12. Calcium and phosphate regulation Flashcards
where is parathyroid hormone (PTH) made and where is this situated?
made by the parathyroid glands
the 4 glands are behind the thyroid gland
what are the 3 functions of PTH?
- instructs the small intestines and kidneys to absorb calcium (to excrete less calcium)
- promotes calcium release from the bones
- regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) to active vitamin D (calcitriol)
what does active vitamin D promote?
calcium reabsorption from the gut and bones leading to increased serum calcium
where and how does phosphate reabsorption occur?
in the nephron (proximal convoluted tubule)
phosphate is reabsorbed using sodium-phosphate co-transporters. phosphate leaves the nephron lumen and enters the cells
what does primary hyperparathyroidism cause?
PTH inhibits the reabsorption of phosphates, therefore primary hyperparathyroidism increases phosphate excretion and less it taken up at the proximal convoluted tubule
what is FGF23 and what does it do?
fibroblast growth factor 23
it inhibits the reabsorption of phosphate
- via the sodium-phosphate cotransporter
- via the inhibition of calcitriol (which assists phosphate absorption from the gut)
how is PTH secretion regulated?
parathyroid cells have calcium-sensing receptors on their surface
when there is high ECF calcium, calcium binds to these receptors and PTH secretion is inhibited
when there is low ECF calcium the reduced binding of calcium means PTH is inhibited less and more is released
how can we get vitamin D?
- from diet (ergocalciferol)
- via UV light (converts 7-dehydrocholesterol to cholecalciferol)
what happens to cholecalciferol in the liver?
it is converted to 25-OH-D3 (which is biologically inactive)
what is the role of renal 1a-hydroxylase?
1a-hydroxylase in the kidney converts 25-OH-D3 to 1,25-(OH)2-D3 (calcitriol), which is biologically active
the conversion is stimulated by PTH
what does active vitamin D do?
- promotes Ca and phosphate reabsorption in the gut
- promotes calcium maintenance in bones
- increases renal calcium reabsorption
- produces negative feedback on PTH (calcitriol receptors on PT cells)
what can cause vitamin D deficiency?
- poor diet or malabsorption (due to coeliac disease, IBD)
- lack of sunlight
- liver disease
- renal disease
- vitamin D resistant rickets (where vitamin D production is normal but there are receptor defects)
how do changes in extracellular calcium affect nerve and skeletal muscle excitability?
to generate an AP in nerves/skeletal muscle requires Na+ influx across the cell membrane
- high EC calcium (hypercalcaemia) = Ca2+ blocks Na+ influx, so less membrane excitability
- low EC calcium (hypocalcaemia) =greater Na+ influx so more membrane excitability
state the normal calcium range and describe the signs and symptoms of hypocalcaemia
normal range for serum Ca2+ = 2.2-2.6mmol/L
SIGNS AND SYMPTOMS OF HYPOCALCAEMIA
- sensitisation of excitable tissues (muscle cramps/tetany, tingling)
- paraesthesia (tingling of the hands, mouth, feet, lips),
- convulsions
- arrhythmias
how can hypocalcaemia be assessed?
- Chvostek’s sign
- Trousseau’s sign
describe how Chvostek’s sign can be used to assess hypocalcaemia
- tap the facial nerve just below the zygomatic arch (cheek bone)
- positive response = twitching of the facial muscles
- this indicates neuromuscular irritability due to hypocalcaemia
describe how Trousseau’s sign can be used to assess hypocalcaemia
- inflate a BP cuff and leave it for several minutes
- this induces carpopedal spasm indicating neuromuscular irritability (hand contracts and cant be relaxed)
what are the causes of hypocalcaemia?
- vitamin D deficiency (required for calcium homeostasis)
- low PTH levels (hypoparathyroidism)
- surgical causes (neck surgery)
- auto-immune
- magnesium deficiency (needed for PTH)
- PTH resistance (pseudohypoparathyroidism) due to receptor defects
- renal failure
what does hypercalcaemia result in?
reduced neuronal excitability
“stones, abdominal moans and psychic groans”:
what does “stones” mean in relation to hypercalcaemia?
STONES = renal effects of hypercalcaemia
- polyuria & thirst
- nephrocalcinosis
- renal colic
- chronic renal failure
what does “abdominal moans” mean in relation to hypercalcaemia?
ABDOMINAL MOANS = GI effects of hypercalcaemia
- anorexia
- nausea
- dyspepsia
- constipation
- pancreatitis
what does “psychic groans” mean in relation to hypercalcaemia?
PSYCHIC GROANS = CNS effects of hypercalcaemia
- fatigue
- depression
- impaired concentration
- altered mental activity
- coma
what are the causes of hypercalcaemia?
- primary hyperparathyroidism
- malignancy (tumours/metastases often secrete a PTH-like peptide)
- conditions with high bone turnover (hyperparathyroidism, Paget’s disease of bone)
- vitamin D excess (rare)
serum Ca fall –> PTH increase
what does this result in and why?
- increased calcium reabsorption from the kidneys
- increased production of calcitriol
- increased calcium reabsorption from bones
PTH exerts -ve feedback to stop production of PTH and maintain normal serum Ca
what is primary hyperparathyroidism?
tumour in the parathyroid which causes a large increase in PTH secretion - there is limited -ve feedback and continued production of PTH despite hypercalcaemia
how is hypercalcaemia with malignancy different from primary hyperparathyroidism?
patients present with high calcium but there is -ve feedback so as serum Ca rises, PTH falls
what is the treatment of primary hyperparathyroidism?
parathyroidectomy
what is vitamin d deficiency?
lack of mineralisation in bone
results in “softening” of bone, bone deformities, bone pain, severe proximal myopathy
in children = rickets, in adults = osteomalacia
what is secondary hyperparathyroidism?
usually due to vitamin D deficiency leading to low calcium
renal failure leads to loss of calcium in the urine which will stimulate the parathyroid to release PTH in an attempt to normalise serum calcium
what is tertiary hyperparathyroidism?
initial chronic low plasma calcium ion concentration followed by massive stimulation of the parathyroid gland for a long time, resulting in desensitisation of the -ve feedback mechanism to PTH so plasma calcium increases
which types of hyperparathyroidism are associated with hypercalcaemia?
primary and tertiary
what are the biochemical findings in vitamin D deficiency?
- plasma [25(OH)D4] usually low
- plasma [Ca2+] low
- plasma [(PO4)3-] low (due to reduced gut absorption)
- [PTH] high
what is the treatment of vitamin D deficiency in patients with normal renal function?
- give 25 hydroxy-vitamin D (which patient will convert to the active form 1,25 dihydroxy-vitamin D via 1a hydroxylase)
- can alternatively give ergocalciferol or cholecalciferol
what is the treatment of vitamin D deficiency in patients with renal failure?
give alfacalcidol (active vitamin D) because they have inadequate 1a hydroxylation
what does vitamin D excess result in?
INTOXICATION
- can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium
what can vitamin D excess be caused by?
- excessive treatment with active metabolites of vitamin D (e.g. wrong dose of alfacalcidol)
- granulomatous diseases such as sarcoidosis, leprosy and TB: macrophages in the granuloma produce 1a-hydroxylase to convert 25(OH)D to the active metabolite (very rare)
