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Block 4 > Calcium and Phosphate Homeostasis > Flashcards

Calcium and Phosphate Homeostasis Flashcards

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1
Q

Which 5 tissues regulate calcium and phosphate homeostasis

A

Parathyroid glands

Kidney

Gut

Thyroid

Bone

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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)

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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

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4
Q

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

A

Site of Ca2+ and PO4 uptake

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5
Q

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

A

Site of calcitonin synthesis

Detects serum Ca2+ levels

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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)

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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

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8
Q

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

A

EDTA - chelates calcium

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9
Q

What is the range for plasma Ca2+?

A

2.12-2.6

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10
Q

What % of plasma calcium is bound calcium?

A

Bound Ca2+ = 55%

Ionised Ca2+ = 45%

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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

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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

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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

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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

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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

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16
Q

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

A

Chief cells

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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

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18
Q

What does a sustained release of PTH require?

A

Gene expression

Proliferative activity of PT cells

Increase in gland and cell size

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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

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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

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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

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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

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23
Q

Where is most of our calcium absorbed?

A

Duodenum and upper jejunum

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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)

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25
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
Ca2+ ATP transporter Ca2+ 3 Na+ exchanger Endocytosis and exocytosis of Ca2+ -CaBP complex Paracellular transport
26
How is Ca2+ up-taken by the brush border?
By TRPV6 calcium transporter
27
How is Ca2+ moved through the cell?
CaBP | Ca2+ binding protein
28
When is calcitonin used?
When there is excess Ca2+
29
Where is calcitonin synthesised?
Synthesised by C cells in the thyroid gland
30
What are the 2 actions of calcitonin?
Inhibits bone resorption by preventing osteoclast action Decreases reabsorption of PO4 and Ca2+ in the kidney
31
What 3 roles does the kidney have in calcium homeostasis?
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
What 3 things regulate calcium reabsorption in the kidney?
PTH Vitamin D Calcitonin
33
What 3 things inhibit phosphate reabsorption in the kidney? What stimulates phosphate reabsorption in the kidney?
Inhibited by PTH, FGF23, calcitonin Stimulated by vitamin D
34
Where in the nephron is most of the Ca2+ reabsorbed? How is it absorbed here?
Proximal tubule (60-70%) Paracellular uptake
35
How is calcium absorbed in the distal convoluted tubule? How is that controlled?
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
What is the name of the calcium transporter in the kidney?
TRPV5 | In GI tract = TRPV6
37
What is Vitamin D?
A steroid hormone
38
What 3 things does vitamin D do in the bones?
Cartilage production and bone mineralisation Required for osteoblast and osteoclast differentiation Increases bone remodelling (by promoting bone resorption = increase Ca2+)
39
Where is most of our vitamin D made from? What mechanism makes this happen?
Sunlight converts 7-dehydro-cholesterol into colecalciferol
40
What inactivates vitamin D? How is vitamin D excreted?
24-hydroxylase Via the kidneys in urine
41
How much of phosphate absorption takes place in the gut?
70-90%
42
Where is the only place that phosphate is excreted?
Kidney
43
Give 3 physiological roles of phosphate
Intracellular metabolism (ATP synthesis) Phosphorylation (e.g. enzyme activation) Phospholipids in membranes
44
What should intake and excretion of phosphate be?
Equal e.g. 900mg dietary intake 600mg absorption 600mg excretion in kidney 300mg faecal excretion
45
Describe the normal process of phosphate homeostasis when there is a LOW phosphate level
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
Describe the normal process of phosphate homeostasis when there is a HIGH phosphate level
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
Which enzyme metabolises vitamin D?
24-OHase
48
Where is fibroblast growth factor (FGF)-23 made?
Osteocytes and osteoblasts
49
Where in the kidney is the majority of phosphate reabsorbed? What is unusual about this?
Proximal convoluted tubule Pretty much the only thing that is regulated by hormones in the PCT
50
What are the sodium phosphate co transporters in the proximal convoluted tubule called?
NPT2c NPT2a
51
What are the sodium phosphate co transporters in the GI tract called?
NPT2b
52
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?
PIT-1/2 Uptake of phosphate is not regulated at these transporters
53
Why would hyperparathyroidism cause a decrease in serum phosphate levels?
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
Why can renal disease cause low phosphate and calcium levels?
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
List 3 ways in which malignancy can cause hypercalcaemia:
- 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
Why does primary hyperparathyroidism cause hypercalcaemia?
PTH increases levels of bone resorption leading to increase serum calcium levels
57
Give some signs and symptoms of hypercalcaemia
Polyuria/polydipsia Tiredness, confusion, depression, headaches N+V, constipation, anorexia Muscle weakness Abdominal pain Shorted QT interval
58
What ECG changes are seen in hypercalcaemia? Why?
Shortened QT interval
59
Why can hypercalcaemia cause kidney stones?
Causes secretion of excess calcium in the urine, can calcify and cause renal stones
60
What is the immediate treatment for severe hypercalcaemia (>3.40mmol/l)?
Fluids (normal saline) Loop diuretic (furosemide) Calcitonin Bisphosphonates Oral phosphates
61
What are some signs and symptoms of hypocalcaemia?
Paraesthesia (tingling, fingers, toes, around mouth) Tetanty Carpopedal spasm (hand deformity thing) Muscle cramps Seizures Prolonged QT interval
62
Why does hypocalcaemia cause tetany?
Extracellular Ca2+ falls, peripheral nerve fibres discharge spontaneously, leading to muscle contractions
63
What are the 2 causes of hypocalcaemia?
Hypoparathyroidism (low PTH) Calcium deficiency
64
What can the consequences oh hypocalcaemia be?
Rickets/osteomalacia Secondary hyperparathyroidism
65
What are the treatment options for hypoparathyroidism (which leads to hypocalcaemia)?
Lifelong vitamin D High Ca2+ diet and supplementation Human parathyroid hormone
66
What is the difference between primary and secondary hyperparathyroidism?
Primary - high Ca2+, high PTH Secondary - low Ca2+, high PTH
67
Describe secondary hyperparathyroidism
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
How do you treat acute hypocalcaemia?
IV calcium gluconate
69
What is an adequate daily amount of vitamin D
>50nmol/l Of serum 25D3 (made by the liver)
70
What is a deficient vitamin D level?
<25/30nmol/l Of serum 25D3
71
What levels of PTH, calcium and phosphate are seen in primary hyperparathyroidism?
PTH - high Calcium - high Phosphate - low
72
What levels of PTH, calcium and phosphate are seen in secondary hyperparathyroidism?
PTH - high Calcium - low/normal Phosphate - low/normal/high
73
What levels of PTH, calcium and phosphate are seen in tertiary hyperparathyroidism?
PTH - high Calcium - high Phosphate - high

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