Calcium dysregulation Flashcards
which hormones act to increase serum calcium
What tissues do these act on
vitamin D (calcitriol)
parathyroid hormone
Main regulators of calcium (& phosphate) homeostasis via actions on kidney, bone and gut
which hormones act to decrease serum calcium
Calcitonin
Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
what are the sources of calcitriol?
synthesised in skin, diet
what are the sources of parathyroid hormone
parathyroid gland
what are the sources of calcitonin
thyroid parafollicular cells
what are the main sources of calcium in the body?
bones, gut, kidney
what is the difference between vitamin D2 and D3
D2 from diet (ergo)
D3 from skin (chole)
which enzymes are essential for vitamin D synthesis
25-hydroxylase (liver)
1-a-hydroxylase (kidney)
Vitamin D metabolism
What do we measure to determine body vitamin D status?
Serum 25-OH vitamin D
How does 1,25(OH)2 vitamin D (calcitriol) regulate its own synthesis?
decreasing transcription of 1 alpha hydroxylase
name all the physiological effects of calcitriol
increases calcium and phosphate reabsorption in kidneys
increases calcium and phosphate absorption in gut
increases osteoblast activity
name all the physiological effects of PTH
increased calcium reabsorption in kidney, increased excretion of phosphate, increased 1ah action (vit D synthesis)
increases calcium and phosphate absorption in the gut
increases osteoclast activity
Via what transporter does phosphate reabsorption occur in the kidneys? What effect reabsorption this have on serum phosphate and urinary sodium?
How is this affected by hyperparathyroidism?
Phosphate is reabsorbed via sodium phosphate transporter cells. In the kidney, reabsorption of phosphate via these transporters results in less sodium excretion in the urine. Reabsorption increases serum phosphate levels.
PTH inhibits renal phosphate reabsorption by inhibiting these transporters – so in primary hyperparathyroidism, serum phosphate is low due to increased urine phoshate excretion.
where is FGF23 made
by osteocytes
what is the main role of FGF23
prevents kidney reabsorption of phosphate
inhibits Vit D synthesis (via reduced activity of 1-a-hydroxylase)
what is FGF23s MOA
inhibits Na/PO4 transporter in proximal tubule of kidney (more excretion of PO4)
inhibits calcitriol synthesis (for less PO4 absorption in gut)
what are the two signs of hypocalcaemia
Chvosteks sign (facial paresthesia)
Trousseaus sign (carpopedal spasm)
what are the symptoms of hypocalcaemia
Hypocalcemia sensitizes excitable tissue
CATs go numb
convulsions, arrhythmias, tetany, paraesthesia
what are the two major causes of hypocalcaemia
due to low PTH
due to low Vit D
what are some causes of low PTH causing hypocalcaemia
neck surgery
autoimmunity
magnesium deficiency
congenital agenesis of Pt gland (rare)
what are some causes of low calcitriol causing hypocalcaemia?
deficiency due to diet, lack of UV (darker skin more prone), malabsorption, impaired production (renal failure)
what are the signs and symptoms of hypercalcaemia
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)
what is the most common cause of hypercalcaemia
primary hyperparathyroidism, usually a parathyroid gland adenoma
what are the main causes of hypercalcaemia
primary hyperparathyroidism
malignancy
vit D excess
how can malignancy cause hypercalcaemia?
bony metastases produce local factors to activate osteoclasts
or certain cancers (squamous cell carcinoma) secrete PTH-related peptide which acts on PTH receptors
what would be the blood results for primary hyperparathyroidism
high calcium, low phosphate (increased renal phosphate excretion due to inhibition of Na+/PO43- transporter in kidney), high PTH
what is the cause of primary hyperparathyroidism?
parathyroid adenoma - autonomous secretion of PTH
how do you treat primary hyperparathyroidism?
parathyroidectomy
what are the long term risks of primary hyperparathyroidism?
osteoporosis
renal calculi
psychological risks of hypercalcemia
what is secondary hyperparathyroidism?
normal physiological response to chronically low calcium
what are the blood results for secondary hyperparathyroidism?
low/norm Ca2+
high PTH secondary to low Ca2+
what is the most common cause of secondary hyperparathyroidism?
Vit D/calcitriol deficiency
what are the causes of secondary hyperparathyroidism?
Vit D deficiency by diet, malabsorption, reduced sunlight, renal failure
how do you treat someone with secondary parathyroidism who has normal renal function?
Give 25 hydroxy vitamin D
Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase
Ergocalciferol 25 hydroxy vitamin D2
Cholecalciferol 25 hydroxy vitamin D3
how do you treat someone with secondary hyperparathyroidism in renal failure?
Why?
give Alfacalcidol - 1-a-hydroxycholecalciferol
Inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
what is tertiary hyperparathyroidism?
Occurs in chronic renal failure
Can’t make calcitriol
Chronic hypocalcemia
PTH increases (hyperparathyroidism)
Parathyroid glands enlarge (hyperplasia)
Autonomous PTH secretion causes hypercalcaemia
how is tertiary hyperparathyroidism treated?
parathyroidectomy
how does high calcium affect the nerves
Calcium ions block sodium ion influx so there is less membrane excitability
how does low calcium affect the nerves
low Ca2+ allows more sodium ion influx so there is increased membrane excitability
