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msk sem 3 > calcium and phosphate metabolism > Flashcards

calcium and phosphate metabolism Flashcards

1
Q

what is calcium important for? (7)

A
  1. bone growth and remodelling
  2. secretion
  3. muscle contraction
  4. blood clotting
  5. co - enzyme
  6. stabilisation of membrane potentials
  7. important secondary messenger - stimulus response coupling
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2
Q

what is the distribution of calcium?

A
  1. 99% in bones
  2. extracellularly: 45% ionised and free and 45% bound to plasma proteins
  3. very small amount intracellularly
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3
Q

what are extracellular calcium levels controlled by? (2)

A
  1. PTH

2. Vitamin D

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4
Q

what are the functions of phosphate? (4)

A
  1. constituent of DNA/RNA and phospholipid membranes
  2. intracellular ion
  3. activation of enzymes by phosphorylation
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5
Q

what is the distribution of phosphate?

A
  1. 90% in bones
  2. small amount extracellular
  3. 10% intracellularly.
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6
Q

what is extracellular phosphate controlled by? (2)

A
  1. PTH

2. FGF23

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7
Q

what is PTH important for? (3)

A
  1. delivering elements to bone with vitamin D
  2. controlling flux of calcium in kidney
  3. controlling flux of phosphate in kidney with FGF23
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8
Q

Where is vitamin D’s major site of action?

A

in the gut for calcium and phosphate absorption.

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9
Q

what builds bone?

A

osteoblasts

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10
Q

what breaks or remodels bone?

A

osteoclasts

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11
Q

what do osteoblasts turn into?

A

osteocytes (mononuclear)

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12
Q

what are the two types of bone

A
  1. cortical (outside)

2. trabecular (inside like bracing)

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13
Q

what are osteoclasts actually

A

modified macrophages.

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14
Q

where do osteoclasts come from?

A

hematopoietic stem cells

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15
Q

where do osteoblasts come from?

A

mesenchymal derived cell

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16
Q

what activates osteoclasts?

A

RANK ligand - through activation of nuclear kappa beta - stimulates differentiation into osteoclasts

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17
Q

what signals the bone resorption and where are its receptors found?

A
  1. PTH

2. osteoblasts

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18
Q

what is the growth of the precursor promoted by?

A

GM - CSF promoted by T cells produced locally

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19
Q

what does the PTH receptor on the osteoblast do?

A

allows co-ordinated resorption of bone.

20
Q

how do osteoblasts know where the line of stress is since bone grows on lines of stress?

A

because electricity is produced when you stress bone and tells osteoblasts when to switch on.

21
Q

what produces FGF23 and what is its action

A

produced by osteocytes.

acts on kidney to decrease synthesis of active vitamin D and to increase excretion of inorganic phosphate.

22
Q

what do osteoblasts produce that acts on pancreatic beta cells?

A

uncarboxylated osteocalcin.

23
Q

what does uncarboxylated osteocalcin do? (2)

A
  1. increase insulin production and secretion.

2. acts on adipocytes to increase adiponectin on muscles to increase insulin sensitivity and glucose uptake

24
Q

what other hormones are involved in bone turnover and bone resorption? (4)

A
  1. sex steroids - stimulate osteoblast precursors
  2. growth hormones stimulatee bone via IGF - 1
  3. thyroxine for boney growth
  4. glucocorticoids inhibit osteoblast maturation
25
Q

what cells in the parathyroid gland produce PTH and what is the other type of cells that doesn’t produce hormone?

A
  1. chief cells

2. oxyphil cells.

26
Q

what is the blood supply for parathyroid gland

A

inferior thyroid artery.

27
Q

what is the synthesis of PTH

A

preopro hormone (signalling sequence)
prohormone
hormone

28
Q

what is the process of using two antibodies to detect PTH, called?

A

immunometric assay

29
Q

what does an increase in plasma proteins and alkalosis mean?

A

a decrease in free ionised calcium

30
Q

what does an decrease in plasma proteins and acidosis mean?

A

an increase in ionised free calcium (H+ displaces calcium)

31
Q

what is free calcium sensed by

A

calcium receptors on PTH producing chief cells - ultra short feedback loop

32
Q

what happens in calcium receptors in PTH happen?

A

increase in PLC and decrease in cAMP - results in decrease PTH production.

33
Q

once ionised calcium goes outside normal range what happens?

A

PTH secretion immediately shuts off - calcium has to be tightly regulated.

34
Q

what does PTH do? (4)

produce it in response to low calcium in order to increase calcium

A
  1. stimulates osteoblasts to produce M-CSF and RANK ligand which increase bone resorption
  2. increases calcium reabsorption in DCT
  3. increases phosphate excretion
  4. increases 1-alpha hydroxyls in the PCT.
35
Q

what is calcium bound to and transported to the basolateral membrane by?

A

bound to calbindin

36
Q

how does PTH increase the amount of calcium channels on the luminal surface?

A

stimulates AC to increase cAMP and activates PKA which increases amount of calcium channels on the luminal surface.

37
Q

what does the foetus produce?

A

PTHrp

38
Q

what are the two major causes of hypercalcaemia?

A
  1. primary hyperparathyroidism

2. malignancy

39
Q

symptoms of hypercalcaemia?

A
  1. shortening of QT interval - bradycardia
  2. decreased concentration, confusion, fatigue, fitting
  3. GI - hypo motility - constipation
  4. excess gastrin - leading to peptic ulcer formation.
  5. renal function - polyuria, polydipsia
  6. muscular weakness and bone pain
40
Q

how is vitamin D produced

A

D3 - cholesterol to cholecalciferol

D2 - ergosterol to ergocalciferol

41
Q

what is the main regulating enzyme in the kidney for vitamin D

A

1-alpha hydroxylase - regulates calcitriol

42
Q

what is renal dysfunction tend to be associated with?

A

low levels of vitamin D

43
Q

what diseases can result in hypercalcemia?

A

sarcoidosis, tubercolosis, and other granulomatous

44
Q

what type of receptor are vitamin D receptors?

A

type 2 nuclear receptors

45
Q

read notes

A

read notes

msk sem 3 (10 decks)

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