Parathyroid - Manautou

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59 Terms

1
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The parathyroid gland is responsible for the synthesis and release of which hormone?
PTH;parathyroid hormone
2
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PTH is a important regulator of__________
calcium homeostasis and phosphate homeostasis
3
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What is the main effect of PTH
Increase the plasma levels of calcium by affecting the target organs
4
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PTH affects which target organs?
bone, kidneys, intestine
5
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What are the 2 functions of PTH

1. increase Ca2+ within the plasma
2. stimulates renal phosphate elimination
6
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What happens if PT has a surgical removal of the parathyroid gland and only one is remaining? What is the outcome of the single parathyroid?
Then the single parathyroid gland will grow in size and try to produce enough PTH to compensate the 3 that were originally producing PTH
7
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What cells are the main source for PTH?
Chief cells
8
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What are 2 cell types that exist within the parathyroid gland

1. chief cells
2. oxyphil cells
9
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Explain the regulation and synthesis of PTH
* The parathyroid gland senses ionized Ca2+ and produces PTH when there are levels of Ca2+
* Low Ca2+ (ionized) → parathyroid gland → chief cells → PTH produced
10
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What type of receptor does Ca2+ bind to in the Chief cells?
GPCR
11
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When ________ or _______ Ca2+ present, PTH is inhibited.
high, sufficient
12
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When ______ Ca2+ present, PTH secretion is activated.
low
13
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What type of relationship does PTH secretion have with plasma Ca2+?
* inverse correlation
* HIGH Ca2+ = DECREASE PTH secretion
* LOW Ca2+ = INCREASE PTH secretion
14
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PTH-receptor are coupled to which 2 different classes of G protein?
Gs and Gq; G stimulatory protein and G q protein
15
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What are the effects of PTH?
* Causes hyperplasia of osteoclasts
* Binds to osteoblasts receptors to increase cAMP and PLC
* The signal transduction will increase osteoclast activity and acid secretion and acid secretion from osteoclasts
* Stimulate biosynthesis of 1-25-dihydroxy vitamin D3 by the kidneys 5) Enhances intestinal uptake of calcium
* Increases phosphate excretion across the proximal tubule
* Increases renal distal tubule reabsorption of calcium
16
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T/F Osteoblast and osteoclasts have receptors for PTH
False, osteoblasts have receptors for PTH but osteoclasts do not

* osteoclasts receive signaling from osteoblasts via paracrine signaling (RANKL)
17
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How does PTH affect the kidneys?

1. PTH increases calcium reabsorption in the distal nephron


2. Calcium channels are inserted into the apical membrane to increase reabsorption via cAMP-and PKA-dependent process
3. In proximal tubules phosphate reabsorption is inhibited by removal of sodium-phosphate co-transporters from luminal membrane
4. 1,25 (OH)2D3 (Vitamin D) synthesis by kidney increases in response to PTH
18
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Contrast the difference between osteoclasts and osteoblasts
Osteoclasts: Breaks down bone and promotes bone resorption Osteoblasts: mediates bone formation
19
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What regulates the coordinates of the function of osteoblasts and osteoclasts?
PTH
20
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What is the importance of the osteocytic membrane?
The importance of the osteocytic membrane is that it is an important source of calcium for rapid correction of plasma calcium. The importance is when PTH is present, calcium is able to move from the bone into the bloodstream after passing the osteocytic membrane
21
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What are the two stages of Ca2+ blood levels in plasma used to try to correct the Ca2+ levels within the body?

1. fast exchange


1. Osteocytic membrane pumps Ca2+ out from the bone fluid that’s available once it’s depleted
2. slow exchange


1. in use once the fast exchange is depleted, the osteoclasts begin chewing on the bone to release more Ca2+
22
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Where can you get sources of vitamin D?
Skin and diet
23
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At which position does the 1st hydroxylation occur for vitamin D?
position 25 at Liver
24
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At which position does the 2nd hydroxylation occur for vitamin D?
position 1 at Kidney
25
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Which hydroxylation step is regulated by PTH?
Hydroxylation at position 1 in Kidney
26
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When is Vitamin D in its fully activated form?
After undergoing 2nd hydroxylation step in position 1 at the kidney
27
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What is the mechanism of vitamin D?
Binds to the nuclear receptor and works as a transcription factor
28
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What are 2 target organs Vitamin D acts on to increase the Ca2+ concentration in plasma (calcium homeostasis)?
intestine and bone
29
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What affect does vitamin D have on intestine for calcium homeostasis?
increase the synthesis and function of calbidins (calcium binding proteins)
30
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What affect does vitamin D have on bones for calcium homeostasis?
increase the activity of osteoclasts
31
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What happens if you have high active form of vitamin D?
Feedback inhibition will repress the synthesis and release of PTH secretion
32
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Smaller quantities of vitamin D under normal plasma calcium concentrations will promote what?
bone calcification (bone formation)
33
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Name the 2 mechanisms for the calcium binding protein (calbidins)

1. uptake of Ca2+ to blood
2. Transcellular transport
3. Endocytosis and exocytosis of Ca2+
34
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Where is calcitonin produced?
Parafollicular cells in @@thyroid gland@@
35
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What are the 2 peptides calcitonin gene encodes for?
Calcitonin and CGRP
36
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If you have complete removal of the thyroid gland and you don’t have any parafollicular cells what do you think it will do the Ca2+ levels in humans?
Nothing, no excess of Calcitonin is associated with any disease but you may have difficulty processing high Ca2+

\[just takes longer to process\]
37
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When is calcitonin released?
When Ca2+ levels are high in the blood it will lower it
38
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What are the 4 functions of calcitonin?

1. Suppresses activity of osteoclasts
2. Causes osteoclasts to lose “ruffled border”
3. Inhibits the formation of citric and lactic acid
4. Release of proteolytic enzymes that destroy the bone matric is inhibited
39
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Describe the symptoms of PRIMARY hyperparathyroidism.
results in excessive secretion of PTH due to the enlargement glands and tumors
40
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What is the consequence if PT has primary hyperparathyroidism?
Hypercalcemia/hypophosphatemia

* too much phosphate will be eliminated via renal
41
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Describe secondary hyperparathyroidism
PTH is also elevated but it is NOT associated with hypercalcemia it is associated with deficiency in vitamin D synthesis and/or its action
42
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What is the difference between primary and secondary hyperparathyroidism?
primary: results from excessive PTH because of enlargement of glands/tumors

secondary: PTH elevated because of low levels of Ca2+ but associated with deficiency of vitamin D synthesis
43
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What are 2 ways to get hypoparathyroidism

1. idiopathic - absence of PTH (from the autoimmune or surgical removal of the thyroid gland)
2. pseudohypoparathyroidism (target tissues resistant to PTH, but the right amount of PTH is made)


1. could be associated with genetic deficiency in cAMP or defective GPCR
44
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What are the symptoms of Hypoparathyroidism
muscle cramps, muscle spasms @@(tetany)@@
45
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Ergocalciferol
pure Vitamin D2

* for PT’s with normal liver and kidney
46
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Dihydroxytachysterol
doesn’t require renal activation
47
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Calcifediol
requires renal activation

* works for PTs that have liver impairment BUT their renal works fine (already bioactivated at position 25)
48
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Calcitrol
full active form on vitamin D

* acts very quickly, very expensive
* works for PTs with liver and renal impairment and PTs with low levels of Ca2+
49
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What are bisphosphonates?
analogs of pyrophosphate that inhibit bone resoprtion\`
50
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What is the MOA of bisphosphonates?
* Bisphosphonates target FPPS which is the major enzyme target. It also covalently attaches to lipids to form a protein prenylation
51
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Which enzyme does the bisphosphonate target to prevent protein prenylation?
Farnesyl pyrophosphate synthase; FPPS
52
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What is the outcome after bisphosphonates block FPPS?
osteoclast will undergo apoptosis
53
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Contrast how persistent exposure to synthetic PTH differs in effects than intermittent exposure
Persistent PTH exposure: will favor bone reabsorption Intermittent exposure: bone formation
54
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What is Forteo used for?
* Used for the treatment for postmenopausal women with osteoprosis at high risk of fracture
* Increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture
* Men and women with glucocorticosteroid treatment at high risk for fracture
55
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Describe how RANKL antagonists work in osteoporosis.
* RANKL is a receptor activator of nuclear factor kappa B ligand and plays a role in bone destruction
* A RANKL antagonist will inhibit osteoclast formation and stop bone destruction in pts with osteoporosis
56
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What is the primary mediator of osteoclast formation, function and survival?
RANKL
57
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What is the denosumab MOA?
RANKL Antagonist, leading the osteoclast to apoptosis
58
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How is hyperparathyroidism treated?
The treatment for hyperparathyroidism would be to surgically remove the gland to make the patient go into hypoparathyroidism (similar with hyperthyroidism). Once the patient is in hypoparathyroidism, we would give the patient calcium, vitamin D, and PTH hormone replacement therapy if needed.
59
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Primary hyperparathyroidism results in _______, and secondary hyperparathyroidism results in ________.
hypercalcemia, hypocalcemia