Regulation Of Calcium And Phosphate Flashcards

1
Q

Recommended intake of calcium

A

Approx 1000mg a day

Most abundant metal in the body and the diet should meet all the requirements

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2
Q

Foods rich in calcium

A

Tahini
Dairy
Fish
Broccoli

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3
Q

Where does most of the calcium reside in the body

A

In skeleton and teeth as calcium hydroxyapatite crystals

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4
Q

Total body calcium

A

Skeleton : 99%
Intracellular : 1%
Extra cellular ;0.1%

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5
Q

Extra cellular calcium

A

Tight regulated . Can be ionised (45%) or bound . Unbound ionised calcium is the biologically active component.

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6
Q

Bound calcium

A

Can be as plasma proteins such as albumin (45%) or anions ( bicarbonate, phosphate, lactate)

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7
Q

Hormonal control of INCREASE in serum calcium and phosphate

A
Parathyroid hormone ( PTH) secreted by the parathyroid glands 
Vitamin D - synthesised in skin or intake via diet 
Main regulators of calcium and phosphate homeostasis via actions on kidney bone and gut
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8
Q

Hormonal DECREASE of serum calcium and phosphate

A

Calcitonin ( secreted by thyroid parafollicular cells )

Can reduce calcium acutely but no negative effect of parafollicular cells are removed ( e.g. thyroid echo my)

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9
Q

Sources of vitamin D

A

Vitamin D2 from diet ( ergocalciferol)

Vitamin D3 from sunshine ( synthesis happens in skin) - cholecalciferol

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10
Q

Vitamin D 3 synthesis

A

UVB - 7-dehydrocholesterol - pre- vitamin D3 - vitamin D3 - hydroxylation by 25 Hydroxylase - 25(OH)cholecalciferol - hydroxylation by 1 alpha Hydroxylase - 1,25(OH)2cholecalciferol

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11
Q

What is a good indicator of calciferol in body

A

Serum 25-OH cholecalciferol as active form of vitamin D is quite unstable

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12
Q

Negative feedback in vitamin D metabolism

A

Calcitriol regulates its own synthesis by decreasing transcription of 1 alpha Hydroxylase

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13
Q

Effects of calcitriol

A

On bone ; calcium reabsorption
Gut ; calcium absorption and phosphate absorption from food
Kidneys ; increased calcium and phosphate reabsorption

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14
Q

Parathyroid hormone

A

Released by chief cells in parathyroid glands
Secreted as large precursor ( pre pro PTH) and cleaved to PTH ( active hormone )
G protein coupled calcium sensing receptor on chief cells detect change in circulating calcium conc
PTH secretion inversely proportional to serum calcium

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15
Q

Calcium sensing receptors on chief cells ( high )

A

High EcF ( Calcium )
Calcium binds to receptors on parathyroid cells
PTH secretion is inhibited

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16
Q

Low calcium chief cells response

A

Low ECF (calcium)
Less calcium binds to receptors on parathyroid cells
PTH secreted

17
Q

Actions of PTH

A

Increased bone reabsorption of calcium
Kidney ; increased calcium reabsorption , increased phosphate excretion , increased 1 alpha Hydroxylase activity

Increased 1 alpha Hydroxylase then increased calcitriol synthesis so active form on vitamin D which goes to gut and increases calcium absorption and phosphate absorption

18
Q

Why is bone resorption and calcium mobilisation imp

A

Regulated uncoupling of resorption to new bone formation for proper growth, remodelling and skeletal maintenance

19
Q

PTH action in bone

A

Binds to PTH receptor in osteoblasts ( builds bone) .
Osteoblasts releases osteoclasts activating factors
Osteoclast activating factors stimulate osteoclasts for bone resorption

20
Q

Action of calcitriol on bone

A

Calcitriol effects in bone depend on serum calcium
Low serum calcium ; calcitriol increases calcium reabsorption from bone and so activity of osteoclasts is greater than osteoblasts

Normal serum calcium ; calcitriol works to increase bone formation and so activity of asteoblasts is greater than osteoclasts

Calcitriol binds to calcitriol receptor on bone

21
Q

PTH regulation

A

When increased PTH causes increased plasma conc, there is negative feedback to parathyroid glands .

PTH can also stimulate active vitamin D to increase plasma calcium but active form of vitamin D can then inhibit the PTH

22
Q

Calcitonin

A

Secreted from oarafollicular cells of the thyroid gland
Reduces serum calcium
Physiological role in calcium homeostasis remains unclear
Removal of thyroid gland does not affect serum calcium

23
Q

Calcitonin actions and regulations

A

Increased plasma calcium is detected by parafollicular cells of thyroid which secreted calcitonin
Calcitonin decreases osteoclast activity and increases calcium excretion in kidney which acts to decrease plasma calcium levels ( limited effect)

24
Q

How does PTH work to decrease serum phosphate in kidneys

A

It inhibits the sodium phosphate co transporter in the kidneys which acts to pump phosphate back into the PCT

25
Q

FGF 23 action

A

FGF23 is an example of a phosphate in which promotes phosphate loss from the body via urine

FGF23 inhibits the sodium phosphate cotransporter in the kidneys and inhibits calcitriol which means there is less phosphate reabsorption from the gut

26
Q

Hugh serum calcium

A

Hyoercalcaemia

27
Q

Low serum calcium

A

Hypocalcaemia

28
Q

Calcium and it’s effects on action potential generation

A

AP in nerves and skeletal muscles requires sodium influx across the cell membrane
High extra cellular calcium ( hypercalcaemia) - calcium blocks sodium influx and so there is less membrane excitability

Low extra cellular calcium ( hypocalcaemia)
Enables greater sodium influx and so more membrane excitability

29
Q

Hypocalcaemia sigh s and symptoms

A

Sensitises excitable tissues ; muscles, cramps , tetany and tingling

Paresthesia of hands , mouth , feet and lips
Convulsions
Arrhythmia
Tetany - can contract but can’t relax

Chvosteks sign

Trousseaus sign

30
Q

How to test for chvosteks sign

A

Tap facial nerve below the zygomatic arch

Positive response results in twitching of facial muscles and indicates neuromuscular irritability due to hypo

31
Q

Testing for trousseau sign

A

Inflation of BP cuff for several minutes induces carpopedal spasm ( tetany ) - neuromuscular irritability due to hypocalcaemia

32
Q

Causes of hypocalcaemia

A

Low PTH levels - hypoparathyroidism

  • surgical neck surgery
  • autoimmune
  • magnesium deficiency as you need magnesium to make parathyroid hormone
  • congenital ( Agnesis, rare)

Vitamin D deficiency

33
Q

Causes of vitamin D deficiency ( think of the diagram )

A

1) malabsorption or dietary insufficiency ( coeliac)
2) inadequate sub exposure
3) liver disease
4) renal disease( renal 1 alpha Hydroxylase is stimulated by PTH)
5) vitamin d receptor defects rare

34
Q

Consequence of vitamin D deficiency

A

Lack of bone mineralisation skin soft bones
Rickets in children and in adults - osteomalacia ( fractures, proximal myopathy)- muscles of thigh particularly are vulnerable

35
Q

Signs and symptoms of hypercalcaemia

A
Stones - renal effects ( nephrocalcinosis ) 
Abdominal moans - GI effects 
Psychic groans ( CNS effects ) 

All lead to reduced neuronal excitability

36
Q

Causes of hypercalcaemia

A

Primary hyperparathyroidism ( too much PTH , usually due to a parathyroid gland adenoidal , no negative feedback - high PTH, but high calcium)

Malignancy - bone metasteses produce local factors to activate osteoclasts which increases calcium reabsorption from bone

Vitamin D excess ( rare)