PTH, FGF23 and phosphate loss through NaPi-IIa
Parathyroid hormone (PTH) and FGF23, a hormone made by bone, cause phosphate loss in the urine by removing NaPi-IIa, a sodium-phosphate carrier, from the proximal tubule, a nephron segment.
Remember
Raised PTH removes NaPi-IIa from the cell surface, so less phosphate is reabsorbed and phosphaturia (phosphate lost in the urine) results. FGF23 has a similar effect through a different pathway.
Phosphate is filtered freely at the glomerulus, and the proximal convoluted tubule (PCT), a segment of the nephron, takes most of it back. Cells there bring phosphate in through sodium-phosphate cotransporters on the apical membrane (the side facing the lumen), mainly NaPi-IIa and NaPi-IIc. These carriers move phosphate into the cell together with sodium.
Parathyroid hormone, made by the parathyroid glands, binds to receptors on the proximal tubule cells and triggers internalisation of NaPi-IIa: the transporters are pulled into the cell by endocytosis and degraded. The brush border is the fringe of microvilli (tiny finger-like projections) on the luminal surface of the cells, and it ends up with fewer carriers. Less phosphate is then reabsorbed, so more is lost in the urine. That loss is called phosphaturia.
FGF23 (fibroblast growth factor 23) is a hormone made by bone. It also lowers proximal phosphate reabsorption, through a different signalling pathway. When a genetic condition causes excess FGF23, phosphate is lost in the urine and the serum phosphate is low (hypophosphataemia).
If PTH falls, for example after a parathyroid adenoma (a benign tumour that makes too much PTH) is removed, fewer transporters are internalised, so more stay on the brush border and more phosphate is reclaimed.
Key facts
- Transporters
- NaPi-IIa and NaPi-IIc sit on the apical membrane of the proximal convoluted tubule and bring phosphate into the cell together with sodium.
- PTH action
- it internalises NaPi-IIa, so phosphate reabsorption falls and phosphaturia results.
- FGF23 action
- a bone-derived hormone with a similar effect on phosphate, through a different pathway.
- Fall in PTH
- more NaPi-IIa stays on the apical membrane, so phosphate reabsorption rises.
- Primary hyperparathyroidism
- a parathyroid gland (for example one containing an adenoma, a benign tumour) makes too much PTH, so the transporters are pulled off the surface continuously and phosphate is lost in the urine.
- Excess FGF23
- in a genetic condition that causes it, phosphate wasting in the urine and a low serum phosphate.
Exam traps
- Aldosterone, which regulates sodium and potassium further along the nephron, does not remove phosphate transporters from the proximal tubule.
- A fall in PTH does not increase the internalisation of NaPi-IIa, because internalisation is what happens when PTH is raised, and with less hormone there is less to pull the transporters off the surface.
- Excess FGF23 does not increase NaPi-IIa transporters on the apical membrane: more transporters would raise the serum phosphate, but FGF23 does the opposite.
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