Endocrine Control of Calcium Metabolism

Question 1

State some roles of calcium in the body.

Answer 1

Control of neuromuscular excitability (hypocalcaemia leads to hyperexcitability because Ca2+ normally blocks the Na+ channels)
Muscle Contraction
Strength in bone
Blood coagulation (Factor IV)- calcium is Factor 4
Intracellular second messenger
Intracellular co-enzyme

Question 2

Where is calcium mainly stored?

Answer 2

Bone - 99% is stored as hydroxyapatite (salt, calcium with phosphorus) crystals in bone

Question 3

How is calcium present in the blood and what is the concentration of the total calcium ion? What is the main component?

Answer 3

-2.5 mM

Unbound ionised calcium (bioactive) - 50%
Bound to plasma proteins - 45% (1.13mM)
Tiny bit as soluble salts (0.13mM)

Question 4

What is the usual daily intake of calcium?

Answer 4

1000 mg/day

Question 5

What is the concentration of unbound ionised calcium in the blood?

Answer 5

1.25 mini Molar (mM), therefore this is the amount that is biologically active component.

Question 6

What two hormones raise plasma calcium concentration?

Answer 6

• Parathyroid Hormone

- Calcitriol (1,25-dihydroxycholecalciferol) Vitamin D3

Question 7

What hormone decreases plasma calcium concentration?

Answer 7

Calcitonin

Question 8

Where is parathyroid hormone produced?

Answer 8

Parathyroid Glands (four of them) -

Question 9

Where is calcitonin produced?

Answer 9

Parafollicular cells (between follicular cells of the thyroid gland) in the thyroid gland.

Question 10

Describe the effects of parathyroid hormone on the kidneys.

Answer 10

Increases calcium reabsorption

Increases phosphate excretion

Question 11

Describe the effects of PTH on bone.

Answer 11

Stimulates osteoclasts

Inhibits osteoblasts, this goes onto increase bone resorption.

Question 12

Describe the effects of PTH on the small intestines.

Answer 12

PTH increases the activity of 1 alpha hydroxylase (in the kidneys), which is involved in the production of calcitriol, which increases calcium and phosphate absorption in the small intestine.

Question 13

How does PTH increase calcium release from bone?

Answer 13

PTH has a direct effect in inhibiting osteoblasts. PTH makes the osteoblasts produce osteoclast activating factors (such as RANKL:Receptor activator of nuclear factor kappa-Β ligand) that bind to receptors on osteoclasts and stimulates the break down of bone matrix to release calcium.

Question 14

What can stimulate PTH release?

Answer 14

Low plasma calcium concentration

Catecholamines (by binding to beta receptors)

Question 15

Describe the negative feedback loops on PTH.

Answer 15

Increased plasma calcium concentration has a negative feedback effect on PTH
Calcitriol also has a negative feedback effect

Question 16

What is the precursor of calcitriol?

Answer 16

Cholecalciferol

Question 17

Where does this precursor come from?

Answer 17

-Diet
-Sun Light (UV light converts 7-dehydrocholesterol to cholecalciferol)
NOTE: cholecalciferol is VITAMIN D3

Question 18

Describe the reactions that have to take place to convert the precursor to calcitriol.

Answer 18

Cholecalciferol travels to the liver where 25-hydroxylase converts it to 25-hydroxycalciferol, which is then stored in the liver.
It then moves to the kidneys where 1 alpha hydroxylase (stimlated by PTH) converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (calcitriol)

Question 19

Describe the effects of calcitriol.

Answer 19

MAIN ACTION: stimulates calcium and phosphate absorption in the SMALL INTESTINE
Increased osteoblast activity on bone.
Kidneys - increases calcium and phosphate reabsorption

Question 20

How does calcitriol and PTH decrease phosphate reabsorption in the kidney?

Answer 20

They block the sodium/phosphate cotransporter

Calcitriol does this via the action of FGF23 (fibroblast growth factor 23)

Question 21

Describe the effects of calcitonin.

Answer 21

Calcitonin inhibits osteoclast activity
Calcitonin also affects the KIDNEYS - increase sodium excretion and hence increase urinary excretion of phosphate and calcium.
This decreases plasma calcium concentration

Question 22

State a physiological benefit of calcitonin.

Answer 22

During pregnancy women need a higher plasma calcium concentration (e.g. for milk), calcitonin protects the bone from break down.

Question 23

State three causes of hypocalcaemia.

Answer 23

Hypoparathyroidism: insufficient PTH
Pseudohypoparathyroidism: resistence to PTH
Vitamin D Deficiency

Question 24

What two signs are used to demonstrate hypocalcaemia?

Answer 24

Trousseau’s Sign: put slight pressure on the arm and the hand can go into contraction
Chvostek’s Sign : tap the facial nerve at the angle of the jaw you get muscles to contract
These are both signs of tetany

Question 25

What is pseudohypoparathyroidism and what are some clinical features?

Answer 25

Target organ resistance to PTH (also called Allbright Heriditary Osteodystrophy) Round face, short, low IQ, short 4th metacarpal, hypothyroidism, hypogonadism

Question 26

What does vitamin D deficiency cause in children and adults and what are the clinical feature?

Answer 26

Children - rickets Adults - osteomalacia Bowing of bones in children Fractures in adults

Question 27

State three causes of hypoparathyroidism

Answer 27

- idiopathic - hympomagneseamia - supression by raised calcium concentration

Question 28

what are some diagnostic results in the different types of hypoparathyroidism

Answer 28

-in hypoparathyroidism you get an increase in plasma phosphate conc because PTH isn't stimulating the excretion of phosphate from the kidneys. Decrease in plasma calcium and PTH -pseudohypoparathyroidism- the parathyroid glands are producing insufficient PTH, but the target organs are resistent to PTH so plasma calcium conc is low and plasma phosphate and PTH increase Vitamin D defiency: phosphate levels low, PTH normal and calcium low

Question 29

State three causes of hypercalcaemia.

Answer 29

Primary hyperparathyroidism Tertiary hyperparathyroidism Vitamin D Toxicosis

Question 30

Describe the differences between primary, secondary and tertiary hyperparathyroidism

Answer 30

Primary - caused by parathyroid adenoma producing huge amounts of PTH Secondary - caused by other reasons e.g. renal excretion of Ca2+ ions leading to compensatory increase in release of PTH (this causes low Ca2+ because it is being lost from the kidneys) Tertiary - initial chronic low plasma calcium concentration - parathyroid gland is massively stimulated for a long time and so PTH production becomes autonomous and stops responding to negative feedback (leads to hypercalcaemia in primary and teritary)

Question 31

State some consequences of parathyroid hormone excess.

Answer 31

``` Kidney stones (calcium deposits) Increased risk of fracture ```

Question 32

What is a distinctive clinical feature of primary hyperparathyroidism?

Answer 32

Clubbing of the fingers

Question 33

Describe how calcium level are detected in the body?

Answer 33

It is detected by calcium sensing receptors which are found in the parathyroid gland and the renal tubules of the kidney.

Question 34

Describe how PTH is formed and how it goes on to effect?

Answer 34

1. Initially synthesized as protein pre-proPTH 2. PTH is a polypeptide of 84 amino acids 3. Binds to transmembrane G-protein linked receptors 4. Activation of adenyl cyclase, but also probably PLC as second messenger systems

Question 35

Describe how calcitonin is formed and how it goes on to effect?

Answer 35

1. Synthesized as pre-procalcitonin 2. Calcitonin is 32 amino acid polypeptide 3. Binds to transmembrane G-protein linked receptor 4. Activation of adenyl cyclase or PLC as second messenger systems