Calcium and Phosphate Regulation Flashcards Preview

FHB Block 4 > Calcium and Phosphate Regulation > Flashcards

Flashcards in Calcium and Phosphate Regulation Deck (96):
1

List the general functions of calcium

Membrane stability and cell function
Neuronal transmission
Bone structure/formation
Blood coagulation
Muscle function
Hormone secretion

2

List the general functions of phosphate

Cellular energy metabolism (ATP)
Intracellular signaling pathways
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation

3

What is a good indicator of free calcium availability?

Albumin levels - calcium is bound to albumin

4

What is the most abundant cation?

Calcium! tightly regulated in plasma (.2-2.6 mM)

5

What can result from hypocalcemia?

Muscle failure, tetany, convulsions, death

6

What can result from hypercalcemia?

renal dysfunction, calcification of soft tissues, muscle weakness, coma

7

What would result in hyperphosphatemia?

Crush injury- 10x more phosphate than Ca in soft tissue

8

What are the two primary regulators of calcium?

PTH
Vit D/Calcitriol (skin, diet)

Calcitonin (thyroid) probably not important in humans

9

What are the three organs regulating Ca homeostasis?

Kidneys
Gut
Bone

10

Discuss the daily calcium turnover in humans

Intake ~1000mg

Gut takes up ~500 but also secrets some, making the net absorption only ~200mg

Urinary excretion same as gut absorption

11

Discuss the general anatomy of the PT glands

paired glands, 4 total, located at posterior borders on lateral lobes of the thyroid gland, usually embedded in a capsule

12

What kind of cells synthesizes PTH?

Chief cells (aka principal cells)

13

What are oxyphil cells?

no known function, increase with age and chronic kidney disease

14

What directs newly synthesized PTH to the ER?

signal peptide

15

What is the form of PTH that is a clinically important measurement, and what is its half life?

Intact 1-84 fragment, half life of 4 minutes

16

What is the biologically active form of PTH?

N-terminal 1-34 fragment, binds to the PTH receptor

17

What segment of PTH has the longest half life? Is it active or inactive?

C-terminal 35-84, inactive

18

What is the role of parathyroid hormone related peptide?

mimics activity of PTH in bone and kidney

normally very low concentrations, does not regulate plasma Ca

19

What produces abnormally high concentrations of PTHrP?

many tumors, resulting in hypercalcemia

20

what is the primary receptor of PTH?

PTH 1R

21

Where is PTH 1R found?

Bone and kidney

22

What are the secondary signaling pathways that PTH 1R utilizes?

GPCR

G-alpha-s: adenylyl cyclase/cAMP

G-alpha-q: PLC/IP3/DAG

23

What does PTH 1R bind?

1-34 fragment, 1-84, PTHrP

24

What is an additional PTH receptor?

PTH 2R

25

What is the function of PTH 2R and what does it bind?

function unclear

binds 1-34 fragment, does not bind PTHrP

26

What does PTH target?

Bone and kidneys

27

What is the overall effects of PTH?

Increase in plasma Ca

Decrease in plasma phosphate

28

Where is the majority of body Ca found?

99% body Ca2+ content in bone

29

What is the function of osteoblasts?

bone formation and mineralization

30

What do osteoblasts express at high concentrations

Receptors for PTH

31

What are osteoblasts derived from?

mesenchymal stem cells

32

What is the function of osteoclasts?

Bone resorption

33

What are osteoclasts derived from?

hematopoietic stem cells

34

Do osteoclasts express PTH receptors?

NO!

35

what are osteocytes and what are the derived from?

make up most of the bone matrix

terminally differentiated from osteoblasts

36

What does PTH stimulate in osteoblasts?

macrophage colony stimulating factor (M-CSF)

RANK Ligand

37

What does M-CSF stimulate?

differentiation of osteoclast precursors

38

How does PTH stimulate osteoclasts?

Indirectly! via M-CSF

39

What does RANK ligand do?

leads to maturation of osteoclasts and bone resorption

40

What is the overall result of bone resorption?

release of calcium and phosphate to the systemic circulation

41

What is osteoprotogerin?

a "soluble decoy" that is an antagonist of RANK ligand

42

How do osteoclasts resorb bone?

secrete H+ and acid proteases into the lacuna

43

What are the regulators of osteoprotogerin?

Estrogens stimulate (protective)

glucocorticoids inhibit (increased osteoclast activity)

44

What does PTH stimulate in the kidney?

CYP1-alpha

calcium channel insertion in apical membrane of distal tubule

45

What does CYP1alpha do?

encodes 1-alpha-hydroxylase which converts the active from of vitamin D

46

What regulates PTH?

CaSR (calcium sensing receptor)

Vitamin D

47

Where is CaSR located?

Chief cells, kidney tubules, C cells

48

what does CaSR do?

binds ionized calcium

inhibits PTH synthesis at the promoter level

stimulates degradation of preformed PTH

49

What does Vitamin D bind?

binds the nuclear receptor VDR

50

How does vit D regulate PTH?

inhibits PTH synthesis at the promoter level

stimulates CaSR gene transcription (indirect PTH regulation)

51

What is calciferol?

general term for vitamin D and other natural structural analogs

52

What is cholecalciferol?

specifically refers to vitamin D3 (from animal tissues)

53

What is calcidiol (calcifidiol)?

25-hydroxy-vitamin D (25-D) = 25-hydroxy-cholecalciferol
(immediate precursor)

54

What is calcitriol (calcifitriol)?

1,25-dihydroxy-vitamin D (1,25-D) = 1,25-dihydroxycholecalciferol

55

What is the active form of vit D?

1,25-dihydroxy-vitamin D (1,25-D) = 1,25-dihydroxycholecalciferol

56

What is ergocalciferol?

Vit D2, from vegetables

57

What is vit D derived from?

Cholesterol (steroid hormone)

58

what is the receptor for vit D, and what kind of receptor is it?

nuclear receptor VDR

59

what is vit D bound to in plasma?

Vit D binding protein (VDBP)

60

How is vitamin D3 synthesized in the skin?

The precursor hormone 7-dehydrocholesterol is converted to cholecalciferol in the skin by UV light and then isomerized to form vitamin
D3

61

Where is vitamin D3 processed after being formed in the skin?

the liver

62

what does bioactivation of vit D3 and D2 (from diet) require?

1-alpha hydroxylase (stimulated by PTH)

63

how is vit D3 transported from the skin the the liver?

VDBP

64

how are vit D3 and D2 transported from the gut to the liver?

either directly via portal circulation or indirectly via chylomicrons (via lymphatics)

65

What happens to vit D in the liver?

converted to 25-hydroxyvitamin D via 25-hydroxylase

66

where does conversion to the active form occur, and what does it require?

in the kidney, requires enzyme 1-alpha-hydroxylase

67

what is the default pathway of vit D processing?

the inactive pathway that forms 24,25-(OH)2-D3

68

what are primary factors that drive conversion to the active from of vit D?

hypocalcemia and hypophosphatemia

69

What organs does vit D target?

bone, kidneys, and gut

70

what are the direct effects of Vit D on bone?

mobilize calcium from the bone
stimulate osteoclast proliferation/differentiation

71

What has VDR in the bone?

osteoclasts and osteoblasts

72

What is an indirect effect of vit D on bone?

increases plasma Ca which stimulates mineralization

73

what does vit D do in the intestines?

increases transcellular Ca absorption in duodenum

stimulates phosphate reabsorption in the small intestine

74

How does vit D result in increased absorption of calcium in the gut?

increases expression of TRPV5/6 (luminal transporter), calbindin (intracellular binding protein), and basolateral membrane calcium ATPase pump

75

How does vit D result in increased reabsorption of phosphate in the gut?

increases expression of Na/P cotransporter

76

What is a deficiency of vit D linked to?

MS
Asthma
Cardiovascular disease
Type II Diabetes mellitus
Colorectal/breast cancer
Major Depressive Disorder (MDD)

77

What is a normal serum calcium level?

2.2-2.6 mM or 8.8-10.3 mg/100 ml

78

What is a normal serum phosphate level?

0.8-1.45 mM or 2.4-4.1 mg/100 ml

79

What is osteoporosis?

reduced bone density, especially trabecular bone

80

What are causes of osteoporosis?

genetic, menopause (low estrogen), glucocorticoid therapy/chronic stress, low dietary Ca

81

What is the treatment of osteoporosis?

estrogens, calcitonin, bisphosphonates (inhibit bone resorption), vit D

82

what is primary hyperparathyroidism due to?

hyperplasia or carcinoma of the PT gland

83

What is the result of primary hyperparathyroidism?

hypercalcemia and kidney stones

84

What is secondary hyperparathyroidism a result of?

due to chronic liver failure

85

What is the result of secondary hyperparathyroidism?

reduced vit d leads to excess PTH synthesis

86

what is a result of hypoparathyroidism?

hypocalcemic tetany

Chvostek sign: twitching of facial muscles in response to tapping of facial nerve

87

what is Rickets (children)/Osteomalacia (adults)?

unmineralized bone due to vit D deficiency

decreased bone strength (bowing in children)

88

What is pseudohypoparathyroidism?

congenital defect in G protein that associates with PTH R1

89

what is a result of pseudohypoparathyrodism?

general resistance to PTH, LH, FSH, TSH

90

What are some clinical signs of pseudohypoparathyroidism?

Low ca, high phosphate, elevated PTH, short stature

91

How could you normalize low plasma Ca and high plasma P?

PTH infusion

92

What is a urinary marker for enhanced bone resorption?

hydroxyproline

93

What is calcitonin?

a 32AA peptide produced by C cells of the thyroid gland

may help in inhibiting calcium resorption in bone

94

What does therapeutic use of calcitonin result in?

Used to treat Paget disease (high bone turnover):

inhibits osteoclast resorption and slows bone turnover (hypocalcemic action)

95

What is the escape phenomenon?

rapid downregulation of calcitonin receptors cause the antiosteoclastic actions of calcitonin to diminish within a few hours making this a less effective treatment option

96

Why are some findings that make the physiological function of calcitonin unclear?

Complete thyroidectomy (with parathyroids left intact) does not alter normal physiological range of Ca2+.

C-cell tumors – extremely high calcitonin – does not affect Ca2+ levels