Lab Investigation of Disorders of Calcium & Phosphate Metabolism Flashcards
Where is calcium and phosphate obtained from?
Calcium and phosphate are obtained through diet and absorbed in the gut
What substances are required for ca and Phosphate absorption in the gut?
Requires calcitriol (Vit. D)
Vitamin D requires PTH and activation occurs in kidneys
How does PTH effect Ca and phosphate metabolism?
PTH promotes Ca absorption and Phosphate excretion
What is FGF-23?
Hormone released from osteocytes involved in phosphate regulation
How does FGF-23 effect phosphate metabolism?
Promotes phosphate excretion through kidneys via -ve feedback
Also has a negative effect on Vit. D conversion
What is the most common cause of osteomalacia?
Vitamin D deficiency
Usually due to combination of low dietary intake and lack of exposure to sunlight
Which members of the population are most at risk of Vit. D?
Elderly at risk, especially if in nursing home and not taking supplements
Breast-fed babies kept out of sunlight
What is vitamin D?
Calcitriol really a steroid hormone, not a vitamin!
Where is vitamin d synthesised?
Synthesised in skin in response to exposure to UV (‘sunshine vitamin’)
Outline the steps of vitamin D synthesis
Activated by 2 metabolic steps
25 hydroxylation in liver to form 25OH D3, major circulating metabolite
1α hydroxylation of 25 OH D3 in kidney produces 1,25(OH)2 D3, or calcitriol, the active hormone
Outline the serum mineral levels in Vit. D deficiency
Ca - low Pi - Low 25OHD - low 1,25(OH)2D - normal PTH - high
Why are there normal 1,25(OH)2D levels in vit. D deficiency?
Low 25OH D3 = less conversion to active form (calcitriol)
Low calcitriol = less absorption of Ca and P from gut ⇒ increased PTH secretion (due to low Ca)
PTH secretion also increases activation of Vit. D
Outline the expected serum minerla levels in 1OH mutation patients
Ca - low Pi - low 25OHD - normal 1,25OHD - V. low PTH - high
In Vit.D receptor mutations, what are the serum endocrine molecule levels?
Ca - low Pi - low 25OHD - normal 1,25OHD - v.high PTH - high
What is hypophosphataemia?
mineral deficiency of phosphate
What are Hypophosphatemic rickets?
rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)
What is the role of FGF-23?
FGF-23 promotes phosphate excretion
What are the causes of phosphate wasting rickets?
- Mutation leading to excess FGF-23 activity
2. Ectopic FGF secretion (benign tumour)
Outline the serum levels in hypophophataemic rickets
Ca - low/normal Pi - low 25OHD - normal 1,25OHD - low / normal PTH - high / normal FGF-23 - high
What is FGF-23?
a hormone secreted by osteocytes; discovered in 2000
How is FGF-23 activity mediated?
FGF-23 regulated by its short half life due to enzymatic cleavage
Outline the normal regulation of FGF-23
Active peptide with a cleavage recognition sequence that is identified by an enzyme and cleaved to produce 2 inactive fragments
How does FGF-23 mutations lead to hypophosphataemic rickets?
Mutation in cleavage recognition sequence causes site not to be recognised - active peptide remains in circulation ⇒ phosphate wasting
How does serum phosphate levels interact with FGF-23?
Inc. serum phosphate = increased FGF-23 secretion from osteocytes
FGF-23 causes phosphate excretion via -ve feedback
What are the effects of FGF-23 on vit d?
FGF-23 has an inhibitory effect on the conversion of precursor to calcitriol 1,25(0H)2D
Outline the relationship between PTH and calcitriol
PTH activates calcitriol; calcitriol self regulates via -ve feedback to inhibit PTH release
-ve feedback between PTH and FGF-23
How does renal disease effect calcium metabolism?
Renal disease can also lead to hypocalcemia
As renal failure progresses to severe stages it may lead to renal osteodystrophy
What is the endocrine function of kidneys?
Endocrine renal function to activate Vit.D
How does renal failure lead to renal osteodystrophy?
As renal failure occurs, all renal functions are affected
Less absorption/filtration etc. ⇒ low Ca and low P excretion ⇒ increases PTH which will try to increase calcitriol but is limited due to renal failure
How does renal failure cause bone lesions?
Secondary HPT, high PTH, prolonged leads to bone reabsorption. In addition, impaired acid excretion, acidosis exacerbating mineral loss from bone = bone lesions
