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parathyroid Flashcards

1
Q

what is 1,25-(OH)2D3, (calcitriol )how is it formed.
- what is its function

A
  • a steroid hormone derivative of vitamin D3.
  • Formed with sunlight in the skin and subsequent processing in the liver and the kidney.
  • enhances intestinal ca absorption

,

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2
Q

what is pth secreted by
- what is its function

A
  • peptide hormone secreted by the parathyroid gland
  • elevates blood ca levels by mobilizing ca from bone and increasing ca reabsorption in the kidney
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3
Q

what is calcitonin, what is it secreted by
- what is the funciton

A
  • a peptide hormone which is secreted by parafollicular cells of the thyroid
  • lowers ca levels
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4
Q

what is right regulation of ca critical for

A
  • cellular functions such as neuronal and muscular activation
  • normal growth and maintains of the skeletal system
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5
Q

what are the regulatory functions of intracellular ca

A
  • muscle contraction
  • neuronal excitability
  • secretion
  • metabolism
  • gene expression
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6
Q

what is ca in plasma and extracellular fluids important for

A
  • generation of intracellular ca signals
  • blood coagulation
  • cell-cell interactions
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7
Q

Calcium salts in bone and teeth are an essential structural component that yield: 2

A
  • stuructural integrity and strength
  • growth and morphogeneisis
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8
Q

what are the 2 ways in which intracellular ca can be increased

A
  • opening of ca channels on the cell membrane and release of ca from the sarcoplasmic reticulum
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9
Q

what is cytosolic free ca concentration at rest and in extracellular fluid

A
  • cytosolic = 0.1uM
  • blood 1-2mM
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10
Q

what are the three basic fractions of ca in plasma

A
  • free ca = 50% improtant!!!
  • ca bound to extracellular proteins such as albumin = 1/2 of extracellular plasma
  • calcium complexed with other plasma ions and metabolites such as citrate and phosphate = 5-10%
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11
Q

why is Ca binding proteins sensitive to pH

A

because the secondary carboxyl group binding sites have a pka in the physiological range and as the pH increases they become more fully deprotanated and ca binding affinity increases.
- conversely as the pH lowers binding affinity lowers

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12
Q

how does acidosis and alkalosis affect free ca

A

acidosis increases free calcium and alkalosis decreases free calcium

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13
Q
  • how can lowering ca lead to a excitatory affect on nerves and muscles
  • what is the syndrome calles
    ( hyperventilation)
A
  • during hyperventilation you are removing more Co2 = alkaline blood
  • less ca = more permeable Na causing excitation of neurons and muscles due to hyperexcitability
  • leads to tingling nerves and hypocalcemic tetany
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14
Q

what is effieceny of the absorption of ca in the gut

A

not very efficent most of it is eliminated via feces

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15
Q

what is the largest ca resvoir

A

bones

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16
Q

where do the largest fluxes of ca occur

A

the largest fluxes of ca occur in the kidney through glomerular filtration but 98% of this is reabsorbed in the loop of henle and distal tubule

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17
Q

how does phosphate absorption differ to ca absorption in the gut how is most of it excreted

A

more phosphate abosrption in the gut and most of it is excreted in through urine however the kidney recovers 80-90%

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18
Q

where can we find the most phosphate? what is the interaction with plasma

A
  • in bone and also soft tissue and are in a rapid exchange equilibrium with plasma phosphate
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19
Q

what are the 3 types of cells involved in bone formation and resorption

A
  • Osteoblasts are the bone-forming
    cells that secrete the bone protein
    matrix (osteoid, primarily collagen) on
    which Ca2+ and PO 4 precipitate to
    form the rigid hydroxyapatite structure.

-Osteoclasts are responsible for bone
resorption and the mobilization of
bone calcium. They are large
multinucleate cells.

  • Osteocytes, the mature bone cells
    are enclosed within the bone matrix.
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20
Q

what is osteocytic osteolysis

A

the rapid transfer of calcium from bone canaliculi to the external surface of the bone

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21
Q

what are the function of cancliculi

A

provide an interface between the interior surface of the bone and the extracellular fluid

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22
Q

what is the predominant method of sustained calcium liberation from bone

A

resroption via osteoclasts

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23
Q

what do osteoclasts secrete that allow them to tunnel into the bone.
- what is liberated

A

collegenase, phosphotse, and lysozomal enzymes that create an acidic environment.
- as osteoclasts tunnel their way through bone calcium, phosphate, and amino acids are liberated

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24
Q

what procceses reverses prolonged hypocalcemia

A

resorption of bone

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25
how do osteolysis and resorption via osteoclasts differ
- osteolysis extracts ca without loss of bone mass - resorption destroys the bone matrix and leads to loss of bone mass
26
what occurs during bone remodeling
osteoblsts lay down new matrix and calcium and phosphate are mineralized
27
what are the 3 principal organ targets for calcium regulation
gut,bone,kidney
28
how is phopate uptake and release relate to ca
regulated coordinately with ca
29
where are vitamin D and D3 synthesized
D- is ingested and formed in the skin with UV D3 occurs in kertinocytes in the skin where 7-dehydrocholesterol is photo-converted to D3
30
how is inactive vitamin D (inactive) converted to 1,25-(OH)2D3 - how many steps, what are the enzymes, what occurs?
- 2 step proccess involving p450 hydroxylase in the kidnkey and liver - first hydrozylation occurs in the liver yielding 25 (oh)2D3 - second occurs in the liver catalyzed by 1-alpha hydroxylase yielding 1-25(oh)2D3 - 24,25 D3 is also synthesized in the other kidney but it is inactive and is a means for removing excess D3
31
what is the primary site of 1,25(OH)2D3 regulation - what stimulates the production and what inhibits it
- the kidney through 1-alpha-hydroxylase - stimulated by PTH and low levels of Ca and ohisphate - inhibited by elevated lebvels of 1,25OHD3 which favors the formation of inactive 24,25 (OH)2D3
32
what is the cellular action of 1,25(OH)D3 What is it bound to when circulating
- when cicrculating bound to the globulin, transcalciferin (TC) with only a small amount circulating freely -the free form crosses the membrane where is targets vitamin D receptor - dimerization occurs with the retinoic acid receptor resulting in stimulation or inhibiition of gene expression
33
what are all the major effects of 1-25OHD3 mediated by
steroid like nuclear receptors that regulate gene transcription
34
was is the most important effect of 125OHD3 - what else does it cause the absorption of
- to stimulate the absorption and active transport of calcium fromm the intestine through increased expresion of Ca binding proteins and Ca pumps - also stimulates the absorption of magnesium and phosphate
35
how does 125OH2 D3 the effects of PTH (2)
- it enhances its affects on bone resorption theough recrutiment of osteoclasts - also acts on the parathyroid gland to reduce PTH synthesis
36
how is 125OHD3 required for the normal mineralization of bone - what disease is vitamin D deficency asscociated with
- supplies ca and phosphate - rickets which causes weakness and and bowing of weight bearing bones
37
what is the movemnt of Ca through the intestine and how does 125Oh2D3 increase this
-Ca enters microvilli at the brush boarder throughh channels - Ca diffuses thorugh enterocyte facilitated by Calbindin - Ca is activley transported across the basolateral membrane by Ca pumps and 125oh2D3 increases the expression of these channels, pumps, and binding proteins enhancing asorption
38
what type of hormones is PTh and and what cell is it secreted by and in what gland
peptide hormone, chief cells, parathyroid gland
39
what is the location of the parathyroid and what is its relationship with the thyroid
4 glands behind the thyroid but although they share circulation they dont have any functional interactions
40
how is PTH inintally translated and what is it cleaved into - where is it stored
- as a pre-prohormone - cleavage of leader and pro sequences yield biologivally active peptide which is stored in secretory granueles - further cleavage may occur in the gland or periphery to yield 34aa active Nterminal fragemnt with a inactive Cterminal fragment
41
how is PTH releasr controled
- under the control of plasma Ca through a receptor
42
half life of PTH
10 min
43
how is PTH secretion regulated by Ca sensing receptor
- at high plasma Ca CaR is activated to turn on PLC and increase IP3 which inhibits PTH secretion - it also inhibits AC to decrease cAMP - at low plasma ca Ca R isint activated and AC inhibition is relieved which increases cAMP whcih stimulates PTH
44
what is the primary regulator of PTH secretion and what is the relationship - when is pth secretion maximal and minimal
- free calcium is the primary regulator - PTH secretion is inversely related to ca - pth is maximal when ca falls below 1.2mM and minimal when ca increases above 1.3mM thus pth is contorlled in a realy narrow range
45
- how does 125OhD3 regulate pth - how do histamine, dopamine, and epinephrine effect pth
- inhibits it - stimulae cAMP in the chief cells
46
what is the mechanism of PTH on target cells
- PTH binds to activate GPCR to stimulate AC and increase cAMP. which activates fiunctions on bones and kidneys
47
what is the effect of PTH on ocsteoclasts
- its indirect and is mediated by receptors on oseobalsts that secrete RANKL that then activate osteoclasts by binding to RANK
48
what do osteoblasts secrete that sequesters RANKL
osteoprotegerin OPG
49
how does estrogen effect PTH
opposes its effect by surpressing RANKL and increasing OPG
50
what are the effects of PTH on bone
- PTH stiumulates osteolysis that transports ca out of canalicular fluid - stimulates bone resorption by osteoclasts liberating ca and phosphate and causing bone destruction
51
what is the effect of PTH on the kidney
- increases calcium reabsorption in the sidstal tubule - inhibits phosphate eabsorption stimulating phosphate excretion - stimulates the synthesis of 125ohd3
52
what type of hormone is calcitonin and what cells is it secreted by and by what gland
- peptide hormone secreted by parafollicular cells of the thyroid gland
53
what is the effect of calcitonin - how does it compare to pth hand 125ohd3 in maintaing calcium homeostasis - what is it stimulated by
- decreases plasma ca - less critical - stimulated by high ca
54
what is the affect of calcitonin on pth, bone, and kidney
- antagonizes pth by inhibiting osteoclast mediated bone resorption - in it increases the reabsorption of cal and phosphorus leading to increased urinary excretion of these ions
55
what is osteoperosis and why are postmenopausal women more succesptable - why do those in space have it
- prolonged osteoclast activity over osteoblast activity - common is menopause bc estrogen deficency. Estrogen surpesses RANKL and so estrogen defiecny increases osteoclasts - inactivity / low gravity
56
what is primary hyperparathyroidism -what other pathology can it cause
- excess PTH secretion leading to hypercalcemia caused by a benign parathyroid neoplasm that secretes PTH - may lead to kidney stones
57
secondary hyperparathyroidsm
- results from hypocalcemia which can occur from renal disease and vitamin D defiency (rickets). Low calcium causes hypertrophy of the PT gland
58
what is primary hypoparathyroidism what other disease can it lead to
- casued by inadverant removal of the parathyroid glands during thyroid surgury - can also be caused by autoimune damage to the PT gland - can cause hypocalcemic tetany
59
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physio (5 decks)

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