0:00 hello and welcome to the final portion
0:01 of the endocrine physiology chapter of
0:03 costanzo's physiology textbook
0:06 in this video we're going to go over the
0:07 regulation of calcium and phosphate
0:09 mainly going over the actions of pth
0:12 or parathyroid hormone if you enjoyed
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0:21 otherwise let's jump straight into
0:22 talking about
0:23 calcium and how it's moved around in the
0:25 blood starting off with the calcium
0:27 that's actually bound to plasma proteins
0:29 about 40 of the total calcium within our
0:32 blood
0:33 is bound to proteins the rest is ultra
0:36 filtratable meaning that it can actually
0:38 go into our nephron because remember
0:40 proteins don't cross that glomerular
0:43 membrane
0:44 out of that 60 that gets ultra filtrated
0:47 50 is ionized so the majority of that 60
0:52 is ionized calcium the remaining 10 is
0:55 complex to anions like phosphate
0:57 now this ionized portion this 50 percent
1:01 this is what is metabolically active and
1:03 this is what the parathyroid hormone is
1:06 regulating it's trying to regulate the
1:08 ionized calcium
1:09 if we are hypocalcemic or hypercalcemic
1:12 to the point of causing clinical signs
1:15 it's because of a change in our ionized
1:17 calcium
1:18 we may get a change in our total calcium
1:21 due to a change in our protein levels
1:23 within our bloodstream
1:25 but it's important to focus on the level
1:27 of the ionized calcium
1:29 so we do have some factors that once
1:31 again alter our total calcium so plasma
1:33 proteins alter it
1:34 anion concentration alter it so if we
1:37 have increased phosphate within our
1:39 system within our bloodstream
1:40 and that's going to increase the amount
1:42 that's complex to iron ions
1:44 so then our ionized calcium is going to
1:46 decrease relatively
1:47 and then our acid-base abnormalities can
1:49 change things in
1:50 acidemia albumin actually binds to more
1:53 of those hydrogen
1:54 ions so it displaces the calcium bound
1:56 to plasma proteins
1:58 so then our ionized calcium is actually
2:00 going to increase
2:01 and vice versa for alkalemia so you may
2:03 actually notice some clinical signs of
2:05 hypocalcemia
2:06 during an alkalotic state now the
2:08 clinical signs associated with
2:11 calcium abnormalities hypocalcemia we
2:14 end up with
2:14 excitability of tissues and cells that's
2:17 because we actually
2:18 lower the threshold potential basically
2:21 we make those
2:22 sodium channels more twitchy to open so
2:25 now it's going to
2:26 open much more readily and therefore we
2:29 need a lower stimulus
2:30 for an action potential to be fired so
2:33 hypocalcemia
2:34 results in increased action potential
2:37 firing in cells
2:38 and basically causes twitches and
2:40 excitability
2:42 hypercalcemia on the other end so high
2:44 calcium
2:45 is going to cause the opposite and slow
2:46 things down so we end up with
2:48 constipation we end up with hyporeflexia
2:52 lethargy coma potentially even death we
2:55 also end up with polyuria and diptyo
2:57 with hypercalcemia because we're
2:58 increasing the amount of calcium going
3:01 into our
3:01 urine which takes with it water so
3:04 getting to overall calcium homeostasis
3:06 this figure down the bottom here depicts
3:08 it nicely we have our extracellular
3:11 fluid concentration so our plasma
3:13 calcium level
3:14 and you can see we have three organ
3:16 systems contributing to it we've got our
3:18 intestine
3:19 our kidney and our bone our bone is
3:21 constantly remodeling so our osteoblasts
3:24 are constantly adding bone to bone and
3:27 our osteoclasts are constantly removing
3:30 old bone so we're constantly recycling
3:33 old bone for new bone
3:34 and that can be altered to increase
3:36 resorption to increase our calcium
3:38 levels within our blood
3:40 or increase deposition to reduce our
3:42 calcium levels within our blood we'll
3:43 get to the hormones that are able to do
3:45 that shortly when it comes to the
3:47 intestine
3:47 we can increase our absorption of
3:49 calcium from our intestine but we can't
3:51 alter
3:52 secreting additional so mainly in the
3:54 intestine we're trying to absorb more
3:55 calcium during hypocalcemic states
3:58 in the kidney we're able to reabsorb
4:01 more calcium as well
4:02 so we are able to increase the amount of
4:04 calcium getting reabsorbed
4:06 from the nephron so we lose less in the
4:08 urine so that's able to also
4:10 increase our calcium during hypocalcemic
4:12 states
4:13 so you'll also see these little plus
4:15 signs which mean that they are
4:16 activating and you'll see that pth and
4:19 125
4:20 dihydroxycholine calciferol which is a
4:23 mouthful
4:24 we're going to call this just activated
4:25 vitamin d they
4:27 activate the reabsorption of calcium
4:30 from each of these
4:31 organs so that increases calcium when we
4:34 have low body calcium levels
4:36 you'll notice that the only other
4:37 hormone here is calcitonin which we'll
4:39 touch on right at the end
4:40 this is an inhibitory effect on boner's
4:42 absorption so that's
4:44 actually going to be secreted when we
4:45 have high calcium levels within the
4:47 bloodstream
4:48 but we're not going to focus on that one
4:50 too much because this chapter is mainly
4:52 about the parathyroid hormone
4:54 so a parathyroid hormone gets released
4:56 whenever we have changes
4:57 and now ionized calcium and you'll see
4:59 in this graph here that we have the
5:01 sigmoidal
5:02 shape to pth secretion compared to our
5:04 total plasma calcium
5:06 so this shows that calcium wants to be
5:09 maintained right
5:10 in the middle here and one minor change
5:12 of calcium in either direction
5:14 will result in a dramatic change in our
5:16 pth secretion
5:18 if we slightly reduce our ionized
5:20 calcium we get a remarkable change with
5:22 an
5:22 increase in pth secretion instantly if
5:25 we slightly increase our calcium then we
5:27 get instantly a reduction in our pth
5:29 secretion
5:30 so we finely tune our calcium level and
5:33 try to keep it as constant as possible
5:36 parathyroid hormone is actually released
5:38 from the chief
5:39 cells within the parathyroid glands it's
5:41 called parathyroid because there are
5:43 these four
5:44 tiny little glands right next to the
5:46 thyroid gland itself
5:47 if we have chronic hypocalcemia so low
5:50 calcium levels
5:52 then we're going to get a constant
5:53 stimulus to produce pth
5:55 and the actual cells themselves the
5:57 chief cells
5:58 will be told to transcribe more of that
6:01 gene
6:02 that's going to synthesize pth so you
6:04 actually see hypertrophy of your
6:06 parathyroid glands
6:07 and a hyperparathyroid state with
6:10 chronic hypocalcemia
6:12 and that's called secondary
6:13 hyperparathyroidism it's a little teaser
6:15 for what we're going to be talking about
6:17 later on in this video now it does touch
6:20 very briefly on magnesium basically
6:22 magnesium
6:23 has similar effects to calcium or pth
6:25 secretion so if we have hypomagnesemia
6:27 then we'll have some pth
6:28 secretion as well it's not really the
6:31 focus of this
6:32 video or this chapter but just a little
6:34 side note there
6:35 so the actions of parathyroid hormone
6:39 it mainly works through the adenylyl
6:40 cyclase secondary messenger system by
6:43 increasing cyclic amp
6:44 and by doing that we increase the
6:46 resorption of bone and we increase the
6:48 reabsorption of calcium within the
6:50 kidney it also works on the intestines
6:53 in an indirect manner by
6:54 activating vitamin d active vitamin d
6:58 then actually increases the reabsorption
6:59 of calcium from the intestines
7:02 so pth works on those three organs but
7:05 in an
7:05 indirect manner works on that intestine
7:07 so in bone
7:08 the first thing pth does is actually
7:11 interestingly this is going to be
7:12 confusing
7:13 it actually increases the activity of
7:15 the osteoblasts so it actually slightly
7:18 increases the deposition of bone
7:20 initially but the long-term effects
7:22 through the increased production of
7:23 cytokines from the osteoblasts
7:25 it's actually going to be a marked
7:27 increase in the osteoclastic activity to
7:30 reabsorb bone
7:31 so really the net effect is a resorption
7:34 of both
7:35 calcium and phosphorus from the bone
7:38 into your
7:39 extracellular fluid space in the kidney
7:42 remember we talked about pth
7:44 in the kidney how it inhibits phosphate
7:46 reabsorption from that proximal
7:48 convoluted tubule so we increase the
7:51 amount of phosphorus
7:52 excretion in the kidney resulting in
7:54 phosphateuria but not only that
7:57 it increases the reabsorption of calcium
8:00 within the kidney
8:01 and this is important because since the
8:02 parathyroid hormone has increased the
8:04 resorption of both calcium and phosphate
8:06 from bone
8:08 if it keeps reabsorbing both of these
8:09 together then calcium will just get
8:11 complexed with phosphate and our ionized
8:13 calcium wouldn't increase as much
8:15 so it needs to actually excrete some
8:17 phosphate and just
8:18 increase the amount of ionized calcium
8:20 within the bloodstream because that's
8:22 what it's trying to maintain that is the
8:23 metabolically active form of calcium
8:26 so in the kidney it increases phosphate
8:28 secretion or excretion
8:30 and also increases calcium reabsorption
8:33 from that distal convoluted tubule in
8:35 the small intestine once again
8:37 it works indirectly via activated
8:39 vitamin d
8:40 to increase the absorption of calcium
8:43 from the intestine and we'll get into
8:44 more details and exactly how it's able
8:47 to
8:47 activate vitamin d in the kidney but at
8:49 least for now just remember
8:51 small intestine is going to increase the
8:53 calcium absorption
8:54 in the presence of pth indirectly due to
8:57 activated vitamin d now how about some
8:59 issues of parathyroid hormone
9:01 we've got a couple conditions here
9:03 number one primary hyperparathyroidism
9:06 think about this logically
9:07 primary means that the issue is the
9:09 parathyroid gland itself so the
9:11 parathyroid gland
9:12 is increasing the secretion of pth this
9:15 is going to occur due to a tumor that's
9:16 producing pth
9:18 if we have excessive pth that means
9:20 we're going to reabsorb a lot of calcium
9:21 and excrete a lot of
9:23 phosphorus from the kidneys so we're
9:25 going to have hypercalcemia
9:27 and hypophosphatemia our bones are going
9:30 to also become very very weak because we
9:32 are
9:32 absorbing a lot of those minerals so you
9:35 end up
9:36 with the saying of stones bones and
9:38 groans
9:39 stones because you start to produce
9:41 calcium stones within your urine
9:43 although there's increased reabsorption
9:44 in your kidneys there's still so much
9:46 calcium in the bloodstream
9:48 that there's a high filtered load so you
9:49 still end up technically with more
9:51 calcium being
9:52 in the urine along with that phosphorus
9:54 so you end up with calcium stones within
9:56 the urine
9:57 your bones become weakened because
9:59 they're getting resolved
10:00 and groans because of the constipation
10:03 from hypercalcemia
10:05 the treatment for this is
10:06 parathyroidectomy secondary
10:08 hyperparathyroidism means that there is
10:10 a hypocalcemic state that is chronic
10:13 that's causing the parathyroid gland to
10:15 increase its secretion
10:17 so something is causing calcium
10:19 deficiency
10:20 and that occurs due to vitamin d
10:22 deficiency so we're unable to reabsorb
10:24 enough calcium from our intestines and
10:26 we have a reduced response
10:28 with bone resorption because our
10:30 activated vitamin d helps to resolve
10:32 calcium from the bones or from chronic
10:34 renal failure so we're just excreting a
10:36 lot of calcium we're unable to reabsorb
10:38 that calcium from the kidneys so
10:40 secondary hyperparathyroidism
10:42 means that we have high pth due to a
10:45 chronic
10:46 low calcium hypoparathyroidism
10:49 is exactly as it says we have low
10:51 parathyroid hormone
10:52 either due to autoimmune destruction
10:54 surgery removing the thyroid gland also
10:57 indirectly
10:58 removing the parathyroid glands or
10:59 congenital hypoparathyroidism
11:01 if we have low pth levels that means
11:04 we're going to have
11:05 low calcium within our bloodstream
11:07 because we are unable to resolve our
11:09 bones
11:10 unable to reabsorb calcium as
11:12 effectively from the kidneys and unable
11:14 to absorb more calcium from our
11:16 intestines
11:17 so we are able to treat this with a
11:18 combination of oral calcium supplement
11:21 with activated vitamin d so then we are
11:23 able to absorb more calcium from our
11:25 intestines
11:26 pseudo pseudohypoparathyroidism is named
11:29 this way because we have what seems to
11:31 be hypoparathyroidism with hypocalcemia
11:34 and hyper
11:35 phosphatemia however circulating levels
11:38 of pth are actually increased and the
11:40 reason behind that
11:41 is because of a defective receptor
11:43 within the kidney and the bone so we
11:45 can't actually reabsorb
11:47 that calcium so pth is trying to do its
11:50 work but it's just not binding to its
11:52 receptor
11:53 last thing we'll mention here when it
11:54 comes to calcium is humeral
11:56 hypercalcemia of malignancy
11:58 this is when tumors start to release
12:01 parathyroid hormone related peptide
12:03 so this is like a pth analog and it does
12:05 the same
12:06 actions as pth to increase our calcium
12:09 levels within our bloodstream and reduce
12:11 our phosphorus levels this means that
12:13 regular pth is going to be chronically
12:15 low
12:16 because it's not going to be secreted in
12:18 the presence of high calcium
12:20 and you treat this by giving furosemide
12:22 to reduce our calcium absorption from
12:24 our kidneys and by giving medications
12:27 that
12:27 inhibit bone resorption so talking about
12:29 calcitonin very briefly here we don't
12:31 talk about this much because it seems
12:33 like it's probably got a pretty minor
12:35 role
12:35 it gets released from cells or
12:38 c cells within the thyroid gland so not
12:42 the parathyroid gland within the thyroid
12:44 gland itself and it gets released
12:46 whenever we have
12:47 high calcium levels within our
12:48 bloodstream now works on
12:50 osteoclasts by inhibiting them so then
12:53 we stop
12:54 resorption of bone and that's trying to
12:56 reduce the amount of calcium entering
12:58 the blood
12:58 because of bone resorption it doesn't
13:00 seem to have that much
13:02 role in the minute to minute regulation
13:04 of plasma calcium but we do mention here
13:06 with our calcium homeostatic mechanisms
13:08 now vitamin d
13:09 plays a role in calcium homeostasis but
13:12 it's important to distinguish how it's
13:14 different to pth
13:16 pth is role is to maintain a normal
13:19 plasma calcium level
13:21 vitamin d's role however is to promote
13:24 the mineralization of new bone so it's
13:26 trying to increase the amount of both
13:28 calcium
13:28 and phosphorus within the bloodstream so
13:31 then that's available for bone to be
13:33 able to be
13:34 deposited now if you're a student you're
13:36 able to pick up
13:38 initially this issue of well i thought
13:40 activated vitamin d
13:42 actually resolved our bone you would be
13:45 correct and i'll touch on that right now
13:46 just to avoid that confusion
13:48 activated vitamin d although its role is
13:51 to mineralize new bone
13:53 it does increase bone resorption but the
13:55 key point is that it's
13:57 increasing the resorption of old bone so
13:59 it's trying to shuttle the
14:01 old calcium and phosphorus away from the
14:03 old bone
14:04 and make it available for deposition of
14:06 new bone so that is important
14:08 vitamin d's role is to increase the
14:11 environment for the mineralization of
14:13 new bone by increasing calcium and
14:15 phosphorus whereas our
14:17 parathyroid hormone is only concerned
14:19 about our calcium levels
14:21 so it's trying to regulate calcium at
14:24 the expense of phosphorus
14:26 so talking about vitamin d its form is
14:28 cholecalciferol and it's either obtained
14:30 from your diet
14:31 or is converted from cholesterol via uv
14:34 light on your skin
14:36 polycalciferol then gets metabolized in
14:38 the liver
14:39 and then finally in the kidneys by one
14:41 alpha hydroxylase
14:43 into our activated vitamin d now this
14:46 one alpha hydroxylase is what gets
14:49 manipulated by parathyroid hormone to
14:51 increase the levels of activated vitamin
14:54 d but this is also going to be activated
14:57 by reduced calcium all together and then
14:59 also reduce
15:00 phosphorus because if we've reduced
15:02 phosphorus then we do not have an
15:03 environment for new bone formation so
15:05 one alpha hydroxylase gets activated to
15:07 produce more activated vitamin d
15:10 so then activated vitamin d once it is
15:12 produced
15:13 it goes to the intestines the kidneys
15:15 and the bone to
15:16 increase the reabsorption of both
15:18 calcium and
15:19 phosphorus so in the intestine it does
15:22 that via this figure 9.4 here
15:24 by increasing this protein called
15:26 calbindin it's not quite clear what this
15:28 does
15:28 whether it's buffering our calcium so
15:30 then the calcium levels seem
15:32 low in the cell so then we increase the
15:34 electrochemical gradient from calcium to
15:36 enter the cell
15:36 or whether it's acting like a shuttle to
15:38 shadow it all the way out into the blood
15:40 but we increase calcium and phosphorous
15:42 reabsorption within our intestine via
15:44 this mechanism
15:45 in the kidneys we increase the
15:47 reabsorption of both calcium and
15:49 phosphate
15:50 and then in the bone we increase the
15:52 resolution of
15:53 old bone so then calcium and phosphorus
15:56 is available
15:57 for new bone formation so then that gets
15:59 us to the pathophysiology of vitamin d
16:01 if we have low vitamin d what's going to
16:04 occur our bones are clearly going to
16:06 become weak and not grow appropriately
16:09 so if you're a child then you're going
16:10 to get rickets and rickets is
16:12 characterized by a failure of growth and
16:14 particularly some skeletal deformities
16:16 as well
16:17 in adults that results in osteomalacia
16:19 which is basically
16:21 really weak or poorly mineralized bones
16:24 because you're unable to mineralize new
16:26 bone so that is our calcium homeostasis
16:28 we do have this portion here of a
16:30 summary
16:31 which i have highlighted if you want the
16:33 key points of this chapter
16:35 otherwise we do also have the chapter
16:37 questions feel free to pause it at this
16:39 point if you want to get these summaries
16:41 and then also we have another page of
16:43 the questions too over here
16:45 the answers of these questions are going
16:47 to be supplied in the description
16:48 once again if you haven't subscribed
16:50 please consider doing so as it does help
16:52 out the channel
16:52 otherwise i hope you enjoyed it feel
16:54 free to drop a comment
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