Regulation Of Calcium and Phosphate

Question 1

What is calcium?

Answer 1

Most abundant metal in the body
99% resides in skeleton and teeth
Unbound ionised calcium = biological active component

Question 2

What increases calcium levels in the body?

Answer 2

Parathyroid hormone (PTH)- secreted by parathyroid gland
Vitamin D

Question 3

What decreases calcium levels in the body?

Answer 3

Calcitonin- secreted by thyroid parafollicular cells

There are no negative effects if parafollicular cells are removed

Question 4

What are sources of vitamin D?

Answer 4

Diet- vitamin D2

Sunshine- vitamin D3 (cholecalciferol)

Question 5

What is a good indicator of vitamin D status?

Answer 5

Serum 25-hydroxycholecalciferol (serum 25-OH vit D)

Question 6

How do we get vitamin D from the sun?

Answer 6

UVB causes production of 7- dehydrocholesterol

This is then converted to pre- Vitamin D3 which is converted to Vitamin D3

Question 7

How is vitamin D activated?

Answer 7

You need 2 hydroxylation steps:

1. Hydroxylation of Vit D3 and D2 in liver to 25 Hydroxy-cholecalciferol
2. In kidney: Hydroxylation of 25 (OH) cholecalciferol to 1, 25 dihydroxycholecalciferol by 1 alpha- hydroxylase

Question 8

What is the active form of vitamin D?

Answer 8

Calcitriol (1,25 dihydroxycholecalciferol)

Question 9

How does calcitriol regulate its synthesis?

Answer 9

Regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
Negative feedback caused by high levels of calcitriol

Question 10

What is the effect of calcitriol?

Answer 10

Effects bone, kidney and gut
Works to increase calcium by increasing calcium absorption by bone
Increases Ca2+ absorption from kidney and gut
Increases phosphate reabsorption from kidney and absorption from gut

Question 11

What is parathyroid hormone secreted by?

Answer 11

chief cells in parathyroid gland

Question 12

How is parathyroid hormone secreted?

Answer 12

Secreted as a large precursor (pre-pro-PTH) and is cleaved to parathyroid hormone

Question 13

When is PTH secreted?

Answer 13

G- protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
PTH secretion is inversely proportional to serum calcium

Question 14

What happens when theres high extracellular fluid calcium conc.?

Answer 14

Ca2+ binds to receptors on parathyroid cells

PTH secretion inhibited

Question 15

What happens when theres low extracellular fluid calcium conc.?

Answer 15

Less Ca2+ binding to receptors on parathyroid cells

Increased PTH secretion

Question 16

What are actions of PTH?

Answer 16

Increased Ca2+ reabsorption from bone,
Increased Ca2+ adsorption from kidney and gut
Increased phosphate absorption from gut
Increased phosphate excretion in kidney
Increased 1- alpha hydroxylase activity in kidney so increased calcitriol synthesis

Question 17

What is the action of PTH in bone?

Answer 17

When PTH binds to PTH receptor, osteoblast activates osteoclast (osteoclast activating factors e.g. RANKL)

Question 18

What is the effect of calcitriol on bone?

Answer 18

Calcitriol effects bone depending on serum calcium
Low serum Ca- calcitriol increases Ca2+ reabsorption from bone (releases calcium into blood) (osteoblast to osteoclast)
Normal serum Ca: calcitriol increases bone formation (osteoclast to osteoblast)

Question 19

How is PTH regulated?

Answer 19

Increased plasma Ca2+ leads to less secretion of PTH in a negative feedback loop

Question 20

What reduces serum phosphate?

Answer 20

Fibroblast growth factor 23 (FGF23)
Inhibits phosphate absorption through inhibition of Na+/PO4- co-transporter and removes phosphate via urine
It also inhibits calcitriol action

Question 21

What is high serum calcium known as?

Answer 21

Hypercalcaemia

Ca2+ blocks Na+ influx so less membrane excitability

Question 22

What is low serum calcium known as and what are symptoms?

Answer 22

Hypocalcaemia
More Na+ influx so more membrane excitability
Symptoms: parasthesia, convulsions, arythmias, tetany

Question 23

How can we diagnose hypocalcaemia?

Answer 23

Chvostek’s sign: tap facial nerve just below zygomatic arch
Positive response= twitching of facial muscle

Trousseaus’s sign: inflation of BP cuff for several mins. Induces caropopedal spasm

Question 24

What are causes of hypocalcaemia?

Answer 24

Low PTH levels
Surgical
Auto-immune
Mg deficiency 
Congenital
Vitamin D deficiency

Question 25

What is low PTH levels known as?

Answer 25

Hypoparathyroidism

Question 26

What are causes of vitamin D deficiency?

Answer 26

1. Malabsorption or dietary insufficiency
2. Inadequate sun exposure
3. Liver disease
4. Renal disease
5. Vitamin D receptor defects

Question 27

What are consequences of vitamin D deficiency?

Answer 27

Loss of bone mineralisation- soft bones
In children- rickets
In adults- osteomalacia

Question 28

What are symptoms of hypercalcaemia?

Answer 28

‘stones, abdominal moans and psychic groans’
Reduced neural excitability
Stones: renal effects- Nephrocalcinosis: kidney stones
Abdominal Moans: GI effects- anorexia, nausea, dyspepsia, constipation
Psychic Groans: CNS effect- fatigue, depression, impaired concentration, coma

Question 29

What are causes of hypercalcaemia?

Answer 29

Primary hyperparathyroidism
Too much PTH
Parathyroid gland adenoma
No negative feedback- high PTH and high Ca
Malignancy: bony metastasis produce local factors to activate osteoclasts increasing Ca reabsorption from bone
Vit. D excess