12. Calcium and Phosphate Regulation Flashcards
Effect on PTH of fall in serum calcium
Increased production
PTH THREE main mechanisms of action
- Mobalises calcium from bone to increase [plasma calcium]
- Direct effect on the kidneys to increase calcium reabsorption
- Indirectly via the activation of vitamin D- stimulates the kidneys to produce 1a-hydroxylase which converts the precursor 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (calcitrol)
TWO effects of calcitrol on serum calcium
- Increases calcium absorption in the intestines
- Increases calcium mobalisation in bone- activate osteoblasts which relesase RANKL
Main aspects of phosphate regulation
Occurs via the gut and the kidneys
- Phosphate is reabsorbed via sodium phosphate transporter cells
- PTH inhibits renal phosphate reabsorption by inhibiting these transporters
- SO in primary hyperparathyroidism serum phosphate is LOW
- FGF23- derivied from bone- also inhibits phosphate reabsorption by blocking the transporters as well as calcitrol
Regulation of PTH Secretion
Via:
- Calcium sensor receptor- when calcium conc. is high it will bind to this on the surface of the parathyroid cell- causes PTH inhibition
Sources and effects of calcitriol (vitamin D)
Sources of vitamin D:
- UV acts on 7-dehydrocholesterol in the skin to form cholecalciferol (D3)
- Our diet contains ergocalciferol (D2)
Colecalciferol is converted to 25-hydroxycholecalciferol in the liver- inactive vitamin D
Then it is activated in into 1,25 dihydroxycholecalciferol (calcitriol) in the kidneys via 1a-hydroxylase
Effects of calcitriol:
- Increased calcium absorption in the intestines
- increased calcium maintainence in bone
- increased renal reabsorption of calcium
- negative feedback on PTH
Causes of Vitamin D deficiency
- Diet (lack of ergocalcitrol)
- Lack of sulight
- Gastrointestinal malabsorption (due to coeliac disease IBS etc.)
- Renal failure, liver failure (cannot produce or store calcitriol)
- Lack of receptors for calcitriol (autosomal recessive- RARE)
How does increasing calcium EC conc. affect nerve and skeletal muscle excitability?
Requires Na+ influx accross cell membrane
HYPERcalcaemia= Ca2+ blcoks Na+ influx, so LESS membrane excitability
Normal range for serum calcium
2.2-2.6 mmol/l
Signs and symptoms of hypocalcaemia
- Parasthesia (numbness in hands, mouth feet and lips)
- Arrhythmias
- Convulsions
- Tetany
CATs GO NUMB
Hypocalcaemia sensitises excitable tissue
Chvostek’s sign for hypocalcaemia
- Tap the fascial nerve just below the zygomatic arch
- POSITIVE response= twitching of fascial muscles
- Indicates neuromuscular irrritability
Trosseau’s Sign for hypocalcaemia
Inflation of the blood pressure cuff induces carpopedal spasm
again due to neuromuscular irritability
Causes of hypocalcaemia
- Vitamin D deficiency
-
Low PTH levels= hypoparathyroidism
- Surgical- parathyroidectomy
- Auto-immune
- Magnesium deficiency (needed for it to function)
- PTH resistence
- Renal failure- impaired 1a-hydroxylase, lack of calcitriol
Signs and symptoms of hypercalcaemia
-
Stones- renal effects
- Polyuria + Thirst
- Nephrocalcinosis (deposition of calcium in the kidneys)
-
Abdominal moans- GI effects
- Anorexia, nausea, dyspepsia, constipation, pancreatitis
-
Phychic groans- CNS effects
- Fatigue, depression, imparied concentration, altered mentation, coma
Causes of Hypercalcaemia
Mostly:
1. PRIMARY HYPERPARATHYROIDISM- due to a parathyroid adenoma which produces excessive amounts of PTH
2. MALIGNANCY- tumours/ metastases- can be due to a bone metastasis which increases turnover or a rumour producing PTH like peptides
Some:
3. Conditions with high bone turnover- Hyperthyroidism, Padget’s disease of bone
4. Vitamin D excess
Diagnosing Primary Hyperparathyroidism
Looking at serum concentrations:
- Calcium- HIGH
- Phosphate- LOW
- PTH- HIGH
Diagnosing hypercalcaemia of malignancy (bone metastases)
Calcium rises but negative feedback is still intact so:
- Calcium- HIGH
- PTH- LOW
Vitamin D Deficiency state definition and result
Lack of mineralisation in bone
results in:
- Softening of bone- characteristic bowing of the legs
- Bone deformities
- Bone pain
- Severe proximal myopathy
Deficiency is: Rickets in children, Osteomalacia in adults
Diagnosing secondary hyperparathyroidism
Vitamin D deficiency leads to decreased calcium
PTH increases to normalise serum calcium
Generally 25-hydroxycholecalciferol is measured as a gage of the amount of calcitriol
Treatment of vitamin D deficiency
- In patients with NORMAL RENAL FUNCTION
- Give 25-hydroxy vitamin D
- Patients can convert this to calcitriol via 1a- hydroxylase
- can be ergocalciferol or cholecalciferol
- In patients with RENAL FAILURE
- Dont have their own 1a- hydroxylase
- So they cant activate 25-hydroxy vitamin D preparations
- Give ALFACALCIDOL- 1-hydroxycholecaliferol
Vitamin D Excess (intoxication)
Can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium
Vitamin D excess can occur as a result of:
- Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure
- Granulomatous Disease - e.g. sarcoidosis, leprosy and tuberculosis
Granulomatous tissue can convert 25-hydroxycholecalciferol to the active metabolite 1,25-dihydroxycholecalciferol
This is because granulomatous tissues have 1a hydroxylase
