Calcium dysregulation Flashcards
what are the two main regulators of calcium and phosphate via the kidney, bone and gut?
vitamin D and parathyroid hormone (PTH)
Outline the process of vitamin D metabolism
D3 made in the skin in response to sunlight. D2 taken in the diet and transported to liver. First hydroxylation via 25 hydroxylase forming 25(OH) cholecalciferol, second hydroxylation via 1-alpha- hydroxylase in the kidneys to produce 1,25(OH)2 cholecalciferol - calcitriol
what is the name of the bio-active form of vitamin D?
calcitriol - 1,25(OH)2 cholecalciferol
what hormone acts to decrease serum calcium and phosphate?
calcitonin, secreted by thyroid parafollicular cells, reduces calcium acutely.
How do we know that the effect of calcitonin and calcium levels is acute?
there is no negative effect if the thyroid parafollicular cells are removed.
How does vitamin D act to increase serum calcium and phosphate?
stimulates reabsorption from the kidney, in the gut, and promotes bone calcium mineralisation via osteoblasts
How does PTH act to increase serum calcium and phosphate?
stimulates osteoclasts, releasing Ca2+ . Stimulates 1-alpha-hydroxylase increasing vit.D metabolism. inhibits sodium phosphate transporter cells
How does vitamin D regulate its own synthesis?
through negative feedback, increased vitamin D results in a decreased transcription of 1-a-hydroxylase
Where does the FGF23 hormone come from?
is derived from osteocytes
describe the relationship between calcium and PTH
when serum calcium falls is detected via calcium-sensing receptor which stimulates the production of PTH
how is phosphate reabsorbed in the gut and kidneys?
via sodium phosphate transporter cells
What is the action of FGF23?
inhibition of sodium phosphate transporter cells and the synthesis of calcitriol resulting indirectly in less phosphate absorption from the gut
How does hypocalcaemia present?
CATs go numb: convulsions, arrhythmias, tetany and paraesthesia
What tests (not blood related) can be used to test for hypocalcaemia?
Chvosteks sign and trousseaus sign
What are the causes of hypocalcaemia?
hypoparathyroidism, surgical, auto-immune, congenital, deficiency, renal failure
How does hypercalcaemia present?
Stones, moans and abdominal groans. Stones: renal effects, results in nephrocalcinosis. Abdominal moans: GI effects such as constipation, anorexia, dyspepsia, pancreatitis. Psychic groans: CNS effects such as fatigue, depression, impaired concentration, altered ment action and even coma
What are the three causes of Hypercalcaemia?
Primary hyperparathyroidism, malignancy, vitamin D excess (rare)
How does primary hyperparathyroidism cause hypercalcaemia?
Too much PTH from parathyroid glands but no negative feedback resulting in high PTH bit high calcium
How does Malignancy result in hypercalcaemia?
Bony metastases produce local factors to activate osteoclasts, and certain cancers secrete PTH-related peptide that acts at PTH receptors
How does renal failure cause Hypocalcaemia?
No 1-a-hydroxylase step therefore no calcitriol
Outline the biochemistry behind primary hyperparathyroidism
Parathyroid adenoma producing too much PTH which increases calcium. Low phosphate due to increased renal phosphate excretion because of inhibition of sodium phosphate transporters in the kidney. the high PTH is not suppressed by hypercalcaemia
how is primary hyperparathyroidism treated?
parathyroidectomy is treatment of choice for primary hyperparathyroidism
what are the risks associated with untreated primary parathyroidism?
osteoporosis, renal calcinosis, psychological impact of hypercalcemia - mental function and mood
what is secondary hyperparathyroidism?
normal physiological response to hypocalcaemia
