Calcium and bone regulation part 1 Flashcards
Learning Outcomes
WHAT IS CALCIUM IMPORTANT FOR?
So first of all I want you to think about why calcium is important.
Okay. So focusing on thinking about what it gets used for, both in a whole body sense and in terms of a tissue or cell sense as well.
Some of the things are more physiological. So we need it structurally to help the structure of bone.
And we’re going to go into that in more detail but also teeth.
If you knock a tooth out. My husband got hit by a car, lost his tooth.
What are you supposed to do with it?
Put it in milk. Okay. Always important thing to remember, calcium is really important for that.
That’s why you put it in milk, not in saline. Okay.
Blood clotting. remember that those coagulation factors need calcium, okay?
So it’s essential for blood clotting. Muscle contraction, exocytosis, cell adhesion as well.
Think of those tight junctions. They need calcium as well.
Intracellular signalling pathways, as you mentioned. And one particular thing of those is oocyte
Fertilisation needs that calcium, um, increase.
So for those of you who are thinking, well, calcium and potassium are very tightly regulated together.
Yes, they are, but for the purpose of this module and to save your brains and mine, we are not going to look at potassium, um, regulation here.
Calcium
so in terms of calcium, most of it is um stored in bone okay.
And when I say stored in bone, it’s put on the surface of the bone matrix, um, to provide strength.
And of course, that makes it more dense. Okay. It’s stored there in the form of hydroxyapatites, okay.
And therefore the rest, the 1%, um, that’s remaining that isn’t in the bone is doing other stuff.
So that might mean it’s intracellular free calcium.
It’s in the extracellular fluid like you mentioned. But most of that 1% is present in blood.
Okay. Um, when it’s floating around in the blood, it needs to be bound to something.
Okay. If you think, um, once you watch the lectures this week, you’ll see that some of what’s produced in the liver is albumin.
Albumin is a protein that’s present in your blood and it binds to ions.
Calcium is one of those ions that it binds to.
So those blood plasma proteins will carry around about 41% of whatever’s left over in the blood.
Some of them will be free ions because they bind to those proteins and then they dissociate
Okay. So some of it will be free. But of course, when it’s free, it’s likely to be taken up into a cell relatively quickly.
Okay. So it can diffuse through the basement membrane by some calcium channels which will allow them to be co-transported
Calcium in the plasma nad extracellular fluid
I’ve given you.
These values on the right hand side. What, uh, constitutes hypercalcemia and what constitutes hypocalcemia?
Again, do not remember these, but these are a good place to come back and look at them should you need to.
So calcium and plasma and extracellular fluid makes up half of the free calcium concentration.
So ionic calcium concentration is what’s really important for calcium maintenance.
So when we look at the daily dose of calcium you can see down here that early
on in life in those very early years where we’re doing quite a bit of growing,
only 700mg is needed. And part of the reason for that is when you’re doing growth, it’s mostly about chondracytes.
Okay. And if you wonder why sometimes when small kids get their hand shot in the door, car door, for example,
and they scream a lot, and then you go take them to A&E and they go, oh yeah, it’ll be fine.
Part of the reason is because it’s mostly cartilage in there.
The bone is an ossified yet okay, it’s not become bone as we know it.
Okay. So there’s quite a lot of cartilage going on here.
But as they hit 4 to 8 years they need a lot more um, calcium.
And this increases as you then hit 8 to 12 years because then the bones have grown quite a lot.
And then this is the point at which there needs to be an increase in calcium being deposited there in the bone to give it strength.
And then once you hit 17 years onwards, um, and you’re an adult, then that levels off a bit at about 1000mg.
So similar to those 4 to 8 years ones, because we’re just taking stuff up.
We might borrow a bit from the pot every now and again and then put some back.
Okay, so it’s more of a maintenance. But over the age of 50 we need to take more on board.
And the reason for that will be present will be become evident in a minute.
So in terms of calcium rich foods, please take note.
These are important things that you might need in future life to include some of the obvious things like, for example, milk.
Uh, but. Things like tofu are quite high in calcium.
For those of you who are veggies. Uh, kidney beans, kale, some of these green vegetables like broccoli and spring greens.
Also some nuts like walnuts and some of our fresh berries blackberries, blueberries, um, uh, apricots, etcetera.
So there are a wide variety of things that are high in calcium,
and we need to make sure that we take plenty of calcium in, in our diet, partially because it’s that.
Whatever we take up is not 100% effective.
Okay, so we might take up 80% of what you eat when you’re very small.
Calcium Metabolism
as you get older and your body becomes more harangued by whatever else you take on board.
Uh, you get less, well, less good at taking that up.
So 99% of that body calcium, like we said before, is stored in teeth and bone.
That means that the calcium that comes in from your diet that’s taken up from the GI tract is then goes into this kind of central bucket.
And we’ll talk about this on the next slide. But so it’s filling up that bucket.
What have you taken in your diet. And the mechanism by which this then this central bucket,
the extracellular fluid that’s going to allow the calcium to move into and out of the blood into and out of cells,
into it, out of the bone, for example, is what we’re going to consider as the important part moving forward.
So that central bucket, if it’s overflowing, we’ll take some of that and we’ll store it in bone.
But if it’s not full, then we need to take some from either from our diet or from the bone,
or we need to recycle it from somewhere and take it back up to fill it back up again.
Okay. So we have this process called resorption, which is where we kind of degrade a little bit to the top of the bone,
take the calcium out that we need and we know that we can we do that again.
We can fix that later on. The laying down of calcium in the bone.
When we’ve got loads of calcium in our bucket’s overflowing is known as bone deposition.
So it’s the opposite process. Um, in terms of other mechanisms of ways that we can take calcium up or keep it in the body.
Of course, we’ve got filtration happening in the kidney. you can reabsorb things in the
proximal convoluted tubule so calcium can be reabsorbed even though it’s filtered in the nephron.
And we can increase the amount of, um, pumps or pores that we have that can allow that process to happen.
Calcium Metabolism2
So I talked about this central pot. So from now on, the extracellular fluid, that central part, that’s what we always consider.
And of course we take up as an adult about 1000mg per day of calcium, some of which will get absorbed.
You’ll notice that this is about 35% of what that total intake was.
Okay. So it’s not actually that much. It will fill up this central bucket, the extracellular fluid.
And then out of that central bucket cells will take some of this.
And they’ll add to it. If they have additional extra the calcium will be filtrated out into the nephron.
And then some will be reabsorbed. And then we’ve got our bone on the right hand side where we’ve got deposition,
which is where we’re adding calcium on to the bone matrix and storing it there.
It has a dual effect. It’s a good storage place, but also it provides additional, um, strength to the bone.
And then if this bucket is starting to look a bit empty, we can do with resorption,
which will take that surface layer of calcium out of the bone matrix and fill the central bucket back up again.
Okay. And so then if this is overflowing, we can carry out secretion and export things back into the GI tract,
of which case we actually get quite a bit out in the faeces.
Now you’ll notice that quite a lot goes out in the faeces that never even gets into the body.
Okay. So this is the key thing. If you are not able to absorb things very well, you may get told to increase the amount of calcium that you take in,
simply because if we increase that by, let’s say, another 50%, you might take in another 10% of actually what you need.
Okay. So the idea is to try and increase how much is coming into the body.
Effects of Calcium on Bone Growth
Okay. So the idea is to try and increase how much is coming into the body.
And in terms of bone growth, as we mentioned just now, is that most of the time.
Um, we’ve got here a bone. This is the end of a bone.
We’ve got the diaphysis here, and then we’ve got the epiphyseal plate which sits just under the head of the long bones.
And this is where most of the bone growth happens.
Okay. And if we zoom in to that area shown over here on the right, you can see that this area has got lots of cells here.
And these cells are chondracytes. So essentially it’s cartilage okay.
And those cartilage linear cells, they’re the ones that increase in number.
And those of you who have listened to the lecture bites on growth hormone.
Well here how we have growth hormone and IGF one increase the number of the cells that are there.
Okay. And so this increases the number that is sat here which will increase the length of bone.
So that will equate to you growing in height okay.
Because these long bones we’re talking about these ones and these ones,
these ones and these ones, we’re not talking about your vertebrae, for example.
Okay. So the key thing is that when we’ve got lots of calcium, these areas just at the top of the diaphysis when bones and growth is continuing in an upwards direction.
the older cells at the bottom then become older.
And they. Um, essentially start to die off and where they start to die off
This then provides you with bone matrix.
And this is where the calcium gets deposited to be stored.
Okay. And you can see that that process has happened over here on the right where you’ve got newly calcified bone,
which is where these old disintegrating chondrocytes are between osteoblasts. Okay. Now, osteoblasts are important because they’re the ones that are bone specific lineage cells.
They are not cartilage cells. Uh, osteoblasts build bone.
So blasts build. Okay.
And these are controlled by a number of different hormones, which we’re going to come up to in a minute.
But they are the ones that will start to induce that, um, laying down of calcium in this area here where we get calcification.
In terms of what happens when we remove calcium from the bone, that resorption process happens.
Um, we use osteoclasts.
And if you want something to help you remember the difference between those blasts build and clasts collapse bone.
Okay. So osteoclasts will come along and they reabsorb the bone.
Essentially what they do is they use acid to denature what’s on the cell surface to allow the release of the calcium.
And of course, then the calcium that’s generated gets put back into that central pot,
that extracellular fluid pot that then can be used for lots of other things.
Okay. And so therefore it’s using hydrogen ions and chloride ions here on the cell surface.
This white area, these enzymes that are In the area of bone resorption and released by this osteoclasts are activated by that high the acidic environment where the H+ ions are being released.
Low calcium lead to Bone Resorption
In terms of what happens when we remove calcium from the bone, that resorption process happens.
Um, we use osteoclasts.
And if you want something to help you remember the difference between those blasts build and clasts collapse bone.
Okay. So osteoclasts will come along and they reabsorb the bone.
Essentially what they do is they use acid to denature what’s on the cell surface to allow the release of the calcium.
And of course, then the calcium that’s generated gets put back into that central pot,
that extracellular fluid pot that then can be used for lots of other things.
Okay. And so therefore it’s using hydrogen ions and chloride ions here on the cell surface.
This white area, these enzymes that are In the area of bone resorption and released by this osteoclasts are activated by that high the acidic environment where the H+ ions are being released.
Controlling Ca2+ Loss
So in terms of controlling the calcium loss, this happens by hormones that we have that are released from the, um.
Thyroid and from the parathyroid.
Um, and you will start to see how these all fit together.
So here on this diagram, dietary calcium is here in the GI tract.
And if it continues along this line is going to be excreted in the faeces.
But our calcium ion here.
Um can be taken up into that central pot here.
The extracellular fluid and the hormones that control this are calcitriol, which is the active form of vitamin D and parathyroid hormone PTA.
Okay. So both of these will impact the uptake.
And then what you’ll seeon the line point to the bone is that calcitonin which is released from the thyroid will stimulate the
laying down or the deposition of calcium onto the bone cell surface in the format of hydroxyapatite.
And then calcium can be resolved from the bone, which is controlled by parathyroid hormone.
At the same time, that parathyroid hormone is able to stimulate the um re uptake of calcium that’s filtered in the kidney at the same time as well.
So it has multiple ways of doing things, this parathyroid hormone, whereas the other hormones have less of an effect on the other parts.
Of course, vitamin D also has an effect on that bone resorption process.
Calcitriol. And what you’ll also notice is that cortisol can also impact here.
We’re not going to talk about that at this point because it will get quite confusing.
But calcitonin can also have a negative impact on that reabsorption process in the kidney.
Please don’t get confused between resorption and reabsorption.
Okay. Reabsorption happening in the kidney. Resorption happening on the bone surface.
I say this every year. And every year it gets to the exam and somebody gets stressed and somebody writes the wrong word and it doesn’t make sense.
Okay. So just be really, really careful that you use the right word.
So we’re going to look at each of these hormones of calcitriol or um vitamin D of parathyroid hormone and of calcitonin.
And look at how they sort of play together if you like
Parathyroid gland
Okay. So if we focus first on parathyroid hormone, it’s generated by the parathyroid glands okay.
The parathyroid glands these little green nuggets that are on the back of the thyroid here.
So we’re actually looking at the back of this person.
Um so they’re on the anterior side.
If we look at the parathyroid, under the microscope, what you’ll see is that there are lots of blood capillaries here,
and it’s the chief cells here, the dark coloured ones that are able to produce this hormone.
Okay. And when I said to you that they are highly vascularised here, you can see that there is blood vessels in multiple places.
Remember this is the back of the thyroid.
So there are going to be areas where you’ve got your follicle here that you would have talked about with Professor Johnson.
Okay. These are very close by. But the parathyroid gland is literally right next to that thyroid gland.
So you can see that it’s highly vascularised. This hormone is released straight into the bloodstream by those chief cells.
And then it circulates the body to get to where it’s going to have its impact.
Parathyroid hormone is the strongest of the hormones that controls calcium concentration.
So parathyroid para meaning beside thyroid, beside the thyroid okay.
There are usually two superior and two inferior parts to it.
We’re not going to expect you to label a diagram. This is where the thyroid is.
This is where the parathyroid is. But it’s important to know that they’re so closely um positioned.
Sometimes in textbooks you might see the chief cells referred to as, uh, principal cells.
So just in case you’ve got those slightly different terminologies, we’ll accept both.
Don’t worry about it.
PTH signalling
Okay. So in terms of parathyroid signalling, um, pretty much up till now, we’ve done lots of stuff to do with steroid hormones.
And, you know, they can easily move through the membrane and they bind to these intracellular receptors.
For those of you who are not doing biochemistry, I’m not expecting you to tell me, um,
the absolute everything of what, you know, every single protein that’s in this signalling cascade.
But I am going to expect you, if you want to get something above 70, to be able to name some of this process.
Okay. So parathyroid hormone binds to what we call a G protein coupled receptor.
And those of you that are doing um experimental biology and biochemistry will have this information.
And so hopefully most of you that are doing also doing uh neuroscience will also have come across these G protein coupled receptors.
The hormone binds the receptor and it causes the activation of three proteins that are on the inner side of the membrane.
And one of these binds to GTP.
When it does that it becomes activated.
And it can then induce another enzyme which is able to turn on um and therefore pass on intracellular signalling.
Sometimes these enzymes may be related to the release of calcium.
This doesn’t happen in every cell, but this is what will happen in terms of the release of calcium intracellularly
Okay. But parathyroid hormone works through these G-protein coupled receptors.
But it turns on the expression of transporters that are in your intestine,
and so it increases the amount you can take up from your diet and fill into your central pot.
Okay, so the key thing to take home from this slide is that.
G-protein coupled receptors, such as parathyroid hormone receptor, is able to not only turn things on inside the cell an enzyme,
but are also able to turn on the expression of genes that are important for the uptake.
Of calcium from your diet. Okay. And so that links on very nicely to those things that we’ve been doing in molecular biology as well.
Parathyroid hormone (PTH)
Okay. So where else does this parathyroid hormone have its effects?
If we’ve got a reduction in calcium. This stimulates calcium sensing receptors, which is what CaSR are in the chief cells okay.
Those chief cells generate parathyroid hormone as a protein okay.
it is already made and it’s in little secretory vesicles waiting for the signal to come.
It doesn’t sense that there’s a problem with calcium and then go, oh,
by the way I need this in 24 hours when transcription and translation has happened, it goes.
I need it now. Okay. So it needs it now.
And then what happens is all that stuff that’s been already prepared and is just sitting underneath the cell membrane,
then has the ability to fuse with the cell membrane and the hormones released by exocytosis.
Okay. So here it’s stored in these secreted granules waiting for the sensor cells to tell it that it’s ready to release.
When that process happens there’s obviously an increase in parathyroid hormone.
And that means that then the parathyroid hormone is going to stimulate not only bone for resorption to happen.
It says, excuse me, we need some more calcium. Start breaking down what is on the cell surface stores and fill up that central pot.
Okay, there is a problem because that pot is low. It also increases the expression of those transporters in the gut that is going to fill up,
so that we’re going to get more from whatever you’re eating a higher percentage and fill up that pot.
But it’s also going to get the kidney.
To reabsorb more in the proximal and distal convoluted tubule so that every
single little bit of calcium that might have thought it was on its way out of the body,
suddenly gets clawed back in a mass attempt to keep more calcium inside the cell.
So in this way, it’s working several angles to increase.
How much is sat here in this pot?
I have given you the normal range, but again, do not need to remember it.
Just come back here and refer to it if you need that.
Okay. So in terms of our focus, we know that this process happens.
We know that there’s uptake um of calcium that’s coming in.
And so we should be filling up that pot nice and slowly.
It’s a bit like an analogy of here is a big bath worth of water, okay.
If water’s going out the bottom and you want it to stay the same level, you’ve got to start filling it up somehow.
And that’s exactly what this bucket, if you like, of calcium is that needs to be maintained.
What kind of hormone is Vitamin D?
a.Steroid
b.Protein
c.Amino acid
d.Nucleotide
e.None of these?
So the next thing we’re going to talk about is vitamin D okay.
Also known as calcitriol, calcitriol is the active form of vitamin D.
And there are multiple forms of vitamin D.
So here’s a quick quiz question for you.
What kind of hormone is vitamin D? Hopefully most of you chose this answer.
It’s a it’s a steroid. If you look at its structure it’s got those four steroid rings okay.
It’s generated from cholesterol. Bonus question was what type of receptor does this bind to?
If it’s a steroid hormone. Anyone.
Does it bind to a receptor that’s on the cell surface? Does it bind to one that’s inside the cell?
Yeah. Shout louder than most intracellular receptor.
Yeah. Um, or a nuclear hormone receptor. Absolutely.
Vitamin D synthesis
So, These intracellular receptors it’s going to bind in the cytoplasm are vitamin D.
Absolutely. So in terms of vitamin D synthesis we can take stuff in from our extracellular environment.
We can take them in in two different forms vitamin D2 and vitamin D3.
And these are both usually um stored in the liver for long term storage.
Um, and they can be then converted in the kidney into the active form which is calcitriol.
We can also synthesise this.
And this is the point where I remind you that we unfortunately live in Britain, where there’s not very much we can do it using sunshine and heat.
Okay. So we use cholesterol in the skin, skin cells in keratinocytes okay.
We have 7-dehydrocholesterol in the keratinocyte cells.
And then in the presence of sunlight or UVA rays and heat.
we can generate vitamin D for ourselves okay.
Parathyroid hormone stimulates the production of calcitriol.
And it does this in the kidney. And we’ll talk a little bit more about that in a minute.
There’s a specific enzyme that’s involved that is turned on.
In terms of transcription and translation by the action of parathyroid hormone.
I’ve given you what the normal range of calcitriol is not of vitamin D2 and D3.
Okay. I’ve also told you what gives you that.
This person is definitely deficient in vitamin D because there are slightly different variations in this.
So in terms of vitamin D two and D three, we get these in lots of oily fish.
So if there’s a reason for you to be pescatarian at least um, then this would probably be it.
So there are lots of omega unsaturated fatty acids that are in our, uh, oily fish.
But we can also get, um, these from eggs as well.
And actually, you probably find if you look at your breakfast cereal, if you have cereal every morning that it’s fortified with things like vitamin D,
there are some baby milks or full fat milks that again, have fortified vitamin D in them as well.
Vitamin D synthesis mechanism
So there are lots of places that you can get your vitamin D from, in addition to a lovely, nice chewy,
gummy sweet type thing that you can have every morning that I say to my kids that they have to have when they get up, okay.
And it’s become a thing with my son. He goes, I need my milk and my vitamin sweets.
And just because I call it vitamin sweet instead of vitamin tablets,
he enjoys it every single morning and thinks it’s great because he can have sweets before he goes to school.
Okay, so. this 7-dehydrocholesterol that we have in our skin cells only gets converted into pre vitamin D three when the sun is at a particular wavelength okay.
You can see here that it’s at that wavelength between 230 to 312 nanometres.
Okay. And that depends on what season We’re in. Okay, so this depends on what season we’re in, um, and how close to the sun we are, etc.,
but we also need some heat as well to convert this pre vitamin D3 into this vitamin D3 and D2,
which sometimes in books you might see referred to as cholecalciferol.
Chole meaning liver okay.
Calciferol meaning the name of this type of molecule.
So here this is what’s stored in the liver.
And it can usually stay there for a couple of months to about three months.
Okay. So usually store it for about up to three months.
And if you need it then the liver will allow it to be degraded into our active component down here at the bottom, Calcitriol
Now what leaves the liver. And goes to the kidneys for conversion is calcifediol and this has a half life of about 15 days.
So two weeks. So if your calcium levels are low this is what gets released from the stool but This will then be there waiting just in case you need to top up your supply.
Okay. And at this point then we need this enzyme C1-alpha-hydroxylase which is going to convert this into calcitriol.
This is the enzyme that parathyroid hormone turns on the expression off.
Okay. So when parathyroid is working it’s going okay.
This is a problem. We need more calcium.
It turns on C1-alpha-hydroxylase to go generate more vitamin D so we can get more calcium into the body.
And the reason that the calcitriol does this is because it’s able to turn on expression.
So there is a negative feedback here between what’s circulating for the 15 days and what’s in the storage.
And of course that makes sense.
You don’t want to start converting everything that’s in storage into this thing that’s going to get broken down in 14 days,
because what happens if you convert it all to the one that runs out in 14 days, and in 20 days you need more, but you didn’t need it in the 14 days.
Wave goodbye to it. All of a sudden it’s gone. Okay, so we have to make sure that there’s a way of only having this if we need it.
So in terms of vitamin D synthesis, we can regulate what’s going on here.
We can regulate how much C1-alpha-hydroxylase is created through parathyroid hormone.
And if parathyroid hormone says that we need more vitamin D, we need more active vitamin D.
So it turns on this enzyme which will help us create more of this.
How is Vitamin D transported?
Okay. So I want you to think for a minute before we go.
How is vitamin D transported around the body, do you think?
You know it’s a steroids. How is it going to be transported around the body?
Is it going to be hydrophilic? Hands up for.
Yes. Hands up for no. Okay.
Some of you are paying attention at least. Right? So it’s not hydrophilic, so it must be bound to a protein okay.
Remember albumin and all those other things you’ve probably heard about thyroid binding globulin
They are there specific binding globulins
We have a proteins carry this around the body as well.
Okay. Vitamin D is carried around in the blood and in the lymph.
But it has to be bound to either albumin or specific globulin.
So here you’ll see in the middle we’ve got our free hormone.
A hormone can be bound to a carrier.
But that’s only a transient interaction. It doesn’t bind to it.
Never let go. Otherwise you’d never have any free vitamin D okay.
So it has to bind and then it will come off at some point.
Okay. Think of it a bit like going along on a roller coaster.
If you don’t have that harness in at some point when you’re going round, you would just slip off.
And that’s a little bit like what goes on here.
And as soon as it slips off, okay, it is able to move through the cell wall because of course it’s lipophilic.
And so it will start to bind to its hormone and therefore it will have its biological effects.
But just because it becomes unbound from here doesn’t mean it won’t immediately bind to another protein.
Okay, so this is how we stop it from being excreted from the body.
Because once it’s bound to a protein, it’s too big to be filtered, okay, in the glomerulus.
So it needs to be bound to that protein to stay in the body and not to be filtered.
And if it is filtered, then it will, um, leave the body.
Likewise, if it’s degraded, it will leave the body.
Vitamin D receptors (VDR)
Okay. So. When our calcitriol, which is the active form of vitamin D.
moves into the cell and it is, as we said yesterday or whenever it was earlier on in the week, um, that it is bound to a globulin.
So vitamin D, um, bound globulin outside the cell
it then uncouples from the globulin and moves through the cell membrane because it’s lipophilic and it’s able to quickly push between the phospholipids and Be
Diffused into the cytoplasm. Once it’s in the cytoplasm.
Or in the nucleus. It binds to the vitamin D receptor.
Which in here is shown as VDR Okay.
And this is an intracellular receptor so it doesn’t um attach the receptor on the top.
But what vitamin D receptor does is it can hetero dimerise.
With another member of the nuclear hormone receptor family.
Okay, so think back to your molecular biology where I said that these types of, um, receptors are promiscuous.
They like to partner up with lots of different people. So for example, here, we’ve given you RXR.
And so once those are all associated together, they are able to induce the expression.
Of the target genes. Now what is important regarding the target genes for vitamin D receptor in terms of, um, activating gene specific transcription.
Is that it’s able to induce the expression of those transporters that are in the, um,
gut mucosa that are going to bring calcium that’s in your diet through the gut mucosa and into the bloodstream.
Okay. So this is how we get an increased uptake from your diet it is through these transporters.
Effects of Vitamin D?
So here this is our blood and on the right hand side of these cells.
And on the left hand side this is our lumen of the gut mucosa.
And calcium can move by lots of different ways.
It can move through channels that are in the membrane.
And then bind to proteins inside and then be transported out by facilitated diffusion.
Or it can be moved through by vesicular transport.
So here you can see calcium is taken up into vesicle and transported across the membrane.
Or we can have um it moving through the lysosome here.
So there are lots of different ways. But these receptors here that allow calcium release from the lysosome and transport out into the, um,
blood and these specific receptors to allow tight uptake from, uh, the lumen of the GI tract and allow transport into the blood.
These are increased. In response to vitamin D.
Okay, so that means that we’re much more efficient at taking calcium up from our diet.
If we’ve got vitamin D either being generated.
Or. That we’re having it also in our diet, okay.
Because somehow it’s going to get into the system, bind to it, it’s receptor and increase this.
This is not the only place though. There’s also reabsorption that happens that stimulated by calcitriol as well.
Okay, so there’s a kidney effect and there’s a GI tract effect.
Okay. Its direct action on bone is not particularly well understood.
There are some suggestions that, um,
there is a direct effect of calcitriol binding to vitamin D that seems to somehow stimulate the osteoblasts to lay down more calcium in the bone.
Um, but it’s not really very well understood. And high levels of the vitamin D receptors are expressed on osteoblasts.
But likewise, if we have huge amounts of vitamin D overexpression,
this is more often seen in those osteoblasts, which causes an increase and a decrease in bone resorption.
So it has effects that we don’t fully understand because sometimes it goes up in terms of bone density and sometimes it goes down.
There seems to be a very fine line. Of the of the normal concentration.
And if there is more than usual, that seems to have some confusing effects.
So. What I don’t want you to worry about is the direct effect on bone.
But I’m just kind of highlighting to you that it has some direct effects on bones.
And if you come across those articles, feel free to read them.
Okay, but I’m not expecting you to tell me those direct effects on bones.
I’m more looking for how they’re involved in the regulation of calcium.
Okay.
Vitamin D SUMMARY:
So in terms of its effects on calcium for calcium trio.
Our dietary vitamin D two and D three.
Or anything that’s generated from 7-DeHydrocholesterol in the skin is stored in the liver for up to about three months.
And once it’s ready, and we have a need for a greater amount of calcitriol.
Well, it’s then moved from the liver and it’s metabolised, um, in the kidney.
by our C1-alpha-hydroxylase?
Which is able to generate calcitriol and calcitriol can have effects, as we said just now on osteoblasts that we don’t really understand.
Okay. But it also has an inhibitory effect on parathyroid hormone.
It has, if there’s too much of it, it has a negative feedback on itself.
But generally it will increase the uptake from the GI tract and it will increase the reabsorption that happens in the kidney,
so that we have an increase in calcium concentrations in the blood in the extracellular fluid.
Okay. And remember, it’s generally turned on by parathyroid hormone.
Parathyroid hormone is the thing that stimulates C1-alpha-hydroxylase to generate calcitriol.
Okay. So remember that it’s parathyroid hormones in charge.
It’s the most potent. If there’s a response to do with calcium.
Parathyroid hormone is your primary culprit.
Okay. This is more of a supporting act that works with it
