Phosphate homeostasis

Plasma phosphate levels are maintained within a
concentration range of 1.12–1.45 mM. The restoration
of the normal plasma calcium level in response to
hypocalcaemia is not accompanied by a rise in plasma
phosphate because PTH independently causes a
phosphate diuresis. Unlike calcium, dietary phosphate
usually exceeds the body’s nutritional requirement,
therefore a major component of phosphate
homeostasis is renal excretion. A diet that is low in
phosphorus is likely to be low also in calcium, which
complicates the picture of phosphate homeostasis.
Let us consider a hypothetical situation of a normal
plasma calcium level during hypophosphataemia.
A lowering of plasma phosphate will stimulate the
kidney to release 1α,25(OH)2D3, which elicits both
the previously mentioned rapid (nongenomic) and
long-term (genomic) responses in the kidney, leading
to increased renal reabsorption of phosphate. The
1α,25(OH)2D3 will also increase the intestinal absorption
of phosphate and calcium. The parathyroids will
not be stimulated to produce PTH. In the absence of
PTH, mobilization of phosphate from the bone will be
retarded and there will be no phosphate diuresis. The
net effect will be an elevation of plasma phosphate.
Hyperphosphataemia is countered through phosphate
excretion, governed by the fact that the blood
phosphate concentration is maintained at or near the
renal transport maximum for the ion.
8.6.11 Effects of vitamin D defi ciency
Vitamin D defi ciency can arise from lack of sunlight
exposure, lack of dietary vitamin D intake, or impaired
intestinal absorption of the vitamin. At the
onset of defi ciency, there is a decreased effi ciency of
intestinal calcium absorption and a consequent fall in
the plasma calcium level. In response to the hypocalcaemia,
the plasma Ca2+ concentration is restored to
normal, but the Pi concentration falls. The rise in Ca2+
concentration is caused principally by two effects.
Firstly, PTH, acting with whatever 1α,25(OH)2D is
still present at the onset of defi ciency, elicits the mobilization
of Ca2+ and Pi from bone; secondly, PTH, acting
alone, causes an increase in the renal reabsorption
of calcium. The decline in plasma Pi concentration is
caused by a very strong effect of PTH on the kidney in
causing excessive phosphate excretion, an effect that is
usually great enough to override increased phosphate
mobilization from the bone.
During prolonged vitamin D defi ciency, the
increase in PTH secretion necessary to maintain
calcium homeostasis causes extreme osteoclastic
resorption of bone. This in turn causes the bone to
become progressively weaker and imposes marked
physical stress on the bone, resulting in rapid osteoblastic
activity. The osteoblasts lay down large quantities
of osteoid but, because of insuffi cient Ca2+ and
Pi, calcifi cation does not occur. Thus failure to calcify
newly formed bone matrix leads ultimately to rickets
or osteomalacia.