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Limbs And Back - Week 1 > Calcium, Phosphate Metabolism And Homeostasis > Flashcards

Calcium, Phosphate Metabolism And Homeostasis Flashcards

1
Q

What is the total amount of calcium normally found in the body?

A

25,000 mmol or 1 kg

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2
Q

How is calcium distributed throughout the body?

A
  • 99% contained in mineral phase of bone as a component of hydroxyapatite
  • remaining 1% split between extracellular ionised Ca and intracellular cytosolic Ca
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3
Q

List some of the biological roles of calcium. (5)

A
  • muscle contraction
  • intracellular messenger
  • nerve excitability
  • blood coagulation
  • cofactor for enzymes of intermediary metabolism
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4
Q

How is calcium distributed in serum?

A
  • approx 47% is free/unbound/ionised
  • approx 47% is bound to proteins, mainly albumin
  • approx 6% complexed to anions e.g. to phosphate
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5
Q

Why is the free fraction of calcium in serum physiologically important?

A

The free fraction regulates many feedback mechanisms

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6
Q

How can calcium be measured?

A

Either by free calcium or total calcium (free + bound)

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7
Q

What is the adjusted calcium level?

A

What the serum total calcium would have been in the albumin had been normal.

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8
Q

What is the equation for the adjusted calcium level?

A

Ca (adj) = Ca (total) + [0.02(45-alb)]

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9
Q

What is the normal range for serum calcium?

A

2.2 - 2.6 mmol/l

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10
Q

Define a serum calcium level above 2.6 mmol/l

A

Hypercalcaemia

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11
Q

Define a serum calcium level below 2.2 mmol/l

A

Hypocalcaemia

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12
Q

List the main organs involved in calcium homeostasis.

A
  • kidney
  • gut
  • bone
  • parathyroid glands (calcium sensing receptors)
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13
Q

What are the two hormones involved in calcium homeostasis?

A

Parathyroid hormone and calcitriol.

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14
Q

What is calcitriol also known as?

A

Vitamin D3 / 1,25 dihydroxyvitamin D / dihydroxycholecalciferol / 1.25DHCC

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15
Q

What is the daily dietary intake of calcium?

A

25 mmol per day

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16
Q

List some dietary sources of calcium.

A
  • milk, cheese and other dairy foods
  • curly kale
  • soya drinks with added calcium
  • bread and anything made with fortified flour
  • fish where you eat the bones e.g. sardines and pilchards
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17
Q

Where does calcium absorption mainly occur?

A

In the duodenum and jejunum.

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18
Q

How is calcium absorbed in the duodenum and jejunum?

A
  • via a cell mediated active transport pathway which is controlled by 1.25 DHCC
  • via passive diffusion which depends on luminal Ca concentration and is unaffected by 1.25 DHCC
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19
Q

How much calcium is filtered through the kidneys each day?

A

Approx 240 mmol

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20
Q

How much calcium is excreted in urine each day?

A

Approx 6 mmol

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21
Q

How much calcium is released and laid down in bone each day?

A

Approx 8 mmol released and then 8 mmol laid down again.

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22
Q

The proportion of ingested calcium that is absorbed can vary from…

A

20% to 60%

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23
Q

How much calcium that filters through the kidney is reabsorbed in the proximal tubule?

A

65%

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24
Q

When calcium is reabsorbed in the proximal tubule what it is coupled to?

A

Bulk transport of solutes such as Na and water.

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25
Q

How much of the calcium that filters through the kidneys is reabsorbed by the cortical thick ascending loop of Henle?

A

20%

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26
Q

How much of the calcium that filters through the kidney is reabsorbed in the distal convoluted tubule?

A

15%

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27
Q

In which areas of the kidney does parathyroid hormone increase re absorption of calcium?

A

Cortical thick ascending loop of Henle and distal convoluted tubule.

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28
Q

What is parathyroid hormone and where is it produced?

A

An 84 amino acid polypeptide that is produced by the parathyroid glands.

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29
Q

How is secretion of PTH regulated?

A

By free calcium levels which are detected by the calcium sensing receptors.

30
Q

Where are calcium sensing receptors found?

A

In parathyroid cells and renal tubules.

31
Q

What type of receptor are the calcium sensing receptors?

A

G protein coupled receptors.

32
Q

What is the function of the calcium sensing receptors on parathyroid cells?

A

To mediate the effect of extracellular ionised Ca on PTH release.

33
Q

What is the function of the calcium sensing receptors in the renal tubules?

A

To mediate the effect of high peritubular ionised Ca to inhibit Ca reabsorption.

34
Q

Name a drug which is used clinically to reduce PTH secretion in patients with conditions such as hyperparathyroidism and parathyroid cancer.

A

Cinacalcet

35
Q

What abnormalities may occur due to disorders of the calcium sensing receptors?

A

Abnormalities in serum calcium concentrations

36
Q

Describe the curve which demonstrates the relationship between ionised calcium and PTH.

A
  • Ca along x axis
  • PTH along y axis
  • steep, inverse sigmoid also curve
  • PTH falls as Ca increases
37
Q

Which point of the PTH/Ca curve gives the sensitivity of the parathyroid gland (calcium sensing receptors) to iCa?

A

The midpoint

38
Q

Summarise the actions of PTH in regards to calcium levels.

A
  1. Stimulates renal tubular calcium reabsorption
  2. Promotes bone resorption
  3. Stimulates formation of 1,25 DHCC in kidney which then enhances calcium absorption from the gut.
39
Q

Will a fall in ionised calcium levels lead to an increase or decrease of PTH secretion?

A

Increase

40
Q

Where can vitamin D be obtained?

A

Through diet (e.g. oily fish like salmon, mackerel) and from sunlight

41
Q

Where is vitamin D initially synthesised?

A

In the skin as cholecalciferol.

42
Q

What happens to vitamin D3/cholecalciferol in the liver?

A

It is converted to 25OH cholecalciferol

43
Q

What happens to 25OH cholecalciferol in the kidney?

A

It is converted to 1,25 DHCC (the active form of vitamin D)

44
Q

What is hypoparathyroidism?

A

A rare condition where the parathyroid glands produce too little PTH which leads to a decrease in calcium levels.

45
Q

List 3 causes of hypoparathyroidism.

A
  1. Neck surgery
  2. Idiopathic
  3. Magnesium deficiency
46
Q

What can cause hypocalcaemia?

A
  • Issues with PTH

- Vitamin D issues

47
Q

List 2 ways in which an issue with vitamin D production may arise.

A
  1. Deficiency from malabsorption or little exposure to sunlight
  2. Renal disease where the kidneys cannot make the active form of vitamin D
48
Q

List 3 causes of hypercalcaemia.

A
  1. Too much PTH due to hyperparathyroidism e.g. adenoma of parathyroid gland
  2. Too much vitamin D due to over dosage
  3. Malignancy e.g. lung cancer, breast cancer, multiple myeloma
49
Q

What happens to calcium and PTH levels in hyperparathyroidism?

A

Calcium levels rise, PTH levels rise

50
Q

What happens to calcium and PTH levels when hypercalcaemia occurs due to malignancy?

A

Calcium levels rise and PTH levels are suppressed

51
Q

Why is phosphate important for the body?

A
  1. Important in bone mineralisation and skeleton development
  2. Component of cell membranes, nucleotides and involved in cell signalling
52
Q

What percentage of phosphate is found in the mineralised matrix of bone?

A

85%

53
Q

Approximately how much phosphate is found intracellularly?

A

14% found as part of cell membranes, nucleic acids, enzyme cofactors, glycolytic intermediates and ATP

54
Q

Approx how much phosphate is found extra cellularly?

A

1%

55
Q

How much extracellular phosphate is inorganic?

A

30%

56
Q

Why is serum phosphate not an accurate depiction of true phosphate stores?

A

Because phosphate shifts between organic/inorganic pools and in and out of cells.

57
Q

State one way in which phosphate enters cells.

A

Via insulin mediated entry of glucose in to cells after meals.

58
Q

List the main organs involved in phosphate homeostasis.

A

Kidney, gut and bone

59
Q

List the main hormones involved in phosphate homeostasis.

A

PTH, FGF23 and 1,25 DHCC

60
Q

How much phosphate is ingested on a daily basis?

A

Approx 45 mmol

61
Q

How much phosphate is filtered through the kidney each day?

A

160 mmol

62
Q

How much phosphate is reabsorbed through the kidney each day?

A

135 mmol

63
Q

How much phosphate is excreted via urine each day?

A

25 mmol

64
Q

Where, in the small intestine, does reabsorption of phosphate occur?

A

Throughout the entire small intestine

65
Q

What increased absorption of phosphate in the small intestine?

A

1,25 DHCC

66
Q

How much phosphate is protein bound?

A

15-20%

67
Q

How much of filtered phosphate is reabsorbed in the proximal tubule?

A

75%

68
Q

How much of filtered phosphate is reabsorbed in the distal tubule?

A

5-20%

69
Q

What inhibits the reabsorption of phosphate by the renal tubules?

A

PTH and FGF23

70
Q

Will PTH and FGF23 increase or decrease in response to increased phosphate levels?

A

Increase

71
Q

State some factors which influence serum phosphate values.

A
  1. Marker diurnal variation rhythm - low before noon, highest after midnight
  2. Dietary effects - will fall due to rise in insulin
  3. Age related changes - highest levels in infancy due to growth velocity being high

Limbs And Back - Week 1 (7 decks)

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