. So, for example, an adenocarcinoma, for example, a gastric one, oftentimes they have a very ulcerated and eroded surface, with haemorrhage that's visible.
Lymphoma could also potentially do the same thing. Mast cell tumours, these are an interesting one. So, even cutaneous mast cell tumours, could kind of remotely cause, GI bleeding.
And the way that that could happen is, that the mast cell tumour could release, histamine, which could cause the, the mast cell, the oxinic cells to, release acid. Gastronomas are uncommon, but obviously, we talked about gastroin being, a potent stimulator of gastric acid production. So, gastronoma is a differential for GI bleeding in dogs, especially when more common things have been rolled out.
And it's interesting that gastronomers tend to mostly be found, in the pancreas, although the pancreas isn't the big producer of, gastrin in adult animals, but they're believed to maybe have embryonic cells that remain in the pancreas, and sometimes those can become malignant. Again, overall, quite an uncommon tumour. A variety of infectious diseases can also cause GI ulcerations, so bacterial infections like Clostridium, parasitic species can cause, GI bleeding further down.
Oftentimes you don't actually kind of notice that bleeding because essentially, the parasites are consuming it all. So those could be tricky cases to actually diagnose, the problem. Parvovirus obviously can cause hemorrhagic, consequences in the GI tract.
If this kind of locally relevant, systemic fungal disease like histoplasmosis can cause GI bleeding. And then also, if they're geographically relevant, which unfortunately, they are in Texas here, algal diseases too like protothea. And looking at this picture of the Anlotova caninum, high magnification, you can see why this, parasite could cause, GI bleeding.
It looks really quite kind of terrifying at that magnification. Hemostatic disorder. So we kind of mentioned those before, but, coagulopathy, so problems with secondary hemostasis could definitely lead to GI bleeding, thrombocytopenia, could also lead to GI bleeding.
And in the class, we tend to forget we're not careful, be platelet function. Disorders, for example, von Willebrand's disease. So all of these potentially could lead to GI bleeding.
Now, usually, there's other signs of bleeding elsewhere in the body, but you may get the initial bleeding through the GI tract. So, an important kind of set of differentials to think about. There's a few other causes.
For example, in Alaskan sled dogs, that, taking part in, for example, ultra endurance races like the Iditarod where they run thousands of kilometres. They can have poor perfusions in the stomach, and, it's found that certain sled dogs would just drop down dead, when they were running this race. And they're found to quite commonly have GI ulceration.
And now a lot of these dogs, or most of them are actually put on antacid therapy, prior to starting the race and during the race. Trauma, for example, the foreign body, you can see in the picture here, could definitely cause bleeding, cause occasions occasionally, stress, and then I mentioned the vascular ectasia before as an uncommon cause of bleeding. So let's move on and talk a little bit about clinical signs of GI bleeding.
And I mentioned before that there's a lot of variation in, the severity of these. So, firstly, let's talk about overt GI bleeding. And melana as we've got in the picture here with the dark tarry stool would be a great example of this.
Hematosis is the other kind of classic one, and hematochezia is also possible. Now, in actual fact, you can have GI bleeding without having any one of these signs, and that's how you get the, the obscure and the occult cases. And it's actually been shown in experiments where they fed dogs, increasing volumes of blood.
You actually have to give them quite a lot of blood before they develop melana. So they found in this study that you had to give dogs 2.5 to 3.5 mL per kilogramme of blood, before you start to recognise melana.
So that's really quite a lot. And if you get less severe bleeding, you might just not see that melana, and so you can't rule out GI bleeding in those cases just because you don't see it. Something else that's really important to do is to try and differentiate hemoptysis, so kind of blood coming from the respiratory tracts from hematosis.
Now, if you actually see the animal bringing up blood, it's not normally too hard for a veterinarian or somebody with veterinary experience to tell the two apart, but sometimes you actually don't get to see it yourself. You're relying on an owner's description. And this is where things can sometimes get a bit complicated.
So we'll recap this. So with hemoptysis, the blood tends to be very, bright red, whereas with hematosis, because of that gastric acid, often tends to be kind of altered and so it's dark red, or brown. If there's sputum present, then it means it's probably come from the respiratory tract.
If you see food or other gastric contents, again, probably from the stomach and so probably hematosis. Hemoptysis often has a lot of air, mixed with it, so it has, a frothy appearance or it can be clotted, whereas you tend to get coffee ground appearance with hematomemesis. You could use a urine dipstick, so you could put a dipstick in, the, stuff that the dogs brought up or the cat's brought up.
If you get an acidic pH again, more likely to be hematomesis. If there's associated nausea and vomiting, again, likely to be hematosis, whereas if you have a patient in front of you that's in respiratory distress, obviously, it's more likely to be from the respiratory tract than hemoptysis. So think about this when you talk to clients because sometimes they find these things harder to differentiate than you would think.
So, I apologise for the, slightly gruesome picture, but this would be an example of hematosis. We can see the kind of coffee ground appearance, and the, the altered blood. The next picture shows hemoptysis, so, kind of bright red arterial blood, lots of kind of, froth and air mixed in with it.
So this would be a more typical appearance, and then there's some clots as well. So, the two are usually fairly easy to differentiate. So, obscure and occult GI haemorrhage.
Let's talk a bit about that next. So, there may be no GI signs. So as well as these dogs not actively vomiting or, having diarrhoea with blood, they may not even be vomiting or have diarrhoea at all.
They may have very non-specific signs, for example, anorexia, and One paper described a, or a case report described a dog that was stargazing, and that was the only clinical sign that it had. When that dog was worked up, it turned out that it had GI haemorrhage and gastric ulcers. And that would not be a, a, a kind of change that I would expect to see with GI haemorrhage.
So, keep an open mind about how these animals present. They may just present with signs of anaemia, so kind of insidious lethargy, maybe tachycardia, tachypnea, weakness, pallor. So, that can be another presentation, although it's a very, it tends to be quite often quite a chronic blood loss for these kind of obscure knock-out cases.
So, it may be a while before the dog develops any signs of anaemia, because they compensate for the blood loss well. And you may only suspect GI haemorrhage after you actually do blood work, so sometimes it's an incidental, discovery. So let's move on and talk about the diagnosis of gastrointestinal haemorrhage.
So, I guess there's, a couple of aims here. The first is to say whether the animal has GI haemorrhage or not. And then the other aim is to try and say what the cause is, what the site is, what's our best kind of treatment option.
And so you kind of take things in a stepwise manner. So, obviously, history and physical exam are a huge part of that. The, the most valuable diagnostic tests of all, the best value in terms of money, so they're really important.
So, obviously, you'll take a thorough history, but there's a few things you want to specifically ask the owners of these patients. So, exposure to NSAIDs, and chemo rodenticides, would be really important things to specifically ask about. Oftentimes, dogs with warfarin-type toxicity, there's a known, kind of exposure to it.
Quiz the owner and try and differentiate hematomesis from hemoptysis. Sometimes the history they give you, isn't as clear as you think it would be. So just take the time to go through things and, and ask the most important questions.
A couple of things to, to remember. Dogs can swallow blood from epistaxis. And so if you have a dog with melana or even hematosis, consider the possibility that they've got nasopharyngeal disease, for example, a big tumour in the nose, as they ask about nasal signs, just keep a bit of an open mind in general.
Also, the, the traditional rule is that when you have large bowel disease, you have fresh blood in the stool and hematochezia, and when you have small bowel disease, you have altered blood and melana. And sometimes if you have really kind of severe small intestinal haemorrhage, it passes, so much blood passes down the large intestine so quickly, and the small intestine, it doesn't get altered and so you can have small bowel disease with fresh blood in the faeces. It doesn't happen often, which is why that kind of rule is useful, but there are exceptions to that rule.
Physical exam, again, really important diagnostic step. You're going to do a thorough physical exam, in all patients, but things you want to pay particular attention to are generally triaging the patient's vital signs. So, if they're in shock and they've got GI bleeding, then you're going to approach things very differently.
You're going to want to start treatment and stabilisation as you're kind of working through things. Whereas if you have a stable patient, You've got more time to kind of work through things, and try different treatments, for example, before you, try other things. Have a good look over the rest of the dog for signs of, hemostatic disorder.
Have a look at the gums for PTA, have a look at the skin for petia and ecchymoses. Is there any blood in the eyes, a good retinal exam is a good idea. and perform a rectal exam, certainly worth doing in every canine patient, obviously with cats, not a well-tolerated procedure in cats.
And so, you have to pick and choose a bit with the cats and rectal exams. Evaluate the patient carefully for cutaneous masses. So I mentioned mast cell tumours can cause GI haemorrhage.
So have a good feel over the dog's skin. If you find an unusual bump, then don't discount it just because you're dealing with a, a primarily GI problem. That skin bump could be a mass cell tumour and could be the, the key to the animal's problems.
So haematology, so this is, can be, provides some important clues. So there's a few things to, to remember, and it, it can be a really variable picture in terms of haematology and haematological findings in animals with GI bleeding, depending on how acute or chronic the disease is. So remember, with her acute blood loss, when it's really, really acute, you may see no decrease in PCV because the body hasn't had time to equilibrate.
So you could be a hemorrhagic shock, with GI bleeding and you could have a normal PCV in total solids. With time, then that PCB will start to drop and that happens fairly rapidly over, you know, a few hours. So then you could start to see anaemia.
So, the first kind of categorization which you think about whenever you have a patient with anaemia is, do I have a regenerative, a pre-regenerative, or a non-regenerative anaemia. So, It's going to be that initial delay of around 3 days while the body kind of starts to, after a hemorrhagic episode, while the body kind of gets into gear and then starts to produce reticulocytes. So, for those 3 days, you're going to be pre-regenerative, but then after that, you're going to start to see a regenerative anaemia with blood loss.
Eventually, though, you can get iron deficient. So these patients lose iron in their stool, and eventually the body's stores are depleted. And then, they may start to become, less regenerative.
Although even with iron deficiency anaemia, reticular counts, reticularcyte counts vary. And obviously, the cardinal, kind of morphological change of red blood cells with iron deficiency anaemia is hypochromic, microcytic anaemia. And here on the, the picture, we have a, a great example where we have these, red blood cells from a dog with a larger area of central pallor.
We don't really have a neutral on this slide to compare the size, but these are smaller as well. Again, you can look at your smear, look at the red blood red blood cell indices too on your CBC. Platelets are variable, so you could have thrombocytopenia if your platelets are being consumed in an acute bleed.
So your platelet count may start to go down. It's probably not going, unless you have, a primary thrombocytopenia, usually with consumption due to kind of GI bleeding, then, the, the platelets aren't going to go down, you know, too low. They might be like 100,000 or something, but typically we start to get spontaneous bleeding when platelet counts get below 30,000.
And with haemorrhage, you shouldn't expect that unless the thrombocytopenia is the primary problem. With iron deficiency though, you can get a thrombocytosis too. So, again, haematology, important, but a very variable, picture with GI blood loss.
Serum chemistry panel. There's a few things you can see here. One thing that you can see, would be a pan hyperprotemia.
So on this particular panel, we have a low total protein, and a low albumin. Don't always have to have pan hyperproteonemia, but the globulins towards the lower end of normal. And, this would be consistent.
There's other things that can cause this, obviously, but, it could be something you see with GI bleeding. And also the other thing that you can get is an elevated urea, relative to the creatinine. So this, urea is 45, with the American or the, the milligrammes per deciliter reference interval, the top end of normal is 33.
So this would be elevated, whereas the creatinine is normal at 1.1 milligrammes per deciliter. Again, not every dog, or every cat with GI bleeding will have these changes.
These are relatively insensitive markers of GI bleeding. So don't rule it out just because you have a, a normal chemistry panel, but if you see these things, then it can be an important clue. There are obviously other things that can make, urea go up and make your albumin in some protein go down.
So, again, not sensitive, and also not specific for GI bleeding, but important things to look out for nonetheless. So let's talk about imaging now. So, most basic form of imaging that's, you know, available in just about every practise would be abdominal radiographs.
And these rarely lead to a definitive diagnosis in case of GI bleeding. But that's not to say they're not useful. So you can help rule out masses or an abdominal effusion.
For example, if you had a perforation of an ulcer, being really important to know about, if you have a foreign body that's causing GI haemorrhage. Again, really important to look about look out for. So, radiographs are a really useful technique.
It's just, don't hold out all your hope that they're going to give you a definitive diagnosis in GI bleeding cases. Barium swallow studies aren't, performed nearly as often as they used to be, say, 2030 years ago. The reason for that, they've largely been superseded by ultrasound.
It's just a, a more user-friendly, less time-consuming, more useful technique in general. But barium swallow studies can sometimes help detect the site of GI bleeding. This is from the, the Essenger textbook, but here we have this kind of, narrowing, in, domestic short-haired cats, with hematomesis.
And this is actually due to, a carcinoma in the gastric outflow tract, causing a partial obstruction in hematomesis. So sometimes barium is useful. Having said that, you know, certainly where I practise, we rarely do it because it takes such a long time and it's hard to interpret.
Ultrasound. So ultrasound probably is, the most useful, imaging technique for looking for GI haemorrhage, well, aside from endoscopy anyway. And so it is helpful, but again, GI ulcers and perforation are actually quite hard to directly detect with, ultrasound.
So if there's a perforation, you may pick up free fluid and that's actually quite easy to pick up, but actually picking up the perforation of the ulcer itself can be quite difficult. So, What can you see? You may see signs of GI thickening, you may see a mass, and you may actually see the ulcer itself, so thickening around the wall, loss of layering and potentially a crater or a defect.
And I'll show you an example of that on the next slide. Also with the ultrasound, just like with radiographs, it can be helpful for looking for lesions of other organs. So is there evidence of evidence of liver disease with portal hypertension?
What's the kidneys look like? Is there a mass somewhere else in the abdomen that could be contributing like a gastronoma or something? So here we have an ultrasound image, of a gastric ulcer.
So at the top here marked F, we have fluid within the stomach. We have the arrow, and the C. The C is the crater of the ulcer, and then K is actually an incidental hepatic cyst.
And so sometimes you can see these craters, they're consistent with a gastric ulcer. Now, the stomach is quite challenging to image with ultrasound because it can have gas in it. It can be quite hard to see the whole wall.
And so just because you don't see a crater in the wall of the stomach does not rule out a gastric ulceration. and so, you know, useful technique, but definitely has limitations. So faecal occult blood tests.
So the idea behind these, the, the blood tests that you perform on the stool, like the name suggests, and there should be a lot more sensitive than just looking for melana. So, in general, they can detect blood loss at levels 2 to 5% of those needed to cause melanin, so way more sensitive. So in theory, these should be really, really useful.
Having said that, we rarely, rarely use them. The reason for that is we get lots and lots of false positives, in our animal patients due to, dietary haemoglobin from the meats they consume in their diet. So, in theory, you can put a dog on a vegetarian diet for a few days before you do the faecal occult blood test.
But in practise, we rarely, rarely use them because it's inconvenient to do that. And also, with cats, a vegetarian diet, isn't probably the, the best idea for, an obligate carnivore. So in human medicine, they're actually really lucky that they have more specific tests of faecal occult blood tests.
So they have immunochemical tests. So rather than a chemical reaction for haemoglobin, that would then cross react with dietary haemoglobin, essentially myoglobin too. They have immunochemical tests, so antibodies directed against human, haemoglobin.
And so these work really well. They're a lot more specific than the traditional faecal occult blood tests. And it'd be really neat if we had one of these for using dogs, and or cats.
Unfortunately, none of these are available yet, but, they would be a, a really nice test for us to, to have. So, hopefully, one day somebody will develop one of those. It can also be important to assess the hemostatic system.
So I don't do this in every case with GI bleeding, but certainly if there's bleeding elsewhere or I was drawing a blank, finding an underlying cause, I do some of these things. I would do a platelet count on all these patients because that's really important, and it's part of the CBC, which would be part of the kind of minimum database for them. Remember though to confirm a platelet count with the blood smear exam.
It's easy when you've been out in practise for a while, and I myself forget that I can actually, I'm perfectly capable of doing a blood smear exam myself. But clumped platelets can confound, you know, the best haematology analyzers. So whenever you think you have, thrombocytopenia, confirm it by doing a smear exam.
Look for those platelet clamps. Bleeding times, this is where I pick and choose, but if I'm worried about a generalised coagulopathy, I'll at least do a prothrombin time and, activate partial thromboplastid time. And then if you really suspect haemorrhage, or generalised bleeding disorder, but you draw a blank on the platelet counts and the BMBT and the bleeding times, Assessing platelet functions is a good idea, and the simplest way to do that and the only really practical way in practise is to do a buco mucosal lead time.
Don't forget about platelet function. That's the aspect of coagulation that is easiest to forget about. So, further evaluation is sometimes needed, and this is when we start to get into more invasive, more expensive tests.
But in some cases, it's not really justified. So when would further evaluation be indicated? Well, if you suspect GI bleeding, for example, based on a, a non-regenerative or on iron deficiency anaemia, but we're not able to confirm it, then that might be a reason for doing some further testing.
If we know this GI bleeding, it's not responding to symptomatic treatment, we don't know what the cause is, then again, we might need to look into things a bit more. Or if that GI bleeding is really severe, then again, we might need to look into, into things some more, especially if they're not responding to symptomatic treatment. But some of these cases, if it's mild GI bleeding, we may just treat and if it resolves, we might be happy with that and not take things further.
So, in general, our options for taking things further, would be to actually look in the GI tract and so, we'd have the options of endoscopy or laparotomy, and I'll talk about the pros and cons of those next. So this is actually really interesting to think about this, because each has good and bad points. I'd say mostly where I practise we'll do endoscopy, and that's partly because we have an endoscope for several, and we actually really like to do endoscopy, but you may work somewhere where you don't have an endoscope, so it's not an option.
Each kind of has pros and cons though. So endoscopy is obviously less invasive, whereas exploratory surgery is more invasive. But, one, issue with the endoscopy is, even if you do an upper and lower GI scope, and I'd encourage you to do that if you are looking for GI haemorrhage and you don't find it on the upper, would be that, with conventional endoscopy, there's a big section of intestine in the middle, you just can't reach with the scope.
It's not long enough. And the other thing, is you think, when you're doing a lower GI scope, if there was a GI bleed in the small intestine, you'd be able to see the blood coming down into the colon or in the ilium, if you can, intubate the ileum. Sometimes you actually don't see it if it is mild bleeding.
Whereas obviously, if you have the dog open and you're doing a surgery, you can potentially access the entire GI tract. You can get biopsies with endoscopy. I would advise against biopsying an ulcer, a biopsy around the ulcer because that's the quickest way to perforate a dog.
And obviously, with exploratory laparotomy, you could biopsy, any lesion and potentially you could do an excision or biopsy of an ulcer. However, colonic biopsies are not commonly performed. So if we have a good suspicion of colonic disease, an endoscopy may be a better bet to get biopsies.
Minimal risk of dehissance and perforation with endoscopy. It can happen now, especially if you have a, a really kind of deep ulcer. And there's a, is a small risk of dehisance after an exploratory laparotomy, especially if you kind of, do an enteroptomy, especially in abnormal tissue too.
You obviously can resect lesions with surgery, which you can't do with a scope. But one important advantage with endoscopy is you're on the inside so you can evaluate the mucosa. So you can look at the gastric mucosa, the oesophagus, the duodenum, and the same on the lower scope, with the colon and the ilium.
But if you do a surgery, you're working from the outside in. And so, you can't actually assess the mucosa unless you make an incision and do a gasttroomy or an enterostomy. And then you can look at a small section of intestine or potentially the whole stomach to look for lesions.
But in some of these cases, With the occult cases, you won't know where the actual bleeding is occurring. And so with the surgery, it could be difficult to actually find which section of intestine to open up and look for the bleeding. So that can be a real problem.
And so some cases, a lot of cases will actually be able to find the source of bleeding with endoscopy. But some cases, there's occult cases we do an upper and lower GI scope, we're still not able to find out where the bleeding is actually from. So what can we do then?
Well, there's a couple of options. And I, I'll show you a couple of pictures first and then we'll go on to them. So this is a duodenal ulcer and a cat with a gastrooma.
So we can see the lumen here, and then, we've got this lesion here, which, isn't too deep an ulcer, but, certainly was causing some issues and pain for this particular cat. Here we have, a gastric ulcer that's actually, I can see a big crater here. It's not actively bleeding, but this is a dog given dexamethasone.
I mentioned before that dexamethasone is a bad one for actually causing ulcers compared with other corticosteroids. This is more generalised bleeding, from the stomach and a dog that was, thrombocytopenic or previously been thrombocytopenic. So this one's just, it's not localised bleeding, it's bleeding, diffusely.
This would be another one, with thrombocytopenia, which is a really pretty picture, but again, just more generalised, bleeding more rather than one site. So this image is really interesting. So this, what's happening here is you can see there's, two people doing surgeons and they're running the intestine, and we can see a light, shining in this, area of small intestine.
So what's happened here is we're doing an exploratory laparotomy. At the same time, somebody's got an endoscope in the dog's upper GI tract. And I mentioned before that the scope can't reach the, the middle section of the GI tracts in the jujunums, the, the big arrow we can't get to.
What we're doing here is we've got the surgeons, working on the outside and the scope, evaluating the mucosal surface, and then the surgeon kind of concertina, the loops of bowel over the scope. And this way, we can actually evaluate. Large areas of the mucosa, we can then get about halfway round and then do a lower GI scope and do the same again and milk the ilium over the scope.
And that way, we can actually evaluate the whole, the entire inside of the DOS GI tract this way. So, we don't have to do this trick very often, but in the odd case, it can be a neat way to actually find whether there is GI bleeding and exactly where that is. The other trick you can do during surgery is to actually aspirate bowel content.
So again, you're working from the outside in, you may not know where the site of bleeding is because you may not be able to find a mass and there may not be an obvious crater. So what you can do is you can use a needle to aspirate bowel contents, and you can start to localise in this area, obviously, that there is no blood, so the bleeding is probably not here. If we work our way down the small bowel, then we may be able to find an area where the blood does start, and then we may be able to localise things a bit better, though it's still kind of tricky to, to do this.
So, until recently, those are the only two tricks that we had. But in the past 3 or 4 years, there's a new modality of, imaging these dogs that's become available to practitioners, and that's actually capsule endoscopy, which they've been doing for about 20 years in people. So, capsule endoscopy involves the patient swallowing a relatively small capsule that has cameras on it.
And we can see the photo of the capsule here, we can see this camera here, you can see on the schematic, it's here. And then, this particular capsule has 4, so it takes a kind of 4 quadrant view. And basically, it's swallowed, it passes from the stomach into the small intestine into the large intestine.
I have to say that imaging in large intestine is harder because there tends to be a bunch of stool there. It's a nice way to image the stomach fairly well, but the small intestine images it's really well. And also, it gets to the areas that a conventional scope doesn't get to.
This particular capsule is the AIA by Infinity Medical, and, it's been used in dogs down to 6 kilogrammes in body weight. I wouldn't use it in a cat or a dog smaller than that. We don't want to get a capsule obstructed in the dog, then you will need to do surgery.
And this particular capsule, it stores the images on flash storage, and then the owner has to collect the capsule at the end of the study when it's in the faeces, and then mail it back to Infinity Medical, who, analyse all the images. And you can imagine if this is taking, an image every 30 seconds or so, for up to 18 hours, that's a lot of images to look at. And so they have a service where a couple of people evaluate those images.
Oops. So this would be an example of a small intestinal mass with the capsule endoscopy system. So we have the four quadrants, so 1234, again, to hit play on the video, and you'll see that the mass can pass on this particular screen.
It's coming now, so you see that the red arrow and it's gone. And what they do is they put the still images together and they make a video. This isn't actually a video coming off the capsule, but it's made into a video.
You can see you have to pay really close attention when you evaluate these studies, because that mass kind of came and gone. And I will show you a couple of still images, from the same mass, and you can see it here, and this was in the small intestine. So, Where I use this particular capsule is in a small group of patients where I suspect or know they have GI bleeding.
I've run the scope, I haven't been able to find the bleeding. I think it's somewhere in that section of the middle of the small intestine that I just can't reach. And then I will, recommend a capsule endoscopy in those particular patients.
In the US it costs about $500 or $500 to do that, procedure, so it's not cheap. But in that group of patients, it's really useful. If you don't have an endoscope though, then you may use these capsules, in a greater number of patients to work things out.
Obviously, you can't tell from the capsule endoscopy exactly where things are. You can tell whether you're in the stomach, you can tell whether you're in the small intestine, you can tell whether you're in the colon, but you can't really say exactly where you are. It gives you an idea of what you're kind of up against and where it is roughly speaking.
Here we actually have a hookworm, and this dog had a cult GI bleeding, treated with fambendazole several times, had a bunch of fecals, and still had hookworms causing GI bleeding. So let's, talk a little bit about kind of putting this together into a kind of flow chart and how we'd approach suspected GI bleeding, and then we'll kind of talk about iron deficiency and then we'll wrap things up by talking about treatment. So here we have, a patient with overt or suspected GI bleeding.
I guess first things I do would rule out metabolic disease and bleeding disorders, with lab work. And then imaging probably with an ultrasound would be, you know, my next step. And then potentially, if you find a source, from those tests, then you may treat symptomatically, or you may go on and do, an EGD, so an upper and lower scope, or, a surgery depending on where the location is.
Obviously, if it's in the dunum, can't reach the scope. So say you don't find a source on the ultrasound, if you have an endoscope, the next step would be to do endoscopy. And if you're lucky, you find the source, and then you can kind of make treatment decisions based on that.
If you don't find the source, or maybe if you don't have an endoscope, then you have a couple of options. One would be to do the capsule endoscopy, or you could potentially do a surgery. And, or you could do a combination of the two, the capsule first, try and localise the lesion and then consider the surgery.
So, a couple of options, but this would be the general kind of, kind of order of diagnostics in which I do things. And again, if you respond to, to kind of symptomatic treatment, you may not need to get down to these more invasive and expensive tests. So iron deficiency anaemia.
So there's a few things that can cause that, but blood loss is the big common one. So in neonates, you can have decreased iron intake because milk doesn't contain very much iron at all, and they don't have good body stores of iron. You can have decreased GI absorption of iron, maybe due to IBD.
I don't recognise this commonly in the clinics, floor, and so blood loss tends to be the big cause of iron deficiency anaemia. And then think about where the blood could be lost. So one potential will be the skin.
Usually, that means there's fleas, shouldn't be super hard to diagnose, but can be a really important problem in some patients. It could be coming from the respiratory tracts. Usually, the animal will have respiratory signs, maybe hemoptysis, maybe just respiratory distress, maybe it's coughing the blood and then swallowing it.
So I keep a bit of an open mind about that. It could be a nasal tuber that the bleeding and then the animal swallows that. GI blood loss tends to be the big one.
So that's the most common, and we talked to quite a bit about that. And then urinary is also possible, but again, usually, you'll see some sign of gross hematuria, certainly on a urinalysis, you would pick that up. So, again, blood loss tends to be the big cause of iron deficiency anaemia and the GI tract tends to be the big source of that.
This is a, a, area, an image from colonoscopy, and this is actually a vascular ectasia lesion. These are actually quite tricky to pick up. You could miss this very easily.
They tend to cause fairly low grade anaemia, but these would be, one of the trickier causes of, of GI haemorrhage. So it's important to keep an eye out for these, with endoscopy. So let's talk about treatments of GI bleeding to wrap things up.
So, in terms of the treatments that we have, we're still using the, the treatments that they've been around for a while. But we're starting to know a bit more about how to use them, in terms of having an evidence base to support our treatment recommendations. So we'll talk about specific agents in a little bit, but obviously, if you can address the animal's underlying cause, that'll be really important.
So, vitamin K for acumain toxicity, resection of a tumour, and homintics, all of those things can be helpful. Occasionally with really bad, non-medically responsive GI ulcers, occasionally surgical resections used, especially if the bleeding is severe or potentially life-threatening, but those are a minority of cases. So, histamine 2 receptor antagonists have been around for a long time in veterinary medicine, used really quite routinely, well tolerated.
They're maybe not the most effective acid suppressants though, but they can definitely help some patients. So, of the gastric, the H2 receptor antagonists formotidine is arguably the most potent. You can give that PO, sub-Q IM or IV.
Usually it's given per us or, IV where I practise. Ranitidine and cimetidine are also options, but one study showed that ranitidine was only effective as a saline placebo, only as effective as a saline placebo. And so because of that study, in my opinion now, if you're going to use, an HT receptor antagonist, skip the ranitidine, go to Formotidine.
Sametidine also isn't that potent and you have to give it Q 6 to 8 hours. So again, skip the cemetidine, and go to Formotidine if you're going to use a HD receptor antagonist. But again, they're not maybe as effective as the, the proton pump inhibitors, which I'll mention next.
So proton pump inhibitors provide the most profound acid suppression. So those H2 blockers only block, gastric acid suppression due to histamine, but they still get the secretion due to acetylcholine and gastrin. So the proton pump inhibitors work at the level kind of closer to the, the gastric acid production to that proton pump, which they irreversibly bind.
Ideally, you give them one hour before a meal, because they bind best to the pumps when they're active. So, ideally you give it before a meal. Having said that, I'm sure with clients that doesn't always happen, and I'm sure they'd have some efficacy given, with a meal.
In theory, they take several days to reach maximum efficacy, and we'll come back to talk about that in a second. So recent studies have suggested that it's most effective for proton pump inhibitors to be given, twice daily, so they have the fastest action, so, they become effective more quickly when given twice daily, and also seem to be more effective when given twice daily. So, usually we're recommending administration every 12 hours, omeprazole is obviously an oral form.
We give 0.7 to 1 metre per cake. Pantoprazole is an injectable form that's available in the US.
If you have an animal that can't tolerate, oral medications and you need to suppress acid to suppress acid production in the stomach, Pantoprazole is a nice option. I would actually, although it says Q24 hours here, and now I'd give the pantoprazole Q12 hours because it's more effective that way at the same dose. So I mentioned there's a few studies out there, and we'll quickly go through these before we wrap things up.
So this study compared omeprazole versus famotidine, and the punchline is the omeprazole was more effective. So the outcome measure was the percent time for which the gastric pH was greater than, 3 or 4. So, depending on the open or closed circles.
So basically, we want this measure to be higher because then the acid suppression is more effective. So first, we have a placebo here, and, and you can see that most of the time, the acid was beneath those two thresholds. Formotidine was a little bit more effective, and about 20% of the time, it was above those thresholds respectively.
We can see that here we have omeprazole tablets and omeprazole reformulated paste, and these were both a lot more effective, than the, famotidine. Now, This isn't to say that some animals don't respond to famotidine, so some animals will respond to famotidine completely, but the omeprazole seems to be more effective, and it is a good idea to give the omeprazole twice a day rather than once a day. So another question is, is combination therapy better?
So, potentially, you could give, a, a proton pump inhibitor along with an H2 blocker like Formostein. So this study looked at pantoprazole alone and pantoprazole in combination with famotidine. And the idea would be that potentially the famotidine acts very, very quickly, whereas the pantoprazole takes a while to really kick in.
So, again, they've used a similar outcome measurements, so mean percentage time for which the gastric pH is above 3 or 4. So we want this to be high if the drug's effective. So we have placebo, and, the two placebo groups here.
And then we have pantoprazole alone, and then pantoprazole in combination with famotidine. And you can see that, it's better than the placebo, which is very reassuring, but there's no difference between whether you give the pantoprazole in combination, with the famotidine or, in, on its own. And this pantoprazole was given twice daily, which is important caveat.
So, I would just give, a proton pump inhibitor. I don't see any evidence that you need to give famotidine at the same time based on this study. Do proton pump inhibitors have any adverse effects?
In humans, they talk about these, so, I haven't got time to go into these too much, but, we don't really know exactly which patients, gastric acid suppression therapy is indicated, and not in terms of prophylaxis. But if you have GI ulcers, it's an easy decision that you need to, to give a similar drug or a proton-pro inhibitor. It can cause things like diarrhoea.
It can affect the pharyngeal and gastric microcrobiotics that increase the pH in the stomach, more bugs can grow. In people, they've associated that with aspiration pneumonia, so that could be a big deal. If you stop these medications, in theory, you can get rebound, acid hypersecretion.
So in theory, you shouldn't suddenly stop a proton pump inhibitor if you've been on, if the animal's been on it long term. So, now I will do a bit of a taper with these, maybe over a week or so. I have stopped it cold turkey in the past before I realised this, it still seemed to be OK.
And, potentially in people, it can cause osteoporosis. No evidence for that in dogs or cats, but it needs to be looked at a bit more thoroughly. Sorallifate, nothing too much has changed here.
Has a bunch of beneficial effects. It forms a protective coat. It does make sense to give this in combination with an antacid.
You give it, away from other medications, which is a little bit of a, a kind of a hassle. And, you know, it, it's a good medication to give. Nothing much has changed here.
Mesoprostol is something I often get asked about, and I rarely use this, has a whole bunch of potentially beneficial effects of decreased acid production, more mucus, more bicarbonates, greater cell turnover, greater perfusion. It can cause some pretty bad side effects of vomiting, diarrhoea, abdominal pain. And also, you have to be really careful with, owners handling it because it's, you know, strictly contraindicated for, pregnant ladies to actually handle the misoprostol because it can cause big problems with pregnancy.
So, I will occasionally use it when I have known NSAID induced GI ulceration. Other than that, it makes more sense to give a proton pump inhibitor, because it doesn't, it doesn't cause nearly as many side effects. I don't use this in combination with the PPI use in place of.
And again, very rarely. Other supportive care may be needed to IV fluids, you may need blood products, you may need whole blood, red blood cells, analgesics, GI ulceration can be really painful in some patients. Anti-emetics may also be indicated.
So, look at the patient on an individual basis. So, to wrap things up, not all patients with GI bleeding have obvious clinical signs. Some of them will have no GI signs whatsoever, others will have very non-specific signs.
GI bleeding is the most common cause of iron deficiency anaemia. And so that's important to remember. There are other causes, but they're usually pretty easy to rule out.
If you know there's GI bleeding, proton pump inhibitors seem to be more effective than HD blockers. So I would go for a proton pump inhibitor. And based on recent studies, I would now use them twice daily.
They're more effective and act more quickly. You don't need that combination treatment. So, again, PPI by itself, and then I would throw toralfate too.
That seems to be a, a good combination. And misoprostol doesn't seem to be, something that's needed, for most cases, and NSAID-induced toxicity would be the one time when I would consider it, or preventing NSAID-induced ulceration would be another potential. Well, thank you very much for your attention.
I'll be, very happy to, to answer any questions and I hand back over to Andrew now. OK, well thank you very much for that Jonathan, a very thorough talk there on all aspects of gastrointestinal bleeding, really good. We've got quite a few questions for you actually.
The first kind of related, . I'll, I'll, I'll, I'll put two together, which is worse, non-steroidals or corticosteroids, and then does the route of delivery of the drugs that the particular question was around corticosteroids, but nevertheless, does the route of delivery affect or impact on GI bleeding? It's a great question.
. In my experience, I put kind of, NSAIDs, in my experience, of course more GI bleeding, than most corticosteroids. And then I would have dexamethasone, probably right up there with the, with the NSAIDs for causing GI bleeding. And, you know, we use NSAIDs in patients for analgesia and, you know, most of the time they're absolutely fine, so I wouldn't necessarily be afraid of them, of using them.
But we just need to be aware of that, potential side effects. Dexamethasone. I think part of the problem is, historically, it's been used at really quite high doses, much higher doses than the equivalent for Prad, and I think that's where part of the problem comes in.
I, DEX has given IV, but I'm not aware that necessarily the route necessarily makes a, a big difference in my experience anyway. OK, thank you. Couple of other questions then.
Which mechanisms cause thrombocytosis in cases of chronic blood loss? So in thrombocytosis, I think it's just stimulation of the, the, so when you have iron deficiency, it kind of, the, the body's trying to get the bone marrow to produce more, red blood cells, but it's struggling because it can't manufacture the haemoglobin because there isn't iron. And then those kind of stimulating signals, kind of as a, a knock-on effects ramp up, platelet production and cause kind of a, a reactive thrombocytosis.
OK, thank you very much. Another one here then, you might want to say what these things are, cos I'll be honest, I don't know what they are. Can you use clean prep or SIM in dogs?
So, I'm not aware of the SIM. I assume clean preps like a, a colonic preparation, so like a hyper osmotic agent before doing, an endoscopy. You can use products like that, to get a really good clean prep on the colon.
The problem is getting them into the dog. So, some people, the dog rarely kind of voluntarily drinks those. And so sometimes people will actually stomach che those or place some nasogastric tube.
The slight concern is that if you have a dog that aspirates an osmotic agent like that, it can, you know, really be quite bad for the lungs as you'd expect. And so some people would do it and they just place that nasogastric tube and they're, they're really happy with the preps they get. Personally, I just use, several warm water enemas.
The prep's probably not quite as good. But there isn't that risk of aspiration, but I think that's a personal choice thing. OK, thank you.
Is there an advantage of using esomeprazole compared to omeprazole? I'll probably pronounce those horrendously, but. Yeah, so esomeprazole versus omeprazole, I think they're both fairly similar, and the dose is the same.
Esomeprazole here in the US anyway, we can give it as an injectable form. So we tend to, we had a problem getting hold of pantoprazole, and we kind of, we, we switched to using it as omeprazole for a while and it, I, I'm not aware that in veterinary medicine anyway that one's better than the other. I think they can all be effective, .
OK, and then, a couple of questions around the Alleycam system. First one, are they reusable or is it just a one shot stop? And you mentioned, only really been used in dogs over 6 kilogrammes.
Are there other manufacturers that produce them that could be used in cats? Yeah, great question. So, the, the reusable question, unfortunately, they're not marketed as being reusable, because, yeah, I just have the one set of data in and you can't wipe that and the batteries are done.
So, yeah, that would be one, and though I have heard about problems where the dogs eat their own stalls and then it goes through a second time, which, can create problems. and then the other question, about the capsule size down to 6 kilogrammes, is there anybody else making a smaller one? I'm not aware of anybody making a smaller one yet.
I'm sure smaller capsules, you know, will become available with, with time, and I think Infinity may be thinking about that at some stage. Just the miniaturisation of the technology is something that seems to be happening on all fronts and, Previously, it wasn't possible to store the images on the capsule itself. It's only with the advent of flash storage, with a high capacity that they've been able to do that because in the old days, or with people, you used to have to wear a receiver, which had a hard drive on and that would record all the images, and then you'd have to buy the system to do it.
So yeah, things on that front are changing all the time, so it's, it's exciting. OK, and then finally, you mentioned about infectious causes, in human medicine, obviously Helicobacter is, is quite prominent, as a cause of, of gastric ulceration. What's the situation in, in dogs and cats?
Yeah, it's a great question. So, yeah, Helicobacter is really important in people in terms of causing ulcers and also, eventually, potentially gastric carcinoma too, and also a trophic gastritis, all kinds of things. In dogs and cats, it doesn't seem to be as worrisome, kind of finding.
So they found very high prevalence rates of, Helicobacter in dogs and cats. I think up to 90% in some studies of healthy animals. And so healthy animals can have these, organisms as well as disease.
And so it's hard to prove kind of whether they're causing disease or not. oftentimes those, organisms on histology aren't associated with inflammation. Most people don't treat for Helicobacter anymore.
Occasionally, some people will, so it's slightly controversial. The treatment tends to be kind of triple therapy with an antibiotic like a kind of metronidazole, bismuth, and then a proton pump inhibitor. And, Some animals will respond to that, whether it's because you're getting rid of the Helicobacter or whether because you're giving a proton pump inhibitor, bismuth and metronidazole to a dog with GI signs.
I think it's hard to tell. I personally don't routinely treat for Helicobacter. OK, right, well, as far as I can see, there are no more questions in either the Q&A or the chat.
I'll just give. Maybe 10 seconds if anybody wants to chip in with the final one. Whilst I'm doing that, can I just, remind everybody please to fill out the feedback questionnaire that you'll receive.
And that doesn't look like there's anything else coming in. So, just finally then, again, just to thank Jonathan very much for a very interesting, oh, hang on, oh, no, somebody's saying excellent talk, thank you. Yes, so please do leave some comments there if you like in the chat, and, we'll feed those back to Jonathan, but, just say Jonathan, that was really very interesting, very informative, very thorough, so thank you very much for that.
Thank you. Bye now. Cheers, bye.