Regulation Of Calcium And Phosphate

Question 1

Where did we get calcium from?

Answer 1

All dietary

Most abundant metal in body

We need 1000mg a day

Question 2

How is calcium distributed round the body?

Answer 2

99% is is skeleton and teeth as calcium hydroxyapatite crystals

Extracellular calcium is tightly regulated

Unbound ionised calcium is biologically active

Question 3

What are the hormones involved In Increasing serum calcium and phosphate?

Answer 3

Parathyroid hormone (PTH)

Vitamin D

These both mainly act on the kidney, bone and gut

Question 4

What is the hormone involved in decreasing serum calcium and phosphate?

Answer 4

Calcitonin (parafolicular cells of thyroid)

But doesn’t have as strong effect. Nothing much happens if you remove the parafollicular cells

Question 5

What are the sources of vitamin D?

Answer 5

The diet - vitamin D2 (ergocalciferol)

Skin synthesis, UVB - vitamin D3 (cholecalciferol)

Question 6

What is the active form of vitamin D?

Answer 6

Calcitriol (1,25(OH)2 cholecalciferol)

Question 7

How does vitamin D metabolism work (to make calcitriol)?

Answer 7

Skin: UVB rays incident in the skin make 7-dehydroxycholesterol

This goes to pre-vitamin D3

Then Vitamin D3

Then into the blood

Vitamin D2 from the diet is also present in the blood

Vitamin D —> 25(OH)cholecalciferol (in the liver using 25-hydroxylase)

25(OH)cholecalciferol —> 1,25(OH)2 cholecalciferol (in the kidney using 1 alpha-hydroxylase)

So vitamin D must be hydroxylated twice to be made into the active form

Btw we use 25(OH)cholecalciferol to indicate how much Vitamin D we have as it is more reliable

Question 8

How is calcitriol synthesis regulated?

Answer 8

By itself

Presences of calcitriol creates a negative feedback loop which decreases transcription of 1 alpha-hydroxylase (that makes calcitriol)

Question 9

What are the effects of calcitriol?

Answer 9

Bone: increAses Ca2+ reabsorbtion

Kidney: increases Ca2+ and phosphate reabsorbtion

Gut: increases calcium and phosphate absorption (into blood)

The calcium from the gut is what is taken into the bones and kidney

Question 10

Where and how does parathyroid hormone come from?

Answer 10

Chief cells in the parathyroid glands

It is secreted as pre-pro-PTH and then undergoes cleavage

G protein coupled receptors on chief cells detect change is circulating calcium concentration

PTH secretion is inversely proportional to serum calcium

(High ECF Ca2+ conc - calcium binds to receptors - this inhibits PTH secretion)

(Low ECF Ca2+ - less calcium binding - more PTH secreted)

Question 11

What are the actions of PTH?

Answer 11

Bone: increases Bone reabsorbtion

Kidney: increases Ca2+ reabsorbtion, increases phosphate excretion, increases 1-alpha-hydroxylase activity

Increases 1,25(OH)2cholecalciferol (calcitriol) synthesis

Gut: increases calcium and phosphate absorption (through calcitriol)

Both increase plasma Ca2+

Question 12

How does PTH work in the bone?

Answer 12

Binds to receptors on osteoblasts (these build bone)

These release osteoclast activating factors

Osteoclasts (which consume bone) then cause bone resorption

Question 13

What do the effects of calcitriol on the bone depend on?

Answer 13

Serum calcium

Low: osteoclasts>osteoblasts so more calcium reabsorption from bone

Normal: osteoblasts>osteoclasts so bone formation increases

Question 14

How is parathyroid hormone regulated?

Answer 14

Increased calcium, decreased PTH (inversely proportional)

Inhibited by synthesis of calcitriol

Question 15

What is calcitonin and where does it come from?

Answer 15

Parafollicular cells of thyroid

Reduces serum calcium But not all that much

Question 16

What are the actions of calcitonin?

Answer 16

Detects increased serum calcium

Bone: decreases osteoclast activity

Kidney: increases calcium excretion

Decreases plasma calcium (with limited effect)

Question 17

What does fibroblast growth factor 23 do?

Answer 17

Regulates serum phosphate

It inhibits the sodium/phosphate cotransporter in the proximal convoluted tubule

This stops reabsorbtion of phosphate so it is excreted in Urine (PTH also does this)

FGF23 also weakly inhibits calcitriol, this means less phosphate is absorbed in the gut

It decreases phosphate

Question 18

What is the difference between hypo and hyper calcaemia in terms of excitability?

Answer 18

Hyper (high calcium) - more calcium ions surrounding neurones, more resistance to the influx of Na required for an action potential. So less excitability

Hypo (low) - more sodium influx, so more membrane excitability

Question 19

What are some symptoms of hypocalcaemia?

Answer 19

Paraesthesia - pins and needles

Convulsions

Arrythmias

Tetany (muscle contraction but no relax)

CATs go numb

May show Chvosteks sign. Tap the facial nerve just below zygomatic arch. Positive response is twitching of facial muscles. This indicates excitability due to hypocalcaemia

May also show trousseaus sign. Inflation of BP cuff for several minutes, induces carpopedal spasm

Question 20

What causes hypocalcaemia?

Answer 20

Low PTH (hypo parathyroidism) - neck surgery, auto immune, magnesium deficiency (used for PTH synthesis), congenital (rare)

Vitamin D deficiency - not enough sun, malabsorption or dietary insufficiency, liver disease, renal disease, vitamin D receptor defects

Question 21

What does a vitamin D deficiency cause?

Answer 21

Lack of bone mineralisation - soft bones

Children- rickets

Adults - osteomalacia (fractures, proximal myopathy)

Question 22

What are some symptoms of hypercalcaemia?

Answer 22

Stones, abdominal groans and psychic groans

Reduces neuronal excitability

Stones- nephrocalcinosis - kidney stones

Moans- anorexia, nausea, dyspepsia, constipation, pancreatitis

Groans- fatigue, depression, impede concentration, coma

Question 23

What causes hypercalcaemia?

Answer 23

Primary hyperparathyroidism - too much PTH (usually due to a parathyroid gland adenoma). Lack of negative feedback, high PTH but high calcium

Malignancy - bony metastases produce local factors to activate osteoclasts, increasing calcium reabsorption from bone

Vitamin D excess - rare