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Hi, everyone. We're going to get started in just a few minutes. So we'll just wait for some more people to log on. Okay. Hi, everybody. Thank you so much for joining us. Um This is part one of our diabetes and endocrine webinar on hypercalcemia. My name is Rachel. I'm an I M T three doctor and I'm working in Roland Hospital um in East London. Um and everyone is very welcome. So we will get started. I'm sure a few more people will um start to log in as we go if you have any questions and please put them in the chat box. Um And myself of ish, we'll try to answer them as we go along. If we don't manage to, then there is a section for questions at the end. Um So we'll try and get the information for you that you need. Um And I just want to say about this webinar, so this is not exam preparation, you know. So we will go over some pathophysiology which may help with your exams. But the main point about this is to help you on your day to day, you know, clinical care. So when you're on court and you have those difficult unwell patient's that. Well, that's what we want to help you with. Okay. So let's get started. Um And as you know, we're running this with the mind the bleed platform, okay. So we'll just get started with what you need to know. So, first of all, why do we care about calcium? You know, why are we doing presentation? Why do we worry about patient's who have high or low calcium? You need to know how the body regulates calcium. So it won't be too much on pathophysiology, but you need to understand it in order to understand how to interpret your investigations, common causes and you know, when to worry about your patient's the initial treatments that we would expect you to start on the ward. Um the investigations that we hope you would order and also very importantly, went to call to help. So why do we care? So as with all electrolytes in our body, we have a very tight normal range that we managed to keep um in that range via our body's homeostasis mechanisms. And that's important because calcium is essential for many, many of our functions that we need in our body. Most importantly for nerve signaling, for managing our bone health and also for clotting coagulation. Um and as we know, and why we're doing the whole talk is that there are significant health consequences if this calcium level is deranged out, those um that normal range. So there are actually a few different ranges for how we classify mild, moderate and severe hypercalcemia. But this is the one that we use the most in the UK. Um, so mild, we'll be counting. This is your adjusted calcium 2.6523, you're moderate, would be 3 to 3.4 and your severe would be over 3.4. And you see patient's obviously most sick when they're in the moderate and mainly in the severe range. And these will probably be the patient's that you encounter um when you're at work or aren't doing your own course. Um So importantly, this is something that I didn't have cleared up for a number of years and I think it's really important to go through. So ionized versus adjusted calcium. Now, you will be sitting in A and E and someone will thrust you a V B G and you'll say I'm not on that, I'm not on the, any team or you might not. But wherever you have to have a look at this BBg, and that will have an ionized calcium and hopefully a normal range on that for you as well. But also we obviously order lab test without calcium levels and it's, you know, important to know what the difference is and what we're actually measuring. So when we think about calcium, our body, 99% of our calcium is actually kept within our bones or store with our bones. So, only 1% is present in our serum and interstitium. And that is the calcium that we're measuring. Now, within that, we can measure your ionized calcium, which is typically represented on your venous or arterial blood gas. Or you can measure your bound calcium. Now, and you're bound calcium is what you get back when you send off your biochemistry blood test and you can get your total calcium and also your adjusted calcium on there. Now, importantly, ionized calcium is your active calcium. So is your calcium cat iron, which you are able to use for those functions that we just mentioned earlier. Whereas bound calcium is an estimate of your ionized calcium in your serum plus the amount calcium that's bound to either small molecules or larger molecules of proteins and most commonly albumin. Now, the important thing to understand is that most of the time you're adjusted calcium is a good estimate of your ionized calcium. And therefore, we can use that to kind of understand and treat outpatients, but sometimes when you have altered physiological states. So for example, if your acid base balance is off, if you're acidotic or help a lot ick or if you're in a low protein state, so say you have a low album, then um the amount you're bound calcium, that uh equation that we use to estimate the amount of ionized calcium is slightly off. And you think, well, why would that matter if you've got a little bit less bound calcium, maybe there's a bit less calcium overall. But the important thing to understand is the changes in your state that adjust your bound calcium do not change the amount of ionized calcium you have. So it's not like when one goes down, the other goes down, your ionized calcium is not affected by that. So if you're ever uncertain and you have a patient in front of you who's in one of these altered states that might affect their bound or adjusted calcium, just do a V B G because then you can get your answer and you can know your ionized calcium. That's the calcium that we actually use for the functions. Um Okay. So that is important to understand and I hope that makes sense going forward. Okay. So I know you've all seen this diagram a million times, but it's really important to just go over and it's pretty basic and it really, really helps you understand to the investigations which you're ordering. So this is your calcium homeostasis access. So at the top here, we have those four little dots are meant to represent your parathyroid glands. And there are four glands that sit on top of your thyroid and they have calcium sensing receptor on them and they sent him out calcium in your serum and then respond to it um uh with either reducing or increasing them out parathyroid hormone they release. So if you have low calcium, your parathyroid gland sense that and the increase the amount of parathyroid woman that they're releasing. And the parathyroid woman has many actions. But the main key ones, I want you to focus on our bone kidney and gut. So just remember it works on bone, kidney and gut. So your bone, it helps you release calcium from your bone or sorry, absorb calcium into your bone, um or release your kidney. It helps you re absorb calcium from your urine and then your gut, your kidney activates vitamin D and you're able to absorb calcium from your gut. So all those actions lead to an increase in your serum calcium. Um and then as it goes up and up and up, you get that negative feedback to your parathyroid glands and they reduce the amount of parathyroid, the hormone that you're releasing. And if this is all working nicely, then your calcium remains in the normal range. And um you don't have any kind of signs and symptoms. So that is how we all hope that our calcium access is working. So, remember bones, kidney gut. So when this goes wrong, what normally happens? Now you see here, I've got a little um screenshot of an image from protocol on the right hand side here, this is a really, really useful and easy to understand protocol. It's from the European European Society um for end technology, it's they're hyper calcemia guidelines. Now, what I would recommend you do. And I put a link to this at the end is that you download this as a PDF on your phone. That what I've done and you save it to say if you have an iphone, I save it to my books app. But I'm sure there's many different apps, you can save it too. So that when you're on call, you have a very quick reference point where you can just scroll through your your protocols and click on hypercalcemia. And as you're going or walking towards a patient or seeing someone, you can have a quick read and a quick refresh. And I find that so, so helpful because you can't remember all these things at the same time on a busy shift. So when we think about common causes, 99% of hypercalcemia is due to either primary hyperparathyroidism or malignancy. So those are the two main causes that you're going to be thinking about when you're assessing a patient and mainly in hospital, what we tend to see is patient's with malignancies because obviously they become unwell and then they get admitted. Now, there are many other causes of high calcium and they're the less common cause is listed here, which we will go through a few. Um But you don't need to remember all of these on every single shift. So what happens in primary hyper parathyroid? So this is the access that we described earlier. So you can see my beautiful graphic design skills. I've given one of these uh I've hyper plays one of these parathyroid glands. So one of them has got a bit larger and therefore, is not responding to changes in calcium as well as the others. And even if you have a higher calcium, it's still pumping out that parathyroid hormone. So, in this situation, you would see a high calcium with inappropriately either normal or high parathyroid hormone. So that should be low, that should be sensing the high calcium and going low. But it's not because one of the parathyroid glands is still secreted parathyroid hormone. And again, that works in the kidneys, bone and the gut to increase your serum calcium. And therefore you end up with the calcium. Now what causes that this the most common cause is a simple adenoma of your parathyroid gland. So, benign overgrowth, you can also get parathyroid hyperplasia. Um So kind of again, overgrowth, but that often commonly happens in things such as chronic kidney disease or patient's with end stage renal failure. Uh more rarely, you can get cancer of the parathyroid gland. And then it can be part of a syndrome such as multiple endocrine neoplasia. And then malignancy is the other really common cause. And again, we see a lot of this in hospital of hypercalcemia. And I guess you would think, you know, why is this actually happening? There's actually quite a few mechanisms at which malignancy causes hypercalcemia. Um but the most common causes are a release of parathyroid hormone related protein which acts like parathyroid hormone to increase calcium absorption into uh increase your serum calcium. But then there's also around 20% is from osteal isis, from metastatic bone disease where you get calcium released from your bones. There are rare causes. You can get cancers would actually release parathyroid hormone or reduce your ability to sense calcium and your parathyroid glands. But again, these are quite rare and the majority of the time it's this ectopic release of P T H related protein. Now, very importantly, when you measure your parathyroid hormone, your serum, you do not pick up this related protein that malignancy releases. It's not quite the same formula as your own parathyroid woman. Okay. So when to expect this. So we all heard a medical school. The bones groan, psychic moans Thrones. And I always think God, there's got to be one more and I can't quite remember it. Um And I guess it is quite a useful adage to go through. I sometimes do still go through it. But what I want you to think about more is I want you to think about patient's who have martin moderate symptoms and patient's who have severe symptoms. And which patient's are we going to expect this in? So most commonly hospital, it's going to be your patient's who have some form of cancer. Um And these will be patient's who either have a known diagnosis of cancer when they've come in. Or maybe this is their first presentation. Actually, they're presenting with hypercalcemia. So if you have patient's who either have a known cancer or they have red flag symptoms, which are making you worried. I want you to consider this in patient's. Now, the signs and symptoms of patient's moderate, moderate hyper calcium are very, very vague and I challenge you to find the patient hospital who says, um, if you ask them if they're tired and they say no, I'm raring to go unless you're in the discharge hours. I really just don't think that's going to happen. But more specific um symptoms that you can ask about a constipation, um It's feeling very thirsty and dehydrated and then moving on to patient's who have more severe hypercalcemia patient's who feel a bit modeled, maybe have some palpitations, bit of chest pain in relation to arrhythmias who present with vomiting. Um and importantly, other patient's and this is specifically in hospital rather than out hospital who you need to consider hypercalcemia with are those who are hyperkalemic. And you might think, why is that? But if you think about the treatment that we give for hyperkalemia, you know, we're giving them rounds of insulin dextrose and also often calcium gluconate um to protect my cardi um which is essential to do if you're worried about, you know, hyperkalemic related E C G changes. But remember some of these patients go through 234 rounds of this, say on a night or a day shift and you're giving them a high calcium load every time you do this. So you need to be aware that that is not innocuous and they are, you know, you are giving them a lot of calcium. So you need to understand that can have side effects. And then other patient's who come in who have known endocrine disorders to say they might have known primary hyper parathyroid or tertiary hyper parathyroid. So those patients' you would want to also, you know, check either with A V B G or with your biochemistry. But if you're worried just always do a V P G, okay. So the E C G changes that I mentioned we can go over. So this is a little clip from life in the fast lane, which is again, again, a great resource and I really recommend you guys using it if you don't before. It's got a good quick summary. It's got lots of images and obviously lots of E G. So they can. So the main abnormalities that we find with hypercalcemia on your E C G is shortly in the QT interval. Um in severe hyper calcium, you can get additional waves. So J waves or sometimes called Osborne waves. And if it's really bad, you can get basically irritability of the venture corn. You can end up in patients who have the fos um just an example of those J ways or otherwise called almost just so, you know what you're looking for. I have to confess, I haven't really seen that in my patient's before. Um, but it is something that comes up. So it's good to know what they look like. Okay. So how are we going to evaluate these patient's? So this is not rocket science, this is day one medical school. What do we do? We take a really good history. Now, obviously, this patient is unwell. Um then you need to approach them in an 80 manner, you know, resuscitate as needed. And it's part of that, you will gain some bloods and then probably, you know, find out they have a high calcium that way and, and start your treatment. Um but if you have a bit more time, then the history is really, really important. So you ask them those symptoms that we described and again, commonly they're dehydrated. So there Thursday, uh they're passing not severe in their constant abdominal pain, they're tired, nauseous. Um and then you can go through common causes. So again, if they haven't been diagnosed with the cancer, then you can think about asking your red flags. So any lumps or bumps or weight loss bleeding from anywhere and then other endocrine causes. So that would more come in at their past medical history or their family history. Um They're drug history is really important back to that slide and now we can talk a little bit about some of the other less common causes, but things you should know about other causes of hypercalcemia. So this actually came up in my patient exam. So, you know, maybe this is used, for example, at my station five as a patient who had constipation um and was on Thiazide diuretics. So, Thiazide diuretics is a cause of hypercalcemia, often can be multifactorial, you know, they may have something else going on. That's an important medication to think about because they're commonly prescribed and you know, consider stopping in this scenario. Um more rare genetic conditions such as familial hyper calcium rick hypercalcemia. And this is where you have a mutation, your calcium sensing receptor on your parathyroid glands, which means that the negative feedback doesn't work as well. And if you have a high calcium, your parathyroid glands can't re sense that and they still release parathyroid hormone. This because it's heterozygous normally. Um it normally uh comes with a more mild phenotypes or kind of borderline calcium and normally just a normal range P th but that's, that's inappropriate. Obviously in the context of a borderline high calcium, but they don't temporary 10% unless they're homozygous in a more serious phenotype. Um there's granulomatous disease um and that is a different mechanism. So in granulomas, you get activation of vitamin D independently and that can lead like we saw to re absorption of calcium from the gut, increasing your serum calcium thyrotoxic osis. Now you'd have other clues about, you know, that that's what's going on. Your patient may have palpitations and tremor and have a bit of history. Um That's important to think about and then also tertiary hyperparathyroidism. So this is where you have hyperplasia of your parathyroid glands, often in scenarios where you have kidney failure or quite bad CKD. And because your kidneys aren't working that well, you can't absorb calcium from your urine, you can't really activate your vitamin D and therefore you get constant stimulation of your parathyroid glands to release more parathyroid hormone. And after a while that causes the gland to hyper plays and then stop responding to the negative feedback so much. So you get an increased release and parathyroid hormone and then hypervitaminosis D or vitamin D toxicity, which is much more common now than you think because people buy this over the counter, it's very much discussed in the public. Um And it's kind of promoted actually on much of websites or social media sites. Now, I won't go through the whole list of the rest of them because you probably won't remember them. But again, I'd find this useful to save in your documents and keep on your phone. So let's go back to uh causes okay. So what investigations are important to do? So we would expect, you know, from the first line to do, like I say a V V G because that can give you a quick answer about your ionized calcium and give you lots of other information about the acid status of your patient and, and all the rest. And if you're worried about them, this is just another top tip, this is your gateway into I see you. You know, if you, if you think the patient is that unwell, we would expect you to obviously do their bone profile and including the calcium, the album and um and they're phosphate and the alkaline phosphatase is, um, we would expect it would be good to do a vitamin D level and you want to do a paired parathyroid hormone and that's important, it needs to be paired. Um, because you need to know what your parathyroid hormone is doing at the time of your calcium. Um, because you need to know if it's appropriately high, normal or low, we would also, if you want to be Uber, uber, you can add on some thyroid function and also do A C K and when you call your happy under fine reg, they'll say that's amazing. Thanks so much. Uh We would expect you to do an E C G and that's because we're looking for those arrhythmias or changes in E C G that we mentioned earlier. Okay. So now how do we interpret these investigations? And I would say this is the crux of this talk. So there is this concept about whether or not a calcium is P T H independent or dependent. And that basically means whether or not, the calcium is a result of a high parathyroid. And there's a problem with your parathyroid calcium access or there's independence, your parathyroid hormone is low. But still, for some reason, your calcium is high and you can show this here. So here you have a high calcium which is appropriate lead to a low parathyroid hormone. But for some reason, that's not resulting in a low calcium, that means there's an independent activity which is causing your high calcium. So this is a P T H independent hypercalcemia. But then if we look at P T H dependent, you have a high calcium. But for some reason, either that the centre mechanism isn't working or you're releasing too much parathyroid hormone, your parathyroid hormone is still high or, or normal and this results in an ongoing hypercalcemia. So this is a P T H dependent process and this is really important to get the difference between those two. And that means you can interpret your results accurately. So, just to hammer this home, so you have hypercalcemia and then you can divide your hypercalcemia two A P T H independent in your PT P T H dependent causes. So P T H dependent causes without have a high or normal calcium. And these would include your primary and your tertiary hyperparathyroidism. And also you're familiar hypercalcemic hypercalcemia again, much more rare and then your P T H independent causes. So your access is working but something else is causing this high potassium would you know, mainly be your malignancy. But there are other other causes which we listed above. So just to hammer home this point, this is another little screen shop from the Society for Endocrinology Guidelines and how to interrupt your P th they say here, high calcium and high P T H is normally primary to actually hypoparathyroidism with, with the caveat that F H is also included like we mentioned before. And then high calcium, a low P T H is either malignancy or one of the less common causes. And that really helps you kind of divide, you know, divide your um results are interpret results and help you work out what's going on with your patient's so treatment wise. So again, not rocket science and the thing that we would expect you to start the main, the main first treatment is hydration. These patient's are dehydrated, some of them are trying to excrete, they're calcium in their urine and therefore water for those calcium and they become very, very dry. So the first thing that we would want you to do is start them on some intravenous fluids. And the Society Friend Technology recommends 4 to 6 liters of 0.9% saline within 24 hours. Now, obviously, this is has to be tailored to your patient. If they're 95 they have florid heart failure. I would be cautious about giving them 4 to 6 liters in 24 hours, you need to tailor this to your patient and do regular monitoring to make sure that you are having an effect with this treatment. Um and that means regular blood tests and V B D s for a quick answer. Now, monitoring wise, if you're really worried about your patient, you've got E C G changes. These patients need to be on the cardiac monitor because you need to pick up a dangerous arrhythmia as quickly. Now, if this isn't working, say after 24 hours, you're repeating your blood test and your calcium isn't budging or if in fact, it's actually getting worse or higher, then then you would consider bisphosphonates. So this is a treatment um such as Solyndra Nick acid or permission eight, which we would start in that incidence and it's normally via an infusion. Uh the site a friend technology says alendronic acid, I think they say 4 mg over 15 minutes. And the important thing to know about this, it takes a few days to have its Axion. Um and it would take kind of 2 to 4 days. Um And I think in our trust, it has to be at least five days before you consider giving another round of this treatment. And importantly, sometimes it works so well that you actually end up with a low calcium and you actually end up having to treat that calcium and the bisphosphonates work by inhibiting the osteoclasts and therefore reducing the calcium release from the bone. There are more specialist treatments which we wouldn't expect you to start. This would be in discussion with your endocrinology team and normally the endocrinology consultant, um and these would include steroids which help reduce the activation of your vitamin D and therefore your calcium absorption from the gut. Um calcium emetics, denosumab and calcitonin other medications that we can use and then total parathyroidectomy in the cases where you have patient's with parathyroid adenoma. Zor, uh mainly adenoma or cancers because the hyperplasia tends to be most of the parathyroid glands. But again, if it's not well controlled, you can just have a total parathyroidectomy, but that does mean that you're then reliant on tablets for the rest of your life in order to maintain a normal calcium seem to not have low calcium for the rest of your life. And these patient's would end up on things such as out Calcitral. Okay. So let's go through a case. Um So I will put a poll on the side. Um and then you can answer and we'll see what the, see what everyone thinks. So I'll talk you through this one. So a 53 year old patient was admitted with abdominal pain and change in bowel habit. His initial biochemistry revealed an adjusted calcium, a 3.6 with your normal range there and alkaline phosphatase of 100 and 10, a parathyroid hormone of 1.5, a vitamin D of 35 what do you think? Um, the most likely pathology would be out of these four options. Now, I will give you one minute to have a think through this time. You got 20 seconds left. We go out, I think. Yeah, it's always tricky trying to work out the blood tests on this. He was like, oh, there's a timer. Okay. All right. That's great. That was a minute. So, let's have a look at the answers. Okay. So we've got a good split here. So we think 11% or 10%. Now think primary hyper parathyroid, 10%. Think malignancy with bone mets, 20%. Think um familiar hypercalcemic hypercalcemia and 60% think malignancy or parathyroid hormone related protein. And I'm not sure if you can see those results. Um my last fish to have a look at that. Hopefully you can see them in the chat box. Okay. So going forward. So the correct answer is malignancy with parathyroid hormone, um, release related protein. Um And I think most of you got that right, which is great, but there is a little bit of ambiguity, which is useful because otherwise you're not learning anything. So how I approach this on non core or whatever shift is I think is this process P T H dependent or independent and you work that out first and then you can get rid of some of your differentials. So with these blood tests, we have a high calcium and the P T H is low. So that is an appropriate response. So we're hoping that your access is working to some degree. So that would be a P T H independent process. So then you can rule out your primary hyper parathyroid. Um and you can also rule out your familiar hypercalcemic hypercalcemia. So those two have on. So now we're left with malignancy with bone mets and malignancy with parathyroid hormone related protein. Now, here you can see that your alkaline phosphatase is within normal range and you would expect a release because when you have osteoporosis with your malignancy, you also get a release of your alkaline phosphatase. So you would expect a slightly high out false. So that's why the more likely pathology here is malignancy with parathyroid hormone related protein. And importantly, like I said before, when you measure your P th it does not pick up this related protein. That would be a separate essay which I haven't seen commonly used in medical practice. Okay, great. That's case number one. Let's move on to case number two. Um And I think we will start the pole in a second. So I will read this out to you. So, a 35 year old Afro Caribbean male presents with lethargy cough and shortness of breath. He's found to have bilateral changes on his chest X ray and is treated for a community acquired pneumonia. His biochemistry is as follows. So it's a just to calcium is three. His parathyroid hormone is 1.1. His alkaline phosphatase is 100 and his vitamin D is 40. What is the most likely pathology? Again? I will give you a minute to have a think about this best. Do you want me to release that poll? Oh, no, it's released. Okay. I don't see where everyone was saying in the chat. So everyone's been shy and not put their grades and training experience and that you guys work this out before I ask you to do two things at once. Okay. Five seconds that just submit your answers. Okay. That's a minute. So we'll stop there. Ok. So again, we've got a good split. This is good. This means we're gonna learn something. Okay. So, tertiary hyper parathyroid, we've got 25% of you. Um oh, it's changing someone's entering okay. 23% granulomatous disease. We've got 53% humeral hypercalcemia, malignancy. We have 23% and vitamin D toxicity, we have 0%. Okay. So let's have a look at the right answer. So the most psychopathology here is granulomatous disease. Now again, we're going to do the same thing that we did last time. So let's work out from the biochemistry. Is this P T H dependent or independent. So you have a calcium which is high, not that high, but you know, moderate um and a parathyroid hormone which is low. So that is an uh an appropriate response, parathyroid hormone um So this is a PT eight independent process. So your access is working but something else is causing this hyper calcium. Okay. So you can get rid of your first option, your tertiary hyperparathyroidism cause that's a P T H dependent process. So then you're left with your last three um pathologies. So, vitamin D toxicity pretty easy. Vitamin D there is okay. So that, that is not the uh most likely pathology, humeral hypercalcemia, malignancy was a bit mean putting this in the humeral aspect just means like we had in the previous case, uh parathyroid hormone related protein release, but humor was just kind of hormonal release, but sometimes it's described as that. So it's important, you know what that means. Um So and then, so that option, then you're granulomatous disease. Um Now going through the stem of this question which again, you know, gives you a little bit extra to the case there. 35. So it does not, you know, it doesn't mean that can't have cancer, but it's a little bit less likely the Afro Caribbean and they have bilateral change in the chest X ray with the cough. So kind of what I'm going for here is this may be a patient who's presenting with sarcoid. So given the biochemistry, you can get rid of a few options and then adding the information from the stem. The most likely pathology here would be a granule over to seize such as sarcoid or if you're in East London, probably it's gonna be TV. Right? Ok, great. So, going forward, um, that was everything that we have today. Um, it's been about half an hour, 35 minutes, which is great. That's just on time again. I'm going to hammer home. You will remember some parts of this talk, hopefully, but you won't remember everything because no one ever does. So I would recommend going to Society of Endocrinology and downloading these guidelines, put it on your phone not sponsored by them, by the way, they're just quite good guidelines. Um And then you have easy access to a protocol on your, on your own course. Um I'd like to open up to any questions now so you can put them in the chat box. Um And while you're doing that, I would say here in my references, mainly images I was using. Um we and absolutely, we value your feedback. So please, can you either use a Q R code um or the link in the chat to give your feedback? That would be, that'd be great. OK. So I'll wait and see if there are any questions just to say that if you, if you don't want to type out a question, if you just put down question, I can, I can um let you um meet yourself and you can come on line if you're feeling brave enough to ask a question as well. I, I doubt they're gonna not want to put in the chat, but really want to say out loud. But if that, if anyone you're more than welcome to join, um or maybe you don't have any questions, sometimes people don't, I often don't at the end. Um So with the feedback, there is the feedback option in the chat and then please, if you fill that out, we really be grateful. And then I'm also going to provide you here on the screen with the QR code for our next session. Um So this will be provided by one of our endocrine and diabetes registrars um at Royal London and it's gonna be on oral diabetic medication on the 20th of January at 1 30. Um Okay, we have a question for all of us. So sorry if I missed this in the beginning as I've been like, but could you explain whether it is better to look at adjusted or normal calcium? So the adjusted calcium is an equation that the biochemists have created in order to help adjust for altered leveled levels of albumin and other protein molecules in our blood. So the adjusted calcium should be more accurate. But what I was getting at before is that even though the adjusted calcium is based on an equation to make it more accurate, if you have really profound changes in your pathology, like you're very acidotic, very alka logic or you have very low albumin, sometimes the biochemistry will just say we can't even read it because of the album is so low. If you have those profound changes, the equation can't really, it's not good, a good enough buffer to still equate for all those changes. So what I would recommend doing is a venous blood gas which will give you your ionized calcium. It give you a quick answer and an accurate reading about your ionized calcium because that is not changed by the acid base balance or the um or the protein content as much as the adjusted calcium. Okay. Um That's, that's great. So thank you everybody for attending. If you enjoyed it, then please let your colleagues know. We will add this a link to this, this uh lecturers recorder. So we'll add a link to mind the bleep and this is part of a series. So we're hoping to have at least 10 sessions um provided by the end technology and diabetes team at Royal London and Bart's um and all of the East Injury. Um And so we will keep going from here and we really, really look forward to seeing the rest of you next time. Okay, thanks everybody.