Endocrine Physiology - Endocrine Control of Calcium Balance Flashcards
What are the roles of calcium?
- Signalling
- Blood clotting
- Apoptosis
- Skeletal strength
- Membrane excitability (Ca2+ decreases Na+ excitability)
How is membrane excitability affected in hypocalcaemia?
Increases neuronal Na+ permeability leading to hyperexcitation of neurones. In extreme cases it causes tetany, if it spreads to the larynx and respiratory muscles → asphyxiation.
How is membrane excitability affected by hypercalcaemia?
Decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrythmias.
Calcium distribution in the body.
- bones 99%
- intracellular 0.9%
- extracellular fluid 0.1% (neraly half ECF Ca2+ is bound to protein. So only 0.05% of the calcium in the body is free in solution and physiologically active)
How does pH affect Ca2+ binding?
Binding capacity increases under alkalotic conditions. (So if someone hyperventialates, plasma pH rises and plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany).
The oppostie occurs with acidosis where binding capacity reduces and free [Ca2+] plasma rises.
What are the three cell types involved in bone?
- Osteoblasts are the bone building cells.
- They differentiate to form osteocytes in established bone.
- Osteoclasts are the cells that are responsible for mobilising bone.
What is the function of osteocytes?
They appear to regulate the activity of osteoblasts and osteoclasts.
How do osteoclasts mobilise bone?
They secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.
Which two key hormones act to ↑ [Ca2+] plasma?
- Parathyroid hormone (PTH) - polypeptide hormone produced by the parathyroid glands
- Calcitrol - (active form of viatmin D3) steroid hormone produced from vitamin D3 by the liver and kidneys
What stimulus results in the release of parathyroid hormone?
↓ in free [Ca2+] plasma
How does parathyroid hormone act to increase free [Ca2+] plasma?
- Stimulating osteoclasts to ↑ resorption of Ca2+ and phosphate in bone (effects seen within 12-24 hours)
- Inhibiting osteoblasts to reduce Ca2+ deposition in bone
- Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine
- Increasing renal excretion of phosphate (this elevates free [Ca2+] by preventing it from being deposited back int bone, a process that requires phosphate)
- Stimulates the kidneys to synthesise calcitrol from vitamin D which promotes Calcium absorption at the gut and kidney
Actions of calcitrol:
- Increases absorption of Ca2+ from the gut
- Facilitates renal absorption of Ca2+
- Mobilises calcium stores in bone by stimulating osteoclast activity
At what level does someone become vitamin D deficient/insufficient?
Less than 20ng/ml
What is the effect of vitamin D on Ca2+?
While the direct effect of vitamin D is to release Ca2+ from the bone, its effects on Ca2+ absorption from gut and reabsorption at the kidneys means the net Vitamin D effect is to ↑ plasma [Ca2+] and ↑ mineralisation of bone.
Which conditions does a vitamin D deficiency result in?
- Rickets in children
- Osteomalacia in adults
Pathophysiology of rickets and osteomalacia.
Vitamin D deficiency → intestinal malabsorption of Ca2+ → ↓ [Ca2+] plasma → ↑PTH which then promotes phosphate deficiency which aggrivates Ca2+ loss form bone.
Which key hormone acts to decrease [Ca2+] plasma?
Calcitonin - a peptide hormone produced by the thyroid gland.
What are calcitonin’s main actions?
It binds to osteoclasts and inhibits bone resorption as well as increases renal excretion so preventing a further rise in Ca2+.
How does cortisol alter Ca2+ balance?
↓plama [Ca2+]
Inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+.
This can, over time, produce osteoporosis.
How does insulin alter Ca2+ balance?
Increases bone formation and antagonises the action of cortisol. Diabetics may have signigicant bone loss.
How does oestrogen alter Ca2+ balance?
Promotes bone formation via oestrogen receptors on osteoblasts. This explains post menopausal osteoporosis.
How does growth hormone alter Ca2+ balance?
Growth hormone is a constant stimulus for bone formation.
How does prolactin alter Ca2+ balance?
Promotes calcium absorption from the gut by stimulating synthesis of calcitrol.
