Our discussion here takes us into calcium
Important that you know the foundation here
so that we can get into the extremes of calcium.
What controls calcium?
How important is calcium?
Well, without calcium, we wouldn’t able
to make proper bone; without the calcium,
we have no signal transduction.
You know about IP3 and phospholipase C, you’ve
heard of calcium calmodulin, calcium is all
over the place.
Calcium, within the heart and also within
your skeletal muscle, responsible to then
bind to your troponin C bringing about muscle
contraction, let it be the heart or it be
the skeletal muscle.
Calcium, crucial for existence.
The bone itself is made up of calcium and
phosphate, together we call this hydroxyapatite.
You also have magnesium who are all regulated
and any time that there is a problem with
calcium, things become a little interesting,
It’s important that you understand the places
in our body where calcium is properly metabolized
We’ll take a look at the bone and you remember
kidney in nephrology.
Those will be the two big ones that we will
be paying attention to.
Now, the hormones that are responsible for
maintaining calcium metabolism include PTH.
So, for example, if for whatever reason, calcium
levels have dropped, for example, most common
cause of osteomalacia in the United States
would be renal failure and if the kidneys
die, then PTH goes along with it, meaning
to say it’s not functioning.
You’re not able to properly activate your
1-alpha-hydroxylase, you do not have calcitriols
so, therefore, your calcium levels will drop.
If the calcium levels will drop, then you
can only expect that the PTH in the parathyroids
will be releasing it resulting in what’s
known as, eventually we’ll talk about, secondary
Vitamin D, from head to toe, and by that I
mean, the different ways in which you can
acquire vitamin D would be perhaps from the
skin upon exposure to UV rays or you’re
drinking vitamin D fortified dairy product.
When you do so, you’re taking in inactive
vitamin D, all these is taken up by the liver
or taken to the liver.
Here, it would be hydroxylated with 25.
This is the major circulating type or form
of vitamin D which then eventually makes its
way to the kidney where, with the help of
PTH and 1-alpha-hydroxylase in the PCT, you
activate your vitamin D… welcome to calcitriol.
Do not get your calcitriol confused with calcitonin.
Calcitonin does play a role with calcium metabolism,
but in terms of its exact effect, we are not
mentioning that here.
A lot of research in exactly as what’s occurring
at least know that calcitonin does play a
role in calcium homeostasis.
Calcitonin can be used as a tumor marker when
you’re thinking about medullary cancer of
the thyroid, your parafollicular C cells will
be releasing your calcitonin.
Once again, do not confuse your calcitonin
I’d like for you to take a look at the picture
here and we have ECF as a very small percentage
of actual calcium…
So, where is majority of your calcium?
Inside my bone.
Next, in order for you to form proper mineralized
bone, you need to acquire both calcium and
There would be constant exchange between the
two of them.
It’s important for you to know that, remodelling
is quite important for the bone.
Meaning to say that there is sufficient amount
of bone breakdown, but at the same time, there
is sufficient amount of replacement of that
bone as well.
Hence, osteoclast and osteoblast play critical
role with maintaining proper remodelling of
the bone hence making it stronger and stronger
Hence, what you recommend to a lady who has
reached menopause at an approximate age of
50 is too oftentimes participate in weight
Now, the exact mechanism is at this point
eludes us, but we do know that weight bearing
exercises promotes remodelling in a female
who has hit menopause and at risk for osteoporosis.
From the food, on your right, you find that
from the intestine with the help of vitamin
D, we’re going to reabsorb that calcium,
but in order for the vitamin D to work upon
your intestine, it is important that you know
that activation will take place down in the
proximal convoluted tubule of your kidney.
Regulation of calcium by PTH.
So, what exactly is occurring here?
Once again, the PTH is made by chief cells
in the four parathyroid glands.
The inferior parathyroids is giving rise to
and binds to the third pharyngeal pouch.
In addition to the inferior parathyroids giving
rise by your third pharyngeal pouch, you also
have the thymus.
And if you have a condition such as DiGeorge
in which your third and fourth pharyngeal
pouches are not working properly or not developed
properly, you would not have the parathyroids
that are responsible for calcium reabsorption,
you can expect there to be hypocalcaemia.
When the serum ionized calcium levels are
low, I gave an example such as renal failure
resulting in osteomalacia.
With that vitamin D deficiency in an adult
renal failure, you can expect your calcium
levels to be low resulting in triggering your
PTH to then increase.
We then call this secondary hypoparathyroidism.
This PTH, we’ll talk about this later in
which it will then play a role in different
organ systems, but any time, homeostatically,
whenever calcium levels are low, the PTH is
quick, quick to be released and when it does,
it then plays a role with normal calcium metabolism.
Regulation of calcium by PTH and our discussion
You must know that PTH works through a G-protein,
this G-protein is known as your Gs and that,
to you, should mean ATP cyclic AMP.
Where does PTH work to reabsorb calcium in
It works in the kidney in the distal convoluted
tubule to reabsorb calcium.
The receptors for PTH for reabsorption, in
fact, are in the DCT.
When PTH binds to the receptor, it will then
increase the amount of cyclic AMP within your
Any time that you have a pathology in which
these receptors for PTH aren’t working,
namely pseudohypoparathyroidism, you would
not find sufficient amounts of cyclic AMP
within your urine.
Increased calcium reabsorption in the kidney
is what PTH does; increases phosphate wasting.
In other words, in the kidney PTH does what?
It flushes out the phosphate, the opposite
effects in the kidney.
Also, in the PCT, PTH works on that enzyme
that I have referred to a few times known
as 1-alpha-hydroxylase adding the 25… adding
to the 25 resulting in our product known as
calcitriol or 1,25 dihydroxycholecalciferol.
Next, vitamin D, as you see-see in the illustration
here, the red arrow, you see the increased
of 1,25 vitamin D, that’s calcitriol.
Did you-Did you identify it?
It works in the intestines so that it reabsorbs
your calcium; it also works in the kidneys
so that it reabsorbs calcium.
The overview of your calcium homeostasis and
PTH we said will flush out the phosphate;
that high phosphate levels promote PTH release.
Once again, if you have hyperphosphataemia,
it will release PTH so that the PTH can flush
out the phosphate in your PCT.
Two major functions of PTH in the PCT - Activate
1-alpha-hydroxylase and to flush out the phosphate.
One major function of the PTH in the DCT and
that is to reabsorb your calcium, if you remember
Ultimately, the renal calcium-calcium handling
by PTH in the nephron would be the following.
I want you to focus upon the DCT, distal convoluted
tubule, we have a drug here that works known
as thiazides and we have a hormone here that
Both of these products either form or your
PTH in physio will work to reabsorb your calcium.
Yes, thiazides remove calcium out of your
nephron, do not ever forget that, that’s