phosphorous homeostasis & disorders Flashcards
where is phosphorus stored in the body
- bone (mostly)
- intracellular organic molecules
- extracellular fluid
describe the relationships between calcium and phosphorus to maintain homeostasis
law of mass action:
- high concentrations of either or both will form insoluble precipitates
- soft tissue mineralisation occurs in renal disease
- homeostasis aims to keep the calcium and phosphate at levels suitable for mineralisation of bone but not soft tissue mineralisation
dietary:
- food high in phosphorus will be low in calcium and vice versa (meats and grains, herbage low in phosphorus)
connected control mechanisms
- calcitriol and PTH
describe how phosphorus is absorbed
- intestinal phosphate absorption promoted by 1,25 dihydroxyvitamin D (calcitriol)
- renal resorption mostly in proximal convoluted tubule, rest distal (body doesnt want to loose all phosphate
explain how phosphate is controlled via excretion
- PTH promotes renal PO4 losses
- salivary losses and recycling (phosphorus high in saliva)
- FGF-23
what is FGF-23`
- not a hormone
- fibroblast growth factor 23
- secreted by bone: osteocytes>osteoblasts in response to PO4
- phosphaturetic
- anti alpha-1 hydroxylase
- anti PTH
what are the actions of FGF-23
discuss dietary phosphorus deficiencies
- herbivores grazing phosphorus deficient pasture without grain
- leads to bone mineralisation (rickets and osteomalacia
- pica
discuss excess dietary phosphorus
- phosphorus excess associated with calcium deficiency
- ideally, Ca:P ratio should be close to or >1
- all meat diets lead to excess phosphorus
- high ceral diets as well
what factors control PO4
- dietary intake and absorption
- calcitriol (resportion from bone and absorption from GI)
- PTH (resorption from bone and absorption from GI)
- renal tubular resorption (increase by tubular filtered load, decreased by PTH
- phosphatonions (FGF-23)
how does hyperphosphatemia occur
- reduced GFR (reduced clearance)
- calcitriol promotes intestinal absorption (in vit D tox)
- hypoparathyroidism (no PTH = no increase loss of PO4 in kidney = increase PO4 concentration)
- young and growing
- other increased bone turnover causes (hyperadrenocorticism, hyperthyroidism)
what is the clinical presentation of hyperphosphatemia
- FGF -23 mediated actions (decreased calcitriol, secondary renal hyperparathyroidism, osteopenis, osteomalacia, rubber jaw, soft tissue mineralisation)
- acute: leads to hypocalcemia and tetany
what is secondary renal hyperparathyroidism
caused by renal disease
- reduced GFR
- reduced clearance of PO4
- increased serum PO4 (bone cells recognize and produce FGF-23)
- complexed Ca fraction increase, ionised Ca fraction decrease
- ionised Ca fraction decreases leading to increase PTH leading to bone resorption
- tubular damage, FGF-23 leads to decreased calcitriol
- PU = calcium losses
- poor appetite and decreased calcitriol leads to poor Ca uptake
solved by therapeutic calcitriol
describe secondary hyperparathyroidism in horses
bran disease/big head
- low calcium grasses
- high phosphorus grains
- low dietary Ca:P ratio
- FGF-23 leads to decreased calcitriol
- ionised Ca fraction decreases, leading to increase PTH, leading to bone resorption
- bone loss from skull leads to swelling
what disease is PO4 restriction important for and how is it acheived
renal failure
- PO4 restricted diets
- PO4 binders (oral antacids - calcium carbonate or lanthanum carbonate)
ruminant urolithiasis is caused by
- high grain diets with dietary phosphorus
- uroliths contain phosphorus (struvite or apatite)
- alkaline urine
- reduced water intake
- obstruction (+/-)
