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Physiology Pt. 4 > Calcium and Phosphate > Flashcards

Calcium and Phosphate Flashcards

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1
Q

In which body tissue is >99% of the body’s calcium stored?

A

Bone

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2
Q

Is intracellular calcium concentration very low?

A

Yeah

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3
Q

True or false: roughly half of all plasma calcium is bound to proteins, and half is diffusable (ionized or complexed to HCO3-, etc.).

A

True

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4
Q

What are the effects of vitamin D and PTH on phosphate homeostasis?

A

Vitamin D promotes phosphate absorption in the GI tract.

PTH promotes phosphate reabsorption from bones but inhibits phosphate reabsorption in the kidneys - net effect is LOSS OF PHOSPHATE.

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5
Q

True or false: concentrations of calcium phosphate in the blood are near the solubility product in order to successfully deposit bone, so a slight elevation in levels can cause precipitations, stones, etc.

A

Tru dat

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6
Q

Name three things that osteoblasts use during bone formation and what the purpose of each is.

A
  1. Type 1 collagen: provides scaffolding for the nucleation of bone minerals.
  2. Osteocalcin: binds calcium and hydroxylapatite.
  3. Osteonectin: binds hydroxylapatite and collagen fibers.
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7
Q

Calcium in bones turns over at a rate of ____% per year in infants and ____% per year in adults.

A

100% in infants, 18% in adults

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8
Q

How long does a local cycle of bone resorption and replacement take?

A

100 days

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9
Q

What is the general effect of PTH and D3?

A

To increase blood Ca2+

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10
Q

What is the general effect of calcitonin?

A

To decrease blood Ca2+

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11
Q

What are the two major tissues that respond to PTH? What happens in them?

A

In bone: increases resorption.
In kidneys: increases reaborption of calcium and increases conversion of 25-hydroxycholecalciferol to 1, 25-dihydroxycholecalciferol (active D3).

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12
Q

True or false: PTH is produced by chief cells and stored as secretory granules in vesicles until secreted.

A

True

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13
Q

How do calcium levels regulate PTH secretion by chief cells?

A

When Ca2+ levels are high, they bind heterotrimeric G protein receptors (calcium-sensing receptor, CaSR) on chief cells, causing INHIBITION of PTH release. When Ca2+ levels drop, calcium dissociates from the receptor –> release of PTH via vesicle fusion.

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14
Q

Can PTH secretion be completely shut off even at very high calcium levels?

A

Nope

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15
Q

PTH is synthesized as ________ that is cleaved twice more to produce the active hormone.

A

pre-propeptide (preproPTH)

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16
Q

______ cells in the liver degrade PTH, and its half-life is ____ minutes.

A

Kupffer cells degrade it, half life is 10 minutes

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17
Q

Describe the PTH receptor and how it works.

A

PTH binds to PTH 1R receptors –> activation of two G proteins:

  • G alpha q activates PLC –> DAG, IP3 –> activation of Ca-dependent kinases.
  • G alpha s activates adenylyl cyclase –> cAMP.
18
Q

What effects does PTH have on phosphate homeostasis in the kidneys?

A

It reduces reabsorption of phosphate in the PCT and DCT because it promotes endocytosis of Na+/Pi cotransporters from the apical cell membranes –> phosphaturia and lower plasma phosphate.

19
Q

Describe the mechanism by which PTH increases osteoclast differentiation and bone resorption.

A

PTH binds to receptors on osteoBLASTS –> expression of M-CSF, RANKL, and IL-6 –> increased macrophage to osteoclast differentiation.

20
Q

What is the function of OPG?

A

It inhibits osteoclast differentiation by binding to RANKL, preventing its interaction with RANK on osteoclast progenitor cells.

21
Q

Pulsatile, low-dose secretion of PTH can actually result in bone _______ by stimulating osteocytes to transfer Ca2+ to osteoblasts.

A

results in bone formation (how paradoxical!)

22
Q

What is PTH-related protein (PTHrp) and what does it do?

A

Both PTH and PTHrp bind to PTH 1R but PTHrp is associated with cartilage growth and development in utero and with Ca++ transport in the placenta.

23
Q

Describe the synthetic pathway of active D3. Which reaction is under the control of PTH?

A

7-dehydrocholesterol –> cholecalciferol in skin from sun exposure –> 25-hydroxycholecalciferol in liver –> 1,25-dihydroxycholecalciferol in kidneys (active form) using the enzyme 1a-hydroxylase.

PTH promotes the final hydroxylation at the C1 position.

24
Q

Where do peeps get vitamin D2? How does it differ from D3? Is it as active as D3?

A

From diet - veggies, fish, tofu. D2 has an extra 2x bond between carbons 22 and 23. Not as active as D3.

25
Q

Where in the body is vitamin D stored? How does it get around in the plasma? What percentage of it is turned over per day?

A

Stored in adipose (its a fat-soluble vitamin). Gets around in the plasma on proteins or in chylomicrons. 1-2% is turned over per day.

26
Q

What is the cellular location of the vitamin D receptor?

A

Nucleus - its a steroid hormone

27
Q

By what mechanisms does vitamin D act on enterocytes to increase calcium absorption from the GI tract?

A

Vitamin D increases synthesis of apical Ca2+ pumps, channels, and calbindin (a protein that binds Ca2+ inside cells to maintain a gradient for further absorption)

28
Q

What effect does Vitamin D have on phosphate homeostasis in the GI tract? How?

A

It increases phosphate absorption by increasing synthesis of the 2Na+/Pi apical co-transporter in the small intestine

29
Q

What is the effect of vitamin D on the kidneys?

A

It acts with PTH to increase calcium reabsorption in the DCT. It also increases phosphate reabsorption but the effects of PTH (inhibition of phosphate reabsorption) outweigh the effects of vitamin D.

30
Q

Does vitamin D inhibit the final hydroxylation of 25-hydroxycholecalciferol?

A

Yeah

31
Q

Describe the direct and indirect effects of vitamin D on bone.

A

Direct effects: Vit D binds to osteoblasts –> secretion of matrix dissolving enzymes. It also promotes osteoclast differentiation.
Indirect effects: once blood calcium is increased, bone mineralization is resumed.

32
Q

How do you keep bone loss from occurring in mice that have no vitamin D receptors?

A

Give them calcium and phosphate supplements.

33
Q

In what organ is calcitonin made and stored? What stimulates its secretion?

A

Inferfollicular cells in the thyroid make and store it. High plasma Ca2+ levels stimulate its secretion.

34
Q

Which tissues and cells are the targets of calcitonin?

A
  1. Osteoclasts - calcitonin binds to G-protein receptors –> adenylyl cyclase or PLC –> inhibition of resorptive activity.
  2. PCT cells in kidney –> inhibition of phosphate transport and produces mild calciuresis.
35
Q

What clinical disorders does vitamin D deficiency cause in children and adults, respectively?

A

Rickets in children, osteomalacia in adults.

36
Q

What is FGF-23 and what does it do?

A

Made in bone, stimulated by increased phosphate in serum. Binds Klotho FGF receptor –> increased phosphate secretion in kidneys, suppresses final hydroxylation of D3, and suppresses PTH production.

37
Q

Mutations in of FGF-23 cause autosomal dominant ________ _________.

A

causes autosomal dominant hypophosphatemic rickets

38
Q

The most important target tissues of PTH are:

a) intestine and bone
b) kidney and bone
c) intestine and kidney
d) parathyroids and bone
e) bone and skin

A

b) kidney and bone

39
Q

The conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol occurs in the ________ and requires the hormone ______.

a) liver, UV light
b) liver, PTH
c) kidney, CT
d) kidney, PTH
e) skin, UV light

A

d) kidney, PTH

40
Q

A 50 year old man presents with low serum calcium and high serum phosphate. What is the most likely cause of these symptoms?

a) hypoparathyroidism
b) hyperparathyroidism
c) vitamin D deficiency
d) Cushing’s syndrome

A

a) hypoparathyroidism

41
Q

What is calcitriol?

A

Same thing as active D3

Physiology Pt. 4 (14 decks)

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