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

What is the normal plasma [Ca]?

9-10.5 mg/dL

2

What three forms does Ca take in the body?

Free/ionized
Protein bound
Anion bound

3

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

Lower pH = less Ca bound to protein

4

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

because of the effect of calcium on nerve excitability

5

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

More

6

What happens to the membrane potential of neurons with hypocalcemia?

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

7

Does hypocalcemia cause tetany or flaccid paralysis?

tetany

8

What is Trousseau sign?

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

9

What is Chvostek sign?

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

What is the effect of hypocalcemia on the heart?

CHF

11

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?

Less

12

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

Lowers threshold, leading to hyperexcitability

13

• 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?

This loss of calcium relatively fixed and less than calcium uptake

14

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

Increases uptake

15

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

higher

16

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

Much less

17

What is the normal range for plasma [phosphate]?

3-4.5 mg/dL

18

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

Free, inorganic ion--very filterable

19

Where is phosphate stored? What form is this in?

Bone
Stored as hydroxyapatite

20

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

Increases, but only marginally

21

What is the role of PTH on phosphate secretion?

greatly increase phosphate excretion by the kidneys.

22

What is the primary regulator of phosphate?

FGF23

23

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

Decreases

24

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

TRPV5/6

25

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

Calbindin

26

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

Plasma membrane Ca ATPase

27

What is the most important bone salt?

hydroxyapatite

28

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

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

29

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

Increases calcitriol synthesis

Increases phosphate excretion

30

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

Decreases calcitriol synthesis

Increases phosphate excretion

31

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

Can increase phosphate excretion without changing calcitriol synthesis

32

What is the major protein found in bone?

Collagen I

33

What is the chemical that stimulates osteoblasts?

Growth hormone

34

What is osteoid formation?

When osteoblasts entrap themselves in bone, becoming osteocytes

35

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

GH

36

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

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

37

What is osteoprotegerin ligand (OPGL)?

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

38

What is osteoprotegerin (OPG)?

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

39

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

Estrogen

40

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

PTH and glucocorticoids

41

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

Large increase in osteoprogenitor cells

42

What temporarily holds fractured bones in place?

A callus

43

What are the nutritional cells of bone?

Astrocytes

44

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

Haversian canals

45

What are the passages that connect Haversian canals in bone?

Canaliculi

46

What is an osteon?

Haversian canal and surrounding canaliculi

47

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

Tight connections--integrins

48

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

PTH and Vit D

49

What is the active form of Vitamin D?

1,25-Dihydroxycholecalciferol

50

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

PTH

51

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

25-Hydroxylase

52

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

1alpha-Hydroxylase

53

What is the effect of 1,25-dihydroxycholecalciferol ?

Increases both calcium and phosphate concentrations in plasma via increased reabsorption

54

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

promotes action of PTH on osteoclasts increasing bone resorption

55

What causes Rickets in children?

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

What is Osteomalacia?

(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

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

7-Dehydrocholesterol

58

What is the primary physiological stimulus for PTH secretion?

Decreased [Ca]

59

How does the absence of PTH cause death?

From hypocalcemic tetany

60

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

Increases [Ca]
Decreases [phosphate]

61

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

Prevents crystallization of calcium phosphate.

62

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

distal portions of the nephron

63

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

Inhibits reabsorption

64

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

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

65

What are the three effects that PTH has on bone?

• 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

Where is calcitonin produced?

parafollicular cells in the thyroid gland

67

What type of hormone is calcitonin?

Polypeptide

68

What stimulates calcitonin release?

Increase in plasma Ca

69

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

Not very

70

What is the effect of calcitonin on bones?

Decreases bone resorption and thus decreases calcium release

71

What is the effect of calcitonin on the kidney?

decrease in reabsorption of calcium and phosphate

72

What is the feedback mechanism for PTH?

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

Where are the parathyroid glands? How many are there?

next to the thyroid, there are four

74

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

Inverse--sigmoidal curve

75

How does PTH increase Ca reabsorption?

Increases Vit D synthesis via activation of 1alpha-hydroxylase

76

What are the effect of hyperparathyroidism?

Hypercalcemia and hypophosphatemia

77

What are the symptoms of hyperparathyroidism?

Renal stones
Weak bones
Constipation

78

What causes secondary hyperparathyroidism?

Anything that causes low Ca levels (kidney disease)

79

Why is it lethal to not have PTH?

steady decline in the plasma concentration of calcium

80

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

PTH
FGF23

81

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

Decreases vit D by inhibiting 1alpha hydroxylase

Stimulates PTH synthesis

82

What is the effect of PTH on bone?

Increases bone reabsorption, and release of Ca + PO3

83

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

Supplement Ca, and Vit D

Restrict PO3