Endocrine Control of Calcium Metabolism

Question 1

What are the roles of calcium?

Answer 1

NEUROMUSCULAR EXCITABILITY

• strength in bone
• intracellular secondary messenger
• intracellular coenzyme
• blood coagulation (Ca2+ is factor IV )

Question 2

Where is calcium mainly found and as what?

Answer 2

In the bone as hydroxyapatite crystal (1KG)

Question 3

What is calcium found in the blood as>

Answer 3

• ionised (Ca2+) = 50%
• bound to plasma proteins = 45%
• little as soluble salts

Only bioactive when free

Question 4

Where is most calcium intake and how much?

Answer 4

In the GI tract and 1000mg/24 hours

Question 5

How much calcium is lost daily and from where?

Answer 5

• faeces = 850mg

- kidney excretion = 150mg

Question 6

What can be done to increase blood calcium levels?

Answer 6

Breakdown of hydroxyapatite crystals

Question 7

What two hormones increase blood calcium?

Answer 7

• Parathyroid Hormone (PTH)

- 1,25-hydroxycholecalciferol (CALCITRIOL)

Question 8

Main hormone for decreasing blood calcium?

Answer 8

Calcitonin

Question 9

Describe the anatomy of the Parathyroid Glands

Answer 9

• 4 of them located at the four poles of the thyroids
• Parathyroid hormone synthesised in the follicles
• Calcitonin synthesised in the parafollicular cells

Question 10

How is parathyroid hormone release controlled?

Answer 10

Binding of calcium to parathyroid receptors (transmembrane g-protein linked receptors) causes release of PTH if calcium is low.

Question 11

Describe PTH synthesis

Answer 11

• as pre-proPTH

- polpeptide (84 amino acids)

Question 12

Describe PTH mechanism

Answer 12

Binds to G-protein linked receptors. This activates adenyl cyclase which raises intracellular cAMP. This activates Phosholipase C to cleave lipids (secondary messenger)

Question 13

Where does PTH have an action?

Answer 13

• Kidneys
• small intestine
• bone
• overall circulating Ca2+

Question 14

Describe PTH action on the kidneys?

Answer 14

• stimulates excretion of more phosphates

As calcium is stored with phosphate in bone, phosphates are produced as calcium is liberated and therefore needs to be excreted

Question 15

Describe PTH action on small intestine

Answer 15

Activation of calcitriol (vit D3). this allows for increased calcium and phosphate absorption

Question 16

Describe PTH action on the bone

Answer 16

Stimulate osteoclast activity
Inhibit osteoblast activity

it does this by stimulating osteoblasts to produce osteoclast activating factors such as RANKL

Question 17

Describe the regulation of PTH

Answer 17

• ve Feedback:
• increased Ca2+ plasma concentration
• PTH
• 25-hydrocycholecalcifriol

+ve Feedback:

• Low Ca2+ plasma concentration
• Catecholamines from Beta receptors

Question 18

Describe the formation of calcitriol

Answer 18

1) Cholecalciferol (D3) from the diet or 7-dehydrocholesterol (in the skin needing UV)
2) 25-hydroxycholecalciferol
3) Calcitriol

Question 19

What are the actions of calcitriol?

Answer 19

• Stimulates absorption of calcium and phosphates in the small intestine and reabsorption in the kidneys
• Increased osteoblast activity

Question 20

How is calcitonin formed?

Answer 20

• as pre-procalcitonin
• produced in the parafollicular cells of the thyroid
• 32 amino acid polypeptide

It binds to transmembrane G-protein linked receptor and activates adenyl cyclase or phospholipase C as the secondary messenger

Question 21

What is the function of calcitonin?

Answer 21

• It acts on bone and inhibits osteoclast activity.
• increases Na+ excretion in the kidneys and therefore Ca2+ and phosphate as well
• therefore, raises calcium levels in pregnancy and protects bone

Question 22

What are endocrine related causes of hypocalcaemia?

Answer 22

• Hypoparathyroidism (low PTH)
• Pseudohypoparathyroidism
• Vitamin D deficiency

Question 23

Causes of hypoparathyroidism?

Answer 23

• idiopathic
• hypomaganesaemia
• suppresion to raised calcium

Question 24

Symptoms of pseudoparathyroidism?

Answer 24

• Short stature, round face
• low IQ
• subcutaenous calcification and various bone abnormalities
• associated endocrine disorders

Question 25

Vitamin D differences?

Answer 25

In children = Rickets

In Adults = osteomalacia

Question 26

How can hypocalcaemia be shown?

Answer 26

Trousseau’s Sign (slight pressure on arm =hand contraction)

Chvosteks Sign (tap facial nerve at jaw angle = jaw contraction)

Question 27

Causes of hypercalcaemia?

Answer 27

• Primary Hyperparathyroidism
• Tertiary Hyperparathyroidism
• Vitamin D toxicosis

Question 28

What causes primary hyperparathyroidism?

Answer 28

Adenoma of the parathyroid

Question 29

What causes tertiary hyperparathyroidism?

Answer 29

Initial chronic low calciumand so the parathyroid becomes autonomous and stops responding the negative feedback once plasma calcium levels eventually increase.

Question 30

Explain Secondary hyperparathyroidism:

Answer 30

This doesnt cause hypercalcaemia. However, in renal failure, there is low Ca2+ reabsorption and therefore low plasma levels. PTH is then released in large amounts to no response.

Question 31

What are the effects of excess PTH?

Answer 31

• polyuria
• renal stones
• nephorcalcinosis
• gastric acid
• duodenal ulcers
• causes bone lesions and rarefication