Regulation of calcium phosphate

Question 1

What increases the concentration of serum calcium and phosphate and where are they synthesised

Answer 1

Parathyroid hormone: synthesised by parathyroid glands

Vitamin D: synthesised in skin or uptake by diet

Question 2

What decreases the concentration of serum calcium and phosphate?

Answer 2

Calcitonin: secreted by parafollicular cells

Question 3

what is serum 25-OH cholecalciferol

Answer 3

its a good indicator of Vitamin D status

biologically inactive

Question 4

How is Vitamin D made into its active form?

Answer 4

From UV: ( in skin cells) 7-dehyrocholesterol -> pre vitamin D3 -> Vitamin D3
(in liver) Vitamin D3-> 25 OH cholecalciferol via 25 alpha hydroxylase
(in kidney) 25 OH cholesterol -> 1 25(0H)2 cholecalciferol via 1-alphahydroxylase

From diet: Vitamin D2 from diet -> Vitamin D3 -> liver and kidney bit repeated

Question 5

how does 1, 25(OH)2 cholecalciferol regulate its own synthesis

Answer 5

Decreases transcription of 1-alpha-hydroxylase

Question 6

Effects of calcitriol

Answer 6

increase calcium and phosphate reabsorption in the kidney
increase phosphate absorption in gut
increase calcium absorption in gut
increase calcium reabsorption in bones

Question 7

Where are parathyroid hormones secreted from

Answer 7

chief cell in parathyroid gland

Question 8

what is the PTH precursor

what detects change in Ca2+ conc to stimulate chief cell to produce PTH

what is the relationship between PTH and serum calcium

Answer 8

pre-pro-PTH

G-protein coupled receptors

inversely proportional

Question 9

how does high serum calcium affect parathyroid cells (vice versa for low serum calc)

Answer 9

many calc bind to receptor on parathyroid cell

PTH secretion inhibited

Question 10

Effects of PTH

Answer 10

Bones: increase calcium conc in blood from bone

Kidney: increase calcium reabsorption
phosphate excretion
increase 1 alpha hydroxylase activity
increases 1 25(OH)2 cholecalciferol

Gut: increase calcium and phosphate reabsorption ( due to increased 1 25(OH)2 cholecalciferol)

Question 11

How does PTH impact bone

Answer 11

PTH binds to PTH receptor on Osteoblast

Osteoblast releases Osteoclast activating factors eg RANKL)

Osteoblasts activates osteoclast

increases bone resorption ( breakdown of bone to release calcium into the bloodstream

Question 12

Effects of Calcitriol on bone for low and high serum calcium

Answer 12

Low serum calcium: calcitriol binds to calcitriol receptor on osteoblast increasing calcium reabsorption from bone to blood. Osteoclasts> osteoblasts

High serum calcium: Increases bone formation
Osteoblasts> osteoclasts

Question 13

How is PTH regulated

Answer 13

increases calcium in plasma decreases secretion of PTH

increased calcium decreases 1 25 (OH)2 D3 synthesis, decreasing PTH conc

Question 14

where is calcitonin secreted

what does it do

does its removal affect serum calcium

Answer 14

parafollicular cells of thyroid gland

reduces serum calcium

no

Question 15

how does calcitonin work

Answer 15

Increases calcium conc detected in blood

increased secretion of calcitonin

In bone: decrease osteoclast activity

In kidney: increase calcium excretion in urine

decreases plasma Ca2+

Question 16

what does FG23 do

how does it work

Answer 16

lowers phosphate

method 1: inhibits sodium phosphate transporter between proximal tubule and blood
cant reabsorb phosphate from urine as more phosphate lost in urine

method 2: Inhibits calcitriol
reduces phosphate reabsorption from gut

Question 17

what is the term for high serum calcium

what is the term for low serum calcium

effects of high serum calcium (vice versa for low)

Answer 17

hypercalcaemia

hypocalcaemia

calcium blocks Na+ influx, less membrane excitability

Question 18

how does Hypocalcaemia affect body

Answer 18

sensitises excitable tissues; muscle cramps, tetany , tingling

signs and symptoms:

Paraesthesia (hands, mouth, feet, lips)
convulsions
arrhythmias
tetany

Question 19

what is Chvostek sign

what is trousseaus sign

Answer 19

when facial muscles twitch after tapping the facial nerve below the zygomatic arch

when inflation of BP cuff induces carpopedal spasm

both indicate neuromuscular irritability due to hypocalcaemia

Question 20

Causes of Hypocalcaemia

Answer 20

Low PTH levels = hypoparathyroidism

Surgical – neck surgery
Auto-immune
Magnesium deficiency
Congenital (agenesis, rare)
Vitamin D deficiency

Question 21

causes of vitamin D deficiency

Answer 21

dietary insufficiency

inadequate sun exposure

liver disease- no synthesis of compounds before calcitriol

renal disease- no 1-alphpa-hydroxylase action stimulated by PTH

Vit D receptor defects (rare)

Question 22

consequences of vit D deficiency

Answer 22

Lack of bone mineralisation = ‘soft’ bones
In children – rickets (bowing of bones)
In adults – osteomalacia (fractures, proximal myopathy)

Question 23

symptoms of hypercalcaemia

Answer 23

‘Stones, abdominal moans and psychic groans’

Reduced neuronal excitability – atonal muscles
Stones – renal effects
Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

Question 24

Causes of hypercalcaemia

Answer 24

Primary hyperparathyroidism

• Too much PTH
• Usually due to a parathyroid gland adenoma
• No negative feedback - high PTH, but high calcium

Malignancy
-Bony metastases produce local factors to activate osteoclasts, increasing calcium reabsorption from bone

Vitamin D excess (rare)