YouTube Transcript:
Costanzo Physiology (Chapter 9F) Endocrine Physiology: Calcium Regulation || Study This!

hello and welcome to the final portion
of the endocrine physiology chapter of
costanzo's physiology textbook
in this video we're going to go over the
regulation of calcium and phosphate
mainly going over the actions of pth
or parathyroid hormone if you enjoyed
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talking about
calcium and how it's moved around in the
blood starting off with the calcium
that's actually bound to plasma proteins
about 40 of the total calcium within our
blood
is bound to proteins the rest is ultra
filtratable meaning that it can actually
go into our nephron because remember
proteins don't cross that glomerular
membrane
out of that 60 that gets ultra filtrated
50 is ionized so the majority of that 60
is ionized calcium the remaining 10 is
complex to anions like phosphate
now this ionized portion this 50 percent
this is what is metabolically active and
this is what the parathyroid hormone is
regulating it's trying to regulate the
ionized calcium
if we are hypocalcemic or hypercalcemic
to the point of causing clinical signs
it's because of a change in our ionized
calcium
we may get a change in our total calcium
due to a change in our protein levels
within our bloodstream
but it's important to focus on the level
of the ionized calcium
so we do have some factors that once
again alter our total calcium so plasma
proteins alter it
anion concentration alter it so if we
have increased phosphate within our
system within our bloodstream
and that's going to increase the amount
that's complex to iron ions
so then our ionized calcium is going to
decrease relatively
and then our acid-base abnormalities can
change things in
acidemia albumin actually binds to more
of those hydrogen
ions so it displaces the calcium bound
to plasma proteins
so then our ionized calcium is actually
going to increase
and vice versa for alkalemia so you may
actually notice some clinical signs of
hypocalcemia
during an alkalotic state now the
clinical signs associated with
calcium abnormalities hypocalcemia we
end up with
excitability of tissues and cells that's
because we actually
lower the threshold potential basically
we make those
sodium channels more twitchy to open so
now it's going to
open much more readily and therefore we
need a lower stimulus
for an action potential to be fired so
hypocalcemia
results in increased action potential
firing in cells
and basically causes twitches and
excitability
hypercalcemia on the other end so high
calcium
is going to cause the opposite and slow
things down so we end up with
constipation we end up with hyporeflexia
lethargy coma potentially even death we
also end up with polyuria and diptyo
with hypercalcemia because we're
increasing the amount of calcium going
into our
urine which takes with it water so
getting to overall calcium homeostasis
this figure down the bottom here depicts
it nicely we have our extracellular
fluid concentration so our plasma
calcium level
and you can see we have three organ
systems contributing to it we've got our
intestine
our kidney and our bone our bone is
constantly remodeling so our osteoblasts
are constantly adding bone to bone and
our osteoclasts are constantly removing
old bone so we're constantly recycling
old bone for new bone
and that can be altered to increase
resorption to increase our calcium
levels within our blood
or increase deposition to reduce our
calcium levels within our blood we'll
get to the hormones that are able to do
that shortly when it comes to the
intestine
we can increase our absorption of
calcium from our intestine but we can't
alter
secreting additional so mainly in the
intestine we're trying to absorb more
calcium during hypocalcemic states
in the kidney we're able to reabsorb
more calcium as well
so we are able to increase the amount of
calcium getting reabsorbed
from the nephron so we lose less in the
urine so that's able to also
increase our calcium during hypocalcemic
states
so you'll also see these little plus
signs which mean that they are
activating and you'll see that pth and
125
dihydroxycholine calciferol which is a
mouthful
we're going to call this just activated
vitamin d they
activate the reabsorption of calcium
from each of these
organs so that increases calcium when we
have low body calcium levels
you'll notice that the only other
hormone here is calcitonin which we'll
touch on right at the end
this is an inhibitory effect on boner's
absorption so that's
actually going to be secreted when we
have high calcium levels within the
bloodstream
but we're not going to focus on that one
too much because this chapter is mainly
about the parathyroid hormone
so a parathyroid hormone gets released
whenever we have changes
and now ionized calcium and you'll see
in this graph here that we have the
sigmoidal
shape to pth secretion compared to our
total plasma calcium
so this shows that calcium wants to be
maintained right
in the middle here and one minor change
of calcium in either direction
will result in a dramatic change in our
pth secretion
if we slightly reduce our ionized
calcium we get a remarkable change with
an
increase in pth secretion instantly if
we slightly increase our calcium then we
get instantly a reduction in our pth
secretion
so we finely tune our calcium level and
try to keep it as constant as possible
parathyroid hormone is actually released
from the chief
cells within the parathyroid glands it's
called parathyroid because there are
these four
tiny little glands right next to the
thyroid gland itself
if we have chronic hypocalcemia so low
calcium levels
then we're going to get a constant
stimulus to produce pth
and the actual cells themselves the
chief cells
will be told to transcribe more of that
gene
that's going to synthesize pth so you
actually see hypertrophy of your
parathyroid glands
and a hyperparathyroid state with
chronic hypocalcemia
and that's called secondary
hyperparathyroidism it's a little teaser
for what we're going to be talking about
later on in this video now it does touch
very briefly on magnesium basically
magnesium
has similar effects to calcium or pth
secretion so if we have hypomagnesemia
then we'll have some pth
secretion as well it's not really the
focus of this
video or this chapter but just a little
side note there
so the actions of parathyroid hormone
it mainly works through the adenylyl
cyclase secondary messenger system by
increasing cyclic amp
and by doing that we increase the
resorption of bone and we increase the
reabsorption of calcium within the
kidney it also works on the intestines
in an indirect manner by
activating vitamin d active vitamin d
then actually increases the reabsorption
of calcium from the intestines
so pth works on those three organs but
in an
indirect manner works on that intestine
so in bone
the first thing pth does is actually
interestingly this is going to be
confusing
it actually increases the activity of
the osteoblasts so it actually slightly
increases the deposition of bone
initially but the long-term effects
through the increased production of
cytokines from the osteoblasts
it's actually going to be a marked
increase in the osteoclastic activity to
reabsorb bone
so really the net effect is a resorption
of both
calcium and phosphorus from the bone
into your
extracellular fluid space in the kidney
remember we talked about pth
in the kidney how it inhibits phosphate
reabsorption from that proximal
convoluted tubule so we increase the
amount of phosphorus
excretion in the kidney resulting in
phosphateuria but not only that
it increases the reabsorption of calcium
within the kidney
and this is important because since the
parathyroid hormone has increased the
resorption of both calcium and phosphate
from bone
if it keeps reabsorbing both of these
together then calcium will just get
complexed with phosphate and our ionized
calcium wouldn't increase as much
so it needs to actually excrete some
phosphate and just
increase the amount of ionized calcium
within the bloodstream because that's
what it's trying to maintain that is the
metabolically active form of calcium
so in the kidney it increases phosphate
secretion or excretion
and also increases calcium reabsorption
from that distal convoluted tubule in
the small intestine once again
it works indirectly via activated
vitamin d
to increase the absorption of calcium
from the intestine and we'll get into
more details and exactly how it's able
to
activate vitamin d in the kidney but at
least for now just remember
small intestine is going to increase the
calcium absorption
in the presence of pth indirectly due to
activated vitamin d now how about some
issues of parathyroid hormone
we've got a couple conditions here
number one primary hyperparathyroidism
think about this logically
primary means that the issue is the
parathyroid gland itself so the
parathyroid gland
is increasing the secretion of pth this
is going to occur due to a tumor that's
producing pth
if we have excessive pth that means
we're going to reabsorb a lot of calcium
and excrete a lot of
phosphorus from the kidneys so we're
going to have hypercalcemia
and hypophosphatemia our bones are going
to also become very very weak because we
are
absorbing a lot of those minerals so you
end up
with the saying of stones bones and
groans
stones because you start to produce
calcium stones within your urine
although there's increased reabsorption
in your kidneys there's still so much
calcium in the bloodstream
that there's a high filtered load so you
still end up technically with more
calcium being
in the urine along with that phosphorus
so you end up with calcium stones within
the urine
your bones become weakened because
they're getting resolved
and groans because of the constipation
from hypercalcemia
the treatment for this is
parathyroidectomy secondary
hyperparathyroidism means that there is
a hypocalcemic state that is chronic
that's causing the parathyroid gland to
increase its secretion
so something is causing calcium
deficiency
and that occurs due to vitamin d
deficiency so we're unable to reabsorb
enough calcium from our intestines and
we have a reduced response
with bone resorption because our
activated vitamin d helps to resolve
calcium from the bones or from chronic
renal failure so we're just excreting a
lot of calcium we're unable to reabsorb
that calcium from the kidneys so
secondary hyperparathyroidism
means that we have high pth due to a
chronic
low calcium hypoparathyroidism
is exactly as it says we have low
parathyroid hormone
either due to autoimmune destruction
surgery removing the thyroid gland also
indirectly
removing the parathyroid glands or
congenital hypoparathyroidism
if we have low pth levels that means
we're going to have
low calcium within our bloodstream
because we are unable to resolve our
bones
unable to reabsorb calcium as
effectively from the kidneys and unable
to absorb more calcium from our
intestines
so we are able to treat this with a
combination of oral calcium supplement
with activated vitamin d so then we are
able to absorb more calcium from our
intestines
pseudo pseudohypoparathyroidism is named
this way because we have what seems to
be hypoparathyroidism with hypocalcemia
and hyper
phosphatemia however circulating levels
of pth are actually increased and the
reason behind that
is because of a defective receptor
within the kidney and the bone so we
can't actually reabsorb
that calcium so pth is trying to do its
work but it's just not binding to its
receptor
last thing we'll mention here when it
comes to calcium is humeral
hypercalcemia of malignancy
this is when tumors start to release
parathyroid hormone related peptide
so this is like a pth analog and it does
the same
actions as pth to increase our calcium
levels within our bloodstream and reduce
our phosphorus levels this means that
regular pth is going to be chronically
low
because it's not going to be secreted in
the presence of high calcium
and you treat this by giving furosemide
to reduce our calcium absorption from
our kidneys and by giving medications
that
inhibit bone resorption so talking about
calcitonin very briefly here we don't
talk about this much because it seems
like it's probably got a pretty minor
role
it gets released from cells or
c cells within the thyroid gland so not
the parathyroid gland within the thyroid
gland itself and it gets released
whenever we have
high calcium levels within our
bloodstream now works on
osteoclasts by inhibiting them so then
we stop
resorption of bone and that's trying to
reduce the amount of calcium entering
the blood
because of bone resorption it doesn't
seem to have that much
role in the minute to minute regulation
of plasma calcium but we do mention here
with our calcium homeostatic mechanisms
now vitamin d
plays a role in calcium homeostasis but
it's important to distinguish how it's
different to pth
pth is role is to maintain a normal
plasma calcium level
vitamin d's role however is to promote
the mineralization of new bone so it's
trying to increase the amount of both
calcium
and phosphorus within the bloodstream so
then that's available for bone to be
able to be
deposited now if you're a student you're
able to pick up
initially this issue of well i thought
activated vitamin d
actually resolved our bone you would be
correct and i'll touch on that right now
just to avoid that confusion
activated vitamin d although its role is
to mineralize new bone
it does increase bone resorption but the
key point is that it's
increasing the resorption of old bone so
it's trying to shuttle the
old calcium and phosphorus away from the
old bone
and make it available for deposition of
new bone so that is important
vitamin d's role is to increase the
environment for the mineralization of
new bone by increasing calcium and
phosphorus whereas our
parathyroid hormone is only concerned
about our calcium levels
so it's trying to regulate calcium at
the expense of phosphorus
so talking about vitamin d its form is
cholecalciferol and it's either obtained
from your diet
or is converted from cholesterol via uv
light on your skin
polycalciferol then gets metabolized in
the liver
and then finally in the kidneys by one
alpha hydroxylase
into our activated vitamin d now this
one alpha hydroxylase is what gets
manipulated by parathyroid hormone to
increase the levels of activated vitamin
d but this is also going to be activated
by reduced calcium all together and then
also reduce
phosphorus because if we've reduced
phosphorus then we do not have an
environment for new bone formation so
one alpha hydroxylase gets activated to
produce more activated vitamin d
so then activated vitamin d once it is
produced
it goes to the intestines the kidneys
and the bone to
increase the reabsorption of both
calcium and
phosphorus so in the intestine it does
that via this figure 9.4 here
by increasing this protein called
calbindin it's not quite clear what this
does
whether it's buffering our calcium so
then the calcium levels seem
low in the cell so then we increase the
electrochemical gradient from calcium to
enter the cell
or whether it's acting like a shuttle to
shadow it all the way out into the blood
but we increase calcium and phosphorous
reabsorption within our intestine via
this mechanism
in the kidneys we increase the
reabsorption of both calcium and
phosphate
and then in the bone we increase the
resolution of
old bone so then calcium and phosphorus
is available
for new bone formation so then that gets
us to the pathophysiology of vitamin d
if we have low vitamin d what's going to
occur our bones are clearly going to
become weak and not grow appropriately
so if you're a child then you're going
to get rickets and rickets is
characterized by a failure of growth and
particularly some skeletal deformities
as well
in adults that results in osteomalacia
which is basically
really weak or poorly mineralized bones
because you're unable to mineralize new
bone so that is our calcium homeostasis
we do have this portion here of a
summary
which i have highlighted if you want the
key points of this chapter
otherwise we do also have the chapter
questions feel free to pause it at this
point if you want to get these summaries
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the questions too over here
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