Endocrinology | Parathyroid Gland | Calcitonin

iron engineer it's what we do in this video is we're going to talk about the parathyroid gland alright so where would you find the parathyroid gland so you would find it actually located in the posterior aspect of the thyroid gland okay where's the thyroid gland found a thyroid gland is actually found kind of like in the its inferior to the larynx so it's an anterior neck inferior to the larynx so it's a butterfly-shaped gland and on the posterior aspect of that gland you're going to have these little parathyroid glands extremely important glands actually in the past when I used to do thyroidectomies they didn't really know that there was the parathyroid glands and they would remove the entire thyroid gland and the parathyroid glands so now whenever they do start active means you have to be very very careful to make sure that you keep these little parathyroid glands so there's actually four of them so you have like two here on this lobe and then two here on this lobe here right there's four parathyroid glands what I'm doing right now is I'm zooming in on these actual thyroid gland right I'm sorry parathyroid gland now here's what I got to make sure I explained to you real quick the parathyroid gland right has two different types of cells that are extremely important one they're still trying to research what's actually the responsibility of this cell that one cell that they're still looking into is called the oxy fill cells so these oxy fuel cells they're still not sure quite yet what they do they do play the bleed that they play a role in stimulating these other cells to produce parathyroid hormone and they believe that they have some type of role what's called a parathyroid hormone-related protein and even vitamin D so but they're still trying to isolate out what exactly these cells do the other cells that we're going to zoom in on is called the chief cells and the chief cells are going to be the ones that are primarily responsible for secreting parathyroid hormone and we're going to take a look at parathyroid harmed before we do that we need to know what exactly gets these cells going what stimulates them to when we release that parathyroid hormone so you know that they make parathyroid hormone what stimulates that what causes these chief cells to want to be able to produce right hormone so now I'll zoom in the left look so I zoom in on one chief cell right here so before we actually see what the stimulus is we have to make our parathyroid hormone right so how do we make parathyroid hormone you know that there's going to be specific genes that are expressed and whenever those genes are transcribed by maybe a specific type of RNA polymerase like type 2 it'll make what it'll make mRNA and then what will happen that mRNA will actually come out here into the cytoplasm and then in the cytoplasm what do you have you have ribosomes and what would those ribosomes do those ribosomes will act on the mRNA to translate that actual what to translate this in Larney into proteins so they'll translate this mRNA into protein molecules so this is going to be our protein here and let's say this protein is the preform of parathyroid hormone he'll undergo some specific modifications and cleavage processes within the rough ER and the golgi but in general afterwards so you know what is this step right here call when you go from DNA to aughh mRNA this is called transcription and what does this process call whenever you take the mRNA and you translate it into proteins this is called translation okay and then it'll undergo some modification so it'll actually go to the golgi so if we were to show here let's say here's the golgi let's say there's the golgi what happens the you know go to the rough ER and then it'll go to the golgi where it gets modified and packaged right so now look look what happens afterwards we got all these vesicles like packaging this hormone and what is that hormone in there called this little dots that I'm drawing in here is all the parathyroid hormone right does all the parathyroid hormone that's sitting in these vesicles it's ready to be released well what's going to get it to go calcium calcium is the primary stimulus here but here's what we got to make sure we explained here is that high calcium levels or is it low blood calcium levels it's actually going to be low blood calcium levels you know what they call below the normal value of calcium they actually call it hypocalcemia right so Pawel hypocalcemia is a very strong stimulus of parathyroid hormone how you see this receptor here it's a seven past receptor seven past transmembrane receptor it's very very sensitive to calcium so this is a calcium sensitive receptor so again what is this receptor called here it's a calcium sensitive receptor very very interesting because usually only hormones bind up to these receptors right but guess what calcium also binds here so calcium binds on to this calcium sensitive receptor and it triggers these different intracellular processes right when calcium levels are high look what it does though it sends these signals through all these different types of intracellular signals that we're not really concerned with here and guess what the overall effect of it is whenever there's high calcium levels it inhibits this process so you see that whenever there's really high calcium levels it inhibits this actual PTH from getting released okay so then what happens if there's very low calcium levels if there's very very low calcium levels this process right here is actually going to be less so there's less inhibitory input coming in right so there's less inhibitory pathways or intercellular pathways here so now what's going to happen if there's less intracellular pathways going in here this low blood calcium levels will actually be a stimulus for PTH secretion so now look when there's low blood calcium levels it'll actually cause the stimulus to do what to cause these vesicles to merge with the actual plasma membrane and look what happens here look what we start releasing out into the blood plasma we start releasing out all of this parathyroid hormone okay so parathyroid hormone stimulus is going to be low blood calcium level so it's a representative of a black dot there as calcium so it's low calcium levels okay and again why is it being sting why's this low calcium level stimulating it because when there's high calcium it was inhibiting the release of PTH through these intracellular pathways when there's low calcium there's not going to be as many of these intracellular pathways occurring right so it's going to release this actual PTH secretion from inhibition and then what's going to happen PTH will start getting released all right so now that we know that that mechanism what about this other side drew another song here what's this cell about okay you're the thyroid gland we talked about this in the thyroid hormone video that we said that there's made up of thyroid follicles right and the spirals are the ones that are basically responding to TSH and making thyroid hormone well in between the thyroid follicle sometimes you'll see squeezed in between the mash between them is this little green cell here what's that green cell they're called that green cell is actually called a pair of follicular cell so it's actually called a para follicular cell sometimes they even call it C cells right so there's C cells or pair follicular cells these guys are important with being able to regulate the the opposite action of calcium so this one this one actually low calcium stimulates PTH secretion this cell right here this pair of follicular cell is actually going to be stimulated by high blood calcium levels okay now it could work through a calcium sensing or scepter or it could even work through calcium channels the mechanism we're not really good at concerned with here but it's just understanding what is the stimulus here so there could be calcium channels that this actual calcium is going to work through or it could actually work through a calcium sensitive receptor so let's show again here what's the stimulus here what's the overall stimulus high blood calcium levels so it's high blood calcium level you call that whenever you have higher than normal calcium levels called hypercalcemia right hypercalcemia and then what's the overall result it could either cause more calcium to come in or it could actually cause these different types of intracellular pathways to occur now before we do that we show this we have to do the same thing we have to make our calcitonin so how do we do that we take this well we take this actual DNA right here let's say this is the gene to make calcitonin and we actually transcribe it into mRNA so here's our mRNA strand then what it comes out into the cytoplasm and what does it actually interact with it interacts with a ribosomes what does the ribosome do it translates this for actual mRNA when it translators it translates it what does it do it converts it into a protein and this protein can go and get modified and the rough ER and then after that it can go to the Golgi right so I can go to the Golgi and then what if the goal is you're going to do it's going to package it into these vesicles right so it's going to package it maybe modify it a little bit and then do what put it into these vesicles and then have it ready for excretion so let's show this one right here in red so this is our calcitonin and again what did we say was the stimulus to cause these guys to get released it was high calcium levels so whether it be through the Rex movement of the calcium or whether it be through these actual inter say the pathways what's happening is actually going to be designed to stimulate what these vesicles to fuse with the cell membrane and if the vesicles fuse with the cell membrane what's the overall result you're going to be releasing out into the plasma the blood plasma kalsa tonin okay so now we have that so real quick hypocalcemia is the stimulus for PTH hypercalcemia is the stimulus for calcitonin all right so now that we know that let's go ahead and zoom in and see how these hormones are going to regulate these actual levels Oh real quick what do you call whenever hormone is actually stimulated to be released or secreted but whenever it's due to some type of ionic stimuli or nutrient stimulus right so it's usually due to like chemicals or ions or nutrients what is that call that's called humoral stimuli so this right here is an example of what's called humoral stimuli I just wanted to mention that because hormones can be secreted in three ways humoral which is due to ions and nutrients and different types of chemicals hormonal which is one hormone can stimulate another in the current gland to make hormones or it could be neural so there could be a neural tissue that actually stimulates an endocrine gland to make hormones so there's three different types but this is an example of humoral all right now let's go ahead and zoom in now on the effects first a parathyroid home because calcitonin he is important in being able to regulate calcium levels but the primary regulator of calcium is parathyroid hormone whose exceeds essential okay calcitonin has a little bit of a roll but it's not going to be anything as craziness drastic as PTH so let's focus on PTH first so we're going to do know PTH and this is actually going to be he's going to be this black dot right here so let's see here let's actually look look here's this guy right here this is our parathyroid hormone and he's ready to freak things up okay so he's ready to start doing some damage so what's he going to do let's focus on the first organ here which is the bone okay so he can act on bone tissue what is he doing the bone tissue well there's two different types of cells that are very very important in being able to regulate and maintain our bone remodeling processes this one right here this blue cell is actually called an osteo clasped so let's call this one an osteo class and it's one over here in red we're going to call this one in osteo blast now a little bit into the bone physiology here is osteoclast you know that these are actually going to be cells that are doing bone resorption what does I mean by bone resorption it means it's trying to break down the bone and resorb out or pull out or leach out any of the calcium's and the phosphates and some of the breakdown products of the collagen out of the bone and put it where into the plasma to the blood plasma right so he's doing that function osteoblasts are responsible for what's called bone deposition what does that mean by bone deposition it means that they're responsible for being able to take calcium take certain types of phosphates take certain types of amino acids to make collagen right and do what deposit it into the bone tissue that's his responsibility so PTH he's his stimulus was what what was the overall stimulus here let's actually put this right here low calcium levels right this was the primary steena so what's his goal going to be he goal is going to be to try to increase the blood calcium levels how is he going to do that he's going to want to stimulate this guy but how he does it is a little weird right because this guy's we'd love to talk to each other so he's going to talk to him first and he's going to talk to him out on this osteoclast I'm sorry Oscar Oblast is a receptor for two PTH low PTH comes in and binds onto this receptor when he binds on to this receptor here it stimulates the osteoblasts to start secreting a specific chemical and what is that chemical call it's called rank ligand what does that rank ligand do well you know this has rank receptors so over here on the osteo class is actually going to be rank receptor so this is actually going to be a rank receptor when rank ligand binds on to the rank receptor guess what it does it triggers this osteoclast to become very very active so when it becomes very very active it starts actually having a detour nekton and integrin and interacting right there's going to be a lot of interaction with the bone then it's going to start secreting a lot of chemicals one of those chemicals call that it's going to start secreting it's going to start secreting chemicals like caciques and k so it's going to start secreting chemicals like beeps and K which is a nice protein digesting enzyme it's also going to secrete acid phosphatases tartar resistant acid phosphatase is a lot of different types of chemicals and then what is that going to do look what it's going to do to the bone it's going to start breaking down some of the chemicals within the bone like the collagen type 1 it's going to start breaking down some of the hydroxyapatite the calcium phosphate and look what it does it starts actually resorbing and breaking the way the bone and but what does it pull what's actually accumulating it out of this now now you're going to have a lot of calcium and a lot of phosphate look at that a lot of calcium and a lot of phosphate are accumulated from this breakdown where is that calcium and phosphate going to go we're going to take that and put it into the blood so that's what were going to do with that we're going to take this calcium in this phosphate right here and we're going to put it into the blood what is that going to do the blood now so now if we look here what was the overall result now if I bring this calcium in this phosphate into the bloodstream I increase my blood calcium levels and I increase the phosphate levels beautiful so that's one way that the PTH helps to regulate the actual calcium levels in the blood one is like causing osteoclast ik activity to occur and inhibiting the osteoblastic activity all right now let's look at the kidneys effect let's look at all the direct effects of PTH and then the indirect effect so what I did right here is I'm taking a piece of the kidney and I'm taking out if you know the kidney has what's called the nephron right so it has the you know you have your Bowman's capsule then you got your proximal convoluted tubule descending limb a sending limb and then you got your collecting duct right what I'm doing is I'm zooming in on two cells in what's called the distal convoluted tubules so I'm zooming in on two of these cells in the distal convoluted tubules because that's where PTH really is working okay so PTH is a protein hormone right so just like we talked about in the receptor video we know that he has to have what extracellular membrane receptors what type okay now this type right here let's actually put it right here this is actually going to be kind of a G stimulatory pathway right here so it could actually be through the G stimulatory pathway and how does this actually work so let's say here we have the actual parathyroid hormone and he was actually going to be in black here right so what did the parathyroid hormone do he comes in and he binds on to this receptor when he binds on to this receptor it activates an intracellular pathway right and activates G stimulatory which activates adenylate cyclase which converts ATP into cyclic GMP cycle JMP activates protein kinase a and then what's the overall result it phosphorylates specific types of transcription factors what could those transcription factors be they could be transcription factors to make specific types of protein molecules so let's say right here is our transcription factor and what does the protein kinase a do what approaching tiny - do we put phosphates on them and activates them right and once this becomes active it starts stimulating this gene sequence and look what it makes out of it it makes a specific type of protein so look out look what it made right here look at this it makes this really really specific special type of protein right here and this protein will get packaged in the golgi and all that stuff like that but then look where it's going to go it's going to get packaged in the golgi so to get packaged in the golgi and then it'll actually get sent out and get embedded into the membrane so a whole bunch of these proteins now look what we're going to have in the membrane now look what we have into the membrane right here look at this protein right here this one right here this one right here just a couple of you right there right we'll put one more one more right there what's the whole purpose of this normally in the distal convoluted tubule it is very impermeable to ions like sodium and chlorine and water and calcium and all different types of substances so usually by the time things get to this point usually need hormones present in order to open up specific channels to get those ions in or they'll be lost in the urine so right now it's getting ready to make urine so right here what could be flowing through right here look who is beautifully flowing through in here it's actually going to be calcium so we can have calcium just chillin out in the lumen of this actual filtrate it's getting ready to go into the urine but what happens this who did this really who is this form over here this is actually parathyroid hormone right what does he do he binds on activates this pathway to make these specific types of calcium channel proteins and they get embedded into the membrane right so this gets embedded all into the membrane what's the overall result then calcium is going to start flowing in from the actual filtrate that's going to go to make the urine into these kidney cells and then where they're going to go straight from here look look where they go now they come in here but guess what there's nothing really here in this memory look they have their had this little protein here there's another protein right here let's actually draw that protein look what it has right here on the membrane it has another protein here in the membrane that's extremely important but it can't get out let's draw this one right here here's this protein right here and it's trying to be able to get out of this protein but it can't and the reason why is moving against its concentration gradient so it's trying to go from areas of low inside the cell to areas of high right so that's going to be really hard to do so what we need is we need someone to assist on that process so you know what every single cell in our entire body we have these special types of channels special types of proteins let's say here's one let's say here's another one you know what this one's called it's called a sodium potassium ATPase pumps so what are they doing they're pumping three sodium they're putting three sodium's out of the cell and two potassium ions into the cell so again three sodium ions out of a cell two potassium ions into the cell so what's happening what's getting really really concentrated out here we're getting a lot of sodium ions counts concentrated out here right when the sodium ions get really really concentrated out here in the extracellular space look what they can do they can actually move like let's say I should actually follow all these guys now look at this they can move so they're really really high out here very very low in here they're going to move from areas of high to low so they're moving by passive diffusion when they move by passive diffusion because this process is active right so this process in general if you're pumping potassium against this concentration gradient sodium against this concentration gradient this requires ATP so it's active transport primary active but then look sodium is really really concentrated out here he can move down its concentration gradient without any energy there but calcium can't but when sodium moves down guess what it helps calcium out and then look what happens calcium can get into the blood so this is an example of a sodium calcium exchanger but this is called secondary active transport so this is called secondary active transport so that's how you help to be able to get these guys in right is by bringing the sodium down its concentration gradient it helps the calcium go against its concentration gradient what do we do here what was the overall result here then look at this what a beautiful thing what do we do we increase the calcium concentration there another thing you know because calcium has to is coming in right so it's coming into the blood guess what this actual PTH does it actually excretes out the phosphates so also at the same time that's actually pushing this calcium in guess what else it's excreting out it's pushing out phosphates because it's important within the buffer system right so it's excreting out phosphates in the form of po4 three- or you actually might even see in the form of hpo4 two- because it's actually going to be a part of a phosphate buffer system right kind of so again what is it doing here in the kidneys it's actually causing calcium reabsorption and then excreting phosphates okay now that we've done that we know how it increases calcium in the kidney now we're going to focus on the last one which is kind of an indirect function of PTH okay you know on your skin you have a very specific chemical what's that chemical called on your skin in your skin you have a chemical which is called seven-d hydro cholesterol okay 70 hydro cholesterol there's just a form of a cholesterol molecule right now what happens is if you're exposed to sunlight right so let's say that you're exposing yourself to sunlight so let's say here some UV light here we'll draw that in green here's some UV light some ultraviolet light right hitting yeah hitting that scan right there and what does it do it actually acts as a stimulus to cause 7g hydro cholesterol to get pulled into the blood and it turns it into another type of molecule so what happens as a result of this when it gets hit by the UV light it actually gets converted into a specific molecule and that molecule is called cholecalciferol I'm not going to try to spell that I'll definitely butcher it guys so I'm just going to put Coley Calcifer raw what is cholecalciferol do well cholecalciferol once it's in the blood it goes to the liver so it goes to delivering in the liver there's a specific enzyme and that enzyme loves to put o H groups hydroxyl groups onto things you know what this enzyme is called this enzyme is called 25 hydroxylase 25 hydroxylase so what do think is going to do it's going to put a hydroxyl group on the 25th carbon of cholecalciferol so look what happens here it's going to come in to this and it's going to react with this enzyme here and look what it does is when it comes out look what it is now now it's actually called 25 hydroxy cholecalciferol that's what it is now now it's 25 hydroxy cholecalciferol and who performed that function that was the 25 hydroxylase enzyme okay well you're I'm still you're probably still wondering where that gets PTH come into this play PTH acts on this kidney cells right so it can act on specific tubular cells within the kidney so can act on specific tubular cells within the kidney to express this very very specific enzyme what is that specific enzyme that it expresses that specific enzyme that it can express is actually called one alpha hydroxylase so it can express something called one alpha hydroxylase let me actually write that up here so it's called one alpha we should actually have a hyphen there 1 alpha hydroxylase so who who does this who actually increases the expression of this molecule this is actually going to be parathyroid hormone so the parathyroid hormone increases the expression of one alpha hydroxyl a so he stimulates this pathway now this 25 hydroxy cholecalciferol is actually going to go to the kidney then and then when it goes to the kidney the kidney is actually going to allow look it's going to interact with that and look look what happens in the result so what happens this 25 hydroxy cholecalciferol comes in to the kidney and when it's in the kidney it interacts with this one alpha hydroxylase and who increases his expression or at the amount of him pth then look what you get out of this one alpha-hydroxy it puts an OHA group on the first carbon now we call it 1 comma 25 dihydroxy cholecalciferol holy Frick right that's a lot right but like that and there's another name that you can actually call this stuff instead of that which makes it a lot easier this is actually called kalsa trial counselor trial this is the active form of vitamin D so what is this guy right here this is the active form of vitamin D why am i mentioning all this because PTH is going to help us to get more calcium into the body he just can't do it directly he's going to do it indirectly how by turning this inactive precursor of vitamin D into the active presearch for active molecule of vitamin D now what is vitamin D going to do let's follow them over here now we're going to do is we're going to zoom in zoom in onto a specific part of the gastrointestinal tract we're going to zoom in onto the small intestine of the wall and write the first part of the foot small intestine the duodenum and we're looking at one cell in the duodenum this is an entire site nor an intestinal epithelial cell right vitamin D is going to come over here let's actually follow this vitamin D over here it's going to come all the way over here and you know vitamin D is actually a steroid hormone he acts like a steroid hormone so in other words he doesn't have extra cellular membrane receptors he has receptors that are present inside of the cell so let's draw that so look here's his receptor which is present inside of the cell and vitamin D will actually pass right through the cell's membrane and bind onto this intracellular receptor when he binds onto this interstate of the receptor what will it do it'll activate a specific gene sequence and that specific gene sequence that it will activate will produce specific types of proteins these proteins will then again get transfer you'll actually get those a translated go to the rough ER go to the Golgi get packaged and then get put up onto the cell membrane look at these beautiful proteins here these proteins are amazing because they helped us to get the calcium from the gut into the blood so what are these proteins here called these are calcium channel proteins so what are they going to do this guy actually be look you could actually have calcium flowing through your actual GI tract right maybe you had a nice little piece of Cooper cheese that's my favorite cheese I love Cooper cheese but it could be flowing through the gut right or you had like a lot of milk I love milk too late' that's not the point but again calcium is actually flowing through the GI tract here right and look we need to get a lot of that calcium where we need to get a lot of that calcium into the bloodstream so what did this this actual vitamin D do it activated specific genes to make these what did it make it made these calcium channel proteins look it made this protein that one it made that one and what's the overall result it opens up these channel proteins for calcium and increased amount of calcium to actually come in because there's normally calcium channel proteins on the membrane what did vitamin D do it made more calcium channel proteins so then what do we do we absorb more calcium so where is this going to go now look where all this calcium is going to go to all the calcium is going to come into the blood right now right and then what's the overall result there's an increase in blood calcium levels so what was the overall result and what did the vitamin D do it increased blood calcium levels how did PTH affect that it increased the expression of the one alpha hydroxy enzyme so PTH didn't do that we would never have gotten the active form of vitamin D and we would have never been able to absorb the calcium so that's why PTH is important in the activation of vitamin D and the overall Szold is everything if look here increases blood calcium levels there increases the blood calcium levels here and then that's how he would deal with that okay now let's go ahead and take a look at the calcitonin out see how calcitonin does this all right so calcitonin what does calcitonin do well again we said the calcitonin was stimulated by high blood calcium levels so he would be stimulated by high blood calcium levels so what do you think he's going to want to do if we were to put calcitonin range let's actually have him at the opposite Pole now so let's actually say we have calcitonin right here calcitonin is stimulated by high blood calcium levels right let's gel calcitonin so here's calcitonin here's our calcitonin dude right so this is our kalsa tonin what is calcitonin going to do to try to be able to do what to bring these calcium levels down that's his entire goal he only really has one target where you what he wants to do is he wants to change the balance of the osteoclasts and osteoblasts activity how he has receptors directly on the osteoclast let's draw this one right here let's draw this red receptor right here here's this red receptor you see that red receptor there that's for calcitonin so calcitonin is going to come in here and he's going to bind so who is this molecule is called calcitonin and calcitonin will bind onto this receptor guess it will do to this receptor it'll cause this receptors to send signals to the osteoclast to inhibit the osteoclast so it won't make it beeps in k it won't make these acid phosphatase and other enzymes that are designed to break down the bone right so this is inhibited what's going to happen let's imagine I have like a seesaw here all right here we go and over here on this side it's osteo clasped so OC and on this side of the seesaw of osteo blast what does calcitonin going to do it's going to inhibit the osteoclast activity it's the osteo classic activity decreases what happens to this now well now we can actually redraw like this right if we change the scale of osteoclast activity is decreasing it will look like this now look at this so now osteoblastic activity is going up and osteoclast activity is going down as a result look what happens then it's kind of like an indirect weird effect right if he's inhibiting osteoclast activity osteoclast can't resorb as much bone away so who's going to be primarily functioning right now osteoblasts and what are the osteoblasts going to be doing they're going to be taking calcium from the blood so they could be taking calcium from the blood and some of those calcium phosphates out of the blood and then they can deposit that into the oan so what would these osteoblasts be doing they could be taking let's say that we draw here we pull calcium out of the bone right I mean out of the blood so we pull a lot of this calcium out of the blood and what is this osteoblasts going to do it's going to take that calcium and it's going to start incorporating it in to the bone tissue right and this osteoblasts will also starts to creating what's called you know not just the actual this will be a component of the osteoid it also starts to creating proteoglycans and collagen type 1 a lot of different proteins in this area right to be able to cause the bone to get thicker all right all right to cause bone deposition so osteo osteoblasts well they're in hey their activity will be increased due to the decreasing activity of osteoclast so it'll alter the normal balance of these two cells and then who does that calcitonin so again who does this activity right here this is the job of calcitonin calcitonin and calcitonin will do what decrease the osteoclast activity which as a result will increase osteoblasts negativity when osteoblastic activity occurs it'll pull more calcium out of the blood which decreases the blood calcium levels and it will take that calcium and phosphate and other types of amino acids and deposit that into the bone right so he'll make collagen type 1 it'll make hydroxyapatite he'll make the different types of proteoglycans right to cause the bone thickening right or increase in bone deposits are in engineers so in this video we talked about parathyroid hormone and calcitonin in great detail I hope it made sense all right engineers until next time

Channel: Ninja Nerd

Views: 226,943

Rating: 4.9549551 out of 5

Keywords: parathyroid gland, calcitonin, endocrinology

Id: y64aXKCkHk4

Length: 35min 3sec (2103 seconds)

Published: Thu May 11 2017