Endo - Calcium Dysregulation Flashcards
How do you hormonally increase calcium + phosphate?
vitamin D
PTH
(acting on kidney, bones, gut)
How do you hormonally decrease calcium + phosphate?
calcitonin (produced by thyroid follicular cells)
How is Vitamin D synthesised through diet?
→ 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
What are our 2 sources of Vitamin D?
→ synthesised form sun
→ absorbed from diet
How is Vitamin D synthesised from the sun?
→ 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
What are the metabolic actions of calcitriol?
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
What are the metabolic actions of PTH?
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
What are the metabolic actions of FGF23?
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
Why does PTH not have much effect on net serum phosphate levels?
→ phosphate excretion in kidneys = phosphate reabsorption in gut
→ no net loss or gain of serum phosphate
What are the symptoms of hypocalcaemia?
sensitises excitable tissues (CATs go numb) → Convulsions → Arrhythmias → Tetany → Parasthesia (hands, mouth, feet, lips) (Chovstek's sign, Trousseau's sign)
What are the 2 main signs of hypocalcaemia?
→ Chvostek’s sign : zygomatic arch twitch
→ Trousseau’s sign : muscle spasms after BP cuff inflated
What are the causes of hypocalcaemia as a result of hypoparathyroidism?
→ surgical (e.g. neck surgery)
→ auto-immune
→ magnesium deficiency
→ congenital reasons
What is hypoparathyroidism?
low PTH levels
What are the causes of hypocalcaemia relating to Vitamin D?
due to Vitamin D deficiency
→ diet
→ UV light malabsorption
→ impaired production (e.g. renal failure)
What is hypercalcaemia?
too much serum Ca2+
What are the signs + symptoms of hypercalcaemia?
“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)
What is hypocalcaemia?
too little serum Ca2+
What are the 3 main causes of hypercalcaemia?
primary hyperparathyroidism
malignancy
vitamin D excess
What happens to PTH levels when serum Ca2 levels decrease?
increases PTH through negative feedback
What happens to PTH levels when serum Ca2 levels increase?
decreases PTH through negative feedback
Why does primary hyperparathyroidism cause hypercalcaemia?
too much PTH, usually due to parathyroid gland adenoma = no negative feedback on PTH
Why do malignancies cause hypercalcaemia?
bone metastases produce local factors to activate osteoclasts
certain cancer secrete PTH peptides = PTH receptors
Why does vitamin D excess cause hypercalcaemia?
too much vitamin D = too much Ca2 reabsorption = too much Ca2 released into the blood
What are the serum levels in someone with hyperparathyroidism (generally)?
→ high PTH (not suppressed by high calcium)
→ high calcium
→ low phosphate (phosphate renal excretion due to FGF23)
How is primary hyperparathyroidism treated?
parathyroidectomy
What are the risks of untreated hyperparathyroidism?
osteoporosis renal calculi (stones) psychological impacts of hypercalcaemia (mental function, mood)
When is secondary hyperparathyroidism a normal physiological response? Why?
hypocalcaemia
Ca2 is low/normal
PTH gets high, secondary to Ca2
What is the most common cause of secondary hyperparathyroidism?
vitamin D deficiency
How is secondary hyperparathyroidism treated in patients with normal renal function?
Vitamin D replacement through 25 hydroxy cholecalciferol
(converted into calcitriol by 1-alpha-hydroxylase in kidney)
→ ergocalciferol tablets
→ cholecalciferol tablets
How is secondary hyperparathyroidism treated in patients without normal renal function? Why?
cannot be replaced by 25 hydroxy cholecalciferol due to inadequate 1-alpha-hydroxylase
→ alfacalcidol tablets (analogue of Vitamin D)
What is tertiary hyperparathyroidism?
prolonged inability to make calcitriol due to chronic renal failure
parathyroid glands work super hard + englarge
starts autonomous PTH secretion
How is tertiary hyperparathyroidism treated?
parathyroidectomy - glands can’t be turned off
How do you differentiate between primary + secondary hyperparathyroidism diagnostically?
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
