Page 1143 - Clinical Small Animal Internal Medicine

119 Disorders of Phosphorus and Magnesium 1081

PTH also increases renal absorption of calcium and Box 119.1 Regulation of phosphate handling by
VetBooks.ir stimulates production of calcitriol. The net effect of the kidney
PTH on the kidney is therefore a reduction in plasma
phosphate and an increase in plasma calcium.
Increased phosphorus concentration also directly stim­ In periods of phosphate excess, increase in PTH concen-
tration favors internalization and lysosomal degradation
●
ulates osteocytes to produce the phosphotonin FGF23. of the NaPi2a co‐transporter, thus limiting phosphate
FGF23 acts on the kidney in a similar manner to PTH, reabsorption and increasing phosphate excretion in the
●
decreasing tubular absorption of phosphorus. urine. Conversely, in periods of hypophosphatemia,
Calcitriol increases absorption of both calcium and decrease in PTH concentrations has a permissive role,
●
phosphorus from the small intestine. This process is favoring insertion and maintenance of the NaPi2a co‐
facilitated indirectly by PTH, which increases renal transporter in the proximal tubular brush border and
production of calcitriol. FGF23 has an opposing action, increasing phosphate reabsorption. PTH is therefore a
inhibiting calcitriol production and therefore decreas­ phosphaturic hormone promoting excretion of phos-
ing absorption of phosphorus from the intestinal tract. phate in the urine.
Calcitriol and PTH also increase reabsorption of cal­ FGF23, produced by osteocytes in response to
●
cium and phosphorus from bone. increased phosphorus concentration, also acts as a phos-
Meat, bone, and fish are food sources high in phospho­ phaturic factor. FGF23 in conjunction with its co‐factor
rus and dietary intake is therefore a major source of klotho decreases expression and activity of NaPi2a co‐
phosphorus for the body. Typical commercial canine and transporter in the proximal tubular cells, thus decreasing
feline diets have a phosphorus concentration of 0.8–1.6% tubular reabsorption and increasing renal excretion of
on a dry matter basis with a calcium to phosphorus ratio phosphorus.
of 1.2–2.1. Most organic phosphate is hydrolyzed in the Other factors which can modulate and increase renal
gastrointestinal tract to inorganic phosphate for absorp­ tubular phosphate reabsorption include growth hor-
tion. Phosphate is absorbed via paracellular pathways in mone, thyroid hormone, insulin, insulin‐like growth fac-
all regions of the small intestine. However, approximately tor 1 (IGF‐1) and 1,25 (OH) 2 cholecalciferol. Reabsorption
30% of intestinal absorption is active and occurs in the can be reduced by parathyroid hormone‐related protein
duodenum, utilizing a sodium‐phosphorus co‐trans­ (PTHrP), glucocorticoids, calcitonin, and atrial natriuretic
porter (NaPi2b). Expression and insertion of the NaPi2b peptide.
co‐transporter are under the control of calcitriol. A
decrease in intestinal phosphate or an increase in calci­
triol will increase intestinal absorption of phosphate.
Once absorbed, inorganic phosphate within the extra­ sodium, is the component routinely quantified by diag­
cellular pool is exchangeable with the skeletal stores nostic laboratories. Serum phosphate concentrations are
under the influence of both PTH and calcitriol. However, slightly higher than plasma phosphate concentrations
because proportionally only a very small amount of due to release of phosphate from cells and platelets dur­
phosphorus is found in the ECF, measurement of plasma ing the clotting process. Normal phosphate reference
phosphorus concentrations does not always provide a intervals will be laboratory dependent but values of
good reflection of total body phosphorus. approximately 2.5–5.5 mg/dL (0.8–1.8 mmol/L) are
Inorganic plasma phosphate that is not bound to pro­ reported for dogs and 2.5–6.0 mg/dL (0.8–1.9 mmol/L)
tein is freely filtered at the glomerulus. Approximately for cats.
85% of filtered phosphate is reabsorbed by active trans­ It is widely recognized that young animals demon­
port in the proximal tubule, with a small amount also strate elevated plasma phosphorus concentrations. This
absorbed in the distal nephron. However, during periods is likely to be the consequence of increased growth hor­
of low dietary intake, efficiency can increase until almost mone facilitating renal tubular reabsorption of phos­
100% of filtered phosphate is reabsorbed. Active trans­ phate and also increased concentrations of calcitriol. In
port occurs via sodium‐phosphate co‐transporters puppies up to 8 weeks of age, plasma phosphate concen­
(NaPi2a and NaPi2c) located in the brush border of trations up to 10.8 mg/dL (3.4 mmol/L) can be consid­
proximal tubular cells. Expression of the NaPi2a co‐ ered normal. However, an age‐related difference in
transporter is under the control of PTH, FGF23, and phosphorus concentrations can be present until 1 year
intestinal phosphate absorption (Box 119.1). of age. This difference is more marked in the dog than
the cat.
Phosphate concentrations can be factitiously increased
Laboratory Assessment of Phosphorus
by lipemia, hyperproteinemia, and hemolysis and can be
Circulating inorganic phosphorus (Pi), which can be increased postprandially, particularly after a high‐pro­
either free or complexed to calcium, magnesium or tein meal. Patients should therefore ideally be fasted for