21. Parathyroid Gland - Calcium and Phosphate Regulation

Question 1

Where is the majority of calcium stored?q

Answer 1

In the skeleton.

Question 2

Give three examples of how the correct calcium levels affect a bodily function.

Answer 2

Eases insomnia, regulates passage of nutrients in and out of the cell walls, assists in normal blood clotting, preserves nerve and muscle function, lowers blood pressure, normal kidney function, reduces blood cholesterol levels etc.

Question 3

Roughly how much calcium does an adult human contain?

Answer 3

About 1000g.

Question 4

In what form is calcium stored in the bone?

Answer 4

Hydroxyapatite crystals in the skeleton.

Question 5

What are the two main roles of the skeleton?

Answer 5

Structural support and major reserve of calcium.

Question 6

Roughly how much calcium is exchanged between bone and ECF every day?

Answer 6

300-600mg.

Question 7

What is the daily intake of calcium from a UK diet and what happens to that calcium?

Answer 7

1000mg.

175mg go to urinary loss and 825mg go to GI loss.

Question 8

What are three regulators of calcium levels?

Answer 8

Parathyroid hormone - stimulates bone resorption and release of calcium into circulation, stimulates calcium reabsorption in kidney and excretion of phosphate, stimulate hydroxylation to make active vitamin D.
Dietary vitamin D - increase intestinal absorption of dietary calcium and renal reabsorption of calcium and increases bone resorption.
Calcitonin - counteracts the effects of PTH.

Question 9

Where are the parathyroid glands found?

Answer 9

On the thyroid gland.

Question 10

What are the three cells types in parathyroid glands?

Answer 10

Chief cells - secrete PTH
Adipose cells
Oxiphil cells - function unknown.

Question 11

What is the effect of PTH on the following?

a. Small intestine
b. Kidney
c. Bone

Answer 11

a. Stimulates Ca2+ absorption indirectly
b. Stimulates synthesis of active vitamin D, stimulates calcium reabsorption and increases phosphate excretion.
c. Increases bone resorption and increases Ca2+ pumping to ECF.

Question 12

How is PTH synthesised?

Answer 12

Pro-pre-hormone (115aa long) is cleaved to pre-hormone (90aa long) then cleaved to hormone (84aa long).

Question 13

How is PTH synthesis regulated?

Answer 13

At transcriptional and post transcriptional levels. Low serum calcium up-regulates gene transcription (high serum down-regulates this), it also prolongs survival of mRNA.

Question 14

How are high Ca2+ levels dealt with?

Answer 14

Ca2+ binds to Gq/i and Gi coupled receptors. PLC inhibiting adenylate cyclase leading to reduced cAMP and reduced PTH release. Reduced PTH release is from increased degradation, not decreased production.

Question 15

In what way is bone dynamic?

Answer 15

It has osteoblasts that produce collagen matrix which is mineralised by hydroxyapatite and build up the bone, and also osteoclasts that produce acid micro-environment hydroxyapatite dissolves.

Question 16

What affect does PTH have on the bone?

Answer 16

It stimulates osteolysis. The osteoblastic cells synthesise and secrete cytokines on the cell surface. The cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis. So PTH decreases osteoblast activity and exposes bony surface ti osteoclasts. This means Pi and Ca2+ are released into ECF.

Question 17

What affect does PTH have on the kidneys?

Answer 17

It affects the tubular cells. It increases Ca2+ reabsorption in ascending limb and DCT, reducing Ca2+ excretion. Pi is removed from circulation by inhibition of Kidney reabsorption. This prevents calcium stone formation.

Question 18

What affect does PTH have on the gut?

Answer 18

It stimulates conversion of vitamin D into its active form which increases Ca2+ intake from the gut.

Question 19

What are the two forms of vitamin D?

Answer 19

D3 (cholecalciferol) made in skin and from dairy, requires sun light.
D2 (ergocalciferol) from east and fungi added to margarines as a supplement.

Question 20

How is vitamin D activated?

Answer 20

In the liver, 25-hydroxyvitamin D. In the kidneys, it produces 1,25(OH2)/ calcitriol.

Question 21

What are the actions of calcitriol on the gut?

Answer 21

Active uptake and extrusion of Ca2+ ions.
Transcellular transport.
Endocytosis and exocytosis of Ca2+-CaBP complex.

Question 22

What effect does calcitriol have on the kidney?

Answer 22

Decreases urinary loss of calcium by stimulation reabsorption.

Question 23

Where is calcitonin secreted from?

Answer 23

The parafollicular cells/ Cc ells of the thyroid gland.

Question 24

What are the clinical features of hypocalcaemia?

Answer 24

Hyper-excitablilty of NMJ, leading to pins and needles, tetany/ muscle spasms, paralysis, convulsions and death is consistently low.

Question 25

What are the clinical feasters of hypercalcaemia?

Answer 25

Renal calculi, kidney damage, constipation, dehydration, tiredness, depression and death eventually.

Question 26

What is the normal response to hypercalcaemia?

Answer 26

Decreased PTH secretion. In the kidney, there is decreased calcitriol release and decreased Ca2+ reabsorption, which means less Ca2+ is take from the gut. In the bone, there is decreased breakdown of the bone and increased bone building. These lower plasms Ca2+ levels.

Question 27

How is hypercalcaemia treated?

Answer 27

In primary hyperparathyroidism - removal of the benign tumour in one of the parathyroid glands.

Question 28

How can a tumour lead to hypercalcaemia?

Answer 28

They may release PTHrp (PTH related peptides) that have the same function as PTH so increase Ca2+ plasma levels.

Question 29

How is serum phosphate maintained?

Answer 29

There is a degree of co-regulation, as vitamin D stimulates uptake of both Ca2+ and Pi in the gut. The actions of vitamin D and PTH on the bone cause an increase in both Ca2+ and Pi. But in the kidney, PTH causes excretion of Pi so kidney stone formation is less likely.

Question 30

What happens in chronic kidney disease, in terms of Ca2+ and Pi regulation?

Answer 30

They become deregulated and Ca2+ levels fall and Pi levels rise.