Regulation of calcium and phosphate (14)

Question 1

How does Vitamin D synthesis work?

Answer 1

• UVB light shines on skin–> triggers series of reactions
• precursor= 7-dehyrocholesterol–> converted to pre-vitamin D3–> vitamin D3 (cholecalciferol) IN SKIN
• vitamin D2 (from diet) and vitamin D3 transported to liver- FIRST STEP: hydroxylated by 25-hyroxylase–> 25(OH)cholecalciferol (inactive)
• SECOND STEP: 25(OH) vitamin D hydroxylated in kidney by 1-alpha-hydroxylase–> 1,25(OH)2 cholecalciferol (active form of vitamin D/ CALCITRIOL)

Question 2

What do we use as an indicator of body vitamin D status?

Answer 2

the inactive form of hormone- serum 25-OH vitamin D

measuring calcitriol v. hard

Question 3

How does calcitriol regulate its own synthesis?

Answer 3

1, 25 (OH)2 cholecalciferol negatively feeds back onto the enzyme that activates it- 1 alpha hydroxylase

Question 4

What are the effects of calcitriol?

Answer 4

• works on kidney to increase Ca2+ and PO43- reabsorption (less lost in urine)
• works on gut to stimulate Ca2+ and PO43- absorption
• increases osteoblast activity

Question 5

What is the parathyroid hormone (PTH)?

Answer 5

• comes from ‘chief cells’ in parathyroid glands (at back of thyroid)
• made from a large precursor- pre-pro-PTH –> cleaved to become PTH
• G-protein coupled calcium sensing receptor on chief cells detect change in serum Ca+ conc.
• PTH secretion inversely proportional to serum calcium

Question 6

How does the calcium sensing receptor work in chief cells?

Answer 6

high calcium levels–> calcium binds to G-protein coupled receptors on chief cells–> PTH secretion inhibited

low calcium–> less calcium binds to calcium sensing receptor–> more PTH secreted (to inc. calcium)

Question 7

What are the actions of PTH/how does it regulate serum calcium and phosphate?

Answer 7

• in KIDNEY, inc. serum calcium by inc. calcium reabsorption, inc. phosphate excretion, and inc. 1-a-hydroxylase activity (meaning more vit. D made–> inc. calcium+phosphate absorption in GUT indirectly)
• stimulating calcium reabsorption from BONES

Question 8

How does PTH act on bone?

Answer 8

converts osteoblasts (build bone)--> to osteoclasts (consume bone)
by binding to PTH receptor--> osteoclast activating factors--> osteoclasts resorb bone--> calcium released

Question 9

How is PTH regulated?

Answer 9

as calcium falls–> more PTH produced by parathyroid glands–> inc. plasma calcium and vitamin D synthesis–> inc. calcium
NEGATIVE FEEDBACK
1. more plasma Ca2+–> inhibits PTH production
2. active vitamin D negatively feeds back onto parathyroid cells

Question 10

What is calcitonin?

Answer 10

• secreted from parafollicular cells in thyroid gland
• REDUCES serum calcium
• physiological role in calcium homeostasis unclear

Question 11

How does calcitonin regulate calcium levels?

Answer 11

• dec. osteoclast activity
• inc. calcium excretion in kidney
• -> less plasma calcium

Question 12

How is serum phosphate regulated?

Answer 12

• PTH inhibits phosphate reabsorption by inhibiting Na+/PO43- co-transporter
• FGF23 inhibits ^ co-transporter AND inhibits calcitriol (active vit.D)–> less phosphate reabsorption from gut

Question 13

How does hypercalcaemia affect action potential generation?

Answer 13

Ca2+ in the way outside cell- blocks Na+ influx–> less membrane excitability

Question 14

How does hypocalcaemia affect action potential generation?

Answer 14

enables greater sodium influx–> more membrane excitability

Question 15

What are the signs and symptoms of hypocalcaemia?

Answer 15

• paraesthesia (pins and needles)- Numb
• Convulsions
• Arrhythmia
• Tetany
  N.B. mnemonic: CATs go numb

Question 16

What is Chvostek’s sign?

Answer 16

sign of hypocalcaemia- indicates neuromuscular irritability

- tap facial nerve just below zygomatic arch–> leads to twitching of facial muscles

Question 17

What is Trousseau’s sign?

Answer 17

sign of hypocalcaemia- indicates neuromuscular irritability

- inflate BP cuff for several minutes on arm–> induces carpopedal spasm (flexion)

Question 18

What are the causes of hypocalcaemia?

Answer 18

low PTH levels- hypoparathyroidism
due to 
- surgery
- autoimmunity
- magnesium deficiency
- congenital (rare)

vit. D deficiency

Question 19

What are the causes of vitamin D deficiency?

Answer 19

1. malabsorption or dietary insufficiency
2. inadequate sun exposure
3. liver disease
4. renal disease (bc 1-alpha-hydroxylase)
5. vit. D receptor defects (rare)

Question 20

What are the consequences of vitamin D deficiency?

Answer 20

lack of bone mineralisation- soft bones
in kids- rickets (bowing of bones)
in adults- osteomalacia (fractures, proximal myopathy)

Question 21

What are the signs and symptoms of hypercalcaemia?

Answer 21

reduced neuronal excitability–> atonal muscles
- kidney stones, renal colic
- GI effects: dyspepsia (heart burn), nausea, pancreatitis
- CNS effects: fatigue, impaired concentration, coma
‘STONES, ABDOMINAL MOANS, AND PSYCHIC GROANS’

Question 22

What are the causes of hypercalcaemia?

Answer 22

Primary hyperparathyroidism: tumour making too much PTH–> inc. calcium- no negative feedback

Malignancy- bony metastases produce local factors to activate osteoclasts
- PTH-related peptide secreted by certain cancers acts at PTH receptors

Vitamin D excess (rare)

Question 23

Why is calcium important?

Answer 23

• muscle contraction
• bone strength
• 2^y messenger
• blood clotting

Question 24

Why is phosphate important?

Answer 24

• component of DNA + ATP etc…
• 2^y messenger

N.B. extracellular phosphate= inversely proportional to extracellular calcium (so both regulated by same hormones)

Question 25

What hormones are involved in control of serum calcium and phosphate?

Answer 25

• increase calcium: PTH (secreted by parathyroid glands) and Vitamin D (synthesised in skin or intake via diet)
• decrease calcium: calcitonin (secreted by thyroid parafollicular cells)

Question 26

What are the sources of vitamin D?

Answer 26

take in via diet- vitamin D2- ergocalciferol

or make via sunshine- vitamin D3- cholecalciferol