What organs/systems regulate calcium balance in the body?
List the uses of calcium in the body
- Maintaining bone and teeth
- Regulates heart rhythm
- Nerve transmission at neuromuscular junction
- Reduces blood cholesterol
- Assists blood clotting
- Normal kidney function
- Lowers blood pressure
- Maintains nerve and muscle function
Where is calcium stored in the body?
99% stored as hydroxyapatite crystals in the skeleton 1Kg of calcium found in humans
In what forms are calcium found in the plasma?
- Biologically active free ionised Ca+
- Bound to plasma protein Eg Albumin
- Bound to citrate (low organic anions)
Describe the structure and half-life of PTH
- Polypeptide hormone
- Synthesised as pre pro hormone and cleaved to 84 aa
- Half-life of 4 minutes
What is the role of parathyroid hormone?
Increases serum calcium concentration
- Stimulates bone resorption
- Stimulates calcium reabsorption and excretion of phosphate
- Stimulates hydroxylation of vitamin D to active calcitrol
How is synthesis of parathyroid hormone regulated?
- Low serum calcium up regulates transcription of PTH in chief cells
- High serum calcium down regulates transcription of PTH Negative feedback mechanism
How is high calcium levels detected by chief cells?
- Calcium ions bind to G-protein coupled calcium receptors
- G protein disassociates and stimulates phospholipase C
- This inhibits adenylyl cyclase leading to reduced cAMP and reduced PTH
How does parathyroid hormone impact vitamin D?
- Stimulates conversion of vitamin D to its active form which increases calcium uptake in the gut
What are the two forms of vitamin D?
D3 - cholecalciferol - made form the skin and from dairy
D2 - ergocalciferol - from yeast and fungi
How is active calcitriol produced?
- Vitamin D3 or D2 undergo two hydroxylation reactions
- One in liver to 25-hydroxyvitamin D - Second in kidney to produce active calcitriol
What is the cause of hypercalcaemia?
- Over secretion of PTH due to primary hyperparathyroidism
- Usually caused by parathyroid adenoma or PTH related peptide (PTHrP) from various tumours
What are the symptoms of hypercalcaemia?
Renal calculi, kidney damage, constipation, dehydration, tiredness and depression
How is hypercalcaemia treated?
- Fluid replacement
- Usually removal of tumour (which could be secreting parathyroid hormone related peptide (PTHrP)
What is hypocalcaemia?
Low serum calcium due to PTH deficiency typically caused by surgical removal of parathyroid glands
What are the symptoms of hypocalcaemia?
Hyper-excitability of the neuromuscular junction, pins and needles, tetany, paralysis, convulsions.....death
How are phosphate levels regulated in the body?
- PTH stimulates phosphate excretion in kidney so reduces likelihood of calcium-phosphate stone formation
- Vitamin D stimulates uptake of both calcium and phosphate in the gut