Endocrine control of calcium metabolism

Question 1

What are the roles of calcium?

Answer 1

Neuromuscular excitability

Muscle contraction

Bone strength

Intracellular second messenger

Intracellular co-enzyme

Hormone stimulus secretion coupling

BLOOD COAGULATION
- factor 4

Question 2

How is calcium present in the body>

Answer 2

Calcium salts

Hydroxyapatite crystals

In blood, soluble ionised Ca2+
- only ionised is the free

Question 3

How is calcium managed in the body?

Answer 3

Absorbed in the Gi tract following ingestion

Then moved into the blood where it can be taken up by bone or excreted through the kidneys

Question 4

How is calcium lost from the body?

Answer 4

Faeces

Urine

Invisible loss

• Dead cells
• Hair
• nails

Question 5

Which hormone are responsible for Ca2+ regulation? How do they do it?

Answer 5

Increased by

• Parathyroid hormone
• Calcitriol - Vit D3

Decreased by
- Calcitonin

Question 6

Where are the parathyroid glands located? Which hormones does it (not) secrete

Answer 6

back of the thyroid gland - 4 of them

PTH
(Calcitonin) - Parafollicular cells

Question 7

How are calcium levels sensed?

Answer 7

Calcium-sensing receptor

• GPCR
  
  • Ca2+ binds that changes conformation and changes intracellular action
  • this prevents PTH release, but if no Ca, it releases

Question 8

How is PTH synthesised?

Answer 8

As pre-proPTH
Cleaved and binds to GPCR
- activates adenyl cyclase - cAMP
- also PLC

Question 9

What are PTH’s actions?

Answer 9

Increases phosphate excretion from the KIDNEYS

Increased Ca2+ reabsorption

Stimulates 1alpha hydroxylase, which stimualtes D3 synthesis

D3 then acts on small intestine to increase both Ca and PO4 uptake

Also PTH increases bone resorption - break down bone

INCREASES FREE CA2+

Question 10

Describe PTH’s action on bones

Answer 10

PTH binds to receptors on osteoblasts

These then release osteoclast activating factors, which lead to osteoclasts working harder and resorbing bone

Question 11

How is PTH regulated?

Answer 11

Upon increasing plasma [Ca2+], it will be negatively fed back by the Ca2+ produced, and stimulated by a drop in Ca2+
Vit D3 also does this

Catecholamines STIMULATE IT

Question 12

How is Vit D3 synthesised?

Answer 12

Cholecalciferol is obtained by diet and from light
- 7-dehydrocholesterol forms cholecalciferol in presence of UV light.

Cholecalciferol then forms 25 OH hydroxy cholecalciferol in the liver

Then activated by addition of another OH - 1 not 25 - b4
Forming Calcitriol - in KIDNEY - active

Question 13

What are the actions of 1, 25 dihydro-cholecalciferol?

Answer 13

Increase Ca2+ and PO4 uptake
Much slower, chronic

Promotion of Ca uptake in bone - increase blast

Increase Ca and PO4 uptake in kidney

Question 14

how are phosphates regualted in blood?

Answer 14

Fibroblast growth factor 23

• If too high PO4
  
  • removes the PO4 from blood
• Prevents reabsorption of PO4 by inhibiting napo4 cotransporter, as PTH does

Question 15

how is calcitonin made?

Answer 15

Formed as pre-procalcitonin

• GPCR
• Activates PLC and adenyl cylcase

Question 16

What does calcitonin do?

Answer 16

Inhibit bone breakdown

Increase ca excretion

Limited effect
- because low Ca more bad than high

Stimulated by high Ca, gastrin
- because stomach acid released if high Ca2+

Question 17

What are the endocrine causes of hypocalcemia?

Answer 17

Hypoparathyroidism
Pseudohypoparathyroidism
Vit D deficiency

Question 18

What are the signs of hypocalcaemia?

Answer 18

Tetany

• Low Ca2+ means Na+ can enter easier and then cause depolarisation quicker
• spasm

Chvostek’s sign
- flick ear and nose twitches

Question 19

What causes hypoparathyroidism?

Answer 19

Idiopathic

• Low circulating PTH
• Hypomagnesaemia
  
  • necessary for function and downstream effects of PTH
• High Ca2+

Question 20

What is pseudohypoparathyroidism

Answer 20

Seems like low PTH, but bad response to PTH - resistance

Cells have pTH but don’t respond to it

Defective Gs protein
- needed to start PTH production

Question 21

What are some features of pseudohypoparathyroidism

Answer 21

Short stature
Round face

Low IQ

Subcut calcification

Associated endocrine disorders

Question 22

What happens as a result of Vitamin D deficiency?

Answer 22

Rickets
Osteomalacia

Decreased calcification of bone leading to softening and bowing in children

Question 23

How can you differentiate between pseudohypoparathyroidism, hypoparathyroidism and Vit D deficiency?

Answer 23

Ps - low Ca and high PTH and PO4

Hp - low Ca and PTH, high PO4

VD - low Ca low PO4 high PTH

Question 24

What are the causes of hypercalcaemia?

Answer 24

Primary hyperparathyroidism
- Increase PTH due to adenoma

Secondary
- Renal failure - can’t restore Ca2+ despite increased PTH

Tertiary hyperparathyroidism

• Chronic low plasma [Ca2+] then cured by transplant
• but Parathyroids are autonomous due to changes because of no response

Vitamin D toxicosis

Question 25

What might occur as a result of higher PTH?

Answer 25

Kidneys

• Increased Ca and PO4 uptake and release resp
• Polyuria
• Renal stones
• Vit D synth

GI

• Gastric acid more so
• Duodenal ulcers

Bone

• lesion
• thinning
• increasing fracture
• finger clubbing