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So, okay. So first learning outcomes is basically this is the biochemistry. So we're going to talk about the fed and Fasted States. Um So, uh start off with just some definitions. So the fed state is just after we've eaten, it lasts 3 to 4 hours after a meal. Uh Basically the feds, it is an anabolic state. We're using all of what we've eaten and we're building things up, we're building up our stools because we don't know when we're going to eat again. Uh And the fastest eight is opposite it because just after the feds state, this after a period of not eating and it starts 3 to 4 hours after a meal. And this is a cata bolic state. So we're going to be breaking down the stores that we've already, uh, that we've already got to use for energy. So I'm gonna go all the way back to our anatomy looking at the pancreas. So remember practice a small organ that sits behind the duodenum and it tucks up into the spleen. Um And it's got X a chronic endocrine functions. So it's extreme functions. It's majority of its role. Um So it's about 90%. Um and this is basically with releasing the digestive enzymes into the second part of the duodenum. Uh And the part of a really interesting today's endocrine function, this is the smaller part of the small part of the role of the pancreas, which sort of attributes about 10%. And this is with the recent incident, Glucagon mainly as well as other hormones and instantly gone. They're released from there, sort of produced and released from these islets of Langerhans. And you can see the histology of that there. Um And the Greek one is made by the alpha cells of these islets and then the insulin is released from the beta cells of these islets. Um And what's really uh sort of important sort of special about the the pancreatic beta cells is that they have um these uh special enzyme called Gluco Keen's. So if you remember back to first year, uh when we spoke about glycolysis, iss uh first of glycolysis is regulated by an enzyme called Hex Akin's. Uh And in the pancreatic beta cells, we have glue cocaine's instead. Uh and uh basically differences is that Glucagon is has a low affinity for glucose. So it works at a much higher concentration and then when it's activated at a higher concentration, it works really, really quickly, such shuttles uh glucose three really quickly to produce glucose, six phosphate. Uh And then glad to glad to is the transporter that is found on these cells. And again, it also has a low affinity. So it only activates are high concentration. And this is really, really important because um because it's got a low affinity, it can act as a glucose sensor. So the role of the pancreas is sort of distinguished from when it wants to release insulin, when we've eaten a meal and got really high amounts of glucose compared to when we're just doing our normal metabolic um sort of needs for the cells. Um And yeah, we'll just move on to the next slide. So, incidents uh so understanding insulin. So insulin uh it's uh uh synthesized. Um So originally we've got our transcription and translation. Uh we've got pre pro insulin, we then cleave off the signal peptide from that we get pro insulin and then pro insulin itself is divided into uh insulin and C peptide. So we can use C peptide to measure the amount of insulin the blood because they're directly reporting each other. They're basically just divided uh cleaved off the equal in concentration. And then the secretion of instances just said is secreted by beta cells of the endocrine pancreas um and glut to on the B cells. That's that glucose sensor. And this triggers a release of insulin. So we have glucose coming in producing high marks of glucose, six phosphate. The glucose six phosphate is the molecule itself that triggers the release of insulin. An incident is released in two phases. So uh to start off with, we have uh this first phase, this first phase is a sort of a quick peek of insulin. Uh And this is where we've released the stores that we already have in these islets. Uh And then the second phase is where we have uh insulin being produced again and it's released as it's being produced. So it's a sort of shallower curve. And then when instance in the periphery, it binds the tires incarnates receptors, he's got four receptors and these glut four receptors move glucose into cells. Okay. So I've tried to simplify the fed state here. You don't need to know biochemistry and massive amounts of detail. There's lots of sort of things going on as long as you have a sort of general understanding of what's happening in the fed and the fasting state and you'll be completely fine. So um I sort of divided these into the liver, the muscles and the fat. So you sort of need to have an understanding of what's going on in each of these three tissues and just start off by explaining what happens in the liver. So incidents really important. It kick starts the whole entire process of what happens in each of these incidents, especially important liver because we have, we have glycolysis and glycogenesis. So uh we're breaking down glucose to make uh make stalls. And then we also have glycogen elicits breaking down these glycogen stores and gluco neogenesis making glucose from what we've just broken down happening at different times depending on the metabolic state of the body. And we don't want these two processes glycolysis and go like a journalist is happening at the same time. Otherwise it's futile. They're not making anything. So, insulin interacts here in the substrate cycle. So what it does use uh interacts here with phosphofructokinase. If you remember in, in first year, phosphofructokinase is the key regulatory enzyme in by in glycolysis and um insulin dephosphorylation foster productive kinase to activate it and by activating it, it converts fructose six phosphate into fructose to six bisphosphate. And this up regulates glycolysis and down regulates gluco neogenesis. And then Glucagon does the opposite and down regulates glycolysis that regulates Kalita neogenesis. And this is really important that we maintain normal glycemia in the liver. Otherwise, we're going to have a sort of a mess really and nothing's going to be happening. Um So because we've now got insulin coming in, it's increased glycolysis iss and it's increased argh like a general isis. Um because it's got okay, we're now producing loads and loads of the sitar co way. So let's see, taco way with all of that sort of um all this is dark okay. We need to put it into something and we need to then uh we can use those stores and store it as fat. So we regulate uh fatty acid synthesis in the liver. Uh The key enzyme ministers the CSL cocarboxylase and then we package these up as try so, glycerol. Um Well, we make them to try so glycerol and we pack them up very low density life of proteins. Uh And then we shuttle these through the blood stream uh and to where they're needed and life of protein lipase breaks them down and then we absorb these into the tissues as free fatty acids again. Um And what's really important with this is in type two diabetics, they're resistant to insulin. So, in response to their resistance and they're insensitivity, their own insulin, their beta cells are producing way, way more really high titers of insulin, which is going to mean that they're going to have a lot of very low density lipoproteins um in their bloodstream at any one time because they've got these, these fats being transported around all the time. They're going to be absorbed into the walls. They're gonna be phagocytosis and form foam cells and they're gonna form atherosclerotic plaques. So this is why type two diabetics are predisposed to atheroma formation. Um And then insulin also in services. Now in the muscles, the insulin increasing the corporation of glut four. And when we have more glut four, we have more glucose coming into the muscle. The increasing glycolysis iss we're increasing um uh like a general isis on our protein synthesis, uh not glycogenolysis, we're building up glycogen and we're building up process, we're re uh replenishing our stores that we, that we've lost before. Um And just an interesting note as well, that exercise also increases glut four and in muscle cells. So exercise actually causes resistance to type two diabetes and then the fasting state, this is just the opposite. And really importantly to see, remember in the fastest states that they've got key to genesis in the liver. So in the absence of glucose, we're not supplying, uh we're not when you haven't got a source of energy for the brain. The brain relies on glucose because it can pass the blood brain barrier. Uh And so we in the absence that we make ketones uh and these can cross the blood brain barrier instead. And then also important to note is that in the muscles, we can't export glucose. So instead, in a fasting state, muscles break down proteins, they increased protocol isis and then these codes the liver, they're deaminate ID and fed into the Krebs cycle. Okay. So that's everything for wire chemistry. Uh huh. So S P A s, so the first S P A uh so which of the following uh my chemical processes does not occur during the fed state? Okay. Okay. Uh You got uh arising interceptor glucose, six phosphate within pancreatic beta cells be an increase in fatty acid synthesis. See an increase in fatty acid uptake D ketogenic icis and E lipid genesis. Okay, essentially on. So the aspect is key to genesis is to remember the key to genesis. This is happening in our, in our fastest state because we don't have enough glucose. So we're making ketones to supply the brain. Okay. Next question. So, pancreatic beta cells responsible for the race of insulin in response to high blood glucose. Uh in order to determine high glucose state, a specific glucose receptor is used as a glucose sensor. Please select the relevant reception white can use as a sense of the glucose. So uh a glut to has a low affinity for glucose. Be glad to it has a high affinity for glucose. See what three, it has a high affinity for glucose. The glut four has a low affinity for glucose and E glut four has a high affinity to glucose. Mhm. So the that's that one is a uh as you mentioned before. Uh so using glut to gluts who's got a low affinity for glucose, which means it only activates when concentrations of glucose are high and therefore it can shuttle glucose in really, really quickly. Uh Gluco canes then with the high concentration of glucose, it's now moved into the cell is also activated and then we produce high amount of glucose six phosphate which triggers insulin release. I mean it's really important this happens so that we distinguish normal uh sort of glucose use from the cells from the glucose intake that's used to release it into them. That's right. So insulin has an important regulatory role in the liver through modification of the substructure cycle. This ensures that glycolysis including the genesis do not concurrently through which regulatory enzyme does into exert these effects. So, absolutely, egg week Aquinas, be hex, Aquinas. See phosphofructokinase D acetyl coa carboxylase and e high relate the hydrogen is. So the answer to this one is see see phosphofructokinase. So the key regulatory enzyme and glycolysis iss um and this stops us having sort of a futile substrate cycle. So they're not doing glycolysis iss and gluconeogenesis at the same time and then not doing anything at the glucose at all because we're just making it and breaking it down at the same time, we avoid that by regulating the social cycle through phosphofructokinase. Uh David uh has presented his general practitioner for a review of his asthma during the consultation, David shed that has also gained a lot of weight due to a high fat diet and a lack of exercise. The G P discusses benefits of exciter. David including reducing the risk of type two diabetes, which the follows most likely explanation as to why exercise reduces the risk of type two diabetes. Okay. It's a bit longer. So I will sleep this up for better. Okay. So um yeah, this one, this one is um be so increases the incorporation of blood four and Myer sites uh there by improving the uptake of glucose by the muscles. Um Yeah, so because we've got more glut four with more sensitive to our own insulin uh and therefore risk of type two diabetes decreases. Uh Lucy is a type two diabetic um who has come to see her general practitioner for a medication review. Her GP explains her the importance of lifestyle modification management of the diabetes that she's more at risk of certain comorbidities by a company. What makes Lucy more at risk of developing coronary heart disease? Um So we spoke about this when we were talking about uh the fed state, what happens with our fats, namely? No. Okay. So uh which means that the answer to this one is um a so type two diabetic patient, as we said, uh they produced really high title of insulin because they're resistant because they're resistance and they're insensitivity, their own insulin, their beta cells work harder to produce more. Uh because you've got so much insulin were moving all of our, we're encouraging glycolysis, building up stores because they wanted to build stores, were moving uh fats in the blood stream as be LDL very low, very low density lipoproteins. Um And then these are absorbed into the capillary walls uh for math Thrones. So, moving on to the next learning outcomes. So we're describing the structure and function to visual apparatus. So uh the anatomy of the eye. So um so you're not familiar with this sort of diagram. Um So yeah, I was going through this, the anterior 16, the eyes visible, the rest is contained within the orbit orbit is that the socket that contains the eye. And then we have three layers to the eye itself. Artemus fibrous layer. This is our sled error and we got the middle vascular layer which is our choroid. And then we've got our inner neural layer which is our retina. Uh and the cornea is a really interesting part of the eye. So uh in the sort of edges at the periphery of the cornea, we have stratified squamous epithelial self and he's continuously divide. Uh And this means that in case of abrasion, uh the cornea can regenerate itself. And also interestingly with the cornea is it's got no blood supply obviously because otherwise we'll be able to see through it. Uh And this means there's no immune system. And so it's immune privileged and can be transplanted without any need for um uh immune suppression to reduce rejection risk. So, we've got the retina, my accommodation to the retina is the focus sensitive part of the eye. And at the back of the restaurant, we have the macula uh and the severe is within the macular and its densely area that's the most densely populated by cone cells are cone cells of what we use to see vision, uh see, see vision to see color. Uh They give us our color vision and uh contract popular belief rods which don't see color vision are more photosensitive and they're more photosensitive because they see in low light. Um And they sort provide our peripheral vision, there's more of those uh sort of around our peripheral retina. Um So, because we've got high density of cones in our severe visual acuity is the highest there. Uh And then we've got the accommodation re reflex, which is really important because it's responsible for focusing the light onto the severe. Uh and the accommodation reflect itself is to do with making the lens thicker or fatter to refract like more or less. So, for near objects, if you think they're closer to your face, you're gonna need to refract the light more. So they're gonna need a fatter rounder lens to uh refract the light uh more towards the at the back of the eye and then for distant objects within their further away, um uh the lens needs to be flatter, uh more stretch to reduce the refraction. So it just goes straight into the retina. Um and the whole accommodation reflexes controlled by the oculomotor nerve. Um and the oculomotor nerve sort of innovating his salary muscles and the surgery muscles. They have these uh celery processes that connects the suspensory ligament which connect onto the lens. Um And basically when the celery muscles contract, uh the they come back, uh they contract outwards from that. So the processes are sort of more slack, which makes the suspensory ligament more slack which makes the lens flatter uh fatter um and more rounded. Whereas when the city must have relax, it, relax more against the wall. Um And this sort of pulls on these processes which pulls on the suspensory ligament and then makes the lens flatter. Mhm. So the optic pathways is, is just uh a slide your sort of familiar with. We've got these uh optic fibers. So we've got temporal optic fibers, we've got uh fibers from uh sort of seeing like well detecting like from the outside of the eye. And we've got these sort of uh nasal, the rostral optic fibers that come from the inside of the I need nose and the temporal ones, they come down, they stay ipsilateral, they stay on the same side. Whereas the nasal optic virus, they cross contralateral e and where they crosses the optic chiasm. Okay. And really important is that pituitary glands at pituitary gland sits underneath the optic chiasm in the solicitor Sica. And so pituitary pathologies can compress the optic chiasm and affect our vision. Um So just sort of building on that diagram. So you've got the iris and the light reflex. So the iris itself is composed of two distinct groups of muscles. So you've got these circular muscle um and the radial muscles. So those are the fancy names for them. Um The circular muscle is going to act to constrict the I whereas the radial muscles going to act to dilate it. So obviously, in bright light, we don't want to have too much light in our I damaging the retina. So we constrict the pupil and in dim light, we dilate the people so that we can see. So um this reflex is um uh it's uh contracting by, by two nerves, we've got the optic nerve which is the different pathway. So the option of comes down um comes in and it connects the pretext of nuclei. Um and the protective nucleus on the ipsilateral side of the, it connects to both Edin Jervis found nuclei. And this means that when we have um the reflex, we have equal and symmetrical reaction in both eyes. Um And then the Evinger vessel nucleus um is connected to the oculomotor nerve which then comes off and um uh connect to this particular and it causes the Irish to contract to constrict and then make the people smaller okay. And I'm just quickly gonna talk about visual field defects. We already spoke about pituitary pathology affecting the optic chiasm. So potentially add name uh is gonna compress, compressing the optic chiasm. Uh And this is going to knock out our nasal um sort of fields of vision. So light is going to come in and hit this part of the retina from this direction. So we lose these or outside vision and we keep the inside and this is a bitemporal hemianopia. Um Whereas um when we have lesion's say like a bleed something that's putting pressure on the tract uh after the optic chiasm, we're going to get left and right homonymous heavier nope is depending on which side is compressed. And then we can get monocular lost, we can get a loss of vision in one eye when we have a, a lesion affecting the optic nerve, um okay. And then just to note as well. So uh peripheral loss of vision. So, um glaucoma causes peripheral severe loss of vision first because actually talk about diabetes. In this case, glaucoma is a uh a complication of diabetes in some instances. And this is where we get gradual death of the optic nerve. Um And it's associated with high intraocular pressure. So, if we go back to the diagram, um we get increased pressure in here because we don't have drainage of this a crease humor that sits here and this then puts pressure on, on the vitreous humor that's in here that rises in pressure and then puts pressure on the, on the retina and the optic nerve as well causing eventually over time damage. And it affects the peripheral retina the first, which is why we get peripheral loss of vision. Let's start. Okay. Okay. So just moving on to the questions then. So uh correctly identified the anatomical beach of the I labeled one and two. Um So the answer to this one is going to be be. So we got celery muscle here which is connecting onto the suspensory ligament below and then the outside uh I have this little layer of the eye is the uh uh quite a long question. This one. So, uh O P A 62 year old female with chronic diabetes, myelitis has presented to her doctor uh with problems to do with her vision after taking a history and examination and following up with relevant investigations. It's concluded that O P has diabetic keratopathy treatment options are discussed with O P and she mentioned she has read about corneal transplants. She's keen on this, but it's worried about needing to undergo immune suppression, posttransplant as she already takes steroids. The COPD, how should the doctor approach? Both piece concerned. So we've got uh a total over that she cannot undergo corneal transplant, post operative immune suppression. So they need to get it in different options. Be explains over that the immunosuppressive Asian and after transportation will only make the diabetes worse as the steroids will raise her blood sugar. So other options need to be explored. See, explains over that she cannot have the corneal transplant as the diabetes is chronic. Uh The reassure O P that she will not need to undergo immunised pressure, corneal transplantation as there is no risk of projection or eats help open that she will not need to undergo uh immune suppression for corneal transplantation. She's already taking steroids. Let me answer to that one is um indeed also um to reassure that she doesn't need to undergo any expression because there's no risk of rejection. As we said, there's no blood supply to the cornea. So there's no immune cells, there's no uh well, there's no risk of rejection because there's nothing to react to. So it's immune privileged. Uh And then Rachel has presented the eye clinic with loss of vision. She states that she feels she is looking through a tunnel after examining the eyes is concluded that she has a bitemporal hemianopia, which the following could be a cause for this presentation. So you got a traumatic uti at you Vitis, be glaucoma, see occipital lobe tumor, the pituitary adenoma or e multiple sclerosis. And the answer to that one is deep, particularly know mercies puts pressure on the optic chiasm as we said, um which compresses the the nasal optic fibers, the cross contralateral e uh and therefore, we have this sort of more tunnel division. Um Yeah, okay. So we've got a diagram here which represents a swinging light test, assessing the function to be Petteri, light reflex, police slept where any reflex authorities occurred from the options below. So, um for this one, so uh this is gonna be the right ocular motor. So you can see all the way through the eye is permanently dilated, which means that there's a problem innovating, this affected your life. Um So here we've got lights coming in, we've got the optic nerve being stimulated that there's too much light. It's coming back to the pretectal nucleus. It's hitting both ngvs, pilots connected to both Edinburgh best for nuclei and it's been transmitted through the left oculomotor nerve from there uh to constrict this people, but the document, the right or commissioner is not working. Uh And therefore this is stayed dilated. And also in this presentation, what you gonna see with the oculomotor nerve is that there's gonna be no accommodation reflex, as we said, uh and there's gonna be a down and out position because of the innovation of the um extraocular muscles. Uh Mr Grant is present in the emergency department following a full where he experienced a blunt force trauma to the head on examination, his cranial nerves report experienced double vision when trying to follow the doctor's finger was also unable to abduct his left eye, which of the following cranial nerves is likely to have been effective eyes for I didn't cover this. This is just a bit of a recap from first year. Um This one is going to be e the abductions nerve. So, abductions nerve innervates the lateral rectus um muscle. So without uh the obvious nerve isn't uh if the lateral rectus isn't innovative, it's not going to function. So it's not gonna be able to pull the eye out to the left. Um So you're not gonna be able to abduct the eye and then the final learning outcome is polyuria. So just quickly recap the Nephron. So we've got a lot of these kids got about a million of them in each kidney. Uh and they're comprised of the corpuscle. So this is the corpuscle is the glamorous, glamorous and the Bowman's capsule. Uh and the tubal uh and the tubal itself can be divided into, into parts. So you've got the proximal convoluted tubule to start off with the loop of Henle is we've got the descending, ascending loot uh the distal convoluted tubule and then the collecting duct uh and then different parts of the tubular responsible for exchanging different salutes. Uh This is something actually covering the case 12 session. Um But important today's to know that we have uh glucose transporters in the proximal convoluted tubule. So, you've got SGLT two, which is the main one and SGLT one. Uh I just come forward there. Um And these are a target for diabetic medication um to reduce uh to actually put glucose uh into the urine so that we can lower blood glucose. Um So diabetes insipidus. So, um so in terms of polyuria, we've got to sort of mechanisms um that can cause us to have a frequent urination. Um So diabetes insipidus is basically through A T H. Um And normal action of 88 we detect through the asthma receptors in the hypothalamus that cause morality is too low, is too high even uh when autumn allergies too high. So we've got too much sodium, we've got too much glucose and we've got too much, you really got too much solid in our blood. Um Then we're going to trigger the hypothalamus to make more ADH. And we're also going to trigger the uh pasta opportunity to release the ADH that is story. And this is then going to act on the collecting ducts of the nephrons and the kidney, uh specifically going to act on the principle cells uh to increase their aquaporin to expression. So with more aquaporin, uh we're going to have more water moving through osmosis uh and back into the bloodstream and that dilutes the blood and it makes uh the as morality return back to normal equally when autumn receptors are sort of detecting the osmolality is too high. We're going to trigger our first response and they're gonna drink more. So in diabetes insipidus where we have too much with, when we've got polly, real urinating too much. There's, there's a dysfunction with A D H um sort of system. Uh and this can either be central or it can be nephrogenic. So, in central, we've got a problem with the hypothalamus called the posterior pituitary releasing ADH into the blood. Uh These are some causes as to why. Uh that, that could be the case. And then for nephrogenic, we've basically got an issue with resistance to 80 88 we're not responsive. Uh And so uh there's some cause is there uh what happens? But then when a day is not working, we're not bringing enough water, not being able to modulate how much water they're releasing and we just urinate too much. And then the other mechanism is, is what we see in diabetes, myelitis is where we got glycosuria. So, um to start off with having um hypoglycemia in any way, it's going to force more glucose into the urine. But hypoglycemia as well as the atherosclerotic process that we were talking about earlier, uh seen in type two diabetic patient is going to cause hypertension. So we've got a high glucose in the blood. Uh This has got osmotic, it's osmotically active. It's going to bring water from the interested in the compartments into the blood to increase by bali. We've got less space because we've got atherosclerosis. We've got lots of plaques happening and therefore, we're gonna have hypertension and that's going going to put more pressure on the filtration systems in the kidney. It's going to force more glucose through. Um And we're gonna have more glucose in the, in the ju Bealls and we can have so much glucose that we're actually gonna overwhelm these um uh transporters, co transporters in the approximate convoluted achievable. So we're not able to take glucose out. And then we end up having glucose in the distal parts of the net of the Nephron, which then goes through sort of unregulated. And then because the osmotic potential, then we're gonna be moving water into the Nephron, we're going to have uh an increase in urine output. And I think that is everything I wanted to cover. So just have our final S B A S. So A D H is released on serum osmolality is too high. Um serum osmolality is awesome receptors where are these asthma receptors found? And where is a de loops produced? So, the answer to this one is going to be e uh it's not a um because uh pasta opportunities where H is stored, it's not actually producing the prostate pituitary is producing the hypothalamus and asthma receptors are also on the hypothalamus. So it's e uh typically flows in is an SGLT two inhibitor using the management of diabetes. It works by blocking the reabsorption of glucose from the renal nephrons. Uh where in the Nephron is glucose is absorbed. So we've just spoken about this at the end. Uh So it's um uh we found in be uh the proximal convoluted tubule. Uh And this is why um diabetes myelitis because we've only got these uh channels to remove glucose from the Nephron. So early on, then we're more susceptible as well to having um uh glucose glucose urea. And then um the polyuria that follows uh and then a 12 year old boy is presented with new onset polyuria. He has a high B M I and lives in uh seven terry lifestyle. Uh around blood glucose reveals a blood glucose of 22.4 minimal pelita and a urine dipstick is also positive for glucose. What is the most likely diagnosis? So, he's, he's got a new onset polyuria. He's 12, uh, and he's got glucose in his urine. So that's, this one is gonna be c type one diabetes. Arthritis, type 1, 12 is the peak age of incidence for type one diabetes. Um, and, um, yeah, and it's, he's got, he's got lots of because in his urine assault, indicative of the glycosuria mechanism for polyuria. And then Duncan is a patient in his seventies on the neurosurgical ward during the morning ward round, he complains that the over the past couple of days, he's having to urinate all the time and is always thirsty has become problems, it's disrupting sleep and he feels that it's slowing his recovery. Duncan has a moderately high BMI and frequently smoked. He underwent surgery for a pituitary adenoma three days ago. It was the most likely cause of Duncan symptoms. Um So for this one, um we're really thinking about uh surgery is the key to all of this. Uh and the fact that the same surgery on his pituitary. So he's uh sustained damage to his pituitary glands. Therefore, he's reducing his ADH release. So he's got a central diabetes insipidus which is causing him to, to urinate all the time. Then Ross presents with symptoms of polyuria, polydipsia and dehydration. Uh You suspect diabetes insipidus. What tests do you perform to differentiate between central and nephrogenic? I did forget to mention this in the slides. So the impressive everyone does know this. Um Yeah, it's, it's the desmopressin test for uh it's just a test that we used to differentiate between the two. Okay, I think that's it. So stop sharing and then passed on to it. Okay. Cheers dog. Just show my screen the rest. Uh uh Hello. I'm just going to make you as cool so you can share your slides and everything as well. Uh Thank you. Noise. Thank you. Okay. Let me see that. Right. Uh So I'll just get started. Um So my learning outcomes are to outline the pathophysiology of diabetes milliliters. So including type one type to outline the pharmacology of incident in or Meral Advil glycemic agents using um dreamin diabetes relating to determinants of glucosamine status around the life course and um the etiology of type two diabetes. Uh so just start some basic um physiology of like insulin production. So when carbohydrate, we take carbohydrates through the mouth, me eat them and ingesting, we produce um increase our serum glucose. And with our idea range of being 4.46 point one. And the main governing hormones were glucose, homeostasis are um incident glucose into with insulin being produced by Peter selves, reducing our blood glucose levels and bloating on increasing our levels. And they really spelled office cells in the um in the pancreas. Um The goal is, has an important role in the um hum the cyst of glucose and that's like a ki that's key to know because the base of these drugs of drugs using type two diabetes, um is underpinned by the knowledge of the hormones of the gut are involved. Uh I'll talk about in a second. Um So as I said earlier, the guy has an important, well, due to releasing homes like the key ones are GLP one and um DPP four. So G P one is an incretin released by the small intestine blood Lucas, a heart, blood glucose is high and then it just sensitize this incident production. So we can by making the cells more active in producing more incident unless inhibit significant production. So we can as a result, lower blood sugar um and also makes you more full, so you're less prone to eat and therefore, once again, can have a consequence effect by reducing blood sugars. DPP four, regulate um GLP one by cleaving it. So reducing um instant production as a result and we'll come onto it later. But some types of diabetic drugs are based on these two hormones. Other homes which I think are quite important are cortisol's released by the adrenal glands. It's quite relevant in cushions and Addison's disease because in Cushing's patient's typically have like a high blood glucose due to the excess cortisol in the system. And patient Addison's as a result, like locals, you can have like a low blood glucose, that's just something quite important to know because it's an Andrew Crinology component of case 11. And yeah. And as as growth growth hormone as well increases blood sugars, just do two gluco neogenesis. And I pollicis, which is why patient's with acromegaly is when you produce access growth hormone are also prone to type two diabetes. Uh But yeah, um so I'm going to go into our intern production because the physiology about how it works. So I think dominated just earlier, like gluten is very key to the production of insulin just tattooed. It's high km. So glucose levels are high, it stimulates um click pollicis due to glue to being activated. And glucose line is is um can't be inhibited, which leads to unlimited production of ATP when glucose levels are high enough in the serum, which means that the ATP can be produced to depolarize the membrane leading to voltage gated calcium channels because in influx of calcium, which is key for x exercises of insulin Granules. These Granules are, these insulin molecules are located like in small um sorry to pocket of cytoplasm. And when calcium is released into the cell, it allows them to be excess exercisers and released into the serum. So instant can have its effect on on the body by reducing um serum glucose as a result. Um is key to understand that incident the insulin receptor tyrosine kinase receptor and that sound, it does come up in exams, an accidental gluten for receptors um and as a result to decrease serum glucose. Um uh yeah, this yeah, this mechanism is really key to the house stuff in your ears work because they act on this potassium channel, too deep pillow as a membrane and therefore trigger this whole cascade allowing the release of incident. Um And in terms of electrolytes, insulins important to regulating potassium. Um for example, the patient's in DKA all the time, their serum potassium will be quite high just because they haven't got enough insulin in um present because insulin cause the potassium to be driven into cells. Um So that's also something very important to know it's quite high yield fact. Um So talk about type one diabetes. So I'm sure you're aware that Elterman disorder um sedated by destruction, the vetoes of the pancreas. Um it's this occurs about auto antibodies with the main one being anti guard. So, Doctor Taylor, I think talks about the same that antigen is the most frequently found auto antibody. I'm seeing in type two diabetes, type one diabetics, but equally, um everyone, everyone of these antibodies in the list, um if they're positive can be diagnostic for type one diabetes. Um it's associated like Coxsackie B anterovirus infections, a child and westernized lifestyle. And as I said earlier, key complications are diabetic ketoacidosis. Um So talking to go into DKA or diabetic ketoacidosis. So it's a lack of insulin needs the body to go into effect for a fasting state. So even though there, there might be lots of sugar within the serum, the body can't necessarily like metabolizer just due to lack of insulin. So I think doc talked about this as well. The fatty acids become the subject of choice, which is why we produce ketones, which leads to the keto acidosis because Keaton's awesome acidic when they accumulate. Um this because yeah, and they can be triggered due to metabolic stress. So I get sepsis or infection um and cause symptoms such as like uh declined gcs and like castle breathing because um once your body is in a metabolic acidotic state, you tend to compensate with, with your respiratory system. So patient will, will breathe quite quickly um to sort of offload that access CO2, which is accumulated within the blood as a result of the acidotic state there. And, and as as I said earlier, they have a high serum potassium is very key to note serum potassium is high because it's different to total body potassium, which it will be low. Um So just keep a note of if that, if that comes up in questions in the future, um moving on to type two diabetes. So this is caused by a combination of insulin resistance and B to south failure. Um the key cause of it just being due to visceral fat. So when visceral fat binds the liver, they deliver can't respond to incident normally, which causes insulin resistance and it binds to the pancreas as well causing reduced into in production. It's important now that for type two diabetes, you need both of these things to happen for you to have type two diabetes. Um The key cell being like the key cells instrument in this pathogenesis being a dip recites which are, which make up fat um um factors involved in type two W two. That genetics has a strong genetic um implication and type of diabetes. Race of patient's um more predisposed if they're of um black, black and ethnic minorities, that sort of thing knee in it environments are being so the Felty syndrome. So if they're starved as a child, are more likely to um gain store the fat. And as a result, more like to get to a diabetes type two diabetes later in life ages associated like typically more elderly patient just do two, I think increased exposure to um sugar and as a result like um increased risk of scaling fat later in life. So you're more printed type two diabetes and lifestyle. Um So poor eating habits. Um contributing to this once again, uh we went to complications but micro three broad or four categories. So, microvascular macrovascular infections and a key one for type two diabetes is hyposmia, um a hyperglycemic state. So, microvascular retinopathy is sort of visual changes. Um neuropathy is when they get sort of like a glove and stock, um lots of like distribution of sensation in the feet and tips of heart tips of fingers. Um nephropathy were the patient's kidney struggling as a result. They tend to, um actually, I love the albumin in their blood and that's a key marker when monitoring patient type two diabetes for the long term complications is if there's any arguing present in their blood, every present present in the urine, macrovascular complications, a stroke or a heart disease and hypertension just to due to increasing the risk of that sclerosis and location as a result as well. Um infections, you know, they're more prone to fit infections and as well as Canada's. So um just due to like the sugar, the it's quite fungus or quite prone to growing in the oral and vaginal regions and hyposmia hypoglycemic states where um it's sort of similar to D K. However, it's just there, there's no ketones. So they're in a U U ketotic state. There's no, there's not a necessary acidotic is just the amount of glucose in their blood cause them to go into a dehydrated state. So the key difference there is that in, in hyperosmia, hypoglycemic state, the ketones will be normal or low. Whereas in DKA, the heat things will be high. So it's a key thing to take and take onboard when deciding the difference between the two. Um and this is just a table which describes the mechanism, actions of the different total diabetes drugs. So the key ones being met form and definitely offers and semaglutide, glipiZIDE and saxagliptin. Um It would take me a while to to talk through all the different um the mos but I've put them in a quite concise table. The key side effects I thought were typical Ifor's and cause an increased risk of UTI and, and you glycemic DK. So you guys have Medicare's that one patient's who don't eat, um Their bodies can go into a fast estate when it was result, key terms of our increased. Um So they sort of go into DKA even though they have still got insulin reduction. Um exenatide um reduces weight um glipiZIDE because awake in the hypoglycemia, the hypoglycemia side effects quite high yield something which is commonly testing exams. Um for my near key to note that patient's in CKD need caution. Just do two key side effect being lactic acidosis. Um that's just relates to its mechanism Axion as it increases lactic to sort of inhibit um looking in Genesis and called and cause gi upset. Yeah. Uh So just moving briefing to incident pharmacology. So mentor types of mentioned are short acting and long acting. Um So short acting, his arm has been trapping and a long acting being Atlantis, an actor have to be something you'd use. Um Just after you've eaten a meal, a response to amount of carbohydrates you've you've consumed. Whereas Lantus to be a longer acting incident, you would have at night or like in the morning before you've eaten anything. So I'm giving you like a baseline incident um level and these onto the basal bolus regime where patient's would use a longer acting incident to give a baseline incident a level and then have a bolus after meals in responsibility carbohydrates, they've consumed um moving on to pump regime. So tethered pump. So uh pump, there's a pump attached to the patient by tubing, it's completely automatic. Whereas a patch pump, um it's sort of like a patch which is combined which is attached to the pump. And once again, that's, that's automatic and that controls the insulin production on its own. Uh Yeah, I move on to the best Pieris. So not on my spears and we're all 15 just in one go. So better than no. Uh So James is a 20 year old Memmel, a 23 year old male who has recently been diagnosed with type one diabetes and is known to be noncompliant with his incident regime. He's presented hospital in DKA, which of the following serum electric changes is most likely to occur as a result of the acute condition. So in this instance, it will be a thank you just um as I said earlier, when you don't have incident in your serum, the potassium that doesn't have anywhere to go. So it is that when your serum, the potassium levels are high um as there's nothing to drive the potassium movement into your cells. Um Next question, Mrs A pre is a pre type two diabetic and is coming to see you see the diabetic nurse but further management, a prediabetic condition, she also has the following risk factors increases the risk of getting type two diabetes the most. Um So our whole lack of exercise, smoking, weight, cane or age. So in a sense, since this weight gain, um just as I said earlier, obesity being a governing factor within the pathophysiology of type two diabetes being the cause of the incident resistance and Peter sulfair that you see in the condition is the weekend is the increase in the risk of most. Um artists type one diabetic is noncompliant with his incident. He presents a any and is noticeably Tocca Phoenix, sweaty, hypertensive and of course, the inspection has breath that smells like pear drops. What substrate is artist body predominantly using as fuel at the moment. Uh Is it glucose, glycogen amino acids, fatty acids lactate? Uh So in this instance, the answer is fatty acids. So as you stated earlier, when you're in DKA, your body goes into a fasting state which means we use fatty acids as fuel to produce ketones as fuel for the brain. Uh And um I didn't spell out but yeah, as you can see through the description Archie is in DKA. So fatty acids would be the substrate of use of his body at the moment. Whomever to use glucose do two. There'll be an absence of insulin in his um in his d-care Dr Terry quizzes you about your knowledge on the pathophysiology of type two diabetes. And I'll see which of the following cells is key to causing insulin resistance. And, and type two diabetes is a different sites. Hepatocytes beta cells, alpha cells, T cells. And the answer is different sites as we said earlier, do besides the key self. And in fact, and is that visceral fat being key to path of physiology of type two diabetes makes us the most correct answer. Um which is the following. Also, antibodies is most associated with type one diabetes. Is it anti guard, anti insulin, anti zero and eight, anti uh slept a two or anti M A uh anti guard. Just uh just a recall recall um question really as as I showed in that um that table and I got is the most frequently found autoantibodies seen in type one diabetics. Um the others aren't as common and anti Emma is uh is an associated with type of diabetes associated with celiac disease. But you'll get that one, you'll have more exposed to that in case. Um I think the case 15 is a lower gi um just Baber terrible. Um during case based learning, professor Professor Coffee is quizzing you on your knowledge of the mechanism of insulin and just an interested arise of which the following islands is required for exercise, tosis of insulin Granules located in the beat isolates. Is it calcium sodium phosphate, potassium magnesium? And the answer is calcium, as you stated earlier, calcium is key to the extra tests of insulin just due to the mechanism with the deep polarization of the B cell membrane causing custom influx through the L type channels. Um James have been prescribed acts rapid as part of his type one diabetes management. He asked you which is the following glute receptors as a primary actor too cause itself to transport glucose from 70 which is a compartment also being gluten. For just remember, gluten is located the pancreas and look for is in the deep insights of muscles. Um but nothing as much else to it. That question. Um You are an endocrine endocrinology clinic and the consultant, it's causing you on your knowledge of diabetes, pharmacology. Um She asked me which part the Nephron does definitely feels an act on cause removal of serum glucose in urine. Um So is the proximal convoluted cereal district, convoluted Dubiel glomerulus, collecting duct or the ascending live with Henley. Um In this instance, it's the PCTs. So Dom Dom talked about this earlier when referring to like enough from physiology, absolute PCT to calls um other escalate to inhibitor I salute to receptor um leading to a loss of glucose in the urine. And um it's also good for patient's and heart failure for this reason as it can also act as a diuretic. Um Roger's a type one, type two diabetes is presented to any looking hot, sweaty and drowsy, which of the following drugs is most likely to be causing symptoms is a ductal flows in Metformin gliclazide, saxagliptin or exenatide. Uh So this instances, colliculus side uh suspicion is suffering with symptoms of hypoglycemia. And we let earlier that glycoside is um one of the only one of the drugs, the only drug on the list which causes hypoglycemia as a result. This is a key side effect of stuff in areas um which are following pharmacological agents, works by depolarizing the membrane of peter cells to increase internet production. As a result is it Metformin gliclazide, saxagliptin exenatide or dapagliflozin. And this instances peliculas isis is public cause I've worked since um active being on the K A T P channels. Um If you can cast your mind back to that incident slide, I showed you um the that perceptive is key to the production of of insulin and softener is sort of like exacerbate this mechanism and take advantage this mechanism to increase the production, which also makes sense as to why patient's are prone to hypoglycemia when they take this drug uh incidents, a hormone produced by beta cells in response to high glucose, which is the following receptors is key to the production, swollen, it is glued to just to, to being high, high km to need a high amount of glucose in serum to trigger um because of the insulin production. Um So it's just key to its mechanism. It wouldn't work if it had a low km. For this reason Um Jamie present any with a hypoglycemic episode. This is thought to be a due to genetic of stimulation of a hormone, which is the following is most likely to be causing these hypoglycemic episodes. Is it looking on a DPP four GLP one adrenaline or growth hormone? So, in this instance, if G L P one, so we stated at a GLP one sort of exacerbated to insulin release and inhibited gloopy one. Um So you're therefore more prone to hypoglycemic episodes. Um I'm not sure if this condition exists. Both, always a good question to sort of test your understanding of the different hormones involved in the home, a status of glue of glucose. Um but I can't be um any of the others as they all increase um glucose levels and D P people clears GLP one. So therefore, it wouldn't lead to hypoglycemia if there's, if this hormone is in excess amount. Um Dr Andrew Lansdowne is testing you an endocrinology clinic about your knowledge of glucose semi status while including he asked you which of the following cells responsible for producing the hormone G L P one that is instrument instrumentals to insulin production. Is it L cells, the cells, alpha cells, beta cells or ice cells, you know ourselves. Uh alpha cells and beta cells produce um moving on an incident respectively. Are cells produced, cc care, diesels produce somatostatin still must be ourselves. And lydia comes into clinic complaining of lethargy and noticing that she has recently become more time despite not going holiday or using sun breads, you suspect Addison's disease and check her blood sugars, which would be reading a 3.5 minimal per liter. Which of the following structures are most likely my functioning. Thus causing hypoglycemia. Is it chromaffin cells. So there's only glomerulosa is only particular toe, there's any reticularis or the butter types. So this is the zona fasciculus to stated earlier, this is the key structure um involved in cortical production. So it's um there's an insult here in patient with Addison's disease due to not producing enough cortisol. And cortisol is also involved in producing a stasis. So with insufficient cortisol being produced, patient's are with medicines are prone to hypoglycemia. Uh Since the last question, diabetes associate amount of risk factors, one of which is obesity and an individual with which of the following BMR values would be classed as obese. So the 26 27 28 29 or 30. Yeah. So it's 30. So a patient with the B M I of 26 to 29 would be classes overweight with A B M of greater than 29 or greater than or equal to 30 being classes. That would be. So that's just sort of testing you on your knowledge of the B M I values. Um Yeah, that's everything I'll pass on to. Uh Thank you. Okay. Hi. Um Just share my slides. Can you see that. Okay. Um Okay. So I'm doing a learning outcome seven, which is outlining the pathophysiology of the complications of diabetes, including the cellular and molecular basis, self accelerated vascular aging. So, the main point for this really um is that um chronic hypoglycemia is pretty toxic to blood vessels. Um so it causes damage of the epithelium. Um well, the endothelium sorry of the blood cells and multiple ways. So firstly, um the glucose in the blood um reacts with proteins and that can change the function and create something called um abnormal location, end products or ages. Um It can also cause oxidative stress by creating reactive oxygen species. Um and that can cause cellular destruction of the endothelium. Um it also increases from basis. So the blood is more likely to form clots, which is very bad for many reasons that will come back to um the, it also breaks down tight junctions in the endothelium which causes the capillaries to become hyper permit ball. Um and that can cause problems with the retina that will come on to. Um and then lastly, um it also can cause basement membrane thickening, which can cause renal problems. So, basically, the chronic hypoglycemia is it's toxic. Um and that is causing the macro and the micro vascular complications of diabetes. So, on to the next side. So the first s be a a 73 year old male patient comes into the GP and attends his diabetic review. The patient has a B M I of 30 which we've just learned means that he's obese and has a medical history of type two diabetes, hypertension hyperlipidemia, and the 20 year history of smoking. So, what disease is this person most likely to die from? Um So a B C D E N A. So the answer is a um coronary artery disease. I've put this in to basically highlights that these are all molecular complications of diabetes and they tend to be more life threatening. Whereas the cellular complications that will get until later tend to more impact quality of life. Um you know, just as serious, but uh the biggest cause of death in diabetes, Taiwan and two is coronary artery disease and that is due to which we're gonna come on to the microvascular complications. Um So basically, um you, you get an increased risk of um arthrosclerosis um due to the glucose, damaging the endothelium of the blood vessels. Um and endothelium can also be damaged by things like hypertension and smoking. And so the patient and the SBA had both of these things. So it's highly likely to get, you know, damage off the endothelium, um which causes it to become more hyper permissible and then this allows an LDL to leak through into the tunica intima. Um LDL is um low density lipoprotein. Um and a build up of that in the tunica intima activates an immune response where macrophages ends the uh to fake atos. So focus I toes the LDL and this forms foam cells. Um the accumulation of the foam cells causes a fatty streak and this can build up over time narrowing the lumen of the blood vessel. Oh, sorry, I just realized that I have not changed these slides. Um Sorry. Yeah. So this narrows the limit of the blood vessel. Um and basically that can erupt. Um And when that breaks a blood clot can form. Um and if that blood clot is big enough to obstruct the vessel completely, that can actually cause an infection which um can lead to coronary artery disease in the heart, peripheral ischemia um in the hands and feet. Um and also a stroke or a tia in the brain. Um And so yeah, these are all very life threatening complications. So, moving on to the microvascular complications, we're going to be looking at peripheral neuropathy, retinopathy and nephropathy. So the next S P A. So you see a 20 year old, your female in the G P, she has a medical history of type one diabetes and anorexia. She's been getting progressively worse parasthesia in her fingers and toes. What kind of neuropathy is this? So, this is so much cool sensor neuropathy. Um And I've actually just put in the fact that this patient is anorexic just to show you that quite young patient's can get complications of diabetes and something that makes them more likely to get complications is if they have something like an eating disorder, which means that the blue glucose is usually a lot worse controlled. Um And so they can actually develop complications pretty young in life and having something like a peripheral neuropathy can occur in patient as young as 20. Um So just explain what neuropathy is about. So, um the hypoglycemia can damage the Schwann cells that make the myelin sheath are on nerves and then that decreases action potential transmission. Um And also another factor is that the damage of the capillary, supplying blood to nerves also can lead to nerve damage. Um and this is most likely to be symmetrical sensor in Europe. So, um which is basically when you get a progressive loss of sensation distally in the glove and stocking distribution, which is the, the diagram shows here and then you get symptoms such as um pins and needles, burning, tingling in your hands and feet and numbness. Um and also erectile dysfunction. Um Other rarer common types of neuropathy include asymmetrical neuropathy and mono neuropathy. So, it symmetrical neuropathy is when you get an acute infarction of the lower motor neurons in the lumbosacral plexus. And that causes severe pain and weakness in the in the lower limb. Um and also has a gradual and see whether the mono neuropathy is when you get a sudden onset of um neuropathy of a single nerve. It's most likely to affect cranial nerve three or six. But those things are quite rare. So bearing in mind that when diabetics get neuropathy, it's most likely to be the symmetrical sensory neuropathy. Okay. So moving on to the next S P A. So Gerard, a 60 year old man with type one diabetes comes to see his GP because he notices that he's got an also on his foot four months ago and it's still not heating healing and looks infected the G P examined it and finds a deep all set with an abscess formation on the bone. What grade of diabetic foot? Will this be classified as? So grade 1 to 5 and the answer is grade three. Um So just a bit about diabetic foot. So patient's um can get this when they either have a peripheral neuropathy, which means that they might get something like a stone in the shoe and because they can't feel that they get a blister or an also in their foot and they don't really notice that and it gets worse and worse until slightly to become infected and um can lead to gun green off the foot. Um This can also occur with peripheral vascular disease because there's a higher risk of false information because there's less blood to the feet and therefore less. Um the wound healing story is delayed and also you're a mean response to any infection is also a reduced. So you're more likely to get quite a nasty infection. And as you can see on these slides there. Um It's grade 1 to 5 with grade zero being no lesion one, a superficial ulcer, too deep ulcer, three abscess formation with the bone involvement, which is what the last SBA was talking about. And then it progresses to go and green and then going green off the whole foot. Okay. An X S P A um Alice, a 45 year old woman with type one diabetes visits the opticians because she has noticed that her vision has been more blurry than usual. The optician examined her retinas and she's a sign of proliferative diabetic retinopathy. What is this most likely to be? So, her are some examples what you might see with diabetic retinopathy. But the answer is b neovascularization, I'll explain this on this slide. So, retinopathy is when you get retinal damage caused by the microvascular complications of diabetes. Um and it actually affects about 30% of all diabetes with type one. So there's actually quite a lot of people and it's one of the leading causes of blindness as well an adult. So, um you have two different classifications of this proliferative and non proliferative. Um And basically, in both you get damage of the endothelium of the blood blood vessels in the retina. Um because there's less blood supply to the retina, it causes ischemia. Um And then so in non proliferative proliferative signs of this can be micro aneurysm which appear as small red dots dots. Um they might hemorrhage and cause um a little bit of bleeding which you can see on the images and also cotton wool spots um which is due to retinal nerve ischemia and they look like little white clouds, which you can also see on the picture there. Um Proliferative retinopathy occurs when there's new growth of blood vessels and that's because of an increase of something called veg F, which stimulates the growth of new vessels. However, these vessels are very weak and they tend to hemorrhage. What's lots and that's what causes the vision loss. And so nonproliferative actually then progresses it into proliferative and that is more serious. Okay. So the next one, you see a patient in the diabetes clinic who has just been diagnosed with diabetes and has hypoglycemia. How is this most likely to affect the glomeruli filtration rate and the presence of protein urea? So this is actually quite a difficult question, I think. Um and the answer is stay. So just to explain that I know that looks like a lot of writing on the slide. But in short, the presence of dipstick protein in the urine in someone that diabetes indicates that that person um has some kind of renal damage, which is known as diabetic nephropathy. And this is also a major cause of end stage renal disease. Um So just to take you through the pathology of it, basically, um when you've got a lot of um glucose in the blood, the kidneys are working hard to try to do it, screwed at all, but they're overwhelmed. And therefore you get more urine into the so more glucose into the urine. Um The presence of all of this glucose in the blood damages the endothelium of the blood vessel, supplying the kidney. It causes basement thickening, narrowing of the Afrin arterial and then delectation of the Afrin arterial. And this is what causes an increase in the capillary capillary pressure and there for an increase in the G F R um and then an increase in this is uh then it causes that to be hyper filtration. So that is why if you just go back to the question, the answer is that there's a high G F R um at the start fun and basically what you don't actually have no net property here because there's no protein. Um So when there's protein, that's when it becomes no profit nephropathy. But basically, if someone's only just been diagnosed with diabetes, they won't have a property. It takes a while to kick in. Um So when the basement membrane thickens, um you then start to progress and get the renal disease and that's when you're getting protein in your urine and that causes after a while in to be a hyper hyper hypertrophy and hyperplasia. And then that causes enlargement of the kidneys and then when that progresses, you don't get a decrease in the G F R. So even though at the start when you get diagnosed with diabetes and you've got hypoglycemia, you actually have an increased your far and then when you get kidney disease, it will decrease over time. Okay. So on to the next learning outcome. So describing the functional anatomy of the arterial system, venous and the lymphatic drainage system. And to be honest, I've just focused on the arterial system because I felt like this was the most high yield. So SBA one, you're revising signs of hemorrhagic stroke and recall signs of the superior cerebella stroke, which letter shows this artery on the angiograph. So A B C D or E and the answer is e so just to explain a bit more about the arches in the brain, it looks like a bit of confusing um slide because it's got so many vessels on it. But basically, if we just start, I'm just gonna put my laser point on, I think uh can you see that now? So if we're starting at the aortic arch, this branches into the left and the left subclavian and then on the right, we get the break a sub cephalic drug before it divides into the right subclavian and the um common carotids on both sides here. Um And then from the subclavian, the the the branch is of the vertebral arteries and the carotid arteries divide into the external and internal carotid and then they give off the middle cerebral and the vertebral arteries join in the middle to form the Brazil a artery here. And then this is what forms the circle of Willis. I'm not going to go through all of that, but I think it's just something that you should spend a bit of time trying to memorize. Um And also it's quite important to see um how it actually looks on the slide. So on the on the brain here, um in case they ask you in an exam um from these kind of diagrams too. Okay. So SBA to um you're on your first day of placement and the doctor ask you to talk to the ct of the thorax, which structure is labeled be. So again, similar question from the last time is just knowing your anatomy, but on images, which I think is probably the most likely thing you're going to get tested on. And the answer is, oh I'm sorry, just accidentally closing it. The answer is either superior vena cava. So again, this is just something you should probably memorize, become familiar with. Um It can be quite confusing start but always remember that you've got the two biggest circles here. Uh normally the ascending and descending aorta and that kind of diagonally opposite. And then you've got the bronchus which is black cause it's got air in a um Yeah, and then the rest of the veins and arteries here. Um Okay. So next slide. So going through the arteries of the A pill. Um So basically, we're starting off with the subclavian again, which we saw in the last slides. Um So the subclavian enters axilla at the lateral border of the first rib and where it becomes the axilla artery, the absolute archery um divides into three parts in relation to the pectoralis minor. And, and then when it gets to the lower border of the terrorism minor, major muscle, sorry, the axillary artery becomes the breaker archery. And this is the main blood supply for the arm. The Brickell artery gives off the profunda break. I um division which supplies the triceps. And then this artery terminates at the cubital foster by dividing into the radio and all the arteries. The radio artery supplies the posterior lateral forum where the owner supplies the Ontario medial four. Um and then they asked, um estimates into the hand by forming the superficial palmer arch and the deep palmar arch is there. So on to the next slide. SBA one and a 65 year old woman presents the and a with severe abdominal pain. After some investigation, she is diagnosed with this chemical colitis of Hispanic flexure, what arteries or artery supplies this part of the colon. So it's just knowing your anatomy basically, and it's the left and right colic arteries. So this is my best attempt at a schematic diagram of the blood supply to the abdomen. Um Basically, the main things to remind remember is that the abdominal aorta has three main divisions at T 12. It gives us the celiac trunk and then the celiac trunk divides into the left gastric artery, the Spanich Archery and the common hepatic artery. And this is what supplies the four got. Um, the Spanich Archie then gives rise to the left gastro, eh, pill OIC artery which supplies the greater curvature of the stomach. And that anastomoses with the right gastroepiploic artery, um, which you can see here, it's a nine. Um And then the next division is the superior mesenteric at one. And the divisions of um the super very mesenteric supply the organs of the mid gut um from the right, from the last question and the right colleagues supply the medial um two thirds of the transverse colon. Um whether the distal one third of the transverse colon is supplied by the a division of the inferior mesenteric, which comes from the left colic archery. Um So the inferior mesenteric country divides at L3 and it supplies the high, the hindgut organs. Um And the reason in the last SBA why I did uh on the spanich fracture is because that is a watershed area. So um it's supplied by the very end part of the inferior and superior mesenteric divisions and that means it's more likely to become ischemic. Um And I'm pretty sure we got tested on that in our S two. So it does come up. So next SBA five, um A diabetic patient comes into the G P for a diabetic foot exam, as she is known to have peripheral vascular disease during the exam. G P checks, pedal pulses, the pulse at the dorsum of the foot is not felt. However, the pulse behind the medial ankle is present, which artery is the G P participating? Okay. So this is either posterior tibial artery. So here are the arteries of the lower limb. Um I'm not going to explain at all because it's going to take me a very long time. Um But I do think it's really important just to remember your, where you feel the pulses, especially in diabetes because a part of a diabetic for exam is feeling for the pulses in the feet. Um and you need to know if you can't feel like the ones in the feet then going up. So, I mean, this is backwards. But yeah, the femoral pulse um is felt in the mid inguinal point. Popliteal pulse is fell behind the knee when the knee is partially flexed and then posterior tibial is behind and below the medial ankle. And then um the dorsum of the foot is the dorsal peter. So you would start uh the most distant one and work your way up to feel um for the post um in a diabetic foot exam. So, next slide and this is actually SBA five. Um you see in the G you see a patient in the G P who presents with a change in bowel habit, weight loss and fatigue. You suspect rectal cancer if the cancer is above the pectinate line, which lymph food is most likely for it to spread to. So this is about the anatomy of lymph nodes. And the answer is see the internal iliac lymph node. So basically, it's just important to know um kind of the what lymph node drains which area, especially in patients with cancer to see where it's most likely to spread to and also to check the stage of the cancer if it's in the lymph nodes. Um And these are, I just put a little table of just some of the ones that I think I'm more likely to come up because they do like to ask questions about the blood supply or the lymph nodes above or below the pectinate line. I think that's also came up in an s to exam. Um So I'm not going to go through that table, but it's just there for you. Um But yeah, lymph nodes sometimes get left out. So it's just important to know a bit about them. Um especially that all of the lymph nodes end up draining into either the right lymphatic duct or the thoracic duck. And the right lymphatic duct is responsible for draining the lymph nodes from the upper right quadrant of the body. So the head neck and the right quadrant of the thorax. And then the thoracic duck is much larger and drains limp from basically the rest of the body. And then these two empty into the venous circulation at the subclavian veins via the right and left in Venus angles. Okay. So I think that I'm done with my presentations. I'll stop. Share. Ng Yeah. Um I'll share instead. Mhm. Okay. So the first L0 is to describe the principles of inheritance in common mixed etiology disorders using diabetes as an example. So disease etiology is more or less the cause of a disease and understanding this can be really important in medicine because it can help with earlier diagnoses and also like future prevention. Um most diseases these days have um more remixed etiology. Um e there's a lot of factors that contribute to its development. Um A good example of this is type two diabetes as it has many environmental and genetic factors, as you can see in this diagram. So um to go over the main genetic aspects of each of the different types of diabetes. Um type one diabetes is an autoimmune disease. However, there are some risk factors that can be inherited and we know this because the overall risk of developing type one diabetes is higher in Children whose parents have the disease, the strongest genetic association has been made to the H L A genes. Um and then the insulin genes. So type two diabetes, it many cases of it could be prevented by adhering to a healthy lifestyle. But there is definitely also a genetic component. Um genome wide association studies have been done to um work out the association of it two different genes and 100 different associations were made showing that it's a highly palla genic picture as in lots of different genes play a role. Um The main groups of genes that were found were two were genes that control insulin sensitivity. Um So finally, modi um which is mature onset diabetes in the young. So this type of diabetes has the strongest genetic component. Family history of diabetes is a major risk factor um in developing it. And the associated mutations cause either beta cell dysfunction. These are the H N F genes or defects in glucose sensing and these are the Gluco Keen, this is the Gluco Keen's gene. Um The single most common genetic cause is the H N F one A gene and this causes modi types three. Mm. So the first S P A which of the following is not considered to play a role in the development of type two diabetes. So the answer is use of recreational drugs. So this is just a list showing all of the main risk factors. And there are definitely some drugs that can um play a role in the development, including statins, thigh sides and beta blockers. However, um there are no um studies that show a role um that show a link between recreational drugs and type two diabetes at the moment. Uh The next S be a, a 23 year old man presents to his G P with a recent history of excessive thirst and urination. He also complains of tiredness and blood vision. His mother was diagnosed with diabetes at around the same age. What is the like likely inheritance pattern of his disease? And the answer is autism more dominant. So, um maturity onset diabetes is um caused by autism a while dominant mutations. A 12 year old patient presents with her parents to the GP surgery with polydipsia and polyuria. What is the most significant factor of the history which suggests they may have type one diabetes. The fact that she is female, the fact that she has a BMA of 23 the fact that her grandfather had diabetes, that she's had her appendix removed or that she has celiac disease. So which of the following would suggest she may have type one diabetes. So it's that she has celiac disease. Um as mentioned before, one of the main genes um that can lead to type one diabetes or mutations in this gene. Um is the HLA genes and these can also cause other autoimmune conditions there which are listed here. Therefore, having one condition is a major risk factor for developing another. The next S P A which of the following is false regarding gestational diabetes, that a women with gestational diabetes have an increased risk of developing type two diabetes after pregnancy, that the offspring of women with gestational diabetes are an increased risk of developing type two direct diabetes later in life. See that a complication is microsomia of the infant d that obesity is a risk factor or e that there are increased risk of developing cardiovascular cardiovascular disease after pregnancy. And the answer is see, um it was a little bit of a trick question because um gestational diabetes increases the risk of macrosomia, not microsomia. And here's some other complications. And the final S P I think on this topic, a 42 year old woman presents to the GP with a one month history of weight loss, diarrhea, and a tremor. She has a past medical history of it'll ligo and type one diabetes on examination. She has exophthalmia costs a fine tremor and pretibial mike's edema. So what is the most likely diagnosis here? And the answer is grave's disease? So, um these are all highly suggestive, the features of Graves disease, particularly the exophthalmia, us and pretibial mike's edema. Very specific signs of graves and there are more signs and symptoms shown here. So the next L0 is the social and psychological impacts of chronic disease. Um People with the chronic disease or 2 to 3 times more likely to experience mental health problems compared to the average person of all people with a chronic disease. One third will experience symptoms of depression. Um So this highlights the intense psychological effect that it can have on a person and it also shows the importance as a medical professional of considering a patient's mental health, not just their physical health. So here are a few links between the social and psychological impacts um by no means all of them, but just a few examples. So psychologically, it can cause you to have stress over your blood sugar levels and socially, it might make socializing more difficult, especially as many social events that we partake in include food and drink. Another psychological effect is anxiety and this can lead to avoidance of social situations that could lead to a hyper hyper. Um thirdly, um people can feel judged or misunderstood. As many people socially have misconceptions about diabetes um or disapprove of insulin injecting in public and finally, feelings of isolations or loneliness as um the avoidance of social simulations situations can lead to feelings of isolations, especially among older people who are already at risk of feeling lonely. So um an SBA here, which of the following is not recommended for a new episode of less severe depression. And the answer is tricyclic antidepressants. So according to the nice guidelines, these are the suggestions for new onset, less severe depression and SSRI s are included, not tricyclics, an excess be a, a 62 year old lady is admitted with palpitations. Um An E C G is done and it reveals prolongation of her QTP interval. Her background includes hypertension, depression, gout gourd and type two diabetes. Her medications include Metformin, sertraline, ramipril, amLODIPine, raNITIdine, and allopurinol. So which what is most likely causing her, her palpitations and Q T elongation and the answer is sexually. Um So a common side effect of all SSRI s include palpitations and Q T elongation. Next s be a, a 22 year old presents with low mood. She explains she's been feeling down is tired all the time to slight, sleeping more and she becomes tearful during the consultation and explains, it started two months ago after she was diagnosed with maturity onset diabetes, her appetite is the same and she still enjoys visiting her friends. She denies any thoughts of harming herself. What is the most appropriate management in this case? So, um the most appropriate management would be to refer her for CBT. Um So we can tell from her symptoms that she has a mild depression because she has only two of the core symptoms plus one biologic symptom. And so the first line treatment would be either self guided help or group CBT. Um You would need five of the core symptoms to have a full diagnosis of depression and the D S M core symptoms are listed here. Moving on to the final L0. So, ethnicity as a determinant of health people from um certain ethnicities such as black African, African Caribbean, Indian, Pakistani and Bangladeshi are at high risk of developing type two diabetes at a younger age. Um So the disparity here is driven by lots of different factors such as biological lifestyle, social clinical and healthcare system factors. Um And one example, here would be different fat distributions and percentages of body fat depending on your ethnicity. Um And it's interesting to note that the prevalence of type two diabetes, there's three is 3 to 5 times higher among ethnic minority communities. So um what other barriers to healthcare, access the cultural barriers to health, to accessing healthcare? Um make one of one of the most important contributions to the ethnic inequalities seen in diabetes. And these barriers include um language barriers, cultural differences, poor health literacy and um lower socioeconomic positions. These often result in people from different ethnic backgrounds, having foreign knowledge of diabetes and poorer control over their disease. And just an extra slide here to show there's also a link between low socio economic status and diabetes. And this could be because being from a lower socioeconomic background can increase your risk of having central die and central obesity, low physical activity, smoking, poor diet among other risk factors. So how can we ensure better ethnic equality? Um It is very important among healthcare professionals. Um So understanding people's customs, beliefs and values are really, really important. Um So it could be achieved through um more bilingual or bicultural professional educators having teaching or counseling about dietary change by modifying ethnic food groups by modifying ethnic foods and recipes. It could be done by teaching and counseling of activity change but using culturally appropriate activities like dancing or walking, um It could be done by attendance of family members um so that they can elicit home based support, use or visual aids to help with um lower literary needs and more exposure of health confessionals to ethnic minority communities. So only two questions here, which of the following is not a risk factor for developing type two diabetes at a younger age. And the answer being a being of Irish ethnicity, it doesn't not have a link to developing type two diabetes at a younger age. And finally, a gentleman of South Asian ethnicity prevents presents to his G P with a complication of his pre existing type two diabetes. During the complications. During the consultation, he, he asks the G P why people of South Asian ascent are at an increased risk among other things, which of the following would the GPB likely to discuss? And the options are here? And the answer is that they are more prone to visceral factors, deposition and central obesity even at lower B M I S.