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Endocrinology > Lecture 8: Calcium and Phosphate Regulation > Flashcards

Lecture 8: Calcium and Phosphate Regulation Flashcards

1
Q

What is the normal serum range of calcium?

A

2.2-2.6mM

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2
Q

Why is calcium important?

A

1) membrane stability
2) neuronal transmission
3) bone structure
4) blood coagulation
5) muscle function
6) hormone secretion

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3
Q

What is phosphate used for?

A

cellular energy metabolism (ATP)

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4
Q

Hypoventiliation leads to ________________ which results in muscle weakness, renal dysfunction, hypoexcitability

A

hypercalcemia

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5
Q

Hyperventilation leads to _______________ which results in hyperexcitability

A

hypocalcemia

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6
Q

True or False: there is 10 fold more P than Ca in soft tissue

A

True

BUT there is more calcium in serum

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7
Q

Calcium travels in the blood bound to what protein?

A

albumin (45% bound, 50% ionized)

therefore, albumin levels are a good indicator of free calcium availability

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8
Q

What are the 3 regulators of calcium

A

1) Parathyroid (PTH)
2) Vitamin D (Calcitriol)
3) Calcitonin

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9
Q

What contributes most to the rapidly exchangeable pool of calcium in the body?

A

constant turnover of bone

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10
Q

What and where are parathyroid glands?

A

paired glands (4 total) at the posterior borders on lateral lobes of thyroid glands

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11
Q

What 2 cells are found in parathyroid glands?

A

1) Chief/Principal —–> make PTH

2) Oxyphil —–> no known function

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12
Q

What is the half life of the entire 84 amino acid PTH?

A

4 minutes!

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13
Q

Which portion of the PTH molecule binds to the receptor?

A

N-terminal fragment

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14
Q

What is PTHrP?

A

parathyroid hormone related peptide

  • mimics PTH in bone and kidney (normally at LOW conc, not regulator of plasma Ca)
  • produced by tumors resulting in hypercalcemia
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15
Q

What is the primary receptor of PTH?

A

PTH 1R (on osteoblasts and kidney)

  • binds N terminal 1-34 fragment, 1-84, PTHrP
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16
Q

What kind of receptor is PTH 1R?

A

GPCR

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17
Q

What does PTH 2R do?

A

binds 1-34, not sure what else

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18
Q

The net effect of PTH is to __________ plasma Ca++ and __________ plasma P

A

increase calcium

decrease phosphate

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19
Q

Where is one of if not the largest PTH target?

A

bone (99% of Ca content is in bone)

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20
Q

True or false: osteoclasts have PTH receptors

A

false – all effects of PTH on bone happen kind of indirectly

KEY: PTH stimulation of osteoclasts is INDIRECT

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21
Q

What kind of cells make up most of the bone matrix?

A

osteocytes (terminally differentiated osteoblasts)

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22
Q

What does PTH stimulate in osteoblasts?

A

macrophage colony stimulating factor (M-CSF)

23
Q

What does M-CSF do?

A

stimulates osteoclast production

24
Q

What is the RANK ligand?

A

agent that activates mature osteoclast (promotes multinucleation to actively reabsorb bone)

25
Q

What stimulates RANK ligand?

A

PTH

26
Q

What are the two important productions released into systemic circulation from bone degradation?

A

Ca and P

27
Q

What is the major antagonist of RANK ligand?

A

OPG (osteoprotegerin)

28
Q

What stimulates OPG?

A

estrogen (protects women from osteoporosis early on)

29
Q

What inhibits OPG?

A

cortisol (more bone resorption)

30
Q

What is the action of PTH on the kidney?

A

stimulates CYP1a - encodes 1a-hydroxylase which converts active form of vitamin D

stimulates Ca++ channel insertion in apical membrane of distal tubule (to reabsorb more)

31
Q

What is the primary regulator of PTH?

A

plasma calcium

32
Q

What senses plasma calcium?

A

CaSR (calcium sensing receptor)

binds ionized Ca++ (inhibits PTH synthesis at promoter level and also stimulates degradation of preformed PTH)

33
Q

Where are CaSRs located?

A

chief cells, kidney tubules, C cell

34
Q

What role does vitamin D play in PTH regulation?

A

binds nuclear receptor VDH which inhibits PTH synthesis at promoter level

also stimulates CaSR gene transcription (indirect effect on PTH)

35
Q

What is calciferol? Cholecalciferol? Calcidiol? Calcitriol? Ergocalciferol?

A 
Calciferol: vitamin D
Cholecalciferol: vitamin D3
Calcidiol: 25-D
Calcitriol: ACTIVE
Ergocalciferol: vitamin D2 (dietary from vegetables)
36
Q

What is vitamin d synthesized from?

A

cholesterol (steroid hormone)

37
Q

What is the active form of vitamin D?

A

1, 25- dihydroxycholecalciferol

38
Q

How does vitamin D travel in the blood?

A

Bound in plasma to vitamin D-binding protein

39
Q

Where is vitamin D made?

A

skin

40
Q

What are the vitamin D targets?

A

bone resorption
gut absorption
kidney reabsorption

41
Q

What effects does vitamin D have on bone?

A

directly mobilizes Ca++ from bone (osteoblasts and clasts have VDRs)

indirectly promotes bone mineralization by increasing plasma Ca++

42
Q

What does vitamin D to in the intestine?

A

increases transcellular Ca++ absorption in duodenum (inhibits calbindin)

stimulates Pi reabsorption from small intestine

43
Q

What are the 3 rapid responses of PTH?

A

1) increase CYP1a (which activates vitamin D)
2) increases bone turnover
3) increases Ca++ reabsorption and phosphate excretion by kidneys

44
Q

What is the slow response of PTH (also elicits negative feedback on PTH action)?

A

activation of vitamin D (1, 25 (OH)2)

45
Q

What is the one thing that vitamin D does that PTH does not?

A

increase dietary Ca++ absorption by small intestine

46
Q

What is the primary cause of hyperparathyroidism?

A

hyperplasia, carcinoma of parathyroid gland

hypercalcemia, kidney stones

47
Q

What is secondary hyperparathyroidism?

A

chronic renal failure (reduced vitamin D leads to excess PTH synthesis)

48
Q

What happens in hypoparathyroidism?

A

hypocalcemic tetany (reduced threshold for depolarization —> MORE firing)

49
Q

What is the Chvostek sign?

A

twitching of facial muscles in response to tapping of facial nerve

50
Q

What is rickets? osteomalacia?

A

unmineralized bone due to vitamin D deficiency

decreased bone strength - bowing of long bones

51
Q

What is pseudohypoparathyroidism

A

congenital defect in G protein that associates with PTHR1 (PTH CANNOT BIND TO RECEPTOR)

resistance to PTH, TSH, LH, FSH (low calcium, high phosphate, elevated PTH, short stature)

52
Q

Where is calcitonin produced?

A

C cells of thyroid gland

53
Q

True or false: thyroidectomy does not alter normal physiological range of Ca++

A

true (dont know what calcitonin does)

54
Q

What is the therapeutic use of calcitonin?

A

inhibits osteoclast reabsorption of and slows bone turnover (hypocalcemia)

Endocrinology (16 decks)

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