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PA10315 2nd semester > Calcium homeostasis: hormonal regulation > Flashcards

Calcium homeostasis: hormonal regulation Flashcards

1
Q

Extracellular Ca 2+ is required for

A 
nerve function
muscle contraction
coagulation
skeletal mineralization
activation of most cell types (signalling pathways)
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2
Q

Physiologically active fraction of total plasma calcium is that which is

A

unbound

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3
Q

Forms of calcium in the blood plasma

A

15 % : complexes with anions eg lactate, sulfate. Diffusable, bu biologically inert
40%: bound to albumin (proteins)- non-diffusable, remains in BVs
45% : unbound ‘ionised’ fraction. Diffusable and biologically active

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4
Q

which hormones control calcium homeostasis

A

calcitriol, calcitonon and parathyroid hormone

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5
Q

PTH

A

Single chain PP

Derived from larger precursor peptides pre-proPTH and proPTH

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6
Q

PTH produced by

A

chief cells of PT gland

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7
Q

PTH half life

A

10 min

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8
Q

Normal plasma level

A

10-55 pg/ml (picogram per ml)

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9
Q

Regulation of PTH minute to minute

A

Ca 2+ acting via the G protein coupled calcium sensing receptor (CaSR)
Decr in ionized (free) plasma Ca2+ causes incr in PTH secretion

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10
Q

Long term regulation of PTH

A

1,25(OH)2D3 acts directly on PTG to decr preproPTH mRNA

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11
Q

Actions of PTH

A

increases plasma Ca 2+ ( and decr plasma PO4 3-) via kidney, bone and GI tract

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12
Q

Kidney (PTH)

A
  • stimulates Ca2+ reabsorption in the distal tubule
  • Inhibits PO4 3- reabsorption in the proximal tubule
  • Incr production of 1,25-(OH)2D3, which increases intestinal absorption of Ca and PO4
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13
Q

Bone (PTH)

A
  • stimulates rapid efflux (out) of Ca2+ from freely exchangeable calcium pool (an effect on osteocytes and bone-lining cells)
  • Incr number and activity of osteoclasts (resorp) via action on osteoblasts
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14
Q

GI tract (PTH)

A

-stimulates absorption of CA2+ and PO43-

effect delayed and indirect (incr renal production of 1,25 (OH)2 D3 )

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15
Q

Summary of regulation of Calcium by PTH

A

Decr plasma CA triggers incr PTH secretion
Effect on bone: incr bone resorption
Effect on kidney: decr phosphate reabsorption, incr Ca reabsorption, incr hydroxylation of 25 OH vtamin D
Intestines: Incr Ca absorption (indirect via 1,25- dihydroxycholecalicferol)

Lead to incr in plasma Ca back to normal

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16
Q

1a, 25- dihydroxyvitamin D3 -calcitriol

A

Abbrev to 1,25(OH)2D3
Active metabolite of vitamin D3
A secosteroid (open B ring)
Produced in kidney by: 1 alpha hydroxylation of 25(OH)D3

Bulk bound to vit D- binding protein (alpha-globulin) transcalferin

Only free fraction is active: half life 3-6h

Interacts with a nuclear receptor- member of the nuclear receptor superfamily

17
Q

1,25(OH)2D3 production

A

Vit D3 (cholecalciferol), whether dietary or synthesised in the skin, is rapidly converted in the liver to 25(OH)D3 (by action of 25-hydroxylase) then into 1,25 Dihydroxyvitamin D3 in the kidney by action of 1a-hydroxylase

18
Q

Plasma levels of 1,25(OH)2D3 are determined by

A

rate of conversion of 25(OH)D3 to 1,25(OH)2 D3 (activation)

Rate of conversion of 1,25 (OH)2D3 to 24,25 (OH)2 D3 (inactivation)

19
Q

Actions of 1,25 (OH)2D3

A

Increases plasma Ca via GI tract, bone and kidney

20
Q

GI tract (main) 1,25

A

Stimulates absorption of Ca (mainly in the duodenum)

Stimulates absorption of PO43- (jejunum and ileum)

21
Q

Bone 1,25

A

Incr number and activity of osteoclasts

Leads to incr in bone resorption and hence incr in CA2+ and PO43- release

22
Q

Kidney 1,25

A

faciltates Ca2+ resorption (DCT)

23
Q

Calcitonin (CT)

A

single chain pp
Selected by parafollicular C cells of thyroid gland
Secretion regulated by Ca2+(incr CA = incr CT secretion) and gastrin incr
Actions lead to a fall in plasma Ca- opposite effect to PTH

24
Q

Calcitonin action on bone

A

decr release of CA and PO4
Decr rapid efflux across the bone membrane
Acts directly on osteoclasts to inhibit resorption

25
Q

calcitonin action on kidney

A

decr tubular reabsorption of CA and PO4

26
Q

Calcitonin action on GI tract

A

no sigfig effect on Ca absorption in small intestine

27
Q

Exact physiological role of Calcitonin in humans

A

uncertain

  • may protect against postprandial hypercalcaemia
  • may protect female skeleton during pregnancy and lactation
  • in pathological states may act to prevent excessive bone destruction
28
Q

overview of regulation of Ca homeostasis

A

high Ca, thyroid gland releases calcitonin, stimulates calcium deposition in bones

low Ca, PTGs release PTH, effect of PTH on bones, kidneys and GI tract results in higher Ca levels

29
Q

hypercalcaemia

A

associated with excess PTH
eg rumour of PTG
affects bones, kidneys GI tract as well as neurological symptoms

30
Q

hypocalcaemia

A

PTH resistance- no effect
Lack of vitamin D effect
symptom related to neuromuscular excitability
Long term lack of vitamin D affects bone growth
eg osteoporosis

31
Q

endocrine regulation of Ca homeostasis summary

A

decreased blood Ca stimulates PTH secretion from PTG
PTH stimulates osteoclasts to break down bone and release Ca
in the kidneys- PTH increases Ca reabsorption and stimulates vitamin D formation
Vitamin D promotes Ca absorption from the small intestine into the blood

Increased Ca stimulates calcitonin secretion from thyroid gland
Calcitonin inhibits osteoclasts, which allows for enhanced osteoblasts uptake of Ca from blood into bone

32
Q

bone structure

A

made up of several cell types surrounded by a collagen matrix called osteoid, upon which are deposited minerals eg crystals of calcium, phosphate

33
Q

Where are PTG’s

A

in the neck

34
Q

Are PTGs endocrine/exocrine

A

endocrine

35
Q

Vitamin D3

A

cholecaliferol

Formed from action of UV on a cholesterol derivative in the skin (7-dehydrocholesterol)

36
Q

cholecalciferol names

A

Vitamin D3

37
Q

Calcifediol names

A

25-Hydroxyvitamin D3

25(OH)D3

38
Q

Calcitriol

A

1,25-dihydroxyvitamin D3

1,25-(OH)2D3

PA10315 2nd semester (27 decks)

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