1. Calcium metabolism Flashcards
How does calcium enter the body?
Already present in cells or enters via the gut
How is calcium excreted?
Via the kidneys
What percentage of calcium is circulating and is in bones?
1% circulating, 99% in bones
Roles of calcium
- To maintain the body’s skeleton; we can slowly sacrifice bone i.e. osteoporosis to maintain nerve muscle function, however low bone calcium -> increased risk of fractures.
- Metabolic role in action potentials and intracellular signalling.
What are the forms serum calcium is found in?
- Free ionised (50%) -> biologically active. 2. Protein bound (40%) -> mainly albumin, changes in albumin can falsely show a deranged calcium. 3. Complexed (10%) -> citrate or phosphate.
Total serum calcium normal ranges
2.2 - 2.6 mmol/L
Corrected calcium formula:
Serum calcium + 0.02 x (40 - serum albumin in g/L)
What is the corrected calcium if serum calcium is 2.2 and serum albumin is 30 g/L?
2.2 + 0.02 x (40-30) = 2.4 mmol/L = NORMAL
Why is free calcium important for nerve depolarisation?
Bound calcium does not have access
Ionised calcium can also be measured via blood gas, true or false?
True
What happens to bound calcium, free calcium when albumin is low? Thus what happens to correct calcium and ionised calcium when albumin is low?
Bound calcium will be low but free calcium will be normal. Thus corrected calcium will be normal and ionised calcium will be normal. (Formula: serum calcium + 0.02 x (40 - serum albumin in g/L) )
Corrected calcium tells you that the problem is albumin.
What detects hypocalcaemia?
Parathyroid gland
In hypocalcaemia, parathyroid gland releases PTH via autoregulatory mechanisms which obtains calcium from 3 sources:
- Bone - activates osteoclasts initiate bone resorption of calcium phosphate. NOTE osteoblasts build up bone and draw calcium in.
- Gut - increased absorption
- Kidney - resorption from tubule, renal phosphate wasting and 1a-OHxylase activation by PTH converts 25-OH Vitamin D (inactive - liver) to 1,25-(OH)2 Vitamin D (active) which increases intestinal calcium absorption as well
Two key hormones in hypocalcaemia
- PTH - 84 amino acid peptide
- Vitamin D - modified steroid hormone absorbed and unfolded in the skin. Vitamin D3 is an animal substance only, D2 is from plants.
How is vitamin D synthesised?
- 7-dehydrocholesterol in the skin is activated by sunlight to cholecalciferol (vitamin D3)
- Ergocalciferol is from plants. The difference between Vit D2 and D3 is a double bond
- 100% of absorbed vitamin D is converted to 25-OH D3 by 25-OHxylase in the liver, where it is stored
- When needed, activated by PTH in the kidney. PTH activates 1a-OHxylase which converts 25-OH D3 (inactive) into 1,25-di-OH D3 (active)
What is the rate limiting step in vitamin D synthesis?
1a-OHxylation - only occurs when calcium levels need to rise
How does sarcoidosis cause hypercalcaemia?
The macrophages in the lung produce 1a-OHxylase which can cause hypercalcaemia.
Seasonal changes of vitamin D
In summer, lot of vitamin D activation, high vitamin D stores in the liver, so patients become hypercalcaemic. In winter, less skin vitamin D activation, low vitamin D stores in the liver, so become hypocalcaemic.
Roles of 1,25-(OH)2 D3
- Intestinal calcium and phosphate absorption. Critical for bone formation and opposite to PTH in kidney causing phosphate wasting.
- Vitamin D receptor also controls many genes e.g. cell proliferation, immune system, etc.
- Vitamin D deficiency is associated with cancer, autoimmune disease and metabolic syndrome -> reason for this is poverty - poor people have vitamin D deficiency
When is ALP raised (bone causes)?
Post fracture, abnormal PTH secretion, children when growing.
Role of the skeleton from an orthopaedic view:
Structural framework, strong, relatively lightweight and mobile, protects vital organs, capable of orderly growth and remodelling.
Role of the skeleton from an endocrine view:
Metabolic role in calcium homeostasis; main reservoir of calcium, phosphate and magnesium
What is osteoporosis?
Occurs when calcium needs to be taken from bone stores. The bone gets thinner but the bone structure itself is normal. Normal feature of ageing, a consequence of living longer is we are likely to die of a fracture.
What is osteomalacia?
Bones are abnormal due to vitamin D deficiency. There is no vitamin D activated calcification of bone.
What happens in Paget’s disease?
Cause unknown ?virus. Thoughts are the virus is disappearing as very few new cases are appearing. Very active osteoclasts and osteoblasts, resulting in bone pain - cure is bisphosphonates.
Parathyroid bone disease
Tumour of parathyroid gland with very elevated PTH levels. Combination of osteoporosis and osteomalacia as you use up vitamin D as it is continuously being activated by PTH
What is renal osteodystrophy?
Renal failure and lack of vitamin D activation therefore you fail to excrete phosphate
Vitamin D deficiency - defective bone mineralisation. What does it cause in childhood and adulthood?
Rickets and osteomalacia
Vitamin D deficiency in the UK epidemiology
more than 50% of adults. 16% have severe deficiency during winter and spring.
Vitamin D deficiency risk factors
Lack of sunlight exposure, dark skin, dietary, malabsorption
Clinical features of vitamin D deficiency in adults
Osteomalacia: Bone and muscle pain; increased risk of fractures; low calcium, low phosphate and raised ALP; Looser’s zones (pseudofractures)
Clinical features of vitamin D deficiency in children
Rickets: Bowed legs, costochondral swelling, widened epiphyses at wrists, myopathy
Causes of osteomalacia
All causes are due to some form of vitamin D deficiency.
- Renal failure - lack of 1a-OHxylase
- Dietary deficiency
- Anticonvulsants induce breakdown of vitamin D (e.g. phenytoin in children to prevent fits)
- Lack of sunlight
- Phytic acid (found in chappatis) - chelates vitamin D in gut reducing absorption
Can pregnancy cause low vitamin D?
Yes, pregnancy where placenta makes PTHrp to steal calcium from mother for foetal one development, results in low vit D. Calcium is lost during breast feeding. NOTE: cancer cells also make PTHrp which is how they invade bone