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Endocrine > Parathyroid and regulation of calcium (L8) > Flashcards

Parathyroid and regulation of calcium (L8) Flashcards

1
Q

Important physiologic processes involving calcium (6)

A 
Membrane stability and cell function
Hormone secretion
Bone structure/formation
Blood coagulation
Muscle function
Neuronal transmission
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2
Q

Important physiologic processes involving phosphate (5)

A 
Cellular energy (ATP)
Intracellular signalling pathways
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation
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3
Q

Indicator of free calcium availability

A

Calcium bound to albumin minus the concentration of albumin

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4
Q

Two primary regulators of calcium concentration

A

Parathyroid hormone and vitamin D/calcitriol

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5
Q

Daily calcium turnover in humans

A 
1000 mg intake
Half absorbed in the intestines
Some also excreted
Net ~200 mg absorption
~200 mg excreted in urine
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6
Q

Chief cells of parathyroid gland

A

Synthesize PTH

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7
Q

Oxyphil cells

A

Unknown function, increase with age

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8
Q

1-84 fragment

A

Half life of 4 minutes, clinically important for measurement

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9
Q

N-terminal fragment

A

1-34: biologically active

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10
Q

C-terminal fragment

A

35-84: has longer half life than others, but is inactive

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11
Q

Parathyroid hormone related peptide

A

Mimics action of PTH in bone and kidney

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12
Q

Physiologic concentration of PTHrP

A

Normally very low, doesn’t affect Ca2+ concentrations; however, some tumors secrete it and cause hypercalcemia

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13
Q

Primary parathyroid hormone receptor

A

PTH1R, present in the osteoblasts and kidneys

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14
Q

Second messengers of PTH1R

A

Adenylyl cyclase/cAMP pathway

IP3/DAG pathway

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15
Q

To what does the PTH1R bind?

A

1-34 fragment, 1-84 fragment, PTHrP

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16
Q

PTH2R

A

Only binds to 1-34 fragment, function is unclear

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17
Q

Net effects of PTH on the bones and kidney

A

Increases plasma Ca2+ concentration, decreases plasma Pi concentration

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18
Q

How much of the body’s calcium is in the bone?

A

99%

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19
Q

PTHR expression on bone cells

A

Present on osteoblasts, but not on osteoclasts

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20
Q

Difference in derivation between osteoclasts and osteoblasts

A

Osteoblasts: from mesenchymal stem cells
Osteoclasts: from hematopoietic stem cells

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21
Q

Osteocytes

A

Terminally differentiated from osteoblasts; make up most of the bone matrix

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22
Q

M-CSF

A

Macrophage colony stimulating factor; stimulates differentiation of osteoclasts

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23
Q

PTH stimulation of osteoclasts

A

INDIRECT through M-CSF

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24
Q

RANK ligand

A

Leads to maturation of osteoclasts and bone resorption, stimulated by PTH

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25
Q

Osteoprotegerin

A

Antagonist of RANKL

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26
Q

Hormonal regulation of OPG

A

Estrogens stimulate; glucocorticoids inhibit

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27
Q

How does the osteoclast resorb bone?

A

Releases H+ and acid proteases into the lacuna, dissolving bone mineral and hydrolyzing bone matrix proteins

28
Q

PTH stimulates what gene in the kidney?

A

CYP1alpha, which encodes for 1alpha-hydroxylase

29
Q

1-alpha-hydroxylase

A

Converts Vitamin D3 into its active form

30
Q

What does PTH do to the infrastructure in the kidney?

A

Stimulates insertion of calcium protein channels into the apical membrane of distal tubule

31
Q

PTH effect on phosphate in the kidney

A

Reduces phosphate absorption in both proximal and distal tubules; greater in the proximal

32
Q

Calcium sensing receptor - location

A

Located in chief cells, kidney tubules, and C cells

33
Q

What does CaSR do?

A

Binds ionized calcium, inhibits PTH synthesis at the promoter level, and degrades existing PTH

34
Q

What does Vitamin D3 do?

A

Binds VDR, inhibits PTH synthesis at the promoter level, and stimulates CaSR transcription

35
Q

Calciferol

A

Refers to vitamin D in all its forms

36
Q

Cholecalciferol

A

Directly refers to vitamin D3

37
Q

Calcidiol

A

25-hydroxyvitamin D3; immediate precursor

38
Q

Calcitriol

A

1,25-dihydroxyvitamin D3 (active form)

39
Q

Ergocalciferol

A

Vitamin D2 from vegetables

40
Q

Synthesis of vitamin D3 in the skin

A

Precursor hormone 7-dehydrocholesterol is converted to cholecalciferol in the skin by UV light, then isomerized to form vit D3

41
Q

How is vitamin D transported to the liver?

A

Either directly through portal circulation or indirectly through chylomicron association

42
Q

Default pathway for vit D3 conversion

A

To the inactive form; 24,25-dihydroxyvitamin D3

43
Q

Factors driving conversion from inactive to active vitamin D3

A

Hypocalcemia or hypophosphatemia

44
Q

Direct effects of vitamin D3 on bone

A

Mobilize calcium from bone

Stimulation of osteoclast proliferation/differentiation

45
Q

Indirect effect of vitamin D3 on bone

A

Increases plasma calcium concentration, which promotes bone mineralization

46
Q

Effects of vitamin D3 on the intestines

A

Increases calcium absorption from duodenum

Increases phosphate absorption from small intestine

47
Q

Vitamin D3 and pathway of calcium reabsorption in the gut

A

Upregulates TRPV5/6 (apical membrane), calbindin (intracellular), and calcium ATPase pump (basolateral)

48
Q

Vitamin D3 and the pathway of phosphate reabsorption in the gut

A

Increases Pi-Na cotransporter

49
Q

Deficiency in vitamin D3 is linked to these conditions (6)

A 
MS
Asthma
Major depressive disorder
Colon/breast cancer
CVD
DMII
50
Q

Normal serum calcium range

A

8.8-10.3mg/dL

51
Q

Normal serum phosphate range

A

2.4-4.1mg/dL

52
Q

Urinary hydroxyproline

A

Evidence of enhanced bone resorption

53
Q

Osteoporosis definition

A

Decreased bone density, mostly in the trabeculae

54
Q

Causes of osteoporosis

A

Genetic, menopause (decreased estrogen), prolonged GC therapy/prolonged stress, low dietary calcium

55
Q

Treatment of osteoporosis

A

Estrogen replacement, bisphosphonates, calcitonin, vitamin D supplementation

56
Q

Primary hyperparathyroidism

A

Hyperplasia or carcinoma of the parathyroid, causing hypercalcemia and kidney stones

57
Q

Secondary hyperparathyroidism

A

Usually due to CRF; lack of vitamin D3 causes excess PTH from lack of inhibition

58
Q

Symptoms of hypoparathyroidism

A

Hypocalcemic tetany

59
Q

Chvostek’s sign

A

Stimulation of facial nerve causes facial muscle twitching

60
Q

Rickets

A

Vitamin D deficiency in children that causes “bowing” of long bones and decreased bone strength

61
Q

Osteomalacia

A

Vitamin D deficiency in adults that causes decreased bone strength

62
Q

Calcitonin - location and length

A

Made in the C cells of the thyroid gland; 32 amino acids long

63
Q

What is the normal physiologic importance of calcitonin?

A

Unclear. Pathology/absence of C-cells does not alter calcium concentration

64
Q

Therapeutic use of calcitonin

A

Slows bone turnover and inhibits osteoclasts

65
Q

Paget disease

A

Localized regions of very high bone resorption rates and reactive sclerosis; cause unknown

66
Q

Escape phenomenon

A

Rapid downregulation of calcitonin receptors inhibits antiosteoclastic actions of calcitonin within a few hours; makes it a less effective treatment option

Endocrine (11 decks)

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