Calcium, Phosphate and Vitamin D

Question 1

How much calcium do we need to absorb a day?

Answer 1

1000mg/1g

Question 2

Where is most of our calcium?

Answer 2

In our skeleton and teeth, bound in calcium hydroxyapatite crystals.

Question 3

Why must extracellular calcium be tightly regulated?

Answer 3

Unbound calcium is ionised and highly active.

Question 4

What are the main regulators of calcium and phosphate homeostasis?

Answer 4

Parathyroid hormone (PTH) and Vitamin D.

Question 5

What has a minor effect on calcium levels and why do we believe that it’s not as important?

Answer 5

Calcitonin.
It is produced by the thyroid follicular cells and when people have a thyroidectomy, no exogenous calcitonin is needed to maintain calcium balance - our bodies do fine without it.

Question 6

What do we call the vitamin D we absorb from the diet?

Answer 6

Ergocalciferol.

Question 7

What do we call vitamin D as a result of exposure to UV light?

Answer 7

Cholecalciferol.

Question 8

How is cholecalciferol regulated?

Answer 8

Cholecalciferol regulates itself by decreasing transcription of 1-alphahydroxylase, which activates 25hydrozycholecalciferol into the active form 1,25-diOHcholecalciferol, AKA calcitriol.

Question 9

How can we find out the levels of Calcitriol in a person?

Answer 9

Calcitriol is very unstable so we cannot measure it directly.
Instead, we measure the levels of serum 25-hydroxycholecalciferol.

Question 10

How is vitamin D3 formed?

Answer 10

UVB light turns 7-dehydrocholesterol into pre-vitamin D3 which turns into vitamin D3.

Question 11

How is Vitamin D3/D2 (D2 is from the diet) converted into Calcitriol?

Answer 11

D2/3 is converted by 25-hydroxylase from the liver into 25(OH)cholecalciferol.
25(OH)cholecalciferol is converted by 1-alphahydroxylase in the kidneys into calcitriol.

Question 12

What does calcitriol do?

Answer 12

Increases Ca2+ absorption from the bones.
Increases Ca2+ absorption in the gut.
Increases Ca2+ and PO4(3-) reabsorption in the kidneys.

Question 13

Where is PTH produced?

Answer 13

PTH is produced by the chief cells in the parathyroid glands, which sit on the back of the thyroid.

Question 14

What do chief cells in the parathyroid gland secrete?

Answer 14

A large precursor to PTH called pre-pro-PTH, which are cleaved to form the active hormone PTH.

Question 15

How are PTH levels regulated?

Answer 15

G-protein coupled calcium sensing receptors on chief cells detect changes in circulating calcium concentration.
When calcium levels are high in the extracellular fluid, Ca2+ binds to receptors on parathyroid cells, inhibiting the secretion of PTH.
PTH is also inhibited by high vitamin D levels.
When calcium levels are high, PTH is low and vice versa.

Question 16

What does PTH do?

Answer 16

PTH increases Ca2+ reabsorption in the bones, absorption in the gut and reabsorption of Ca2+ in the kidney.
It also increases 1-alpha-hydroxylase activity in the kidneys (which increases calcitriol synthesis).
It also increases phosphate EXCRETION in the kidneys but this is largely offset by increasing its absorption in the gut.

Question 17

How does PTH and calcitriol work on the bones to increase calcium levels?
How do the actions of PTH and calcitriol differ?

Answer 17

PTH/calcitriol binds to osteoblasts, stimulating them to create osteoclast activating factors (OAFs).
Osteoclasts consume bones to release calcium.
Calcitriol works in the same way as PTH when serum calcium is low, but if it is normal calcitriol increase the number of osteoblasts to stimulate bone growth.

Question 18

How does calcitonin work?

Answer 18

Calcitonin decreases osteoclast activity and increases calcium’s excretion from the kidneys.

Question 19

What does fibroblast growth factor 23 do?

Answer 19

It reduces phosphate serum phosphate levels.

Question 20

How doe FGF-23 work?

Answer 20

It works by inhibiting calcitriol production and so stopping the reabsorption of PO4(3-) in the gut and also works by stopping PO4(3-) entering the kidneys through its ion channel in the proximal convoluted tubules.

Question 21

Why is there less membrane excitability in people with hypercalcaemia?

Answer 21

Ca2+ blocks Na+ influx

Question 22

What are the symptoms of hypercalcaemia?

Answer 22

Stones, moans and groans.

Stones - renal effects
Nephrocalcinosis

Abdominal moans - GI effects.
Anorexia, nausea, dyspepsia, constipation, pancreatitis .

Psychic groans - CNS effects.
Fatigue, depression, impaired concentration.

Question 23

What are some causes of hypercalcaemia?

Answer 23

Primary hyperparathyroidism
Malignancy
Vitamin D excess (rare)

Question 24

Why is there too much membrane excitability in people with hypocalcaemia?

Answer 24

Low Ca2+ levels enables greater Na+ influx.

Question 25

What are some symptoms of hypocalcaemia?

Answer 25

CATs go numb.
Convulsions
Arrhythmias
Tetany
Paraesthesia/numbness.

Question 26

What are the two signs of hypocalcaemia?

Answer 26

We can check for hypocalcaemia with by checking for Chvostek sign or Trousseau’s sign.

Question 27

What is Chvostek’s sign?

Answer 27

Chvostek’s sign can be checked for by tapping the facial nerve just below the zygomatic arch - a positive response causing twitching of the facial muscles as it indicates neuromuscular irritability due to hypocalcaemia.

Question 28

What is Trousseau’s sign?

Answer 28

Trousseau’s sign can be checked for by inflating a blood pressure cuff for several minutes.
It induces a carpopedal spasm due to neuromuscular irritability due to hypocalcaemia.

Question 29

What are some causes of hypocalcaemia?

Answer 29

Low PTH levels

Vitamin D deficiency

Question 30

Why may someone have low PTH levels?

Answer 30

Surgical error
Auto-immune (autoimmune causes are very common for endocrine problems)
Magnesium deficiency
Congenital (rare)

Question 31

Why may someone have a Vitamin D deficiency?

Answer 31

Inadequate intake.
Liver disease (not enough 25 hydroxylase)
Renal disease (not enough renal 1-alpha hydroxylase)
Receptor defects so calcitriol is not having an effect.