- Why is the calcium level in the blood so tightly controlled?
Nerves and muscles rely on calcium to cause depolarisation
- What are the consequences of high and low plasma calcium for nerve conduction?
High calcium – failure of depolarisation
Low calcium – trigger happy neurological system leading to epilepsy
- What is the normal range for plasma calcium concentration?
2.2-2.6 mmol/L
- What are the three forms in which calcium is present in the plasma?
Free (ionised) – 50% - biologically active
Protein-bound – 40% - bound to albumin
Complexed – 10% - citrate/phosphate
- State the equation for corrected calcium.
Corrected calcium = serum calcium + (0.02 x (40 – serum albumin in g/L))
NOTE: if your albumin level is constant, the total serum calcium will be roughly double the concentration of free calcium
- What are the main effects of PTH?
Liberation of calcium from the bone (increased bone breakdown) and kidneys (increased calcium resorption)
Stimulates 1-hydroxylase activity resulting in increased activated vitamin D
Stimulates renal phosphate excretion
- What is the rate-limiting step in vitamin D activation?
1alpha-hydroxylase
- What are the two forms of vitamin D?
Vitamin D2 (ergocalciferol) – from plants Vitamin D3 (cholecalciferol) – produced when UV hits the skin and converts 7-dehydrocholesterol to cholecalciferol NOTE: both are active
- Outline how 7-dehydrocholesterol is converted to activated vitamin D.
UV converts 7-dehydrocholesterol to cholecalciferol
This is then converted by 25-hydroxylase in the liver to 25-hydroxycholecalciferol
This then gets converted by 1-hydroxylase in the kidneys to 1,25-dihydroxycholecalciferol
NOTE: when you measure vitamin D levels, you’re actually measuring 25-hydroxy vitamin D levels. 25-hydroxy vitamin D is stored and converted to the active form when needed under the influence of PTH
- How can sarcoidosis lead to hypercalcaemia?
Lung cells of sarcoid tissue express 1-hydroxylase
NOTE: hypercalcaemia tends to be seasonal (i.e. during the summer months when more sunlight means more vitamin D which can be activated
- What are the main roles of vitamin D?
Increased intestinal calcium absorption
Increased intestinal phosphate absorption
Critical for bone formation
- What is ALP?
By-product of osteoblast activity
- What is bone a reservoir of?
Calcium
Phosphate
Magnesium
- What disease states does vitamin D deficiency cause?
Osteomalacia
Rickets
- List some risk factors for vitamin D deficiency.
Lack of sunlight
Dark skin
Dietary
Malabsorption
- Outline some clinical features of osteomalacia.
Bone and muscle pain
Increased fracture risk
Looser’s zones
- Outline the biochemical changes in osteomalacia.
Low calcium
Low phosphate
High ALP
- List some clinical features of rickets.
Bowed legs
Costochondral swelling
Widened epiphyses of the wrists
Myopathy
- Outline the pathophysiology of osteomalacia.
Vitamin D deficiency leads to secondary hyperparathyroidism which stimulates the liberation of calcium from the bone (leading to demineralisation of the bone)
- How can renal failure cause vitamin D deficiency?
A lack of 1alpha-hydroxylase means that you are unable to activate vitamin D
- Which group of drugs is associated with vitamin D deficiency?
Anticonvulsants – promote the breakdown of vitamin D
- Which component of common foods chelates vitamin D in the gut?
Phytic acid – food like chapatis have a high level of phytic acid which chelates vitamin D in the gut and reduces absorption
- How does acromegaly lead to osteoporosis?
Causes testosterone deficiency
- Describe the changes in serum biochemistry in osteoporosis.
Normal
