Calcium and phosphate regulation Flashcards
What do osteoclasts and osteoblasts do?
Osteoblasts produce bone
Osteoclasts break bone down
What are the 3 functions of PTH?
- PTH instructs the kidney to absorb calcium
- PTH also promotes calcium release from the bones
- PTH regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) to active vitamin D (calcitriol)
How is phosphate concentration regulated?
In the nephron (PCT), phosphate is reabsorbed using sodium-transport co-transporters – phosphate leaves the nephron lumen and enters the cells
- PTH inhibits this
What happens to phosphate excretion in primary hyperparathyroidism?
Increase in phosphate excretion. These patients have a low serum phosphate due to inhibition of phosphate reuptake at the proximal convoluted tubule.
How does FG23 affect reabsorption of phosphate?
- Via the sodium-phosphate cotransporter
- Inhibits calcitriol (calcitriol assists phosphate reabsorption from gut).
How do parathyroid cells detect calcium?
What happens if calcium level is high?
They have calcium –sensing receptors on their surface. When you have high calcium in the ECF, calcium binds to these receptors. This inhibits PTH secretion – when your Ca is high, PTH is inhibited.
Where is vitamin D obtained from?
- Diet (ergocalciferol)
- Via UVB light (converts 7-dehydrocholesterol -> cholecalciferol (vit D3))
What happens to cholecalciferol in the liver and is the product made active?
Cholecalciferol is converted to 25-OH-D3 – biologically inactive
What happens to 25-OH-D3 in the kidneys?
It is converted into 1,25-(OH)2-D3 which is buologically active. This is timulated by PTH
What are the roles of vit D?
- Promotes calcium reabsorption from the gut and bones
- It increases renal Ca reabsorption, and produces negative feedback on PTH
- Helps phosphate reabsorption from the gut
What are the causes of vitamin D deficiency?
- A poor diet and malabsorption (e.g. coeliac disease)
- Lack of sun /too much sun cream,
- Liver and renal diseases
- A rare cause is vitamin D resistant rickets – vitamin D production is normal, but there are receptor defects (recessive, rare)
What is the normal serum range for calcium?
2.2–2.6 mmol/
What is chvostek’s sign and its use?
- Tap the facial nerve just below the zygomatic arch (cheek bone)
- A positive response will involve twitching of the facial muscles
- This indicates neuromuscular irritability due to hypocalcaemia
What is trousseau’s sign and its use?
- Also assesses for neuromuscular irritability in a patient with hypocalcaemia
- You inflate a BP cuff and leave it like that for several minutes
- This induces carpopedal spasm = neuromuscular irritability (hand contracts and can’t be relaxed)
What are the causes of hypocalcaemia?
- Vitamin D deficiency
- Low PTH levels = hypoparathyroidism
- Can be surgical causes (neck surgery), auto-immune or magnesium deficiency (needed for PTH)
- PTH resistance e.g. pseudohypoparathyroidism (patient can make PTH but have receptor defects)
- Renal failure: Impaired 1a hydroxylation -> decreased production of 1,25(OH)2D3
What are the effects of hypercalcaemia?
Stones (renal effects of hypercalcaemia)
- Polyuria & thirst
- Nephrocalcinosis, renal colic, chronic renal failure
Abdominal moans (GI effects of hypercalcaemia) - Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans (CNS effects of hypercalcaemia) - Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
How can hypocalcaemia be assessed for?
using chvostek’s sign and trousseau’s sign
What are the causes of hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy (tumours/metastases often secrete a PTH-like peptide)
- Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)
- Vitamin D excess (rare)
What is primary hyperparathyrodism?
Pattern of hormone and calcium/phosphate levels?
Treatment?
- Tumour in the parathyroid causes a large increase in PTH secretion
- Because it is a tumour it is unlikely to be regulated by the normal negative feedback
- It will continue to produce large amounts of PTH leading to an increased plasma calcium ion concentration
- Raised calcium, low phosphate, raised PTH
- Treatment is parathryroidectomy
What would hypercalcaemia of malignancy look like?
How can you differentiate between hypercalcaemia of malignancy and primary hyperparathyroidism?
Patients present with high calcium, but this is not due to a parathyroid adenoma making too much PTH. There is -ve feedback as serum calcium rises, PTH falls (nothing wrong with the parathyroid gland). High calcium and supressed PTH. This is how you differentiate between the two causes.
What does vit D deficiency lead to?
- Lack of mineralisation in bone
- 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 -> low calcium
- Some people have low plasma calcium concentration for a variety of other reasons such as renal failure
- Renal failure leads to loss of calcium in the urine which will stimulate the parathyroid to release PTH
- PTH will do its best to maintain the plasma calcium ion level by increasing
What is tertiary hyperparathyroidism?
- Initial chronic low plasma calcium ion concentration
- The parathyroid gland is being massively stimulated for a long time
- Eventually, the PTH becomes autonomous and stops responding to negative feedback
What are the biochemical findings in vit D deficiency?
*calcium, phosphate, PTH levels
- Plasma [25(OH)D3] usually low (we don’t measure 1,25 (OH)2 D to assess body vitamin D stores
- Plasma [Ca2+] will be low (may be normal if secondary hyperparathyroidism has developed)
- Plasma [PO43-] will be low (due to reduced gut absorption)
- [PTH] high (secondary hyperparathyroidism)
