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Flashcards in Ca and bone physiology Deck (83)
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1
Q

What is the normal plasma [Ca]?

A

9-10.5 mg/dL

2
Q

What three forms does Ca take in the body?

A

Free/ionized
Protein bound
Anion bound

3
Q

What is the relationship between plasma pH and bound Ca levels?

A

Lower pH = less Ca bound to protein

4
Q

Significant decrease in plasma calcium can lead to death because of what effect?

A

because of the effect of calcium on nerve excitability

5
Q

As extracellular calcium concentration gets lower, sodium channels open (more/less) readily?

A

More

6
Q

What happens to the membrane potential of neurons with hypocalcemia?

A

Makes it closer to membrane potential, making the neuron more excitable

7
Q

Does hypocalcemia cause tetany or flaccid paralysis?

A

tetany

8
Q

What is Trousseau sign?

A

Contraction of the hand when a BP cuff is applied. This is caused by hypocalcemia

9
Q

What is Chvostek sign?

A

When the facial nerve is tapped at the angle of the jaw, the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcemia

10
Q

What is the effect of hypocalcemia on the heart?

A

CHF

11
Q

When the concentration of calcium is higher than normal the voltage-regulated sodium channels are (more or less) likely to open at any given cell membrane potential?

A

Less

12
Q

What is the effect of low [Ca] on membrane potential?

A

Lowers threshold, leading to hyperexcitability

13
Q

• Some calcium enters the GI tract from the body e.g. sloughing of cells that line GI tract, in various secretions into GI tract. Why is this not problematic?

A

This loss of calcium relatively fixed and less than calcium uptake

14
Q

What is the effect of increased Vitamin D on calcium uptake?

A

Increases uptake

15
Q

The higher the plasma [Ca] levels, the higher or lower the threshold?

A

higher

16
Q

How tightly regulated is plasma phosphate concentration relative to [Ca]?

A

Much less

17
Q

What is the normal range for plasma [phosphate]?

A

3-4.5 mg/dL

18
Q

What is the main circulating form of phosphate? How filterable is this?

A

Free, inorganic ion–very filterable

19
Q

Where is phosphate stored? What form is this in?

A

Bone

Stored as hydroxyapatite

20
Q

What is the role that vitamin D plays in phosphate uptake from the diet?

A

Increases, but only marginally

21
Q

What is the role of PTH on phosphate secretion?

A

greatly increase phosphate excretion by the kidneys.

22
Q

What is the primary regulator of phosphate?

A

FGF23

23
Q

What is the effect of FGF23 on the production of calcitriol?

A

Decreases

24
Q

What is the specialized channel on the intestinal epithelium that moves Ca into the epithelial cells?

A

TRPV5/6

25
Q

What is the protein in the intestinal epithelial cells that binds to Ca and moves it across the lumen?

A

Calbindin

26
Q

What is the transporter that moves Ca from the intracellular fluid of the intestinal cytoplasm to the plasma?

A

Plasma membrane Ca ATPase

27
Q

What is the most important bone salt?

A

hydroxyapatite

28
Q

Why does hydroxyapatite precipitate in bone and not in other tissues?

A

There are inhibitors found in other body tissues including plasma to prevent precipitation.

29
Q

What are the two effects of PTH has in the Ca pathway?

A

Increases calcitriol synthesis

Increases phosphate excretion

30
Q

What are the two effects of FGF23 has in the Ca pathway?

A

Decreases calcitriol synthesis

Increases phosphate excretion

31
Q

Why is it important that PTH and calcitriol have opposite effects on calcitriol synthesis, but both contribute to phosphate excretion?

A

Can increase phosphate excretion without changing calcitriol synthesis

32
Q

What is the major protein found in bone?

A

Collagen I

33
Q

What is the chemical that stimulates osteoblasts?

A

Growth hormone

34
Q

What is osteoid formation?

A

When osteoblasts entrap themselves in bone, becoming osteocytes

35
Q

The growth of long bones at epiphyseal cartilages is under the control of what hormone?

A

GH

36
Q

What is the effect PTH has on osteoclast activity? How?

A

Increases activity by binding to receptors on osteoblasts, which release osteoprotegerin ligand (OPGL).

37
Q

What is osteoprotegerin ligand (OPGL)?

A

A hormone released by osteoclasts that activates receptors on preosteoclast cells to stimulate their growth

38
Q

What is osteoprotegerin (OPG)?

A

Hormone released by osteoblasts that inhibits the binding of OPGL on pre-osteoclasts, preventing their maturation.

39
Q

What is the hormone that stimulates osteoprotegerin (OPG) production?

A

Estrogen

40
Q

What is the hormone that decreases osteoprotegerin (OPG) production?

A

PTH and glucocorticoids

41
Q

What happens to osteoclasts/blast activity when a bone is fractured?

A

Large increase in osteoprogenitor cells

42
Q

What temporarily holds fractured bones in place?

A

A callus

43
Q

What are the nutritional cells of bone?

A

Astrocytes

44
Q

What are the canals in bone that allows for the transport of nutrients?

A

Haversian canals

45
Q

What are the passages that connect Haversian canals in bone?

A

Canaliculi

46
Q

What is an osteon?

A

Haversian canal and surrounding canaliculi

47
Q

What prevents the osteoclasts enzymes from spreading outside the site of degradation?

A

Tight connections–integrins

48
Q

What are the two hormones that act on osteoblasts to stimulate OPGL production (thus stimulating Pre-osteoclast maturation)?

A

PTH and Vit D

49
Q

What is the active form of Vitamin D?

A

1,25-Dihydroxycholecalciferol

50
Q

What is the hormone required to have the proximal tubules in the kidney convert 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol?

A

PTH

51
Q

What is the enzymes that converts Vitamin D3 into 25-hydroxycholecalciferol?

A

25-Hydroxylase

52
Q

What is the enzyme that converts 25 hydroxycholecalciferol to 1,25- dihydroxycholecalciferol?

A

1alpha-Hydroxylase

53
Q

What is the effect of 1,25-dihydroxycholecalciferol ?

A

Increases both calcium and phosphate concentrations in plasma via increased reabsorption

54
Q

What is the effect of 1,25-dihydroxycholecalciferol on bones?

A

promotes action of PTH on osteoclasts increasing bone resorption

55
Q

What causes Rickets in children?

A

caused by a calcium or phosphate deficiency in the extracellular fluid usually caused by a lack of vitamin D. Children are more susceptible since childhood is a period of bone growth so large amounts of calcium are needed.

56
Q

What is Osteomalacia?

A

(softening of the bone due to deficient mineralization) can be caused by a type of “Renal rickets” due to the failure of the damaged kidney to produce the active form of vitamin D.

57
Q

What is the substrate that changes to previtamin D3 in the presence of sunlight?

A

7-Dehydrocholesterol

58
Q

What is the primary physiological stimulus for PTH secretion?

A

Decreased [Ca]

59
Q

How does the absence of PTH cause death?

A

From hypocalcemic tetany

60
Q

What is the effect of PTH on plasma [Ca] and [phosphate]?

A

Increases [Ca]

Decreases [phosphate]

61
Q

Why is it important that PTH decreases plasma [phosphate] with increasing [Ca]?

A

Prevents crystallization of calcium phosphate.

62
Q

Where in the nephron does PTH regulate the reuptake of Ca?

A

distal portions of the nephron

63
Q

What is the effect PTH has on the reabsorption of phosphate at the kidney?

A

Inhibits reabsorption

64
Q

What is hormone that increases 1alpha-hydroxylase activity? What does this do?

A

PTH–increases Vitamin D synthesis, thus increases Ca reabsorption in the intestines

65
Q

What are the three effects that PTH has on bone?

A
  • Increases bone resorption and delivery of calcium to plasma
  • Inhibits collagen synthesis by osteoblasts
  • Active form of vitamin D increases PTH driven bone resorption
66
Q

Where is calcitonin produced?

A

parafollicular cells in the thyroid gland

67
Q

What type of hormone is calcitonin?

A

Polypeptide

68
Q

What stimulates calcitonin release?

A

Increase in plasma Ca

69
Q

How significant of a role does calcitonin play in Ca homeostasis?

A

Not very

70
Q

What is the effect of calcitonin on bones?

A

Decreases bone resorption and thus decreases calcium release

71
Q

What is the effect of calcitonin on the kidney?

A

decrease in reabsorption of calcium and phosphate

72
Q

What is the feedback mechanism for PTH?

A

PTH causes increase in vit D, thus increasing Ca reabsorption via CBP + Ca stimulated ATPase in the intestine. Resulting increase in plasma [Ca] inhibits PTH

73
Q

Where are the parathyroid glands? How many are there?

A

next to the thyroid, there are four

74
Q

What is the relationship between plasma [Ca] and [PTH]?

A

Inverse–sigmoidal curve

75
Q

How does PTH increase Ca reabsorption?

A

Increases Vit D synthesis via activation of 1alpha-hydroxylase

76
Q

What are the effect of hyperparathyroidism?

A

Hypercalcemia and hypophosphatemia

77
Q

What are the symptoms of hyperparathyroidism?

A

Renal stones
Weak bones
Constipation

78
Q

What causes secondary hyperparathyroidism?

A

Anything that causes low Ca levels (kidney disease)

79
Q

Why is it lethal to not have PTH?

A

steady decline in the plasma concentration of calcium

80
Q

Renal function may increase plasma [PO3], causing hyperphosphatemia. What are the two main hormones that this lead to an increase in production of?

A

PTH

FGF23

81
Q

What is the effect of FGF23 on vit D synthesis? How? What is the effect of this on [PTH]?

A

Decreases vit D by inhibiting 1alpha hydroxylase

Stimulates PTH synthesis

82
Q

What is the effect of PTH on bone?

A

Increases bone reabsorption, and release of Ca + PO3

83
Q

What are the two supplements and one dietary restriction that patients with CKD should be prescribed?

A

Supplement Ca, and Vit D

Restrict PO3