Calcium Dysregulation Flashcards
What increases plasma calcium levels?
- Vitamin D - synthesised in the skin and intake via diet
- Parathyroid hormone - secreted by parathyroid glands
Are the main regulators of calcium & phosphate homeostasis via actions on kidney, bone and gut.
What decreases plasma calcium levels?
Calcitonin which is secreted by the parafollicular cells of thyroid gland. Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy.
How is vitamin D metabolised?
UVB helps 7-dehydrocholestrol in the skin metabolise to pre-vitamin D3 and then vitamin D3. Vitamin D2 from diet and D3 from skin travel via systemic circulation to liver where 25-hydroxylase converts both into 25-(OH)cholecalciferol and then, in the kidney, 1-alpha-hydroxylase converts both to 1.25-(OH)cholecalciferol.
How is calcitriol synthesis regulated and detected?
Serum 25-OH vitamin D = good indicator of body vitamin D status. Calcitriol regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase.
What are the effects of calcitriol?
Increases calcium and phosphate reabsorption in the kidney.
Increases calcium and phosphate absorption in small intestine.
Increased osteoblast activity so calcium stored in bones.
What are the actions of parathyroid hormone?
Increased calcium reabsorption + phosphate excretion in kidney. Increased 1-alpha-hydroxylase activity so greater calcitriol synthesis. Therefore calcium and phosphate reabsorption increased in small intestine. Increased calcium resorption from bone.
How is serum phosphate regulated by FGF23?
FGF23 reduces serum phosphate. It does this through 2 means:
- Inhibits sodium-phosphate transporters in the kidneys so less sodium + phosphate reabsorbed from urine
- Inhibits calcitriol synthesis –> less calcium reabsorption and phosphate reabsorption
How is phosphate normally absorbed?
Phosphate reabsorption occurs via the gut and the kidneys. Phosphate is reabsorbed via sodium phosphate transporter cells. In the kidney, shown here, reabsorption of phosphate via these transporters results in less sodium excretion in the urine. Increased phosphate loss in the urine would lower serum phosphate levels.
Why is phosphate low in primary hyperparathyroidism?
PTH inhibits renal phosphate reabsorption by inhibiting these transporters so in primary hyperparathyroidism, high PTH causes low phosphate.
What are signs and symptoms of hypocalcaemia?
Sensitisation of excitable tissues; muscle cramps, tetany, tingling. Paraesthesia (hands, mouth, feet , lips), Convulsions, Arrhythmias, Tetany. Chvosteks’ sign is facial paraesthesia while Trousseau’s sign is a carpopedal spasm.
What are 2 causes of hypocalcaemia?
1. Low PTH levels = hypoparathyroidism Surgical – neck surgery Auto-immune Magnesium deficiency Congenital (agenesis, rare)
- Low vitamin D levels
Deficiency – diet, UV light, malabsorption, impaired production (renal failure)
What are signs and symptoms of hypercalcaemia?
‘Stones, abdominal moans and psychic groans’
Nephrocalcinosis - kidney stones, renal colic
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
What is a cause of hypercalcaemia?
- Primary hyperparathyroidism - high PTH, usually caused by a parathyroid gland adenoma and hence not subject to negative feedback
- Vitamin D excess is rare
- Malignancy can have 2 reasons:
- Bony metastases produce local factors activating osteoclasts
- Squamous cell carcinomas can produce PTH related peptides which can stimulate parathyroid gland.
Describe the biochemistry of primary hyperparathyroidism
- High calcium
- Low phosphate as increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
- High PTH (not suppressed by hypercalcaemia)
What is the treatment for primary hyperparathyroidism?
Parathyroidectomy. Untreated hyperparathyroidism has risks of: Osteoporosis, Renal calculi (stones), Psychological impact of hypercalcaemia – mental function, mood.
