Calcium + phosphate regulation Flashcards
How is blood [Ca] controlled hormonally?
Parathyroid glands sense low serum Ca and increase PTH secretion
PTH effects:
- Reduces renal Ca excretion
- Promotes Ca release from bone
- Regulates conversion of inactive vit D –> active vit D (calcitriol)
Calcitriol effects:
- Increase absorption of dietary Ca
- Promotes Ca + phosphate release from bone
All increase serum calcium
What are the causes of hypercalcaemia?
- Primary hyperparathyroidism
- Parathyroid adenoma producing excessive PTH - Malignancy - tumour/metastases
- Bone metastases - increased bone turnover –> increased serum Ca
- Tumours can produce PTH-related peptide - Conditions w/high bone turnover
- Hyperthyroidism
- Paget’s disease - immobilised patient - Vitamin D excess (rare)
What are the causes of hypocalcaemia?
- Vitamin D deficiency
- Low PTH (hypoparathyroidism)
- Surgical - neck surgery (e.g. parathyroidectomy)
- AI
- Magnesium deficiency (need to make PTH) - PTH resistance
- Pseudohypoparathyroidism - Renal failure
- Impaired 1a-hydroxylase
- Decreased calcitriol production
What are the clinical features of hypercalcaemia?
- Reduced neuronal excitability + atonal muscles
- Stones - renal effects: polyuria, thirst, nephrocalcinosis, renal colic, chronic renal failure
- Abdominal moans: anorexia, nausea, dyspepsia, constipation, pancreatitis
- Psychic groans: fatigue, depression, impaired concentration, altered mentation, coma
What are the clinical features of hypocalcaemia?
Hypocalcaemia sensitises excitable tissues:
- Parasthesia (numbness in hands, mouth, feet, lips)
- Convulsions
- Arrhythmias
- Tetany
(CATs go numb)
- Chvostek’s sign: tap facial nerve above zygomtic arch –> twitching of facial muscles)
How is vitamin D synthesised?
- 7-dehydrocholesterol precursor in skin converted to vit D3 (cholecalciferol) by UVB light
- Vit D3 (cholecalciferol) + vitamin D2 from diet (ergocalciferol) are converted to 25-OH D3 in liver
- 25-OH D3 activated to 1,25(OH)2D3 (calcitriol) by renal 1a-hydroxylase (stimulated by PTH) in kidneys
What is the role of vitamin D and its metabolites in calcium regulation?
- Increases Ca absorption in gut
- Increases Ca and phosphate release from bone
- Negative feedback on PTH
What are the clinical features of vitamin D deficiency?
- Softening of bone
- Bone deformities
- Bone pain
- Severe proximal myopathy (can’t rise from squat)
- Rickets in children
- Osteomalacia in adults
- Low plasma [25(OH)D3]
- Low plasma [Ca]
- Low plasma [PO43-]
- High [PTH] if secondary hyperparathyroidism
What are the predisposing factors of vitamin D deficiency?
Non-modifiable:
- Age
- Female sex
- Non-white race
- Anti-epileptic therapy
- Malabsorption (IBD, CF)
- Burns
Modifiable:
- Obesity
- Less milk drinking
- Not taking vitamin D supplements
- Less outdoor physical activity
- Exclusive breast-feeding
- Sunscreen use
- Clothing
Non-patient factors:
- Higher latitude
- Season of year
- Lower altitude
- More cloud cover
What can cause vitamin D excess?
- Excessive treatment w/active metabolites of vit D (patients w/chronic renal failure)
- Granulomatous disease, e.g. sarcoidosis, leprosy, TB
What are the effects of vitamin D excess?
- Hypercalcaemia
- Hypercalciuria (both due to increased intestinal Ca absorption)
How is the cause of hypercalcaemia determined?
High Ca + high PTH = primary hyperparathyroidism
High Ca + low PTH = hypercalcaemia of malignancy
What is the main effect vitamin D deficiency?
Lack of mineralisation in bone
How does granulomatous disease cause vitamin D intoxication?
- Granulomatous tissue can convert 25-hydroxycalciferol to active metabolite 1,25-dihydroxycholecalciferol
- Granulomatous tissues have 1a hydroxylase
- Ectopic production of calcitriol
How is PTH secretion regulated?
- Calcium sensing receptors on PT cells
- High [Ca] ECF - Ca binds to receptor, activation inhibits PTH secretion
