Endo - Calcium Dysregulation

Question 1

How do you hormonally increase calcium + phosphate?

Answer 1

vitamin D
PTH
(acting on kidney, bones, gut)

Question 2

How do you hormonally decrease calcium + phosphate?

Answer 2

calcitonin (produced by thyroid follicular cells)

Question 3

How is Vitamin D synthesised through diet?

Answer 3

→ Vitamin D2 absorbed from diet converted to Vitamin D3
→ Vitamin D3 converted to 25(OH)cholecalciferol in liver by 25-hydroxylase
→ 25(OH)cholecalciferol converted to 1,25 (OH)2 cholecalciferol in kidney by 1-alpha-hydroxylase

Question 4

What are our 2 sources of Vitamin D?

Answer 4

→ synthesised form sun

→ absorbed from diet

Question 5

How is Vitamin D synthesised from the sun?

Answer 5

→ UVB light converts 7-dehydrocholesterol into Vitamin D3
→ Vitamin D3 converted to 25(OH)cholecalciferol in liver by 25-hydroxylase
→ 25(OH)cholecalciferol converted to 1,25 (OH)2 cholecalciferol in kidney by 1-alpha-hydroxylase

Question 6

What are the metabolic actions of calcitriol?

Answer 6

INCREASED serum Ca2+ and PO43- levels
→ bone : increased Ca2+ reabsorption (due to increased osteoblast activity)
→ kidneys : increased Ca2+ + PO43- reabsorption
→ gut : increased Ca2+ + PO43- reabsorption

Question 7

What are the metabolic actions of PTH?

Answer 7

INCREASED serum Ca2+ levels
→ bone : increased Ca2+ reabsorption (due to increased osteoblast activity)
→ kidneys : increased Ca2+ reabsorption and PO43 excretion
→ kidneys : increased 1 alpha-hydroxylase activity = more calcitriol
→ gut : increased Ca2+ + PO43 reabsorption

Question 8

What are the metabolic actions of FGF23?

Answer 8

DECREASES serum Ca2+ + PO34 reabsorption
→ secreted by osteocytes in response to elevation calcitriol
→ decreases expression of sodium-phosphate co-transporter = decreases PO34 reabsorption in kidneys
→ suppresses 1-alpha-hydroxylase in kidney = unable to activate Vitamin D

Question 9

Why does PTH not have much effect on net serum phosphate levels?

Answer 9

→ phosphate excretion in kidneys = phosphate reabsorption in gut
→ no net loss or gain of serum phosphate

Question 10

What are the symptoms of hypocalcaemia?

Answer 10

sensitises excitable tissues (CATs go numb)
→ Convulsions
→ Arrhythmias
→ Tetany
→ Parasthesia (hands, mouth, feet, lips)
(Chovstek's sign, Trousseau's sign)

Question 11

What are the 2 main signs of hypocalcaemia?

Answer 11

→ Chvostek’s sign : zygomatic arch twitch

→ Trousseau’s sign : muscle spasms after BP cuff inflated

Question 12

What are the causes of hypocalcaemia as a result of hypoparathyroidism?

Answer 12

→ surgical (e.g. neck surgery)
→ auto-immune
→ magnesium deficiency
→ congenital reasons

Question 13

What is hypoparathyroidism?

Answer 13

low PTH levels

Question 14

What are the causes of hypocalcaemia relating to Vitamin D?

Answer 14

due to Vitamin D deficiency
→ diet
→ UV light malabsorption
→ impaired production (e.g. renal failure)

Question 15

What is hypercalcaemia?

Answer 15

too much serum Ca2+

Question 16

What are the signs + symptoms of hypercalcaemia?

Answer 16

“Stones, abdominal moans + psychic groans”
→ stones = renal effects (nephrocalcinosis, stones, renal colic)
→ ab moans = GI effects (anorexia, constipation, nausea, dyspepsia, pancreatitis)
→ psychic groans = CNS effects (fatigue, depression, impaired conc, altered mentation, coma)

Question 17

What is hypocalcaemia?

Answer 17

too little serum Ca2+

Question 18

What are the 3 main causes of hypercalcaemia?

Answer 18

primary hyperparathyroidism
malignancy
vitamin D excess

Question 19

What happens to PTH levels when serum Ca2 levels decrease?

Answer 19

increases PTH through negative feedback

Question 20

What happens to PTH levels when serum Ca2 levels increase?

Answer 20

decreases PTH through negative feedback

Question 21

Why does primary hyperparathyroidism cause hypercalcaemia?

Answer 21

too much PTH, usually due to parathyroid gland adenoma = no negative feedback on PTH

Question 22

Why do malignancies cause hypercalcaemia?

Answer 22

bone metastases produce local factors to activate osteoclasts
certain cancer secrete PTH peptides = PTH receptors

Question 23

Why does vitamin D excess cause hypercalcaemia?

Answer 23

too much vitamin D = too much Ca2 reabsorption = too much Ca2 released into the blood

Question 24

What are the serum levels in someone with hyperparathyroidism (generally)?

Answer 24

→ high PTH (not suppressed by high calcium)
→ high calcium
→ low phosphate (phosphate renal excretion due to FGF23)

Question 25

How is primary hyperparathyroidism treated?

Answer 25

parathyroidectomy

Question 26

What are the risks of untreated hyperparathyroidism?

Answer 26

osteoporosis
renal calculi (stones)
psychological impacts of hypercalcaemia (mental function, mood)

Question 27

When is secondary hyperparathyroidism a normal physiological response? Why?

Answer 27

hypocalcaemia
Ca2 is low/normal
PTH gets high, secondary to Ca2

Question 28

What is the most common cause of secondary hyperparathyroidism?

Answer 28

vitamin D deficiency

Question 29

How is secondary hyperparathyroidism treated in patients with normal renal function?

Answer 29

Vitamin D replacement through 25 hydroxy cholecalciferol
(converted into calcitriol by 1-alpha-hydroxylase in kidney)
→ ergocalciferol tablets
→ cholecalciferol tablets

Question 30

How is secondary hyperparathyroidism treated in patients without normal renal function? Why?

Answer 30

cannot be replaced by 25 hydroxy cholecalciferol due to inadequate 1-alpha-hydroxylase
→ alfacalcidol tablets (analogue of Vitamin D)

Question 31

What is tertiary hyperparathyroidism?

Answer 31

prolonged inability to make calcitriol due to chronic renal failure
parathyroid glands work super hard + englarge
starts autonomous PTH secretion

Question 32

How is tertiary hyperparathyroidism treated?

Answer 32

parathyroidectomy - glands can’t be turned off

Question 33

How do you differentiate between primary + secondary hyperparathyroidism diagnostically?

Answer 33

check PTH
primary (adenoma) = increased PTH with normal renal function
secondary = high but low or low/normal Ca2
tertiary = increased PTH with chronic renal failure + enlarged parathyroid glands