Calcium and Phosphate Homeostasis Flashcards

1
Q

Which 5 tissues regulate calcium and phosphate homeostasis

A

Parathyroid glands

Kidney

Gut

Thyroid

Bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the role of parathyroid glands in Ca2+ and PO4 homeostasis?

A

Detect levels of plasma Ca2+ amd PO4

Make parathyroid hormone (PTH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the role of the kidney in Ca2+ and PO4 homeostasis?

A

Site of Ca2+ and PO4 reabsorption

Site of vitamin D activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of the gut in Ca2+ and PO4 homeostasis?

A

Site of Ca2+ and PO4 uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the role of the thyroid in Ca2+ and PO4 homeostasis?

A

Site of calcitonin synthesis

Detects serum Ca2+ levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the role of bone in Ca2+ and PO4 homeostasis?

A

Body store of Ca2+ and PO4

Mike fibroblast growth factor 23 (FGF-23)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the 6 physiological roles of calcium

A

Bone formation (growth and remodelling) and teeth

Muscle contraction

Nerve function

Enzyme co-factor

Intracellular second messenger

Stabilisation of membrane potentials

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is added to blood tubes to stop the blood from clotting?

A

EDTA - chelates calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the range for plasma Ca2+?

A

2.12-2.6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What % of plasma calcium is bound calcium?

A

Bound Ca2+ = 55%

Ionised Ca2+ = 45%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is bound Ca2+ distributed, i.e. what is it bound to and in what

A

Bicarbonate, phosphate - 10%

Albumin - 80%

Globulins - 20%

Most of the bound Ca2+ in plasma is bound to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What will an increase in albumin do to the plasma levels of Ca2+?

A

Increased albumin will increase the total plasma levels of Ca2+

Albumin binds to calcium

Ionised Ca2+ (the active portion of plasma Ca2+) will be unaffected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe normal Ca2+ homeostasis

A

Low serum Ca2+ stimulates the parathyroids to secrete PTH

An increase in PTH has 3 actions:

  • increase bone resorption and increase Ca2+ release
  • acts on the kidneys to increase Ca2+ reabsorption
  • alters the enzyme 1a-OHase which converts inactive vitamin D (calcidiol) to active vitamin D (calcitriol). Calcitriol increase reabsorption in the kidney, and increases absorption of Ca2+ from the GI tract

An increase in serum Ca2+ and vitamin D switches off PTH secretion

An increase in serum Ca2+ causes the thyroid to produce calcitonin which inhibits reabsorption of Ca2+ in the bone and kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How many parathyroid glands are there and where are they located?

A

4 parathyroid glands

Located on the posterior surfaces of the thyroid gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is it important that the parathyroid glands have a separate blood supply?

A

Because a thyroidectomy should leave the parathyroid glands in tact and working

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which cells within the parathyroid glands synthesis and secrete parathyroid hormone?

A

Chief cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does PTH bind to?

What else can bind to this receptor?

A

PTHR1 - a G-protein coupled receptor

PTH-related peptide (PTHrP) can also bind to PTHR1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does a sustained release of PTH require?

A

Gene expression

Proliferative activity of PT cells

Increase in gland and cell size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe how a HIGH level of Ca2+ is detected and PTH is regulated

A

High Ca2+ levels are detected by calcium-sensing receptor (CaSR) in the parathyroid gland

This increases activation of a G protein coupled receptor

This activates PLC, which increase IP3 levels, which DECREASES PTH release from the parathyroid hormone

Activation of the G protein coupled receptor also inhibits a pathway that increases cAMP and increases PTH, leading to a further reduction in PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe how a LOW level of Ca2+ is detected and PTH is regulated

A

Low serum Ca2+ levels means there is less binding to CaSR

This leads to less activation of the G protein coupled receptor

Which leads to less inhibition of adenylate cyclase, therefore increases levels of cAMP leading to an INCREASE in PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How can a malignancy cause hypercalcaemia?

A

Can cause a loss of Ca2+ from the bone due to osteolytic metastases

OR

the malignancy can produce parathyroid hormone-related peptide (PTHrP), which mimics exactly the action of PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does parathyroid hormone related peptide (PTHrP) NOT increase?

Why is this useful?

A

Does not increase vitamin D levels

Good for diagnosis - can distinguish between PTH and PTHrP hypercalcaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where is most of our calcium absorbed?

A

Duodenum and upper jejunum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How is calcium absorption facilitated in the GI tract?

A

By vitamin D

Vitamin D up-regulates luminal Ca2+ channels (TRPV6)

It also increases the amount of calcium binding protein (CaBP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Name the 3 ways Ca2+ is moved out of the basolateral surface of the epithelial cell in the GI tract?

How else can Ca2+ be absorbed by the GI tract

A

Ca2+ ATP transporter

Ca2+ 3 Na+ exchanger

Endocytosis and exocytosis of Ca2+ -CaBP complex

Paracellular transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How is Ca2+ up-taken by the brush border?

A

By TRPV6 calcium transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How is Ca2+ moved through the cell?

A

CaBP

Ca2+ binding protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

When is calcitonin used?

A

When there is excess Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Where is calcitonin synthesised?

A

Synthesised by C cells in the thyroid gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the 2 actions of calcitonin?

A

Inhibits bone resorption by preventing osteoclast action

Decreases reabsorption of PO4 and Ca2+ in the kidney

31
Q

What 3 roles does the kidney have in calcium homeostasis?

A

Calcium reabsorption from filtrate

  • passive
  • active (regulated by PTH, vitamin D, calcitonin)

Phosphate reabsorption from filtrate

  • inhibited by PTH, FGF23, calcitonin
  • stimulated by vitamin D

Makes active vitamin D (calcitriol)

32
Q

What 3 things regulate calcium reabsorption in the kidney?

A

PTH

Vitamin D

Calcitonin

33
Q

What 3 things inhibit phosphate reabsorption in the kidney?

What stimulates phosphate reabsorption in the kidney?

A

Inhibited by PTH, FGF23, calcitonin

Stimulated by vitamin D

34
Q

Where in the nephron is most of the Ca2+ reabsorbed?

How is it absorbed here?

A

Proximal tubule (60-70%)

Paracellular uptake

35
Q

How is calcium absorbed in the distal convoluted tubule?

How is that controlled?

A

Through TRPV5 transporters

Taken out of the renal cell by Ca2+/ATPase OR Ca2+/3 Na+ exchanger

Controlled by hormones - PTH and vitamin D upregulates TRPV5 transporters

36
Q

What is the name of the calcium transporter in the kidney?

A

TRPV5

In GI tract = TRPV6

37
Q

What is Vitamin D?

A

A steroid hormone

38
Q

What 3 things does vitamin D do in the bones?

A

Cartilage production and bone mineralisation

Required for osteoblast and osteoclast differentiation

Increases bone remodelling (by promoting bone resorption = increase Ca2+)

39
Q

Where is most of our vitamin D made from?

What mechanism makes this happen?

A

Sunlight converts 7-dehydro-cholesterol into colecalciferol

40
Q

What inactivates vitamin D?

How is vitamin D excreted?

A

24-hydroxylase

Via the kidneys in urine

41
Q

How much of phosphate absorption takes place in the gut?

A

70-90%

42
Q

Where is the only place that phosphate is excreted?

A

Kidney

43
Q

Give 3 physiological roles of phosphate

A

Intracellular metabolism (ATP synthesis)

Phosphorylation (e.g. enzyme activation)

Phospholipids in membranes

44
Q

What should intake and excretion of phosphate be?

A

Equal

e.g. 900mg dietary intake
600mg absorption
600mg excretion in kidney
300mg faecal excretion

45
Q

Describe the normal process of phosphate homeostasis when there is a LOW phosphate level

A

Low phosphate level activates 1a-OHase to create active vitamin D (calcitriol)

1a-OHase also makes the enzyme Klotho. Klotho can be made directly by low PO4 levels

Active vitamin D acts on the bones to increase resorption, releasing PO4 into the blood.

At the bones, vitamin D also encourages FGF23 to be made

FGF23 and Klotho work together to do 3 things:

  • inhibit 1a-OHase (less vit D activation)
  • increase 24-OHase which metabolises vitamin D
  • inhibits phosphate reabsorption in the kidney
46
Q

Describe the normal process of phosphate homeostasis when there is a HIGH phosphate level

A

High phosphate level activate FGF23 directly (in the bones)

FGF23 and Klotho work together to:

  • inhibit 1a-OHase (less vitamin D activation)
  • increase 24-OHase which metabolises vitamin D
  • inhibit phosphate reabsorption in the kidney
47
Q

Which enzyme metabolises vitamin D?

A

24-OHase

48
Q

Where is fibroblast growth factor (FGF)-23 made?

A

Osteocytes and osteoblasts

49
Q

Where in the kidney is the majority of phosphate reabsorbed?

What is unusual about this?

A

Proximal convoluted tubule

Pretty much the only thing that is regulated by hormones in the PCT

50
Q

What are the sodium phosphate co transporters in the proximal convoluted tubule called?

A

NPT2c

NPT2a

51
Q

What are the sodium phosphate co transporters in the GI tract called?

A

NPT2b

52
Q

Apart NPT2a/b/c, which other transporters are there in the kidney and the GI tract that absorb phosphate?

What is different about these transporters?

A

PIT-1/2

Uptake of phosphate is not regulated at these transporters

53
Q

Why would hyperparathyroidism cause a decrease in serum phosphate levels?

A

Hyperparathyroidism would cause excess PTH to be made

PTH blocks NPT2c cotransporter in the kidney, therefore inhibiting the reabsorption of phosphate in the proximal convoluted tubule (PCT).

54
Q

Why can renal disease cause low phosphate and calcium levels?

A

Renal disease will alter the ability of the glomerulus to reabsorb calcium and phosphate from the filtrate

Enzyme 1a-OHase not efficient and stimulating vitamin D which increases reabsorption

55
Q

List 3 ways in which malignancy can cause hypercalcaemia:

A
  • osteolytic bone mets release cytokines which stimulates the maturity of osteoclasts and activates bone resorption
  • tumour secretion of PTH-related protein (PTHrP)
  • and tumour production of calcitriol (active vitamin D)
56
Q

Why does primary hyperparathyroidism cause hypercalcaemia?

A

PTH increases levels of bone resorption leading to increase serum calcium levels

57
Q

Give some signs and symptoms of hypercalcaemia

A

Polyuria/polydipsia

Tiredness, confusion, depression, headaches

N+V, constipation, anorexia

Muscle weakness

Abdominal pain

Shorted QT interval

58
Q

What ECG changes are seen in hypercalcaemia?

Why?

A

Shortened QT interval

59
Q

Why can hypercalcaemia cause kidney stones?

A

Causes secretion of excess calcium in the urine, can calcify and cause renal stones

60
Q

What is the immediate treatment for severe hypercalcaemia (>3.40mmol/l)?

A

Fluids (normal saline)

Loop diuretic (furosemide)

Calcitonin

Bisphosphonates

Oral phosphates

61
Q

What are some signs and symptoms of hypocalcaemia?

A

Paraesthesia (tingling, fingers, toes, around mouth)

Tetanty

Carpopedal spasm (hand deformity thing)

Muscle cramps

Seizures

Prolonged QT interval

62
Q

Why does hypocalcaemia cause tetany?

A

Extracellular Ca2+ falls, peripheral nerve fibres discharge spontaneously, leading to muscle contractions

63
Q

What are the 2 causes of hypocalcaemia?

A

Hypoparathyroidism (low PTH)

Calcium deficiency

64
Q

What can the consequences oh hypocalcaemia be?

A

Rickets/osteomalacia

Secondary hyperparathyroidism

65
Q

What are the treatment options for hypoparathyroidism (which leads to hypocalcaemia)?

A

Lifelong vitamin D

High Ca2+ diet and supplementation

Human parathyroid hormone

66
Q

What is the difference between primary and secondary hyperparathyroidism?

A

Primary - high Ca2+, high PTH

Secondary - low Ca2+, high PTH

67
Q

Describe secondary hyperparathyroidism

A

Excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia.

Usually seen in kidney disease because:

  • they can’t response to PTH
  • can’t make activate vitamin D
  • can’t increase absorption of Ca2+

Only place Ca2+ can come from is bone

These actions then lead serum Ca2+ levels to rise, causing tertiary hyperparathyroidism

68
Q

How do you treat acute hypocalcaemia?

A

IV calcium gluconate

69
Q

What is an adequate daily amount of vitamin D

A

> 50nmol/l

Of serum 25D3 (made by the liver)

70
Q

What is a deficient vitamin D level?

A

<25/30nmol/l

Of serum 25D3

71
Q

What levels of PTH, calcium and phosphate are seen in primary hyperparathyroidism?

A

PTH - high

Calcium - high

Phosphate - low

72
Q

What levels of PTH, calcium and phosphate are seen in secondary hyperparathyroidism?

A

PTH - high

Calcium - low/normal

Phosphate - low/normal/high

73
Q

What levels of PTH, calcium and phosphate are seen in tertiary hyperparathyroidism?

A

PTH - high

Calcium - high

Phosphate - high