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Metabolic endocrinology 2 > Ca Metabolism > Flashcards

Ca Metabolism Flashcards

1
Q

What 3 hormones are responsible for Ca metabolism?

A

PTH, calcitonin, calcitriol (active vitamin D)

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2
Q

Describe what happens when low blood Ca is detected.

A

PTH is secreted in the blood

In response to PTH:
Osteoclasts resorb bone tissue
Kidneys retain Ca2+ and promote activation of vitamin D to calcitriol
Calcitriol promotes Ca absorption in small intestine

Ca rises in the blood as tissues respond to PTH

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3
Q

Describe what happens when high blood calcium is detected.

A

The thyroid gland releases calcitonin
Calcitonin stimulates Ca deposition in bone for storage
Kidneys reduce their uptake
Ca blood levels drop

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4
Q

What is rickets?

A

softening and bending of bone in children

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5
Q

What active ingredient is responsible for rickets? How can the issue be solved?

A

vitamin D deficiency, so not enough Ca absorption in the gut

fish liver oil, sun exposure, UV irradiation of certain foods

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6
Q

True or False. After bone, the majority of body calcium is circulating in the extracellular space.

A

False, intracellular

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7
Q

True or False. Hyperventilating can affect Ca equilibrium.

A

True.

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8
Q

What roles does calcium have in the body.

A

nervous cell excitability
structural component of skeleton
blood clotting
enzyme activity regulation
excitability of membrane (neurotransmitter action, exocytosis
second messager system
muscle contraction (Ca release from sarcoplastic reticulum)

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9
Q

In what 3 ways does Ca circulate in the blood?

A

Bound to albumin (50%)
Complexed to citrate (8%)
non-complexed (free) ionized Ca++ (42%)

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10
Q

Which of the 3 forms of Ca circulating in the blood is the most important?

A

free ionized Ca because it is most readily available, this is the only one that is regulated by hormones.
the other forms (bound to albumin, complexed) are inert and not regulated by hormones

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11
Q

How can hyperventilation lead to tetany?

A

hyperventilation reduces the CO2 partial pressure. This means less H2CO2 is produced. This leads to less H+ in the blood –> alkalosis
To compensate, serum proteins release H+, the negative charge proteins bind free Ca++. No calcium available –> spasm of skeletal muscle (tetany)

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12
Q

True or False. The body works to maintain a Ca gradient to drive biological processes using ATP dependent Ca pumps.

A

True

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13
Q

Which cells produce PTH?

A

chief cells and oxyphil cells in response to low levels of ionized Ca in ECF

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14
Q

Which cells produce calcitonin?

A

parafollicular or C-cells

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15
Q

What receptor binds to ECF Ca++? What is the intracellular response on teh production of PTH in response to high levels of Ca++?

A

calcium sensing receptor

inhibition of PTH secretion

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16
Q

True or False? PTH is a highly conserved hormone with a medium half life of 50 minutes.

A

False. highly conserved with a short half life of 2-4 minutes.

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17
Q

PTH is cleaved into 2 non active fragments, what are they?

A

amino terminus and carboxy terminus

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18
Q

Considering that PTH is kept cleaved to avoid degradation, how can we measure the levels of bioactive PTH?

A

immunoassay with 2 antibodies where we can see if the 2 Ab are attached (1 for each half) and close to eachother

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19
Q

In one serious condition, fragments of PTH can accumulate. What is this condition?

A

renal failure

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20
Q

What type of receptor is the Ca sensing receptor on the parathyroid? What is the conformation of the receptor dependent on?

A

G protein coupled receptor, the conformation is dependent on the concentration of calcium

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21
Q

How does calcium levels in the blood affect the production of cAMP in the cell?

A

high Ca –> decreased cAMP, increased IP3

low Ca –> increased cAMP, decreased IP3

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22
Q

What are the 2 signal transduction pathways for the chief cell Ca receptor and what effect do they have on PTH secretion?

A

phospholipase C –> less Ionositol triphosphate (IP3) –> more PTH release

adenylyl cyclase –> less cAMP –> less PTH

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23
Q

PTH affect which 3 tissues for Ca metabolism and how?

A

bone: resorption by stimulating osteoclasts
kidneys: renal resorption
intestine: indirectly through vitamin D active form calcium absorption

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24
Q

Serum levels of osteocalcin is an indicator of what?

A

bone growth

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25
Although small in quantity (% bone protein), osteocalcin has an important role, what is it?
bone matrix can build itself on it 1:17
26
What are the functions of osteonectin?
binds collagen and hydroxyapatite | may serve as nucleator for Ca deposition
27
Describe the formation of bone from original stem cells of osteoblasts.
some mesenchymal stem cells differentiate into osteoprogenitor cells on bone surface. These become osteoblasts which secrete collagen and proteins to form matrix called osteoid The osteoid gets mineralized by deposition of hydroxyapatite in 2 stages. The trapped osteoblasts differentiate into osteocytes making a network
28
What is the name of the interconnected cell network within bone and what cells are connected?
osteoblasts and osteocytes connected through cytoplasmic processes in canaliculi called osteocytic-osteoblastic bone membrane
29
There are 2 methods of exchange to increase blood Ca, what are they and where does the Ca originate from?
Fast exchange: from bone fluid | Slow exchange: from mineralized bone
30
What types of factors regulate balance of calcium in bone remodeling?
``` mechanical factors hormonal factors (PTH) ```
31
What cell gives rise to osteoclasts? Where is it found in the body?
monocytes in bone marrow
32
Describe osteoclast action.
They attach to bone via integrins and make a tight seal proton pumps move from endosomes to cell membrane and pump out H+ (acid) The acid dissolves the hydroxyapatite, acid proteases dissolve collagen. The degraded product is transcytosed to intercistial fluid
33
What biochemical marker can be used to evaluate bone resorption activity?
pyridinoline in urine
34
Describe how hormones control bone remodeling though osteoclasts and osteoblasts.
``` Vitamin D (calcitriol) and PTH act on osteoblasts to produce osteoclast activating factors that stimulate osteoclasts to begin resorption activity. Calcitriol also stimulates the differentiation of hematopoietic stem cells into osteoclasts Calcitonin inhibits osteoclasts activity directly ```
35
What effect does PTH have on the kidneys?
increase Ca resorption and inhibit reabsorption of phosphate
36
What are the functions of PTHrP, how does it function?
Binds to PTH receptor because it has a similar structure. causes Ca resorption in kidneys stimulates resorption from bone
37
Where are the receptors for PTH? Which one can be used for PTHrP as well?
2 types of G protein coupled receptor PTHR-1 binds both PTH and PTHrP located in bone and kidneys PTHR-2 is only for PTH
38
What is osteopetrosis?
Marble bone, defective osteoclasts, increase in bone density --> harder but more brittle
39
what is osteoporosis?
excess osteoclast function, leads to frequent fractures
40
What is the difference between osteoporosis and involutional osteoporosis?
involutional is the loss of bone density with age | just osteoporosis is excess function of osteoclasts
41
How does estrogen down-regulate osteoclast activity?
inhibits cytokines IL-1, IL-6 and TGF alpha that stimulates the development of osteoclasts stimulation of cytokine TGFbeta that causes apoptosis of osteoclasts
42
Why is exogenous estrogen not recommended to prevent osteoprosis?
drawbacks: when you stop therapy --> osteoporosis | increase risk of myocardial disease, strokes, breast cancer
43
True or False. Hyperthyroidism is more common in men as they are more likely to have a 5th parathyroid gland.
False. more likely in women just because :D | etiology unknown
44
What is primary parathyroidism?
increased parathyroid cell proliferation, increased PTH secretion regarless of calcium levels
45
What is the most common physiological consequence of hyperparathyroidism?
enlargement of a single gland
46
What are the signs and symptoms of primary hyperparathyroidism?
Stones, bones, groans and psychic moans
47
What is the vicious cycle of hypercalcemia?
is can only be maintained or aggravated. not sure how though something about decreasing ECF volume which decreases Ca excretion
48
What is the treatment of hyperparathyroidism?
remove the affected parathyroid gland, usually transplanted to arm muscle unless parathyroidadenoma then its just removed
49
PTHrP in excess can lead to ______.
hypercalcemia
50
In what way can recombinant PTH help treat osteoporosis despite its role in bone resorption?
increases osteoblasts numbers osteoblasts precursors osteoblasts survival inhibit sclerostin (bone formation inhibitor)
51
What are possible biochemical causes of hypoparathyroidism?
no PTH secreted changed responsiveness to PTH vit D deficiency resistance to vit D
52
What can lead to hypoparathyroidism?
surgery familial causes autoimmune disorders idiopathic causes (unkown)
53
How is hypoparathyroidism treated?
Ca and vit D
54
What is the relationship of calcitonin and PTH? what stimulates the release of calcitonin?
rise in serum Ca causes calcitonin release. one inhibits the other, so calcitonin release inhibits PTH
55
What is the only known hormone that reduces hypercalcaemia? How does this hormone acheive this?
Calcitonin binding to osteoclasts and inhibiting them decreasing blood levels of calcium
56
What are the consequences of an overproduction of calcitonin that can occur from tumors or thyroidectomy?
no phenotype consequences
57
What is CGRP? Where is it made? What are its functions?
calcitonin gene related protein | secreted by neurons, may act as neurotransmitter for vasodilation
58
True or False. Calcitonin is essential for calcium homeostasis.
False. over or underproduction has no effect
59
True or False. Salmon calcitonin can be administered as a nasal spray to treat both hypercalcemia and osteoporosis.
True
60
True or False. Vitamin D is a family of fat soluble compounds, also a hormone.
True
61
A vitamin D deficiency can lead to what?
bone defects and rickets/osteomalacia
62
Vitamin D can be formed in the skin from _________ in a ________ reaction requiring sunlight. Vitamin D is converted in the liver to a hormone that regulates ________ _________.
7-dehydrocholesterol photochemical calcium uptake
63
What effects does vitamin D have on tissues?
intestine: increase Ca/PO4 -3 absorption bone: increase bone mineralization (increased osteoblast and osteoclast activity) immune cells: induces differentiation kidneys: renal vitamin D degradation increases Less PTH tumor microenvironment: inhibit proliferation, induce differentiation, inhibit angiogenesis
64
True or False. Sunburns are caused by the accumulation of D3 that cannot be cleared from the skin fast enough and accumulate to toxic damaging levels. This leads to the characteristic burning sensation followed by sensitization as collagen was damaged and needs to be repaired by chondrocytes.
False. toxic levels cannot be reached by sun
65
How does vitamin D circulate in the blood?
vit D binding protein majority, but also albumin
66
What is the difference between 1-hydroxylase and 24-hydroxylase in regards to their products?
1-hydroxylase yields the biologically active vitamin D3 | 24-hydroxylation yields 24-25 dihydroxyvitamin D3 whose role is unclear
67
What form does vitamin D travel in the blood in?
25-OH-cholecalciferol
68
What biochemical factors promote the transformation of vitamin D3 into active vitamin D3?
decreased plasma Ca decreased plasma PO4 -3 excess active vitamin D3
69
Where in the GI tract is the most Ca absorbed?
Ileum
70
What 2 pathways are used to absorb Ca in intestine?
Passive pathway between cells driven by concentration gradient Active pathway trans-cellular modulated by calcitriol
71
How does calcitriol promote active Ca uptake?
by maintaining the Ca gradient by inducing the synthesis of calbindin protein which bind free Ca in cytoplasm for transport outside.
72
Describe passive pathway of Ca absorption.
Uptake of calcium→binding to myosin/calmodulin complex→ move to the bottom of the microvilli driven by differential binding to proteins →free Ca2+in cytoplasm is released by exocytosis or pumps
73
Vitamin D receptors are found in what tissues?
many, endocrine, skin ect.
74
What the symptoms of vitamin D toxicity and how is it treated?
symptoms: weakness, headaches, nausea, polyurea from hypercalcemia and hypercalciuria can lead to ectopic calcification if chronic Tx: reduced calcium intake and vit D, rehydration and cortisol which antagonizes the action of vit D on gut absorption. time

Metabolic endocrinology 2 (4 decks)

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