Regulation Of Calcium And Phosphate

Question 1

Recommended intake of calcium

Answer 1

Approx 1000mg a day

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

Question 2

Foods rich in calcium

Answer 2

Tahini
Dairy
Fish
Broccoli

Question 3

Where does most of the calcium reside in the body

Answer 3

In skeleton and teeth as calcium hydroxyapatite crystals

Question 4

Total body calcium

Answer 4

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

Question 5

Extra cellular calcium

Answer 5

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

Question 6

Bound calcium

Answer 6

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

Question 7

Hormonal control of INCREASE in serum calcium and phosphate

Answer 7

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

Question 8

Hormonal DECREASE of serum calcium and phosphate

Answer 8

Calcitonin ( secreted by thyroid parafollicular cells )

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

Question 9

Sources of vitamin D

Answer 9

Vitamin D2 from diet ( ergocalciferol)

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

Question 10

Vitamin D 3 synthesis

Answer 10

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

Question 11

What is a good indicator of calciferol in body

Answer 11

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

Question 12

Negative feedback in vitamin D metabolism

Answer 12

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

Question 13

Effects of calcitriol

Answer 13

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

Question 14

Parathyroid hormone

Answer 14

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

Question 15

Calcium sensing receptors on chief cells ( high )

Answer 15

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

Question 16

Low calcium chief cells response

Answer 16

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

Question 17

Actions of PTH

Answer 17

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

Question 18

Why is bone resorption and calcium mobilisation imp

Answer 18

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

Question 19

PTH action in bone

Answer 19

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

Question 20

Action of calcitriol on bone

Answer 20

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

Question 21

PTH regulation

Answer 21

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

Question 22

Calcitonin

Answer 22

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

Question 23

Calcitonin actions and regulations

Answer 23

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)

Question 24

How does PTH work to decrease serum phosphate in kidneys

Answer 24

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

Question 25

FGF 23 action

Answer 25

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

Question 26

Hugh serum calcium

Answer 26

Hyoercalcaemia

Question 27

Low serum calcium

Answer 27

Hypocalcaemia

Question 28

Calcium and it’s effects on action potential generation

Answer 28

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

Question 29

Hypocalcaemia sigh s and symptoms

Answer 29

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

Question 30

How to test for chvosteks sign

Answer 30

Tap facial nerve below the zygomatic arch | Positive response results in twitching of facial muscles and indicates neuromuscular irritability due to hypo

Question 31

Testing for trousseau sign

Answer 31

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

Question 32

Causes of hypocalcaemia

Answer 32

Low PTH levels - hypoparathyroidism - surgical neck surgery - autoimmune - magnesium deficiency as you need magnesium to make parathyroid hormone - congenital ( Agnesis, rare) Vitamin D deficiency

Question 33

Causes of vitamin D deficiency ( think of the diagram )

Answer 33

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

Question 34

Consequence of vitamin D deficiency

Answer 34

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

Question 35

Signs and symptoms of hypercalcaemia

Answer 35

``` Stones - renal effects ( nephrocalcinosis ) Abdominal moans - GI effects Psychic groans ( CNS effects ) ``` All lead to reduced neuronal excitability

Question 36

Causes of hypercalcaemia

Answer 36

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)