00:00:06
iron engineer it's what we do in this
00:00:08
video is we're going to talk about the
00:00:10
parathyroid gland alright so where would
00:00:12
you find the parathyroid gland so you
00:00:13
would find it actually located in the
00:00:15
posterior aspect of the thyroid gland
00:00:17
okay where's the thyroid gland found a
00:00:19
thyroid gland is actually found kind of
00:00:22
like in the its inferior to the larynx
00:00:24
so it's an anterior neck inferior to the
00:00:26
larynx so it's a butterfly-shaped gland
00:00:28
and on the posterior aspect of that
00:00:31
gland you're going to have these little
00:00:32
parathyroid glands extremely important
00:00:34
glands actually in the past when I used
00:00:36
to do thyroidectomies they didn't really
00:00:38
know that there was the parathyroid
00:00:40
glands and they would remove the entire
00:00:41
thyroid gland and the parathyroid glands
00:00:43
so now whenever they do start active
00:00:45
means you have to be very very careful
00:00:46
to make sure that you keep these little
00:00:48
parathyroid glands so there's actually
00:00:49
four of them so you have like two here
00:00:52
on this lobe and then two here on this
00:00:55
lobe here right there's four parathyroid
00:00:57
glands what I'm doing right now is I'm
00:01:00
zooming in on these actual thyroid gland
00:01:02
right I'm sorry
00:01:03
parathyroid gland now here's what I got
00:01:04
to make sure I explained to you real
00:01:05
quick the parathyroid gland right has
00:01:08
two different types of cells that are
00:01:10
extremely important one they're still
00:01:12
trying to research what's actually the
00:01:14
responsibility of this cell that one
00:01:17
cell that they're still looking into is
00:01:19
called the oxy fill cells so these oxy
00:01:22
fuel cells they're still not sure quite
00:01:24
yet what they do they do play the bleed
00:01:26
that they play a role in stimulating
00:01:28
these other cells to produce parathyroid
00:01:30
hormone and they believe that they have
00:01:31
some type of role what's called a
00:01:32
parathyroid hormone-related protein and
00:01:35
even vitamin D so but they're still
00:01:38
trying to isolate out what exactly these
00:01:40
cells do the other cells that we're
00:01:43
going to zoom in on is called the chief
00:01:45
cells and the chief cells are going to
00:01:47
be the ones that are primarily
00:01:48
responsible for secreting parathyroid
00:01:52
hormone and we're going to take a look
00:01:54
at parathyroid harmed before we do that
00:01:57
we need to know what exactly gets these
00:02:00
cells going what stimulates them to when
00:02:02
we release that parathyroid hormone so
00:02:04
you know that they make parathyroid
00:02:06
hormone what stimulates that what causes
00:02:09
these chief cells to want to be able to
00:02:11
produce
00:02:13
right hormone so now I'll zoom in the
00:02:15
left look so I zoom in on one chief cell
00:02:18
right here so before we actually see
00:02:20
what the stimulus is we have to make our
00:02:21
parathyroid hormone right so how do we
00:02:23
make parathyroid hormone you know that
00:02:25
there's going to be specific genes that
00:02:26
are expressed and whenever those genes
00:02:28
are transcribed by maybe a specific type
00:02:31
of RNA polymerase like type 2
00:02:33
it'll make what it'll make mRNA and then
00:02:38
what will happen that mRNA will actually
00:02:39
come out here into the cytoplasm and
00:02:41
then in the cytoplasm what do you have
00:02:43
you have ribosomes and what would those
00:02:45
ribosomes do those ribosomes will act on
00:02:47
the mRNA to translate that actual what
00:02:50
to translate this in Larney into
00:02:53
proteins so they'll translate this mRNA
00:02:57
into protein molecules so this is going
00:02:59
to be our protein here and let's say
00:03:02
this protein is the preform of
00:03:04
parathyroid hormone he'll undergo some
00:03:06
specific modifications and cleavage
00:03:08
processes within the rough ER and the
00:03:10
golgi but in general afterwards so you
00:03:13
know what is this step right here call
00:03:15
when you go from DNA to aughh mRNA this
00:03:17
is called transcription and what does
00:03:22
this process call whenever you take the
00:03:23
mRNA and you translate it into proteins
00:03:26
this is called translation okay and then
00:03:30
it'll undergo some modification so it'll
00:03:31
actually go to the golgi so if we were
00:03:33
to show here let's say here's the golgi
00:03:35
let's say there's the golgi what happens
00:03:37
the you know go to the rough ER and then
00:03:39
it'll go to the golgi where it gets
00:03:40
modified and packaged right so now look
00:03:43
look what happens afterwards we got all
00:03:45
these vesicles like packaging this
00:03:47
hormone and what is that hormone in
00:03:49
there called this little dots that I'm
00:03:52
drawing in here is all the parathyroid
00:03:53
hormone right does all the parathyroid
00:03:56
hormone that's sitting in these vesicles
00:03:57
it's ready to be released well what's
00:04:00
going to get it to go
00:04:02
calcium calcium is the primary stimulus
00:04:05
here but here's what we got to make sure
00:04:07
we explained here is that high calcium
00:04:09
levels or is it low blood calcium levels
00:04:11
it's actually going to be low blood
00:04:16
calcium levels you know what they call
00:04:19
below the normal value of calcium they
00:04:23
actually call it hypocalcemia right so
00:04:26
Pawel hypocalcemia is a very strong
00:04:29
stimulus of parathyroid hormone how you
00:04:33
see this receptor here it's a seven past
00:04:35
receptor seven past transmembrane
00:04:37
receptor it's very very sensitive to
00:04:40
calcium so this is a calcium sensitive
00:04:42
receptor so again what is this receptor
00:04:44
called here it's a calcium sensitive
00:04:49
receptor very very interesting because
00:04:52
usually only hormones bind up to these
00:04:54
receptors right but guess what
00:04:56
calcium also binds here so calcium binds
00:04:59
on to this calcium sensitive receptor
00:05:01
and it triggers these different
00:05:03
intracellular processes right when
00:05:05
calcium levels are high look what it
00:05:08
does though it sends these signals
00:05:09
through all these different types of
00:05:10
intracellular signals that we're not
00:05:11
really concerned with here and guess
00:05:13
what the overall effect of it is
00:05:15
whenever there's high calcium levels it
00:05:18
inhibits this process so you see that
00:05:21
whenever there's really high calcium
00:05:22
levels it inhibits this actual PTH from
00:05:24
getting released okay so then what
00:05:28
happens if there's very low calcium
00:05:31
levels if there's very very low calcium
00:05:34
levels this process right here is
00:05:37
actually going to be less so there's
00:05:39
less inhibitory input coming in right so
00:05:43
there's less inhibitory pathways or
00:05:44
intercellular pathways here so now
00:05:46
what's going to happen if there's less
00:05:48
intracellular pathways going in here
00:05:50
this low blood calcium levels will
00:05:53
actually be a stimulus for PTH secretion
00:05:57
so now look when there's low blood
00:05:59
calcium levels it'll actually cause the
00:06:01
stimulus to do what to cause these
00:06:03
vesicles to merge with the actual plasma
00:06:06
membrane and look what happens here look
00:06:08
what we start releasing out into the
00:06:09
blood plasma we start releasing out all
00:06:12
of this parathyroid hormone okay so
00:06:15
parathyroid hormone stimulus is going to
00:06:17
be low blood calcium level so it's a
00:06:20
representative of a black dot there as
00:06:22
calcium so it's low calcium levels okay
00:06:27
and again why is it being sting why's
00:06:29
this low calcium level stimulating it
00:06:31
because when there's high calcium it was
00:06:32
inhibiting the release of PTH through
00:06:34
these intracellular pathways when
00:06:36
there's low calcium there's not going to
00:06:37
be as many of these intracellular
00:06:38
pathways occurring right
00:06:40
so it's going to release this actual PTH
00:06:42
secretion from inhibition and then
00:06:44
what's going to happen PTH will start
00:06:45
getting released all right so now that
00:06:48
we know that that mechanism what about
00:06:50
this other side drew another song here
00:06:52
what's this cell about okay you're the
00:06:55
thyroid gland we talked about this in
00:06:56
the thyroid hormone video that we said
00:06:58
that there's made up of thyroid
00:06:59
follicles right and the spirals are the
00:07:02
ones that are basically responding to
00:07:03
TSH and making thyroid hormone well in
00:07:07
between the thyroid follicle sometimes
00:07:09
you'll see squeezed in between the mash
00:07:11
between them is this little green cell
00:07:13
here what's that green cell they're
00:07:14
called that green cell is actually
00:07:17
called a pair of follicular cell so it's
00:07:21
actually called a para follicular cell
00:07:25
sometimes they even call it C cells
00:07:28
right so there's C cells or pair
00:07:29
follicular cells these guys are
00:07:32
important with being able to regulate
00:07:33
the the opposite action of calcium so
00:07:36
this one this one actually low calcium
00:07:38
stimulates PTH secretion this cell right
00:07:41
here this pair of follicular cell is
00:07:43
actually going to be stimulated by high
00:07:45
blood calcium levels okay now it could
00:07:48
work through a calcium sensing or
00:07:50
scepter or it could even work through
00:07:51
calcium channels the mechanism we're not
00:07:54
really good at concerned with here but
00:07:56
it's just understanding what is the
00:07:58
stimulus here so there could be calcium
00:08:00
channels that this actual calcium is
00:08:01
going to work through or it could
00:08:03
actually work through a calcium
00:08:04
sensitive receptor so let's show again
00:08:06
here
00:08:06
what's the stimulus here what's the
00:08:09
overall stimulus high blood calcium
00:08:13
levels so it's high blood calcium level
00:08:16
you call that whenever you have higher
00:08:18
than normal calcium levels called
00:08:20
hypercalcemia right hypercalcemia and
00:08:23
then what's the overall result it could
00:08:24
either cause more calcium to come in or
00:08:26
it could actually cause these different
00:08:28
types of intracellular pathways to occur
00:08:30
now before we do that we show this we
00:08:32
have to do the same thing we have to
00:08:34
make our calcitonin so how do we do that
00:08:36
we take this well we take this actual
00:08:39
DNA right here let's say this is the
00:08:41
gene to make calcitonin and we actually
00:08:44
transcribe it into mRNA so here's our
00:08:47
mRNA strand then what it comes out into
00:08:50
the cytoplasm and what does it actually
00:08:51
interact with it interacts with a
00:08:54
ribosomes what does the ribosome do it
00:08:56
translates this for actual mRNA when it
00:08:59
translators it translates it what does
00:09:01
it do it converts it into a protein and
00:09:04
this protein can go and get modified and
00:09:07
the rough ER and then after that it can
00:09:09
go to the Golgi right so I can go to the
00:09:13
Golgi and then what if the goal is
00:09:14
you're going to do it's going to package
00:09:15
it into these vesicles right so it's
00:09:17
going to package it maybe modify it a
00:09:19
little bit and then do what put it into
00:09:21
these vesicles and then have it ready
00:09:23
for excretion so let's show this one
00:09:27
right here in red so this is our
00:09:28
calcitonin and again what did we say was
00:09:30
the stimulus to cause these guys to get
00:09:32
released it was high calcium levels so
00:09:35
whether it be through the Rex movement
00:09:37
of the calcium or whether it be through
00:09:39
these actual inter say the pathways
00:09:41
what's happening is actually going to be
00:09:43
designed to stimulate what these
00:09:46
vesicles to fuse with the cell membrane
00:09:48
and if the vesicles fuse with the cell
00:09:51
membrane what's the overall result
00:09:53
you're going to be releasing out into
00:09:56
the plasma the blood plasma kalsa tonin
00:10:00
okay so now we have that so real quick
00:10:04
hypocalcemia is the stimulus for PTH
00:10:07
hypercalcemia is the stimulus for
00:10:10
calcitonin all right so now that we know
00:10:12
that let's go ahead and zoom in and see
00:10:14
how these hormones are going to regulate
00:10:17
these actual levels Oh real quick what
00:10:20
do you call whenever hormone is actually
00:10:22
stimulated to be released or secreted
00:10:24
but whenever it's due to some type of
00:10:27
ionic stimuli or nutrient stimulus right
00:10:31
so it's usually due to like chemicals or
00:10:33
ions or nutrients what is that call
00:10:35
that's called humoral stimuli so this
00:10:38
right here is an example of what's
00:10:39
called humoral stimuli I just wanted to
00:10:44
mention that because hormones can be
00:10:45
secreted in three ways humoral which is
00:10:47
due to ions and nutrients and different
00:10:49
types of chemicals hormonal which is one
00:10:52
hormone can stimulate another in the
00:10:54
current gland to make hormones or it
00:10:55
could be neural so there could be a
00:10:57
neural tissue that actually stimulates
00:10:59
an endocrine gland to make hormones so
00:11:01
there's three different types but this
00:11:02
is an example of humoral all right now
00:11:06
let's go ahead and zoom in now on the
00:11:08
effects first a parathyroid home because
00:11:10
calcitonin he is important in being able
00:11:12
to regulate calcium levels but the
00:11:14
primary regulator of calcium is
00:11:16
parathyroid hormone whose exceeds
00:11:17
essential okay calcitonin has a little
00:11:20
bit of a roll but it's not going to be
00:11:22
anything as craziness drastic as PTH so
00:11:24
let's focus on PTH first so we're going
00:11:27
to do know PTH and this is actually
00:11:29
going to be he's going to be this black
00:11:31
dot right here so let's see here let's
00:11:32
actually look look here's this guy right
00:11:34
here this is our parathyroid hormone and
00:11:38
he's ready to freak things up okay so
00:11:42
he's ready to start doing some damage so
00:11:44
what's he going to do let's focus on the
00:11:48
first organ here which is the bone okay
00:11:50
so he can act on bone tissue what is he
00:11:52
doing the bone tissue well there's two
00:11:54
different types of cells that are very
00:11:55
very important in being able to regulate
00:11:57
and maintain our bone remodeling
00:11:59
processes this one right here this blue
00:12:02
cell is actually called an osteo clasped
00:12:06
so let's call this one an osteo class
00:12:10
and it's one over here in red we're
00:12:13
going to call this one in osteo blast
00:12:16
now a little bit into the bone
00:12:19
physiology here is osteoclast you know
00:12:21
that these are actually going to be
00:12:22
cells that are doing bone resorption
00:12:24
what does I mean by bone resorption
00:12:26
it means it's trying to break down the
00:12:28
bone and resorb out or pull out or leach
00:12:33
out any of the calcium's and the
00:12:36
phosphates and some of the breakdown
00:12:37
products of the collagen out of the bone
00:12:40
and put it where into the plasma to the
00:12:42
blood plasma right so he's doing that
00:12:44
function osteoblasts are responsible for
00:12:49
what's called bone deposition what does
00:12:52
that mean by bone deposition it means
00:12:54
that they're responsible for being able
00:12:55
to take calcium take certain types of
00:12:58
phosphates take certain types of amino
00:13:00
acids to make collagen right and do what
00:13:03
deposit it into the bone tissue that's
00:13:06
his responsibility
00:13:07
so PTH he's his stimulus was what what
00:13:10
was the overall stimulus here let's
00:13:12
actually put this right here low calcium
00:13:15
levels right this was the primary steena
00:13:17
so what's his goal going to be he
00:13:19
goal is going to be to try to increase
00:13:22
the blood calcium levels how is he going
00:13:23
to do that he's going to want to
00:13:25
stimulate this guy but how he does it is
00:13:27
a little weird right because this guy's
00:13:29
we'd love to talk to each other so he's
00:13:30
going to talk to him first and he's
00:13:31
going to talk to him out on this
00:13:34
osteoclast I'm sorry Oscar Oblast is a
00:13:36
receptor for two PTH low PTH comes in
00:13:40
and binds onto this receptor when he
00:13:43
binds on to this receptor here it
00:13:45
stimulates the osteoblasts to start
00:13:48
secreting a specific chemical and what
00:13:50
is that chemical call it's called rank
00:13:53
ligand what does that rank ligand do
00:13:58
well you know this has rank receptors so
00:14:01
over here on the osteo class is actually
00:14:03
going to be rank receptor so this is
00:14:06
actually going to be a rank receptor
00:14:10
when rank ligand binds on to the rank
00:14:13
receptor guess what it does it triggers
00:14:15
this osteoclast to become very very
00:14:18
active so when it becomes very very
00:14:20
active it starts actually having a
00:14:22
detour nekton and integrin and
00:14:24
interacting right there's going to be a
00:14:25
lot of interaction with the bone then
00:14:27
it's going to start secreting a lot of
00:14:28
chemicals one of those chemicals call
00:14:30
that it's going to start secreting it's
00:14:31
going to start secreting chemicals like
00:14:33
caciques and k so it's going to start
00:14:35
secreting chemicals like beeps and K
00:14:37
which is a nice protein digesting enzyme
00:14:40
it's also going to secrete acid
00:14:41
phosphatases
00:14:42
tartar resistant acid phosphatase is a
00:14:45
lot of different types of chemicals and
00:14:48
then what is that going to do look what
00:14:51
it's going to do to the bone it's going
00:14:52
to start breaking down some of the
00:14:54
chemicals within the bone like the
00:14:56
collagen type 1 it's going to start
00:14:58
breaking down some of the hydroxyapatite
00:15:00
the calcium phosphate and look what it
00:15:03
does it starts actually resorbing and
00:15:05
breaking the way the bone and but what
00:15:07
does it pull what's actually
00:15:08
accumulating it out of this now now
00:15:10
you're going to have a lot of calcium
00:15:11
and a lot of phosphate look at that a
00:15:16
lot of calcium and a lot of phosphate
00:15:18
are accumulated from this breakdown
00:15:19
where is that calcium and phosphate
00:15:20
going to go we're going to take that and
00:15:23
put it into the blood so that's what
00:15:24
were going to do with that we're going
00:15:25
to take this calcium in this phosphate
00:15:27
right here and we're going to put it
00:15:30
into the blood
00:15:32
what is that going to do the blood now
00:15:34
so now if we look here what was the
00:15:36
overall result now if I bring this
00:15:38
calcium in this phosphate into the
00:15:39
bloodstream I increase my blood calcium
00:15:42
levels and I increase the phosphate
00:15:45
levels beautiful so that's one way that
00:15:47
the PTH helps to regulate the actual
00:15:50
calcium levels in the blood one is like
00:15:52
causing osteoclast ik activity to occur
00:15:54
and inhibiting the osteoblastic activity
00:15:57
all right now let's look at the kidneys
00:15:59
effect let's look at all the direct
00:16:00
effects of PTH and then the indirect
00:16:02
effect so what I did right here is I'm
00:16:04
taking a piece of the kidney and I'm
00:16:06
taking out if you know the kidney has
00:16:08
what's called the nephron right so it
00:16:09
has the you know you have your Bowman's
00:16:11
capsule then you got your proximal
00:16:13
convoluted tubule descending limb a
00:16:16
sending limb and then you got your
00:16:18
collecting duct right what I'm doing is
00:16:20
I'm zooming in on two cells in what's
00:16:24
called the distal convoluted tubules so
00:16:28
I'm zooming in on two of these cells in
00:16:30
the distal convoluted tubules because
00:16:31
that's where PTH really is working okay
00:16:33
so PTH is a protein hormone right so
00:16:36
just like we talked about in the
00:16:37
receptor video we know that he has to
00:16:41
have what extracellular membrane
00:16:44
receptors what type okay now this type
00:16:48
right here let's actually put it right
00:16:50
here
00:16:50
this is actually going to be kind of a G
00:16:52
stimulatory pathway right here so it
00:16:54
could actually be through the G
00:16:56
stimulatory pathway and how does this
00:16:59
actually work so let's say here we have
00:17:01
the actual parathyroid hormone and he
00:17:05
was actually going to be in black here
00:17:06
right so what did the parathyroid
00:17:07
hormone do he comes in and he binds on
00:17:10
to this receptor when he binds on to
00:17:13
this receptor it activates an
00:17:14
intracellular pathway right and
00:17:16
activates G stimulatory which activates
00:17:18
adenylate cyclase which converts ATP
00:17:21
into cyclic GMP cycle JMP activates
00:17:25
protein kinase a and then what's the
00:17:26
overall result it phosphorylates
00:17:28
specific types of transcription factors
00:17:31
what could those transcription factors
00:17:34
be they could be transcription factors
00:17:36
to make specific types of protein
00:17:38
molecules so let's say right here is our
00:17:40
transcription factor and what does the
00:17:43
protein kinase a do what approaching
00:17:46
tiny
00:17:46
- do we put phosphates on them and
00:17:49
activates them right and once this
00:17:51
becomes active it starts stimulating
00:17:53
this gene sequence and look what it
00:17:55
makes out of it it makes a specific type
00:17:57
of protein so look out look what it made
00:17:59
right here look at this it makes this
00:18:01
really really specific special type of
00:18:02
protein right here and this protein will
00:18:06
get packaged in the golgi and all that
00:18:08
stuff like that but then look where it's
00:18:10
going to go it's going to get packaged
00:18:11
in the golgi so to get packaged in the
00:18:14
golgi and then it'll actually get sent
00:18:15
out and get embedded into the membrane
00:18:17
so a whole bunch of these proteins now
00:18:19
look what we're going to have in the
00:18:20
membrane now look what we have into the
00:18:21
membrane right here look at this protein
00:18:23
right here this one right here this one
00:18:27
right here just a couple of you right
00:18:29
there right we'll put one more one more
00:18:30
right there what's the whole purpose of
00:18:32
this normally in the distal convoluted
00:18:35
tubule it is very impermeable to ions
00:18:38
like sodium and chlorine and water and
00:18:41
calcium and all different types of
00:18:42
substances so usually by the time things
00:18:44
get to this point usually need hormones
00:18:46
present in order to open up specific
00:18:49
channels to get those ions in or they'll
00:18:51
be lost in the urine so right now it's
00:18:53
getting ready to make urine so right
00:18:54
here what could be flowing through right
00:18:56
here look who is beautifully flowing
00:18:58
through in here it's actually going to
00:19:00
be calcium so we can have calcium just
00:19:04
chillin out in the lumen of this actual
00:19:06
filtrate it's getting ready to go into
00:19:07
the urine but what happens this who did
00:19:11
this really who is this form over here
00:19:12
this is actually parathyroid hormone
00:19:15
right what does he do he binds on
00:19:16
activates this pathway to make these
00:19:19
specific types of calcium channel
00:19:20
proteins and they get embedded into the
00:19:24
membrane right so this gets embedded all
00:19:25
into the membrane what's the overall
00:19:27
result then calcium is going to start
00:19:30
flowing in from the actual filtrate
00:19:35
that's going to go to make the urine
00:19:36
into these kidney cells and then where
00:19:39
they're going to go straight from here
00:19:40
look look where they go now they come in
00:19:43
here but guess what there's nothing
00:19:46
really here in this memory look they
00:19:47
have their had this little protein here
00:19:48
there's another protein right here let's
00:19:51
actually draw that protein look what it
00:19:54
has right here on the membrane it has
00:19:56
another protein here in the membrane
00:19:57
that's extremely important but it can't
00:19:59
get out
00:20:00
let's draw this one right here here's
00:20:02
this protein right here and it's trying
00:20:06
to be able to get out of this protein
00:20:08
but it can't and the reason why is
00:20:09
moving against its concentration
00:20:11
gradient so it's trying to go from areas
00:20:13
of low inside the cell to areas of high
00:20:15
right so that's going to be really hard
00:20:18
to do so what we need is we need someone
00:20:20
to assist on that process so you know
00:20:22
what every single cell in our entire
00:20:24
body we have these special types of
00:20:27
channels special types of proteins let's
00:20:30
say here's one let's say here's another
00:20:31
one you know what this one's called it's
00:20:34
called a sodium potassium ATPase pumps
00:20:36
so what are they doing they're pumping
00:20:39
three sodium they're putting three
00:20:42
sodium's out of the cell and two
00:20:46
potassium ions into the cell so again
00:20:48
three sodium ions out of a cell two
00:20:51
potassium ions into the cell so what's
00:20:53
happening what's getting really really
00:20:54
concentrated out here we're getting a
00:20:57
lot of sodium ions counts concentrated
00:20:59
out here right when the sodium ions get
00:21:02
really really concentrated out here in
00:21:03
the extracellular space look what they
00:21:05
can do they can actually move like let's
00:21:08
say I should actually follow all these
00:21:09
guys now look at this they can move so
00:21:12
they're really really high out here very
00:21:13
very low in here they're going to move
00:21:15
from areas of high to low so they're
00:21:18
moving by passive diffusion when they
00:21:21
move by passive diffusion because this
00:21:23
process is active right so this process
00:21:25
in general if you're pumping potassium
00:21:27
against this concentration gradient
00:21:29
sodium against this concentration
00:21:30
gradient this requires ATP so it's
00:21:33
active transport primary active but then
00:21:36
look sodium is really really
00:21:37
concentrated out here he can move down
00:21:39
its concentration gradient without any
00:21:41
energy there but calcium can't but when
00:21:44
sodium moves down guess what it helps
00:21:46
calcium out and then look what happens
00:21:49
calcium can get into the blood so this
00:21:52
is an example of a sodium calcium
00:21:54
exchanger but this is called secondary
00:21:57
active transport so this is called
00:21:59
secondary active transport so that's how
00:22:05
you help to be able to get these guys in
00:22:07
right is by bringing the sodium down its
00:22:09
concentration gradient it helps the
00:22:10
calcium go against its concentration
00:22:12
gradient
00:22:13
what do we do here what was the overall
00:22:14
result here then look at this what a
00:22:17
beautiful thing what do we do we
00:22:19
increase the calcium concentration there
00:22:22
another thing you know because calcium
00:22:25
has to is coming in right so it's coming
00:22:27
into the blood guess what this actual
00:22:28
PTH does it actually excretes out the
00:22:31
phosphates so also at the same time
00:22:33
that's actually pushing this calcium in
00:22:35
guess what else it's excreting out it's
00:22:38
pushing out phosphates because it's
00:22:41
important within the buffer system right
00:22:42
so it's excreting out phosphates in the
00:22:45
form of po4 three- or you actually might
00:22:47
even see in the form of hpo4 two-
00:22:52
because it's actually going to be a part
00:22:54
of a phosphate buffer system right kind
00:22:56
of so again what is it doing here in the
00:22:58
kidneys it's actually causing calcium
00:23:00
reabsorption and then excreting
00:23:03
phosphates okay now that we've done that
00:23:06
we know how it increases calcium in the
00:23:07
kidney now we're going to focus on the
00:23:09
last one which is kind of an indirect
00:23:11
function of PTH okay you know on your
00:23:15
skin you have a very specific chemical
00:23:17
what's that chemical called on your skin
00:23:19
in your skin you have a chemical which
00:23:21
is called seven-d hydro cholesterol okay
00:23:30
70 hydro cholesterol there's just a form
00:23:34
of a cholesterol molecule right now what
00:23:36
happens is if you're exposed to sunlight
00:23:38
right so let's say that you're exposing
00:23:40
yourself to sunlight so let's say here
00:23:42
some UV light here we'll draw that in
00:23:44
green here's some UV light some
00:23:47
ultraviolet light right hitting yeah
00:23:49
hitting that scan right there and what
00:23:52
does it do it actually acts as a
00:23:54
stimulus to cause 7g hydro cholesterol
00:23:59
to get pulled into the blood and it
00:24:01
turns it into another type of molecule
00:24:03
so what happens as a result of this when
00:24:05
it gets hit by the UV light it actually
00:24:07
gets converted into a specific molecule
00:24:10
and that molecule is called
00:24:12
cholecalciferol I'm not going to try to
00:24:15
spell that I'll definitely butcher it
00:24:16
guys
00:24:17
so I'm just going to put Coley Calcifer
00:24:19
raw what is cholecalciferol do well
00:24:23
cholecalciferol once it's in the blood
00:24:25
it goes to the liver
00:24:27
so it goes to delivering in the liver
00:24:29
there's a specific enzyme and that
00:24:32
enzyme loves to put o H groups hydroxyl
00:24:36
groups onto things you know what this
00:24:38
enzyme is called this enzyme is called
00:24:40
25 hydroxylase 25 hydroxylase so what do
00:24:48
think is going to do it's going to put a
00:24:48
hydroxyl group on the 25th carbon of
00:24:50
cholecalciferol so look what happens
00:24:52
here it's going to come in to this and
00:24:54
it's going to react with this enzyme
00:24:56
here and look what it does is when it
00:24:58
comes out look what it is now now it's
00:25:00
actually called 25 hydroxy
00:25:03
cholecalciferol that's what it is now
00:25:06
now it's 25 hydroxy cholecalciferol and
00:25:11
who performed that function that was the
00:25:15
25 hydroxylase enzyme okay well you're
00:25:18
I'm still you're probably still
00:25:19
wondering where that gets PTH come into
00:25:20
this play PTH acts on this kidney cells
00:25:24
right so it can act on specific tubular
00:25:26
cells within the kidney so can act on
00:25:28
specific tubular cells within the kidney
00:25:30
to express this very very specific
00:25:32
enzyme what is that specific enzyme that
00:25:34
it expresses that specific enzyme that
00:25:38
it can express is actually called one
00:25:40
alpha hydroxylase so it can express
00:25:44
something called one alpha
00:25:46
hydroxylase let me actually write that
00:25:49
up here so it's called one alpha we
00:25:53
should actually have a hyphen there 1
00:25:54
alpha hydroxylase so who who does this
00:26:00
who actually increases the expression of
00:26:01
this molecule this is actually going to
00:26:03
be parathyroid hormone so the
00:26:05
parathyroid hormone increases the
00:26:08
expression of one alpha hydroxyl a so he
00:26:12
stimulates this pathway now this 25
00:26:16
hydroxy cholecalciferol is actually
00:26:18
going to go to the kidney then and then
00:26:20
when it goes to the kidney the kidney is
00:26:23
actually going to allow look it's going
00:26:26
to interact with that and look look what
00:26:28
happens in the result so what happens
00:26:30
this 25 hydroxy cholecalciferol comes in
00:26:33
to the kidney and when it's in the
00:26:35
kidney it interacts with this one alpha
00:26:37
hydroxylase and who increases his
00:26:40
expression or at the
00:26:41
amount of him pth then look what you get
00:26:43
out of this one alpha-hydroxy it puts an
00:26:46
OHA group on the first carbon now we
00:26:49
call it 1 comma 25 dihydroxy
00:26:55
cholecalciferol holy Frick right that's
00:26:59
a lot right but like that and there's
00:27:02
another name that you can actually call
00:27:03
this stuff instead of that which makes
00:27:04
it a lot easier this is actually called
00:27:07
kalsa trial counselor trial this is the
00:27:13
active form of vitamin D so what is this
00:27:16
guy right here this is the active form
00:27:17
of vitamin D why am i mentioning all
00:27:23
this because PTH is going to help us to
00:27:25
get more calcium into the body he just
00:27:27
can't do it directly he's going to do it
00:27:28
indirectly how by turning this inactive
00:27:31
precursor of vitamin D into the active
00:27:34
presearch for active molecule of vitamin
00:27:37
D now what is vitamin D going to do
00:27:39
let's follow them over here now we're
00:27:42
going to do is we're going to zoom in
00:27:43
zoom in onto a specific part of the
00:27:45
gastrointestinal tract we're going to
00:27:47
zoom in onto the small intestine of the
00:27:48
wall and write the first part of the
00:27:49
foot small intestine the duodenum and
00:27:51
we're looking at one cell in the
00:27:54
duodenum this is an entire site nor an
00:27:57
intestinal epithelial cell right vitamin
00:28:00
D is going to come over here let's
00:28:02
actually follow this vitamin D over here
00:28:04
it's going to come all the way over here
00:28:05
and you know vitamin D is actually a
00:28:07
steroid hormone he acts like a steroid
00:28:09
hormone so in other words he doesn't
00:28:12
have extra cellular membrane receptors
00:28:14
he has receptors that are present inside
00:28:16
of the cell so let's draw that so look
00:28:18
here's his receptor which is present
00:28:19
inside of the cell and vitamin D will
00:28:24
actually pass right through the cell's
00:28:25
membrane and bind onto this
00:28:27
intracellular receptor when he binds
00:28:30
onto this interstate of the receptor
00:28:31
what will it do it'll activate a
00:28:33
specific gene sequence and that specific
00:28:36
gene sequence that it will activate will
00:28:38
produce specific types of proteins these
00:28:41
proteins will then again get transfer
00:28:43
you'll actually get those a translated
00:28:44
go to the rough ER go to the Golgi get
00:28:46
packaged and then get put up onto the
00:28:48
cell membrane look at these beautiful
00:28:50
proteins here these proteins are amazing
00:28:54
because they helped us to get the
00:28:55
calcium from the gut into the blood so
00:29:00
what are these proteins here called
00:29:01
these are calcium channel proteins so
00:29:04
what are they going to do this guy
00:29:05
actually be look you could actually have
00:29:06
calcium flowing through your actual GI
00:29:08
tract right maybe you had a nice little
00:29:10
piece of Cooper cheese that's my
00:29:11
favorite cheese I love Cooper cheese but
00:29:13
it could be flowing through the gut
00:29:14
right or you had like a lot of milk I
00:29:16
love milk too late' that's not the point
00:29:18
but again calcium is actually flowing
00:29:20
through the GI tract here right and look
00:29:22
we need to get a lot of that calcium
00:29:23
where we need to get a lot of that
00:29:25
calcium into the bloodstream so what did
00:29:28
this this actual vitamin D do it
00:29:30
activated specific genes to make these
00:29:33
what did it make it made these calcium
00:29:36
channel proteins look it made this
00:29:37
protein that one it made that one and
00:29:40
what's the overall result it opens up
00:29:42
these channel proteins for calcium and
00:29:44
increased amount of calcium to actually
00:29:48
come in because there's normally calcium
00:29:50
channel proteins on the membrane what
00:29:52
did vitamin D do it made more calcium
00:29:55
channel proteins so then what do we do
00:29:56
we absorb more calcium so where is this
00:29:59
going to go now look where all this
00:30:00
calcium is going to go to all the
00:30:02
calcium is going to come into the blood
00:30:03
right now right and then what's the
00:30:05
overall result there's an increase in
00:30:07
blood calcium levels so what was the
00:30:10
overall result and what did the vitamin
00:30:12
D do it increased blood calcium levels
00:30:14
how did PTH affect that it increased the
00:30:17
expression of the one alpha hydroxy
00:30:19
enzyme so PTH didn't do that we would
00:30:22
never have gotten the active form of
00:30:24
vitamin D and we would have never been
00:30:25
able to absorb the calcium so that's why
00:30:27
PTH is important in the activation of
00:30:30
vitamin D and the overall Szold is
00:30:31
everything if look here increases blood
00:30:34
calcium levels there increases the blood
00:30:37
calcium levels here and then that's how
00:30:40
he would deal with that okay now let's
00:30:42
go ahead and take a look at the
00:30:43
calcitonin out see how calcitonin does
00:30:45
this all right so calcitonin what does
00:30:47
calcitonin do well again we said the
00:30:49
calcitonin was stimulated by high blood
00:30:51
calcium levels so he would be stimulated
00:30:54
by high blood calcium levels so what do
00:30:56
you think he's going to want to do if we
00:30:58
were to put calcitonin range let's
00:31:00
actually have him at the opposite Pole
00:31:01
now
00:31:02
so let's actually say we have calcitonin
00:31:03
right here calcitonin is stimulated by
00:31:06
high
00:31:08
blood calcium levels right let's gel
00:31:10
calcitonin so here's calcitonin here's
00:31:17
our calcitonin dude right so this is our
00:31:19
kalsa tonin
00:31:22
what is calcitonin going to do to try to
00:31:24
be able to do what to bring these
00:31:26
calcium levels down that's his entire
00:31:28
goal he only really has one target where
00:31:31
you what he wants to do is he wants to
00:31:34
change the balance of the osteoclasts
00:31:37
and osteoblasts activity how he has
00:31:40
receptors directly on the osteoclast
00:31:42
let's draw this one right here let's
00:31:43
draw this red receptor right here here's
00:31:45
this red receptor you see that red
00:31:47
receptor there that's for calcitonin so
00:31:50
calcitonin is going to come in here and
00:31:51
he's going to bind so who is this
00:31:53
molecule is called calcitonin and
00:31:57
calcitonin will bind onto this receptor
00:31:59
guess it will do to this receptor it'll
00:32:02
cause this receptors to send signals to
00:32:04
the osteoclast to inhibit the osteoclast
00:32:07
so it won't make it beeps in k it won't
00:32:10
make these acid phosphatase and other
00:32:12
enzymes that are designed to break down
00:32:14
the bone right so this is inhibited
00:32:17
what's going to happen let's imagine I
00:32:18
have like a seesaw here all right here
00:32:22
we go and over here on this side it's
00:32:24
osteo clasped
00:32:25
so OC and on this side of the seesaw of
00:32:28
osteo blast
00:32:30
what does calcitonin going to do it's
00:32:32
going to inhibit the osteoclast activity
00:32:35
it's the osteo classic activity
00:32:37
decreases what happens to this now well
00:32:38
now we can actually redraw like this
00:32:40
right if we change the scale of
00:32:42
osteoclast activity is decreasing it
00:32:43
will look like this now look at this so
00:32:47
now osteoblastic activity is going up
00:32:49
and osteoclast activity is going down as
00:32:53
a result look what happens then it's
00:32:56
kind of like an indirect weird effect
00:32:58
right if he's inhibiting osteoclast
00:33:00
activity osteoclast can't resorb
00:33:03
as much bone away so who's going to be
00:33:05
primarily functioning right now
00:33:07
osteoblasts and what are the osteoblasts
00:33:10
going to be doing they're going to be
00:33:11
taking calcium from the blood so they
00:33:14
could be taking calcium from the blood
00:33:16
and some of those calcium phosphates out
00:33:18
of the blood and then they can deposit
00:33:20
that into the
00:33:21
oan so what would these osteoblasts be
00:33:23
doing they could be taking let's say
00:33:25
that we draw here we pull calcium out of
00:33:27
the bone right I mean out of the blood
00:33:29
so we pull a lot of this calcium out of
00:33:32
the blood and what is this osteoblasts
00:33:35
going to do it's going to take that
00:33:36
calcium and it's going to start
00:33:38
incorporating it in to the bone tissue
00:33:42
right and this osteoblasts will also
00:33:44
starts to creating what's called you
00:33:46
know not just the actual this will be a
00:33:47
component of the osteoid it also starts
00:33:50
to creating proteoglycans and collagen
00:33:52
type 1 a lot of different proteins in
00:33:55
this area right to be able to cause the
00:33:58
bone to get thicker all right all right
00:34:01
to cause bone deposition so osteo
00:34:05
osteoblasts well they're in hey their
00:34:07
activity will be increased due to the
00:34:09
decreasing activity of osteoclast so
00:34:12
it'll alter the normal balance of these
00:34:14
two cells and then who does that
00:34:16
calcitonin so again who does this
00:34:18
activity right here this is the job of
00:34:20
calcitonin calcitonin and calcitonin
00:34:25
will do what decrease the osteoclast
00:34:27
activity which as a result will increase
00:34:29
osteoblasts negativity when osteoblastic
00:34:31
activity occurs it'll pull more calcium
00:34:34
out of the blood which decreases the
00:34:35
blood calcium levels and it will take
00:34:37
that calcium and phosphate and other
00:34:39
types of amino acids and deposit that
00:34:41
into the bone right so he'll make
00:34:43
collagen type 1
00:34:44
it'll make hydroxyapatite he'll make the
00:34:46
different types of proteoglycans right
00:34:48
to cause the bone thickening right or
00:34:50
increase in bone deposits are in
00:34:53
engineers so in this video we talked
00:34:55
about parathyroid hormone and calcitonin
00:34:57
in great detail I hope it made sense
00:35:00
all right engineers until next time
