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In this on-demand teaching session, second-year med students at the University of Buckingham, Kevin and Joseph, present a thorough exploration of the metabolic system. Their session, geared towards the UK MLA, has a particular emphasis on clinical diseases. The session includes an interactive examination of medicinal biochemistry, metabolism, and the main clinical pathologies involved in the endocrine and metabolic system. The students delve into the causes, complications, symptoms, and treatments related to Type 1 and Type 2 diabetes and diabetic neuropathy. The teaching session is recorded and will be available on demand for later review. This informative and engaging session is relevant for all medical professionals, particularly those studying for the UK MLA.
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UKMLA Revision held by Kevin Wogu BSc. & Yusuf Ahmad

The session will be 1 hour and 30mins with UKMLA style questions at the end.

Explore relationship between the Metabolic system and endocrinology as well nutrition and be able to apply this understanding to clinical practice in the future as well as part of the UKMLA Revision.

Learning objectives

1. Understand the pathophysiology of type I and type II diabetes, and be able to differentiate between the two based on patient symptoms and presentation. 2. Gain knowledge about the various treatment options for type I and type II diabetes, and what makes a patient eligible for each. 3. Understand the mechanism of action of medications used in the treatment of diabetes, including Metformin, DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 receptor agonists. 4. Learn and be able to identify the common complications of hyperglycemia and diabetes such as diabetic neuropathy, cataracts, atherosclerosis, ulcers and decreased renal function. 5. Be able to interpret blood glucose and HbA1C lab results, and using them to diagnose diabetes and monitor a patient’s glycemic control over time.
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Computer generated transcript

The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hi, Doctor X. We're just waiting for a few more people to join into the meeting. Hello, let me just check. Hello, Doctor. How are you? Hello, Kevin. Um, can you hear my voice? Am I loud enough? Oh, yeah, my, um, my gear is set up properly. I'll be right back. No worries. I just wanna change to webcam. If I may. Everything looks better. I forgot to put it on. I'm not a genius at, um, Texans. Are you all using webcams? Yeah, an inbuilt one on my laptop. I think. I think they make things look better, don't they? That's, can you see and hear me? Oh, well, we can't, we can hear you but we can hear you. Uh, I'm just going to leave and go back in. So I tell everybody. Hello? Yeah, we can hear and see you now. Ok. I'll, I'll stop my video and I'll mute myself if you like, sorry if I'm interrupting what you've already started. Just, it's all the best for today anyway. Um, and, um, I will be watching with interest. Thank you. Thanks. I can see and hear you. So do go ahead whenever you're ready. Yeah. We're just wait, we're, we're gonna wait for a few more people. But um, I'll start us now and then um just let people join as, as they're ready. So I, everyone, oh, let me, I put my camera on there. We are. Hi, everyone. Um Thank you so much for joining today's medical UK MLA revision session for those who are new. We're aiming to host um monthly sessions. However, I believe the next session will be uh next Saturday. Uh and these sessions are all geared towards the UK MLA. So in today's session, we'll be going over the meta metabolic system mainly with a focus on clinical diseases. Um This is presented by Kevin and you who you see on your screens. They are both second year med students at the University of Buckingham. And just so everyone is aware, the session is recorded and the slides will be uploaded onto med all so you can watch it on demand. Um But before we start, I'd like to just say, um these sessions are usually quite interactive. So if everyone can just keep your mic muted, unless you've been asked to unmute yourself. If you do have a question, you can pop it in the chat. Um and it'll be read out by either me or one of our members. If you have a really burning question that you wanna ask, then by all means, feel free to raise your hand and we'll um ask you to unmute yourself at the end of the session. Uh I'll send out a feedback form and if I can just ask everyone to fill it out as professionally as they can cause it'll help with the um presenters in their e portfolios. So that's all for me. And I'm gonna let Kevin and Yusuf uh take the wheel here. OK. So, hi, my name is Joseph. I'm a second year medical student and then this is my mate, Kevin. Yeah. Hello guys. My name is Kevin medical student. Yeah. So today what we're gonna be doing is um medicinal biochemistry. So, metabolism and is covering the main clinical pathologies, um involved in the endocrine system and the metabolic system. So let's make a start. So, first of all, what we're gonna talk about is, um, diabetes, diabetes is a very common pathology and people you'll see this everywhere again, it's unfortunately, um increasing in the population, especially in the UK, the United States. Um, due to like sedentary lifestyle, um, poor diet, lack of exercise. Um, so it's again, it's a big problem to really wrap our heads around and to understand the pathology and how to actually treat patients best. So, diabetes. So there's two main types, there are other types as well. For example, diabetes insipidus. But uh we won't cover that today. So type one and type two. So in broad spec b broadly, diabetes is uh your un inability to control your blood glucose levels either due to lack of insulin due to autoimmune destruction, type one or it could be due to insulin sensitive, uh ins um sensitivity in type two where the receptors just do, even if incidents present the receptors uh won't bind to it leading to glucose remaining in the blood. Um, and as a result of this, this leads to a hyperglycemic state which can cause multiple problems, which we'll get onto later. So, one of the, the key symptoms, the er things you really need to remember are, oh, go back. Sorry. Yeah. So it is gonna be polyuria, polydipsia, polyphagia. What do I mean by that? So, increased urination, uh polydipsia, increased, increased thirst and also polyphagia. Um it's gonna be like you increase hunger, but again, you're not absorbing the glucose into your cells and also glycosuria. So that's gonna be increased amount of sugar. Um You know, you, we start it. Thanks. So this is just a general overview of the pathology of type one. So in type one, again, it's autoimmune attack. So I just remember a as one which is the first that now that autoimmune. So what happens is that your um your immune system is unable to suppress CD four and CD. Um eight T cells CD four are that help the T cells which again, are present into antigens really cytokines to activate other immune cells. For example, plasma B cells which make antibodies and also regulatory or CD eight. Sorry. CD eight cells are cytotoxic uh cells which gra enzyme and perforin which destroy um the um destroy the cells. And this, this is what leads to the destruction of uh the beta cells in the pancreas. This is where they're made. So the pancreas has a few different types of cells. Yeah, beta alpha, delta alpha cells um make glucagon which um helps to raise blood glucose levels. Um in times of when you need glucose, insulin helps to decrease blood glucose levels. Delta cells make somatostatin. Um just we'll come onto this later. The somatostatin helps to suppress pancreatic secretions. So why in type one, it's a bit strange and type two is normally associated with obesity. However, type one is normally associated with weight loss and present at a younger age will get to the differences later. But why do we actually get weight, weight loss? Um In type one? Well, obviously in states um of, of um there's more glucagone than insulin isn'tt there. So we get increased adipose um and lipolysis and obviously when we're burning fat, um we're not uh storing glucose. Um this is what leads to um DK A and ketone acids are formed. Therefore, the amount of ketone bodies actually hinder and to cause me uh muscle catabolism. And therefore, we're breaking down proteins or um we're also breaking down fats for energy leading to um atrophy and weight loss, worsened complications of type one, the main complication of type one is DK or diabetic ketoacidosis? Why we have keto embodies while keto embodies form, our brain needs energy. However, fatty acids cannot cross the blood brain barrier. Therefore, what are we gonna use as energy while plain simply it's going to be ketone bodies. So what happens is in the fatty acid synthesis pathway? Um You get the formation of ketone bodies. Now, the ketone bodies can cross the blood brain barrier and uses energy and they eventually become a sho coa. However, there are some publications a as it is in the name acid, therefore, is going to decrease the ph of the blood leading to acidosis. So, some common signs of um acidosis are decay, nausea, vomiting, dehydration, um small breathing and also an increase in um potassium, which could lead to hyperkalemia which can lead to cardiac um uh arrhythmias. And also a really important sign is gonna be the nail varnish breath. Uh ketone acids uh produces a particular type of smell. So if you smell it on a patient, think DK a very important to uh treatment is fluids, potassium and insulin. But we don't get this in type two. we mainly get this in type one. We can, can you go to the next side, please? Ok. So this is type two. this is type two. Now, so in type two, what happens is or so imagine it as imagine insulin as a key and the tisin kin is receptor as a um lock. So when insulin binds the key, uh key to the lock, what happens is it opens, allowing glucose to move into the cell, glucose to open the door, move into the cell. However, over time, the more you use the key, the blunter and blunter it gets, therefore, it can no longer, it can no longer fit inside the hole of the um door of the lock. This leads to insensitivity. So what happens is to compensate for this, the body's still in a hypoglycemic state. We can still make incidents, not like type one for now and then to compensate for it, the beta cells hypertrophy which means increase in size to make more insulin, they also something called amylin. Therefore, the more insulin, the more amylin they produce. However, this is unsustainable. Um So as a result of this, what happens is the cells become damaged and lead to death amyloid plaques. And as a result of this, the beta cells begins to die, but that happens later on. Um And that's why people on type with type two diabetes actually have to get treated with insulin as well. Cos they eventually lose their ability to produce insulin as well. A problem with um type two. Is this something called hyperosmolar hyperglycemic state? What is this in really simple terms is understand that glucose is polar. Therefore, it's gonna draw water out of the cells into the bloodstream and this is gonna eventually lead to dehydration. In a very simple term. Here's some severe complications of diabetes. You get peripheral neuropathy, uh cataracts, atherosclerosis, ulcers and decreased renal function. The atherosclerosis is due to endothelial cell dysfunction which leads to plaque forming and its plaque hardens the blood vessels, hence atherosclerosis and leads to calcium depositions and it could eventually break to form a thrombus and it can lead to ischemic heart disease and potentially myocardial infarctions. Um Yeah, your next slide. Thank you. So, here's some treatment and diagnosis um for um type uh type two. So type one is only treated by insulin, plain and simple type two, however, is a bit more complicated. So the first line treatment for type one is gonna be Metformin. Then you have your DPP four inhibitors, um sulfaSALAzine SDL two inhibitors and uh G LP one receptor agonists like for example, Ozempic and these are helping in either um in increasing insulin release or de decreasing blood glucose levels and helping to move into the cell diagnosis is fairly straightforward. You need um one of these tests positive with at least one of the symptoms we mentioned earlier. So just remember these values are quite important random glucose above 11, fasting glucose above 72 hour. Um So OG TT above 11 as well. And you can also do something called HBA1C. This checks for glycated hemoglobin. So this is long term exposure. Uh remember the life cycle of red blood cells, roughly 100 and 20 days um take or give four months. So this levels accumulated glucose exposure. Uh it should normally be above 48 minimums per liter. Ok. Next slide. So a massive complication, diabetes is diabetic neuropathy. So, in diabetic neuropathy, it's quite actually complex. However, just remember the pathology of it and you'll be able to identify the signs um and treat it early. You normally treat it with amitriptyline and gabapentin and DULoxetine stuff to treat neuropathic pain. So what happens in a diabetic neuropathy is you've got a lot of glucose in your blood. And as you mentioned earlier, it is going to lead to uh macro and microvascular damage because it's going to cause in endothelial cell dysfunction. And as a result of this, there's less glucose, uh less, less blood available to the nerves and they begin to die. And there's also oxidative stress as high glucose levels lead to free radical forming free radicals can damage um the blood vessels. And also we have um microvascular damage in microvascular damage. Um uh sorry in um advanced GC of end products, elevated blood glucose can lead to the formation of glycated end products. These are proteins or lipids that become aggregated on the tissue nervous tissue. And as a result of that, um this damages nerves over time. For example, think of Alzheimer's and beta amyloid plaques when they develop, they inhibit anaptic connections. It's um very similar in this case. Um Yeah. Next slide please. So here's just a summary of the differences in type one and type two. So I'll just go for it. Quickly onset is below, normally below as a child or below the age of 30. Um, onset and type two is older. Um Normally you have a family history, um history of and weight loss. Type two. Normally you're overweight, um absence of a fatty liver in type one, a the presence of a fatty liver in uh type two. And in type one can only be treated by insulin. Type two has many different uh treatment options, including non pharmacological like weight loss, better diet, lack of uh decreased smoking and more exercise. Next sli sli please. Now let's move on to the thyroid gland. The thyroid gland is again a very important part of the endocrine system. You get your pancreas and then you got your thyroid gland. So you got two hormones in the er, three hormones. Sorry that the thyroid gland releases. There are two main ones. You got, um, calcitonin T four, T three and all T four is converted to T three. So T four is made of uh d uh dit uh two, dit ST um T three is made of one mit and uh one dit so understanding thyroid disease is very, II would say it's very simple. You've gotta understand what thyroid hormones do. If you understand that you will understand an e what excess of thyroid hormones will do. And what a decrease in thyroid hormones would do. So let's go over this. So, thyroid hormones help to increase metabolic rate and they increase heart rate by increasing the beta receptors. For example, in the heart beta one receptors to catecholamine. So they're more sensitive. So less has to bind to cause a bigger mass effect. They increase sympathetic nerve um uh activity again, operating up regulating beta receptors. Um they increase the production of heat. How they do this is actually they increase the size of the mitochondria. And we know um that the air transport chain produces heat, increases bone resorption, increases of protein to increase bone synthesis, increasing seba secretions and hair follicle stimulation. Next slide, please. Cheers. So this is how uh thyroid hormones are made. So very simply, there's a really important um element of iodine. We really need iodine for this. So what happens is iodine moves into the thyrocyte by a sodium iodine transporter on the apical side in the blood. So this is secondary to. So sodium potassium pump, iodine moves into the colloid by a pendrin channel. And when you think pendrin it's normally exchanged by a chloride thyroperoxidase is an enzyme which is located in the colored fluid um which is gonna convert uh the I minus er which is the iron of iodine to iodine, which is I two. Um And this and this helps to assemble into T three and T four. Next time, please. Thank you. So the way it works is that you have your control center, also known as the hypothalamus, giving signals to the pituitary gland. And the pituitary gland also called the macular gland, um gives signals off to the um uh thyroid gland and the endocrine glands. So, the thyroid gland, the pituitary gland is connected to the uh hypothalamus by the hypophyseal hypothalamic portal system. The hypothalamo, what it does is releases a releasing hormone trh. Um and trh, what this does is binds to cells on the anterior pituitary gland. Um and forms TSH, which is a tropic hormone. Tropical hormone basically means a hormone which has to be activated. So, th TSH um is made of alpha and beta change this um and this follows all the negative cycle. TSH, then goes to the thyroid, um binds to TS TSH receptors to stimulate the um cleavage of uh thyroperoxidase into T three and T four, which is then released into the bloodstream. Um Yeah. Next slide. Ok. So let's go to first of all, hypothyroidism. So, what are some causes of hypothyroidism? Remember the really important ion called iodine. So if you have, for example, have an iodine deficiency, um and we can also have, for example, trauma or radioactive um uh lithium, which could cause damage to the thyroid gland. So what what do we mean by primary um hypothyroidism and primary hypothyroidism? Think any anything endocide, primary, secondary primary is normally due to the endocrine gland itself secondary is due to the pituitary gland and ter tertiary which is rarer is due to the hypothalamus. It does happen. However, so primary of a known cause is called hashimoto's thyroiditis, which is an autoimmune destruction of thyroid follicular cells. And this causes the uh decrease of T three and T four. Um ok. Yeah. And this uh and also what are some signs of um hypothyroidism. So, remember, think in your head understand what thyroid hormones do. So, here are some clinical features. We're going to have some uh weight gain. Remember. Um and, and hypothermia because decrease um mitochondrial size. Therefore, we're making less heat. Uh We're gonna have depression, um lethargy, decrease um sympathetic activity, lower heart rate because it's decreased um sensitivity to catecholamines. We're gonna have constipation as thyroid hormones normally help water to be excreted um from cells into the lumen of the gi system. And then myalgia um is again decrease um uh decrease me, me, me like activity uh leads to muscle pain. So, in um and also get growth restriction in uh hypothyroidism. What happens is thyroid hormones help to release insulin like growth factor, which is really important in growth, especially if you're at the end of your epiphyseal growth plates. Um It leads to a little bit of more of a short stature. So how can we treat this well? Simply levothyroxine iodine supplements and surgery. For example, if there's any tumors, um diagnostics, the best to look for is low T three T four A and also you're gonna look for thyroid blocking receptor antibody positives. Um If there's hashimoto's thyroiditis, next slide, please. Yeah. So um this is just a um this is a summary of what we've just been uh talked uh talked about. So you can go to the next slide. OK. So now let's talk about hypothyroidism. So the exact opposite of hypo. So again, think about what thyroid hormones do and what happens if there's too much. So obviously, there's an increase in the blood. So primary causes, for example, uh the, again, the problem is in the thyroid gland, right? So we could have for example, a TSH tumor in the pituitary gland um medication like amiodarone which causes thyroid toxicity. Um And the main autoimmune disease is called Graves disease. Um So where we have IgG antibodies, what they have, they bind to the TSH receptors and remember when TSH receptors are bound to it increases the production of T three and also uh increases the production of T four. So w and we also get something called congenital hyperthyroidism. This is where remember I GG antibodies can cross the placenta. I GM can't. So how, what happens is unfortunately, I GG antibodies cross the placenta into the fetus and it starts producing way too much thyroid hormones. So, what are some symptoms? Again, think we too much thyroid. Think about what it normally does. You're gonna get weight loss, you uh increased metabolism, you're gonna burn more calories to consume. You're gonna have overheating. Uh you're gonna get sweating, bone thinning, uh increased heart rate due to the increased sensitivity to catecholamines and also trouble sleeping with your brain and your sympathetic activity is gonna be on overdrive. Um treatments, for example, are radioactive iodine therapy, um nausea, carbimazole, carbimazole normally inhibits um uh thyroid and perox um in inhibits thyroperoxidase. Therefore, iodine cannot combine with thyroglobulin next time please. And this is just talking about Graves Disease and I wanna talk about something called um thyroid eye. So normally, if you've learned about uh thyroid disease, you're familiar with the really common sign of the um um bulging our eyes. But why does that actually happen? So what happens is that auto antibodies against the um attack the eye muscles? But why basically eye muscles have this receptor, the I GF one R receptor, which is found in the. So the antibodies, again, the immune system is intelligent, but it's not that intelligent. It can't tell clearly, can't tell foreign antigen from our own tissues, especially in ultra conditions. Therefore, what happens is it binds to these I GF one R receptors and this leads to avenal destruction and immune response leading to fibrosis. And this pushes on the nerves and the vessels of the eye leading to the bulging of the eye. Um That's why you get the um th sta and grave disease. Um Yeah. Next LA. Ok. So let's talk about. Now, we're talking about congenital hyper, let's talk about congenital hypo. So in congenital hypothyroidism, um there's primary and secondary causes. So primary causes agenesis. Therefore, the thyroid gland just doesn't develop ectopic thyroid surface in the wrong location. Therefore, inhibiting its function. Um and a secondary which is hyperpituitarism, therefore, decrease T HS symptoms. Um very similar. We have decreased activity, increased sleep constipation. Remember, thyroid hormones help fluid move into the lumen of gi tract. Um are gonna be a prolonged jaundice. Some common sign is a myxodermus space. Uh large fronton macroglossia, which means in uh tongue size and then the distended abdomen treatment, um lifelong levothyroxine, which actually leads to a very good prognosis. Next slide please. Thyroid stone in, you can see this light in the end of where because these are quite common. This is where the symptoms of hyperthyroidism basically go into overdrive and lead to a hypermetabolic state. So um mainly occurs due to graves disease, toxic nodular goiter, even hypothyroidism, taking too much thyroid medication can lead to a thyroid stroke. So, lost some triggers. Some triggers are going to be uh surgery, trauma, infection or childbirth. Uh and symptoms, it can be very similar. There can be fever, agitation, confusion, seizures due to increased metabolic activity, coma, and cardiac arrhythmias. Next start, please. Right. So now we're gonna go on to the hypothalamus and then the pituitary gland. So the hypothalamus again is the massive control center and followed by the master gland, pituitary gland. So here is some fun. And again, remember the Pneumonic ta hats. So it's gonna be th adenohypophysis, neurohypophysis, hunger, autonomic nervous system, temperature control and sexual response. If you remember these, you should be fine um in exams and they help to regulate a lot of body functions. For example, the ones that I mentioned heart rate, BP, osmolarity, goal seeking, behavior, and motivation, emotion, um the nervous system uh and uh aggression as well. Pituitary gland is also really important. It's known as the master gland. So what these make are pro hormones are tropic hormones. So, for example, I remember a few of them in the anterior posterior. I remember the posterior, it makes a few, it makes 80 antidiuretic hormone. Um It also makes um Oxytocin um then the anterior remember makes everything else basically. So TSH G um it's gonna make growth hormones, it's gonna make um prolactin. Uh It's gonna make ACTH which helps in adrenal which recover later. Yeah. Next slide blues. Yes, it is um control of the PP axis. So the brain sends a signal to the hypothalamus is is detected, the is gonna release signals to the pituitary gland by um hormones or neurocircuitry. And then it's the pituitary gland is going to go to the endocrine gland and this follows a negative feedback cycle. The table to your right represents uh the tropic. Um the trh from the hypothalamus, then going to the pituitary. So for example, um C Rh goes um to pituitary gland and this releases ACTH where it increases uh cortisol production. Um GH Rh growth hormone, a recent hormone uh activates the release of growth hormone which goes to cells to increase uh proliferation at the end of end of epihyal growth plates and also uh goes to the liver to make more insulin like growth factor. Yeah, next slide, please. So here's some complications with the pituitary gland um and the hypothalamus. So really common is acromegaly. So what happened to acromegaly? There's way too much growth hormone, but this happens after your epiphyseal have closed up. Unlike giantism, giantism, you get way too much growth hormone release um during uh puberty. So when your growth plates have not sealed up. So what are some features? So you're gonna have, for example, spade like cancer, increased finger, uh finger size, increased shoe size, large tongue. Um you're gonna have enlarged hands and feet, enlarged facial features, uh fatigue, libido, visual problems, headaches and menstrual cycle irregularities. Um So why does it cause a and and it also causes diabetes? I look back but why does it actually cause diabetes? Well, in simple, what happens in acro is you'll get an increase um in growth hormone growth hormone obviously in helps to increase the growth in your bones. But the thing is your bones can't grow from anything. They need energy and they need fuel. Therefore, growth hormone also helps in myolysis and it also helps in um uh it helps in uh GlucaGen. Therefore, there's a lot of glucose in the blood and we know what that means. More insulin. And as a result of that, the lot the key uh gets dull over time and is unable to open the lock leading to diabetes. The treatment for this um is something called, I can never pronounce this um octreotide. So, oxide is basically a analog of somatostatin or we know what somatostatin does. It inhibits the release of other hormones um and it inhibits the release of growth hormone which is also released in the pancreas. Um an insulin therefore, um helps to treat the symptoms. However, it could just have a few side effects for uh a major one could be cast. No syndrome, cast. No syndrome is the increase in serotonin which leads to subcutaneous flushing, valvular heart disease and also diarrhea, a big serotonin. Obviously, gi mobility leading to this diarrhea. Next um slide please. Now, I wanna talk about um a common pathology called multiple endocrine neoplasia. A also known as mid one and two. So, these are a group of inherited diseases that cause tumors. Um and endocrine the they're very similar, but they do, they have a bit of overlap. However, there's a a few differences. So the main endocrines, uh endocrine glands affected are the pancreas, the adrenal pituitary, thyroid and parathyroid there are three, main types. It could be men. One, it could be all men two A or men two B in men. One, the ret gene is mutated and found on chromosome 11, chromosome 11. Um, codes for a tumor suppressor protein. Um, and then re, for example, um, which is in, er, men two me, ahe is a pro to oncogene. So, um, a pro to oncogene is basically, um, actually, yeah, you guys told me in the chat. Um does anyone know the definition of an approach to oncogene? Anyone or you can um put your mics on and what's the difference between a pro to oncogene and oncogene? Anyone? Let's just check the chart. No, nothing. OK. So difference between A and this is really good for your mod and your cancer lectures. Uh Proto oncogene is a normal gene and it helps to code for, for example, cyclins and CDK complexes which increase cell proliferation, which is normal. That's fine. We need to increase cell proliferation to repair. However, an onc gene is where the approach to oncogene has been mutated. And therefore, it's uh basically making way too many growth factors. And what happens is it eventually leads to uncontrollable cell division. That's the main difference. It started, please. So this is men men two A. So you get thyroid medullary cancer, which is the most common type of cancer. So, in thyroid medullary cancer, um this is the cancer cells make way too much calcitonin. Um And as a result of that, um you get decreased calcium levels. Our main symptom is a horse voice. Your adrenal, um, adrenal tumors and adrenal tumors, you get a pheochromocytoma, phaeochromocytoma. What happens here is basically, you get way too much catecholamines, catecholamines are gonna uh constrict, the blood vessels increase the heart rate leading to hypertension and it could potentially be fatal as it can lead to strokes. Um and also myocardial infarctions. So meant to be you get multiple neuromas. Um and you get most mucosal neuromas, for example, in the oral intestinal um associated with mafi inhabited uh mutation in the red gene, which is about oncogene thyroid cancer. And your next slide, please. So in men, one, I don't know why I did it this way. But like in men, one, there are three tumors get parathyroid most common and this causes kidney stones. Parathyroid makes um calcitriol which decrease uh which increases bone resorption leading to hypercalcemia and osteoporosis. You get your pituitary adenomas, for example, pro adenoma. Um and you can, which can lead to card Claas in um men and also you get um symptoms like visual uh headaches uh or visual loss. Um because again, remember, the optic chiasm is situated a little bit of the pituitary gland, sorry. Uh Yeah, pituitary gland sits here. So as a result of that, the uh tumor could compress the optic chiasm. And what happens these two visual loss and in your pancreatic cancers, you get gastrinomas, which make way too much gastrin liken Zolate Ellison syndrome, which could lead to peptic ulcers. Uh hypoglycemia. Uh you uh in insuloma, you get glucon reduce to hypoglycemia. Again, it causes a whole range of different pathologies. Next, other place. Ok. Guys, just changing gears now. So what we have in front of us is the adrenal glands, otherwise not under the suprarenal glands. And one thing you'll realize is in, in medicine that once you understand the medical terminologies in front of you, it's usually a lot easier to help you for the functions and uh the structure anatomy. So SRE refers to the fact that it is superior to the, to the kidneys. And as we can see, the thing about the adrenal glands is they have quite a holistic and broad view, um holistic and broad functions in um our bodies. So as Yusuf has briefly mentioned the hypothalamic pituitary um and um hyperthy pituitary um system, they are interlinked in a sense that the hypothalamus obviously send neurohormones, um which would act on the secretory cells of the pituitary gland for the corresponding secretions for different aspects. For example, um trh from the pituitary gland to then lead to the form for the release of TSH and, and to do for the release of the thyroid hormones from the, the thyroid. So with regards to the adrenal glands, I have two main layers, which is an outer cortex and the inner medulla um to which the alco cortex is further divided into three additional layers. That being the zona grasa, the zona fasciculata and the zona reticularis. And I think with, with medicine, especially the way I like to learn it is the fact that you have to try and make things simpler for yourself. So I usually like to use mnemonics and pneumonic we're using today for remembering the layers from um superficial to deep is eeg G fr All right. And another new on that will go hand in hand with this is the deeper you go the streeter it gets. So um starting with the zo glomerulosa. So here we have the mineralcorticoid which release mainly aldosterone. And I think the beautiful thing about aldosterone is that it's the main hormone that regulates the reabsorption of sodium and the excretion of potassium. So, why is this important? So, aldosterone has a very, has a very interesting link to the regulation of our body circulation. So it can regulate our BP because our very essential relationship to remember is that water always goes where sodium goes. So as you can imagine, when aldosterone is leading to the increased reabsorption of sodium and water is start swallowing, you did have an increase in your blood volume. And with that increased blood volume within your circulation, you then have increased crushing of the the blood against the vascular wall, which can lead to to increased BP or hypertension. And we also have an interesting system called the renin angiotensin aldosterone system, which in itself does deserve its own lecture. But essentially what you have is um within the kidneys, you have a makeup of three essential cells, namely being a macular denser. Um the extramesangial cells and the doxylar cells by which they have a um they function as a system in which the macular denser senses the sodium levels in the blood in times of low um BP, otherwise identified as low sodium levels. This will uh macular will identify this and through extra mesangial cells will send signals to the drug to glomerular cells to release another central component called renin by the release of renin. Then we then go through the process of forming key components such as angiotensin and angiotensin. Two particularly will then function by increasing vasoconstriction which increase the total peripheral resistance. And as you can imagine if you make your vessels smaller, you can then indirectly cause the increase of your BP because the blood is able to be more propelled for um further along the body and also leads to be. And as I previously mentioned here, so we have um our sodium and edema, our sodium and the right system when dysregulated and lead to something called edema. So in other words, edema is known as swelling and what happens is essentially as there's increased BP, you also have an increase in something called hydrostatic pressure, which in other words, is a pulling force. And while hydrostatic pressure works in conjunction with another force called the colloid oncotic pressure. The hydrostatic is put cool fluid out from the vascular system or you have ac oncotic pressure, which refers to the pressure exerted by components such as albumin in the blood, which has like a, a retention type of force to try and keep the fluid within the system. However, in such an occasion where you have high BP, what would happen is the high BP will ex exceed that of the colon oncotic pressure leading to the pulling of fluid out of the extravascular out of the vascular spaces. And they can only go into compartments within your tissues where you have cases like edema and swelling, which is why um in situations such as um um cardiovascular issues, they can also present with things like edema. Additionally, you can also have hyperkalemia, which is a, a consequence of the excess aldosterone in the system. And hyperkalemia can also lead into situations with metabolic acidosis, which is um derived from the fact that the cells have a relationship between potassium and and um acidity also known as protons in which when um potassium levels are in a very um low level, the cells will decide to um take in the um I think, I think sorry, there may be a mistake here as so may decide to take in the, the the the protons and pump out. Um um I pump out potassium to try and make up for this. Um I have a type here. This should be alkalosis apologies. Um Going forward the puzzle. Um like I said here, um the alkalosis, which is the correction there. All right. Now, moving on to the zone of ausa which secretes Glucorticoid, which is where it is getting a bit sweeter and this is where we have the release of a central uh hormone called cortisol. Now, cortisol is the infamous stress hormone, which is basically it is a hormone responsible for protecting the body in time of stress. So it does this by regulating our metabolism, providing energy. And as you said, that's correctly mentioned, one of our key energy sources is glucose. So what cortisol tries to do is cortisol tries to increase the glucose availability within the body and it can control is therefore, nourish ourselves, try to maintain our BP. Uh has an intrinsic link by working alongside a fati called amines, which are part of our sympathetic um nervous system. And it is essential for our heart rate, our BP, um even things such as our ability to if it's the time, if it's adequate time to urinate, if it's adequate time to get more air into the lungs. But when it go, when it goes wrong, you can actually lead to more mental health related issues such as depression or have syndrome, artificial disease, which I'll go into more detail later. Add disease, we go into more detail later. But what's interesting is depression. So, depression obviously is a mental health condition derived um characterized by uh chronic state of low mood. But how can it link to situation? How can it link to our, our, our cortisol levels? Well, cortisol is a, is a stress hormone that within, it has to be kept within reason because as you have also mentioned, there is a negative feedback loop that is designed to keep our cortisol levels within uh um a a adequate level. However, what cortisol can do is in times of chronic stress, when you have excess muscle cortisol in the body, what cortisol could do it can, it can disregulate the negative feedback group and it disregulate the the negative feedback loop. What you have is cortisol basically leading to even more excess release of cortisol. And this folk, this um manifest manifest in decreased hippocampus volume and hippocampus. What I'm sorry? And hippocampus is the key point of the brain that's responsible for our memory, our ability to make long term memory and and retain our memory and also have increase in the volume of the Amygdala and the Amygdala amygdala responsible for regulating our emotions. So, when you have a combination of the hippocampus, um being affected, that's where you have like um patients with depression who are unable to maybe recall some short term memory or maybe their long term memory is also affected. And with the amygdala volume must have been increasing. You have patients who are able to um which are un unfortunately less able to regulate their, their negative emotions and they hyper focus on the negative emotions which often in the main symptom of depression such as um low interest in social interactions, more social withdrawal, general unhappiness. And it's because it all comes from these underlying um metabolic mechanisms. And this is just some further um inquiry and further um summaries. Ok. Now there's no particular and this is the sweetest aspect. Obviously, it's a tongue and cheek money, of course. So take it within reason. So this is for sex stories and our androgens and why these are important is because these form the basis of who we are as people. So we have the se se se secondary sexual characteristics such as and it regulate stuff like the, the muscle mass will be deposited within males and females are also responsible for the pubic hairs um forming a lot of our behavioral characteristics as well. And our mood in women is very important in their menstrual cycle in which you have uh the secret the interrelation between LH to luteinizing the hormone FS H. So, FS H functions um in developing of the, the eggs and ensuring that they mature to an ovum and luteinizing the hormone responsible for when it increases in level when increasing in its level over time. When it reaches a, a peak surge, it will lead to ovulation, which is the release of the egg from the release of the of the mature ovum from the ovaries. And with regards to maintaining the pregnancy, what then happens is you have progesterone, which is an essential hormone secreted by the corpus luteum, which is, which is formed from the remnants of the, the ruptured egg. And this progesterone would basically then lead to the thick glandular nature of the uterus lining. And essentially what happens is, is essentially waiting for the event where in the in the event of sexual intercourse, where the sperm and the eggs can fuse, it can eventually implant at a particular site called a decidua within the the uterus and a lactation in um breastfeeding in the event that uh the child has been born. But I think another interesting thing to also keep note on is the the bone health. So as I briefly mentioned, type one os um osteoporosis represents a very interesting link between the sex story and our bone and our bones and the integrity of our bones. So, postmenopausal women are most at risk of type one osteoporosis. And this is the event where um women who haven't undergone menopause obviously have a um serious decline in their estrogen levels which often correlates to increase in their osteoclast activity. So, while osteoclasts, osteoclasts are bone degrading components of the of the of the bone, which usually under normal circumstances, work in conjunction with osteoblasts which are required to then form the bone. However, with the severe upper regulation of osteoclastic activity, you have severe degradation of the bone over time that makes the bone a lot less dense. And the reason why women obviously are a bit at a risk of osteoporosis is because women on average do have less bone density compared to men. Which is why when you see in the type two variant osteoporosis, which is more a senile type of osteoporosis. And that is usually seen in older men because then over time, the bone density has been worn away and worn away. Then we also have um now switching to a Polycystic Ovarian Syndrome. This is development of cysts within the ovaries and this is when there's a severe increase in the sex steroids. And this usually manifests in the development of um cysts in the ovaries which can have impact on the fertility. It can also cause irregular or absent menstruation and subfertility. Subfertility is defined as the decreased in um the um delayed conception in couples who have had for over um who have had unprotected sex for over a year. And with the dysregulation of the sex steroids, as I briefly mentioned before, you obviously will have dysregulation of the menstrual cycle. Therefore, the ability to have a motor o them ready to be fertilized by the sperm will be impacted that it makes it a lot harder for couples who are trying to have Children, to them to have Children can't forget about the adrenal medulla. So, you know, which is the inner layer is, is sible for secreting our pity called amines, which is ad and no adrenaline and is a key modulator of a fight or flight response to sympathetic nervous system and it will release that common in cells. So how do I think about a sympathetic nervous system when it comes to exams or it's just a general holistic view of it is what would your body want to do in the event of a fight? So when it comes to the pupils dilating, essentially just has to do with the, the um the um the regulation of the iris muscles to ensure that you can see more. And this is because we wanna be able to see what's coming at you. Um The s the the general digestive system will be inhibited. Uh um salivary glands will be inhibited the stomach that will be inhibited. And um the urinary system will also be inhibited because in the event of a fight, you would, the last thing you wanna be doing is urinating. So the body kind of thinks about it as like a as like an evolutionary advantage to try and protect the body from times of the stress. Ok. However, this is all fine and dandy. But what when things go wrong? So you briefly mentioned the p um in numerous ways that can be very a aberrant for the patient. In addition, we also have Addison's disease, which is the damage to the adrenal growth that can lead to deficiency in the no. So we then also have the opposite, which once again will also manifest in the opposing consequences for the patient. Ok. So let's go into more detail of Addison's disease and, and, and also I'm gonna mention Conn's Syndrome. So, Addison's disease, Addison's disease is the autoimmune destruction of the adrenal cortex. Has the efficiency in all secretions. And this can manifest as hyperpigmentation, upper and hypertension and drop of BP when standing or sitting down. The reason why is because when you're in a, in a standing position, you must um when you're in a standing position, you must realize that it actually does take a lot more for your heart to actually perfuse what happened to the body. Um It can also lead to severe weight loss because obviously with the lack of secretions, you also have a severe slowing down of all your body systems, nausea or vomiting will obviously will manifest muscle pain, abdominal pain and general fatigue and depression. I briefly mentioned, I think key diagnostic options to also re um realize is blood tests. So if you do a blood test, you can obviously identify the the um the level of the secretions within the blood or ACTH stimulation test which evaluates the adrenal response to ACTH imaging or CT or MRI is always um is always good imaging um modalities to ensure you can view the adrenal glands, identification of any tumors, authentication of any abnormalities and an antibody test to identify any auto antibodies. A general rule, usually when it comes to autoimmune conditions, we should always look out for the immune aspect of things, which usually is the auto antibody that is obviously damaging the the cell cells. And hormone replacement therapy is a key component for um replacing these um deficiencies and these secretions in order to try and mesh the body back into the synchrony and increasing the salt intake. Because obviously, as I've seen, you have decreased in the mineral corticoids, ie aldosterone. So if you can increase the salt intake, you can somewhat try and increase the blood volume and get the BP going again. Based on the relationship that I briefly mentioned with regards to the blood volume and the BP. How about when we talk about the opposite? So we have Conn's syndrome, which is the excess production of aldosterone and it's usually caused by a tumor in like an adrenal adenoma. So, adenoma refers to glandular benign tumors. So any time you have omma as the suffix refers to a benign tumor. An adenoma refers to the fact it is related to the glands and a carcinoma now refers to a malignant variant of this where it's now cancer and this can manifest as high BP derived from the relationship between increased sodium intake, increased water, increased blood volume, increased BP, the muscle weakness and cramps because um over time, your perfusion of these muscles will become affected, be concerned. The fact that high BP does have a detrimental implication on arterial blood vessels. So if this then manifests in decreased perfusion of your muscles, it can then lead to muscle cramps or muscle weakness, fatigue, you have headaches because the head is a confined space. So if this BP then gets access to the cerebral circulation, it can manifest with severe headaches and hyperkalemia. Because the function of aldosterone is to is to excrete potassium from the body. Once again, the main diagnostic options are blood tests which is high aldosterone and low renin levels. And this kind of refers to the fact of um the negative feedback loop. So high aldosterone obviously leads, leads to increase of reabsorption of sodium. But renin usually functions when there is low sodium. So the negative body is exemplified here where there's low renin secretions due to the high amounts of sodium and hypokalemia excess in the context of severe low potassium. And once again, CT or MRI of the adrenal glands and management, it would usually just be the surgical removal of the adrenal um of the of the tumor to ensure to try and alleviate the this consequence of excessive aldosterone secretions and medications are usually to Antone and um around to block the action of aldosterone. These usually function. Um These I think they usually are type of and essentially what they do is they prevent abdo from functioning by doing so, then um reduce the of sodium and water, therefore, eventually lowering the blood volume and then lowering the the BP lifestyle changes, which is a common theme of of usually preventative medicine where you can with a healthy diet and more balanced diet, you're able to, I won't say it's not every condition but you can slower, lower the chances of developing a lot of conditions with living on a balanced diet. Ok. Now, Cushing's disease and Cushing's syndrome. Now, as I II must admit, this was something I did struggle to get my head around initially. But essentially Cushing's disease refers to a type of disease caused by excess release of um of, of ACTH, which leads to excess release of cortisol from adrenal glands. Whereas Cushing's syndrome refers to amalgamation of symptoms derived from excess cortisol in the body. So what usually uh what usually causes Cushing's syndrome is a prolonged use of corticosteroid medication, adrenal tumors, a topic ACTH which are produced by nonpituitary tumors. So let me just quickly touch on that. So in adrenal tumors uh bear me a moment. Let me um yeah. So what is, what, what, what, what um what you, what you, what this means is in um adrenal tumors. Um This means that the tumor itself is causing the extra of ACTH. Whereas ectopic ACTH production by nonpituitary tumors, literally just means that there is an increase in ACTH hormones from a tumor outside the pituitary gland. And this is important because that then comes in that then um leads the way to need to distinguish this in a clinical practice where you have the HD DST test for depicting the cause of Cushing's Syndrome. But before we get there, the general symptoms of Cohen Syndrome is the weight gain and this especially around the abdomen and face. This can be universally known as increased central adiposity. We have purple stretch marks on the skin, on the stria, high BP, muscle weakness, osteoporosis, excess, hair growth, mood changes, fatigue and high blood sugar levels. The general trend here is that there is um this is derived from the fact that cortisol function has been hyper activated. So all your glucose stores, all the stores of energy is, is basically trying to increase the glucose levels in the body. We just take you to a hyperactive level. So everything's just working way uh w way more than is needed. And the main diagnostic methods are MRI and the CT scan, the HD DST. So it's like I said, it's important to distinguish in the Cushing's disease versus the Cushing's syndrome. And in the comments of you can obviously feel free to correct me, but the HED DST is in the event where um a high dose is unable to a higher dose is unable to be um, a high dose of cortisone, unable to be um corrected. It would suggest that is an ectopic ACTH because it's a non pituitary tumor. Whereas if it is able to correct it, then it is derived in the pituitary gland, then with regards to other diagnostic options is 24 hour urinary test, late night, sali saliva and a low dexamethasone suppression test. And management will obviously involve surgery to remove the tumor radiotherapy, which is usually radiotherapy and chemotherapy, which usually use as a precursor to surgery, which is trying to target that tumor try to make it as small as possible to try and lower the implication of healthy tissue around the tumor. And medications that can talk course for production such as ketoconazole and metopone. Ok. So I have a case study here. So John do 45 year old male presents with a um persistent high BP, severe headache, palpitations, excess sweating and at least unstained weight loss of 10 lbs over the last three months. So how you look at it? So we already have some symptoms here. So some high BP, severe headache, palpitations, excess sweating. The first thing I would say is there's clearly upregulation of the bodily systems and severe weight loss also refers to severe metabolic activity that upregulated for leading to severe weight loss. His family increased, increased hypertension but has no significant past medical history of chronic diseases during the during the physical examination, his BP was recorded at 100 and 80. Over 100 and 10 notes that normal BP usually around 100 and 20/80 with the higher normal has been around 100 and 35 to about 85 and the heart rate was about 100 and 10. So he's hypertensive and he's tachycardic. So, um and his notable sweating and anxiety were observed during the examination, laboratory results of what elevated levels of particulate means a non in both blood and urine test. A ct scan identified a two centimeter mass on his right adrenal gland. So based on six and laboratory results, what is the most likely diagnosis? You can just try messaging the chat? Ok. Ok. Well, the way I'll look at this is let's, let's let's go based on the facts. So I usually like to do um see what is less likely to be the diagnosis and then go from there. Uh But we do have some things in the chart. OK. See. Yeah. Ok. OK. I like the, I like the fact the disparity. So I have b so you have to remember, we mentioned that the, I think usually at the end of the question is where I seem to see a lot of the answers. So we've under, I've identified a tumor, a two centimeter mass on the right adrenal gland which shows you that it's, it's most likely it could be tumor related at the very least. So let's look at it. So, Addison's disease, what he, what he stated is um is something is, is, is related to uh aldosterone. Then we have um we have the tumor here which is related to the um the tumor within the adrenal medulla, which is also related to the C called Amy and noradrenaline, which does also integrate with our case study and the symptoms correlate with hyperactivation of the sympathetic sympathetic nervous system. Therefore, most likely to be our symptoms. Yes, hyperaldosteronism could manifest as high BP. But at the same time, what is the single best answer it? We feel um it would be the tumor because we have more indicators for it. OK. OK. What you following is a complication of this condition. If left untreated, you just sign the chart. OK. OK. Five D in the chart. Is there anyone else? Oh B so hyperglycemia, you have to remember, I just um needs to have a intrinsic link in inducing gluconeogenesis. So, gluconeogenesis and glycolysis for the increase of glucose levels in the body in order to increase the stores. But everything is hyper activated or your system hyper activated. In order for you to do this, it requires an energy source. OK? You and your genes. OK. Let's change gears a bit. So we are in the western world and a lot of, and the, the number one cause of death in our western world is ischemic heart disease and ischemic heart disease refers to the compromised supply of blood to our hearts that manifests in cardiovascular issues. And when we look at our day to day life in the western world, we have diabetes as, as you, you has mentioned, which can be an autoimmune variant or can be uh a variant that's acquired over time, usually associated with lifestyle choices and a sedentary lifestyle and the diet that we consume. we also have smoking. Um We have obesity and sedentary lifestyle. Wild stress who have hypertension, which all of these things in one way or the other are linked to a certain degree that can cause ischemic heart disease. But the one I'm most interested in, if high cholesterol, which I think more often than not, people are less able to like pay attention to II think because when it comes to diabetes, uh outside of the realms of having an autoimmune condition, most people are somewhat aware and somewhat cautious of diabetes. Smoking is is very well and fit that smoking not good for you. Exercising is obviously will push stress. Try to stress is well, pressure on hypertension is is is well well pushed and and stated that you should try to control your BP but high cholesterol, especially with the development of things like Uber eats deliveroo is very easy to increase your cholesterol levels without realizing you've done so. But if it's so bad, why do we need, why do we don't need it. Well, let's think about this. Let's first talk about how cholesterols produced. So, cholesterol production can be really pinpointed in the liver of a key enzyme called H MG co A reductase. And it essentially cata catalyzes the production of cholesterol o over a period of sequential enzymatic reactions. And it's absorbed in the in emulsification and packaged into these structures called myo meaning of hydrophobic and hydrophilic. And then go through a process of uh and then, and then transported in the blood through a process of chom micros or lipoproteins or transporting the cholesterol on the blood stream. So if I stand on this, the chance for cholesterol in the blood is mediated by two key players, namely li lipoprotein and apoproteins. So how I like to look at this is essentially imagine it's like a cycle between the, the liver. The target cell is small intestine. So we have omicrons which are um the. So we talk about transporting the cholesterol from intestines to the target tissue and the AP protein that used to do this are a four C two and AP B 48. And essentially what it does is it goes to uh enzymatic receptor on target tissue where it will essentially then deliver cholesterol into those target tissues via the hydrolysis of the shalom micro. And over time it will then deplete the shalom micro to aic remnant, which would then use AAE to bind to the scavenger receptor So let's break this down. So imagine it's a, it's a carrier bag filled with cholesterol and it goes to a target tissue where it will put some of this cholesterol it's got in this bag into the target tissue and then whatever's remains inside this target tissue can then go back to its source of can then go back to its source to then change it carrier bag and start the process again. When it returns to the liver, this is where it will then be degraded and remodeled to a very low density lipoprotein density. Obviously referring to the space within it. And what how this is formed is this last one, the greater around it is a phospholipid triglycerides, which is where we remodeled into forming V LDL similarly once again, VLDL, however, then goes to peripheral tissues and use ABC two and AP B1 100 to once again bind to enzymatic receptors on target tissues, which I the very low density lipoprotein into intermediate density lipoprotein, the intermediate density lipoprotein. And they use AP E to then return to the liver and they bind to discover the receptors. Now, this is what's interesting. The VLDL or the intermediate density lipoprotein can either do one of two things. It can then go into the liver itself or it can then be converted into low density laop protein, which is where things get interesting. So let's say the idea of having converted by the hepatic lab page into the low density lack of protein. We don't have a gene called bad cholesterol. Now, bad cholesterol, obviously, quotation marks it is based around the mechanism of action of LDL which under normal conditions is to deliver cholesterol into the cells. But my question to you is what happens if the LDL receptor becomes effective? Where is this cholesterol going to go? And the only place it can go is in the blood, more of that layer. Then we have the highest in lipoprotein, which is a good cholesterol, which is OK. You know what, what's going on here, it collects the excess cholesterol from the tissues and return to liver for excretion out of the body. So what you can see here is you would obviously want a higher proportion of high HDL going to LDL. But in the event where you have more LDL S than HDL is when you have the manifestation of problems. So eloquently wondering this, this question sounds awful. Why do we need it? We need it for a lot of different reasons. The reason why I need cholesterol is to regulate the summary fluidity. So the cell membrane is a quintessential part of our cells functionality in the sense that it is responsible for controlling what comes in what comes out our ability for ourselves, to communicate the ability for ourselves to release ions to release or um to interact with the hormones required essentially our day to day functioning of our cellular spaces requires the cell membrane to be intact. In addition, the precursor to steroid hormones. So, the hormones that w you mentioned cortisol, aldosterone and sex hormones, they won't exist about cholesterol. So, cholesterol is required to form the key structure components of these hormones. It aids in bile acid production. Bile acid is literally a component released by the, that were produced by the liver stored in the gallbladder, which is responsible for the digestion of our fats. A modification of something called digestion of our fats, which is required for us to maintain, to be healthy. And for our dietary intakes Vitamin D synthesis, which also has an, which has a, a link to our calcium is a, it's a cholesterol to peer such as dehydrocholesterol, which do which by a series of hydroxylation reactions and actually form calcitriol for the increased calcium levels in our body. Then the myelin sheath, it forms a component of our myelin sheath, which are like these fatty layers of our nerve cells, which essentially allow for the increased speed of nerve communication. Now, in process of multiple sclerosis, why you have the manifestation of symptoms such as jerky movements. Uh and things of that nature is because with the lack of the myelin sheath, the nerves will just communicate with each other far too slow. So if the nerves are unable to communicate with each other, you'll basically be unable to move and do your main sport processes. And your main day to day function and obviously, lipoprotein formation, which is probably responsible for the transport of cholesterol in the body. Ok. So let's talk about clinical a and clinical applications. So let's talk about hypercholesteremia. This essentially just refers to high levels of cholesterol in the in the blood. So, hyper means high cholesterol means cholesterol and means relation in relation to the blood and the main causes and risk factors are genetics. It is very possible to have a generally high predisposition for cholesterol in your blood. And this will then have to be made up for by embodying a healthy diet, uh by embodying a healthy diet and ensuring that you try to keep your cholesterol levels per minimal diet. You obviously the high intake of uh if you have a high intake of saturated fats, trans fats for cholesterol, which unfortunately, in the modern western world is a lot of our, our intake, especially in our generation where fast foods are, our fingers is very easy to get access to unhealthy food that can build the cholesterol deposits within our our vascular systems lifestyle such as an inactive lifestyle. So, sedentary, obesity and smoking, I briefly mentioned and medical conditions such as diabetes, hypothyroidism, chronic kidney disease, and liver diseases. The main complications are chest pain such as um which is derived from reduced blood flow to the heart because I think about it if cholesterol is building up within your blood vessels and you have reduced blood flow to the heart. This can manifest as chest pain. It can also manifest as palpitations as well. And the myocardial infarction kind of is the step up combat where yes, with chest pain, you got reduced blood flow. But what if it's completely blocked? Now, the heart is literally getting no blood whatsoever that can now lead to a myocardial infarction, which actually leads to the death of cartilage or of heart tissue, which is not obviously not a good thing. I would probably, I require immediate medical attention. They have a stroke which kind of have a similar principle which in which they now have reduced blood flow to the brain or what is usually paid less attention to is something called transient ischemic attacks, which are, which is a short term loss of of cerebral function, which is usually resolved within 24 hours. However, can be overlooked because it can kind of span for a couple of seconds to like an hour. People can obviously can usually just kind of this and not think it's a problem. But see it as ati A is to a stroke or angina is to a heart attack. Therefore, in is in need of serious medical attention, peripheral artery disease, which kind of just reduce blood flow to the limbs. Whereas on thomas, which is where this cholesterol has to deposit somewhere over time as this fatty tissue as this as this fatty deposits are developing, we are developing under your limbs, which kind of manifest as nodules and things like that and atherosclerosis. Now, atherosclerosis, which, which is what I've expanded on the right hand side is essential because the hardening and narrowing of arteries that are back from plaque build up and these plaques are comprised of cholesterol fats and calcium. So I would have briefly mentioned what happens when the LD O receptor defective. But the real reason why LD O is known as bad cholesterol is derived from two factors here, which is the long halflife and is prone to oxidative damage. Now, the combination of these two factors and the fact that LD receptors have become defective means that cholesterol is able to be influx into the cell and hence can only accumulate in the blood. But what can happen is this LDL can become oxidized and accumulate within the inner layer of the blood vessels. Also the tin intima where it can then rupture and age can engulf this forming foam cells. This foam cells over time through the action of three muscles and differentiation process mechanisms can then form into a fatty streak and a ventral plaque. When these plaques stand over time, if you can focus on these figures in the middle, when these plaques over time, then continue to accumulate and accumulate and accumulate, accumulate. It starts to narrow, narrow and narrow the arteries for depending whether the circulation, what circulation is responsible for can lead to the myocardial infarction uh coronary artery disease, stroke and things of that nature. And what can also happen is the fact that if these plaques then break off these now become embolisms, they can then gain access to other circulations within the body. And this then leads to detrimental implications for these. These can lead to detrimental consequences for other systems that were not originally in mind, which is why it's always good to always check for the lipid profile for, for a lot of cardiovascular blood related um conditions. So my cholesterol ultimately, II, like what I like about this is it kind of refers to that ratio I've spoke about before, which is the high density lipoprotein and lowest lipoprotein. So as you can see on the right over here is high, which is extremely narrow, extremely occluded blood vessel where it's circulation for the heart or circulation for the brain, little to no blood will be getting access to uh we'll get you access to the targets in the situation. So over time, you want to try to have a management plan that can reduce this, reduce this level, reduce the um the amount of cholesterol build up within the the vessels and increase the LD um increase the H especially increase the HD O in respect to the LDL ratios. The ways of achieving this is let's try preventative stuff. First, some more conservative things you can advise patients is exercise, get um normalizing the body to exercise, get the heart pumping have the blood flowing is really good practice for ensuring your body is used to a well perfused environment, preventing organ failure, stop smoking and stop drinking and a more balanced diet to ensure you reduce your chances of occlusion and in increase cholesterol build up. However, in the event where your OD have high cholesterol, one of the biggest, one of the main gold standard is statins, which usually function by inhibiting the H MG CO A reductase. For reducing cholesterol production in the liver, we have five breaks which lower LDL while increasing HDL. So if you have a ratio where you have more HDL, which is removing cholesterol excess cholesterol excretion and you have less LDL, which means less cholesterol will be inserted into the cells. You obviously have a situation that is more in line with the left side of this diagram, which is what we're looking for. Now as the my which reduces cholesterol absorption um in the intestines, the intestines, especially the small intestine responsible for reabsorbing a lot of components from our diet. So if you reduce the cholesterol absorption, you have cholesterol within your, you have less cholesterol within your secondary system. Therefore, it can lower the chance of it accumulating in the blood. And in the event, this is usually kind of more to handle more of the secondary symptoms. Blood thinners are are are adequate consideration in the situation because if you already have narrowing of the arteries, it can thin the blood, it be able to somewhat um preserve some perfusion of the organs. However, what must be remembered when it comes to blood thinners is um blood thinners can manifest, especially with like Warfarin can manifest with like th and narrow therapeutic windows. You also wanna be careful because in the event of maybe a sort um sort of trauma or injury that it will also affect the clotting ability of the blood that can then lead to severe hemorrhage, then also managing associated conditions. So with diabetes, as I used to mention, you have a balanced diet, you also have Metformin, which also increase the um the ability the sensitivity of the cells to insulin which therefore increase glucose rever to the body. Um insulin, as you, as you sort of mentioned is a, is a key to allow glucose sensor to the blood and general exercise. Then when it comes to controlling the hypertension because you don't want the the arteries to eventually rupture because the blood obviously has to travel somewhere. And cholesterol is obviously built up within the arteries. You don't want a case where your BP becomes so severe that can rupture your blood vessels. But that's a whole different board game. So you can have ace inhibitors will basically inhibit the conversion of Atensin one to Atensin two, which can then prevent the, the um the they can, they have to prevent to the increase in total peripheral resistance and decrease the amount of aldosterone in the system. They have beta blockers which will control the heart contraction and the heart rate, preventing the heart from overworking itself and preventing heart failure. Calcium channel blockers reduce the chances of depolarization. And you want attachability of the cardiac tissue to once again control the heart rate. You on diuretics to expel as much sodium and water out of the system as possible. Because once again, if you expel sodium, you expel water, you decrease the blood volume, you decrease the BP. And that's is a statement required for reducing the sodium intake when it comes to coronary artery disease. Once again, you have the last time modifications which once again, diet and exercise and smoke cessation. So in keeping in line with making every contact count, I can't stress enough the preventative methods that can be taken to preventing a lot of conditions. So in ensuring that you're um trying to die as much as possible, having a good exercise and trying to stop smoking, you can lower your chance of developing a lot of associated conditions, which these same conditions are also present in other, in other diseases. So if you're able to control your, your day to day living, you can also prevent your chance of developing a lot diseases and you have antiplatelets which obviously developed um reduce the chance of platelets. Developing. The reason why this is important is because your arteries are already narrowed. So if your arteries are narrowed and you have the development of clots that cl these arteries, these are these already narrowed arteries. We do have a situation where you now have complete auction of your blood flow, complete cessation of the blood flow which can lead to infarctions and necrosis. There are some interesting surgical procedures here such as angioplasty and stent stent placement. There usually is a penultimate, um penultimate form of management in which it's kind of the the stretching of narrowed arteries and the insertion of balloons, the insertion of a balloon and uh a stent like a mesh like framework within the arteries to keep the arteries open, to try and improve perfusion. And when in doubt, you can also use a coronary artery bypass which essentially you rewire the heart essentially to try and maintain coronary uh coronary perfusion in the event that some arteries are are are occluded or otherwise known as blocked. Ok, found a case study. So John Dole is a 55 year old officer worker and worker, a medication of type two diabetes, hypertension and a family history of heart disease. So from the beginning, you have to take into not his age, his gender. Um he has type two diabetes. He has a history of hypertension and a family history of heart disease. So this can obviously always point you towards what it could be. Um fatigue and occasional chest pain could just be potentially the low blood supply. Is there some partial occlusion um in the event of a history I'll ask is, do you feel these symptoms upon exertion? Do you feel these smptom at rest? His routine checkup reports, elevated BP. A BMI of 29 and normal blood test results including a total cholesterol. 260 mg per per per this liter LDL cholesterol, 1 70 80 cholesterol, 35 and triglycerides of 200. 1 thing I will say is straight away, we can see that his LDL to HDL ratio is very, very bad. He's got a lot of LDL in comparison to HDL. So my question to you is where is lipoprotein known as the bad cholesterol and why? 00 Jesus, I hope you didn't see that in the chat. Please just let me know what cholester know about. Question. Why? Yeah. OK. I have B in the B fantastic. And the reason why, as we said is LD O usually functions to deposit cholesterol to the cells. However, if the LD receptor now becomes defective, this cholesterol one is now deposit within arterial wall will have um deposit within arterial walls. Then what role does HDEL play in? What role does HDL play in cholesterol metabolism? No, anything on the top BB, any o any other takers? OK. Correct. The answer is B so essentially it transports cholesterol away from the arteries to the liver because remember LDL is bad cholesterol, bad cholesterol and HDL is good cholesterol in that it tries to extra strength, the excess cholesterol way to liver for excretion in order to keep our cholesterol levels within adequate levels. Thank you so much. Any questions? Um I look forward to any questions in the chat. Fine. Mhm. Oh, you're very welcome. Yes. Uh session was very helpful. Great job, Kevin and Yusuf. Thank you guys so much for uh this session. Uh Just so everyone is aware. Uh We've got just a little bit of a technical issue going on with our feedback form currently. So we will be posting that in the Buckingham Group chats and as well as um a link on med all as well, but that will be available um like probably by Monday, Sunday or Monday. Uh But thank you very much, Kevin and Yusuf again. Great job if no one has any questions. Um Doctor X. Oh, yes. Hello. It. Thank you very much to both speakers. You're both very enthusiastic, which I like very much. Um And I'm sure um they'll receive feedback um appropriately from all the viewers and the uh trainees. Um I'm just going to ask them again, would they like to stay behind a little later so I can give individual feedback to each of them, which would be mainly positive. Um But no one is perfect and um um would that be alright or would you prefer me to give feedback now with the other people present? Mm I don't, I don't mind. I'm, I'm ok. Uh, I'm just gonna stop the recording right now. I wear shops.