Phosphate Flashcards
What is the weight and % of whole body phosphate
500-800g
1% total body weight
90% in bone mineral
What is the weight and % of serum phosphate
0.8-1.5 mmol/L
50% free ions
35% complexed with Na, Ca, Mg
10% protein-bound
What is the result of high phosphate
Excessive formation of hydroxyapatite
Deposition in tissues other than bone
What is the result of low phosphate
Poor bone mineralisation
- rickets or osteomalacia
- pain, fractures
What are the dietary source of phosphate
Protein
- animal
- dairy
- soy
- seeds and nuts
What is the daily recommended intake for phosphate
700mg
What regulates phosphate metabolism
Parathyroid hormone
1,25 dihydroxyvitamin D
FGF-23
What is the role of parathyroid hormone
Main function is regulation of calcium
Also affects phosphate
Increases 1,25 vitamin D - increases active gut absorption
Decreases tubular reabsorption of phosphate - increases renal excretion
What is the role of FGF-23 (fibroblast growth factor 23)
Now known to be a major regulator of phosphate metabolism
Produced by osteocytes
In response to
- rise in phosphate levels
- dietary phosphate loading
- PTH
- 1,25 vitamin D
What would genetic investigation be for rickets
Linkage analysis
- fixed genetic markers
- identify on which chromosome and region the abnormal gene is likely to be
Sequencing
- identify where DNA differs between affected and unaffected people
What are the actions of FGF-23
Decreases expression of Na transporter in renal tubule - increases renal excretion of phosphate
Decreases 1a-hydroxylation of vitamin D - decreases gut absorption of phosphate
Decreases whole body phosphate
How is phosphate secreted
Unbound phosphate (about 90%) is filtered
80% reabsorbed in proximal tubule by Na co-transporter
10% reabsorbed in distal tubule
Maximum rate of reabsorption is limited - excess is secreted
Describe inherited rickets
Presents in childhood or adulthood
Bone pain, deformity, fracture
Low bone density
Low serum phosphate
High urine phosphate
X-linked hypophosphatemic rickets
Autosomal dominant rickets
Describe tumour-induced osteomalacia
Rare form of osteomalacia with low phosphate
Seen in patients with small benign mesodermal tumours
Osteomalacia heals when tumour removed
- low serum phosphate
- high urine phosphate
What are the actions of FDF-23
Decreases expression of Na transporter in the renal tubule - increased renal excretion phosphate
Decrease 1a-hydroxylation of vitamin D - decreases gut absorption of phosphate
Decreases whole body phosphate
What does low phosphate cause
Osteomalacia
What does high phosphate result in
Excess calcification
What is the main regulator of phosphate
FGF-23
- Drives renal excretion
- disruption of FGF-23 causes clinical disease
What is the secondary regulator for phosphate
PTH