**_🧪Endocrinology🧪 - Calcium Dysregulation Flashcards
What are the main regulatory hormones of calcium homeostasis?
Vitamin D and parathyroid hormone (PTH)
What acts to increase calcium levels?
Vitamin D and PTH
What acts to decrease calcium levels?
Calcitonin
Outline calcitonin
Secreted by thyroid parafollicular cells (note not parathyroid cells)
Can reduce calcium acutely, not physiologically important as thyroidectomy shows no negative impact on calcium levels
Outline Vitamin D3 production
Occurs in skin - 7-dehydrocholesterol interacts with UVB light to make pre-vitamin D3, which is then converted into vitamin D3
Outline vitamin D production
Vitamin D3 from skin and D2 from diet enters the liver through the bloodstream
25-hydroxylase catalyses conversion into 25(OH)cholecalciferol in the liver
25(OH)cholecalciferol converted to 1,25(OH)2cholecalciferol (calcitriol) in the kidney, catalysed by 1 alpha-hydroxylase
How is serum vitamin D measured?
Calcitriol never measured itself
25-OH much more stable in blood and easy to measure - gives good indicator of vitamin D status
What are the actions of calcitriol?
Overall effect is increase in serum calcium and phosphate
Increases calcium and phosphate reabsorption in kidney
Increases calcium and phosphate absorption in the gut
What are the actions of PTH?
Net effects is increased calcium and decreased phosphate
Increases calcium resorption from bone(increases osteoclast activity)
Increases calcium reabsorption in the kidney
Increases phosphate excretion/decreases phosphate reabsorption
Increase 1 alpha-hydroxylase activity (therefore increases calcitriol synthesis)
Indirectly increases gut absorption of calcium and phosphate (overall net decrease in phosphate due to increased excretion)
How does PTH increase renal phosphate excretion?
Inhibits sodium phosphate co-transporter in the kidney - responsible for reabsorption of phosphate
Inhibits this transporter along with FGF23
What is the overall role of FGF23?
Increases phosphate excretion by preventing phosphate reabsorption, and also decreases phosphate absorption in the gut
What is the mechanism of FGF23?
FGF23 prevents renal phosphate reabsorption by inhibiting the sodium/phosphate co-transporter from transporting sodium and phosphate out of the renal filtrate (note sodium is affected here, not calcium)
FGF23 also reduces 1 alpha-hydroxylase activity and promotes calcitriol degradation, lowering calcitriol levels and reduces phosphate absorption in the gut
What are the signs and symptoms of hypocalcaemia?
Sensitises excitable tissue; muscles, neurons etc…
Paresthesia (hands, mouth, feet, lips)
Convulsions
Arrythmias
Tetany (muscle contracts and cannot relax)
Chvostek’s sign - tapping of zygomatic arch causes facial twitch
Trousseau’s sign - carpopedal spasm induced by inflating of blood pressure cuff
What are the 2 main causes of hypocalcaemia?
Low PTH levels - hypoparathyroidism
Low vitamin D levels - vitamin D deficiency
(can have low calcium in diet, but generally looking at the 2 above causes)
How can hypoparathyroidism arise?
Surgery - neck surgery, classic example is a thyroidectomy
Autoimmune damage
Congenital (agenesis, rare, would present as a neonate)