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 clotting
Intracellular second messenger

Question 2

Where is calcium mainly stored?

Answer 2

Bone - 99% is stored as hydroxyapatite crystals in bone

Question 3

How is calcium present in the blood? What is the main component?

Answer 3

Unbound ionised calcium - 50%
Bound to plasma proteins - 45%
Tiny bit as soluble salts

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 Mm

Question 6

What two hormones raise plasma calcium concentration?

Answer 6

Parathyroid Hormone

Calcitriol (1,25-dihydroxycholecalciferol)

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) - produced in the follicular cells

Question 9

Where is calcitonin produced?

Answer 9

Parafollicular cells 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

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) 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 B 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 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
Minor effect on bone
Kidneys - increases calcium reabsorption and increases phosphate excretion

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.

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
Pseudohypoparathyroidism
Vitamin D Deficiency

Question 24

What two signs are used to demonstrate hypocalcaemia?

Answer 24

Trousseau’s Sign
Chvostek’s Sign
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?

Answer 26

Children - rickets

Adults - osteomalacia

Question 27

State three causes of hypercalcaemia.

Answer 27

Primary hyperparathyroidism
Tertiary hyperparathyroidism
Vitamin D Toxicosis

Question 28

Describe the differences between primary, secondary and tertiary hyperparathyroidism.

Answer 28

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)

Question 29

State some consequences of parathyroid hormone excess.

Answer 29

Kidney stones (calcium deposits) 
Increased risk of fracture

Question 30

What is a distinctive clinical feature of primary hyperparathyroidism?

Answer 30

Clubbing of the fingers