calcium homeostasis

Question 1

What are the roles of calcium in the body?

Answer 1

• Signalling
• Blood clotting: essential component of clotting cascade
• Apoptosis: programmed cell death
• Skeletal strength: 99% of calcium in the body is wrapped up in bone where it gives strength to the skeleton
• Membrane excitability: calcium decreases sodium permeability (most critical in short term homeostasis)
• Storage in bone

Question 2

What does calcium do in cell signalling?

Answer 2

○ Exocytosis of important vesicles e.g. neurotransmitters, hormones etc.
○ Contraction of muscle fibers
○ Alters enzyme function

Question 3

Explain calcium distabution in the body

Answer 3

○ Stored in the extracellular bone matrix mostly in the form of hydroxyapatite
○ Phosphate homeostasis is important in determining calcium balance
○ 0.9% of calcium is stored in cells other than bone
○ 0.1% of calcium is found in the extracellular fluid
- The calcium in the extracellular fluid is maintained within tight limits (even to the detriment of the bones)
- Calcium has a high affinity for proteins and so will bind to plasma proteins (around 40%)
- Free ionised and therefor physiologically active calcium accounts for 50% of the plasma calcium
- The remaining 10% bind to plasma anions

Question 4

What happens in hypo- and hypercalcaemia?

Answer 4

○ Hypocalcaemia: Increases neuronal sodium permeability leading to hyperexcitation of neurons. In extreme cases cause tetany, if spreads to larynx and respiratory muscles- asphyxiation
○ Hypercalcaemia: decreases neuronal sodium permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias

Question 5

What allows calcium to be stored in bones and then to be taken out of bones to maintain extracellular homeostasis?

Answer 5

○ Osteoblasts: bone building cells which are highly active cells that lay down collagen in the extracellular matrix
○ Osteocytes: in established bone osteoblasts differentiate to become osteocytes which appear to regulate the activity of osteoblasts and osteoclasts
○ Osteoclasts: cells that are responsible for mobilising bone, they secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix

Question 6

When is PTH released?

Answer 6

PTH is released in response to low calcium levels in the plasma

Question 7

What does PTH do? (in terms of calcium and phosphate levels)

Answer 7

○ Stimulating osteoclasts to increase reabsorption (release) of calcium and phosphate in bone
○ Inhibiting osteoblasts to reduce calcium deposition in bone
○ Increasing reabsorption of calcium from the kidney tubules, therefor decreasing its excretion in the urine
○ Increasing renal excretion of phosphate which elevates free calcium by preventing it from being deposited in the bone (a process that requires phosphate)
○ Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney

Question 8

What does PTH do? (in terms of renal formation of 1,25-dihydroxycalciferol)

Answer 8

• AKA active vitamin D3 or Calcitriol
• It complements the action of PTH to increase the level of calcium in the plasma
• Binds to nuclear receptors in target tissues (intestine, bone and kidney) to:
○ Increase absorption of calcium from the gut
○ Facilitate renal absorption of calcium
○ Mobilise calcium stores in bone by stimulating osteoclast activity

Question 9

What is the effect of 1,25-dihydroxycalciferol on the absorption of calcium from the gut?

Answer 9

• Much of the calcium in the diet passes straight through the gut and is excreted in the faeces
• The active transport system which moves calcium from the intestinal lumen to the blood is under the control of calcitriol

Question 10

What is the nature and function of calcitonin?

Answer 10

• Peptide hormone produced by the thyroid gland
• Its secretion is stimulated by increased plasma levels of calcium
• Main actions: bind to osteoclasts and inhibit bone reabsorption as well as increasing renal excretion so preventing a further increase in calcium
• There is little evidence that suggests that it is important to humans
• In thyroid disease such as tumours where calcitonin levels are very high, plasma calcium levels are normal and there are no abnormalities of bone structure
• Any activities of calcitonin is overridden by PTH
• Patients with no calcitonin secretion have normal calcium levels
• May be used (rarely) to treat Paget’s disease (overactive osteoclasts)