Page 214 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

204 ELECTROLYTE DISORDERS

reduces intestinal calcium absorption), and decreases mineralization, inflammation, fibrosis) could be
serum ionized calcium concentration by the mass law prevented and residual renal function maintained by die-
effect ([Ca] [Pi] ¼ constant). The resultant hypocalce- tary phosphorus restriction. 76,84 In cats with experimen-
mia and the decreased serum calcitriol concentration tally induced renal disease, histologic changes were
stimulate PTH secretion. This increased PTH secretion prevented by phosphorus restriction. 139 In a study in rats
increases renal excretion of phosphate and release of with 80% nephrectomy, diet was carefully controlled so
calcium and phosphate from bone. It also stimulates that only phosphorus intake differed between groups,
production of calcitriol. These actions normalize serum and a beneficial effect of phosphorus restriction was
phosphorus and ionized calcium concentrations. Thus, clearly demonstrated with regard to mortality, protein-
calcium and phosphorus balance is maintained by a pro- uria, histologic changes, creatinine clearance, and serum
gressive increase in serum PTH concentration (in early lipid concentrations over a period of 14 weeks. 102 Similar
chronic renal failure). However, as renal tubular destruc- beneficial effects were observed in dogs with 90%
tion progresses, there are fewer proximal renal tubules nephrectomy fed diets differing only in phosphorus con-
and a decrease in the amount of 1a-hydroxylase enzyme tent and followed for 12 months. 22 A similar experiment
present. This reduction in 1a-hydroxylase means that it is using 48 dogs with experimentally induced renal failure
harder for increased concentrations of PTH to increase found that the amount of dietary phosphorus was more
serum calcium concentration. It also means that calcitriol important in clinical management than the amount of
is not available to inhibit PTH secretion. 117 As serum dietary protein. 57 In studies of cats with naturally occur-
phosphate concentrations persistently remain increased, ring chronic renal failure, renal secondary hyperparathy-
other changes also occur. Persistent hyperphosphatemia roidism was successfully managed using a combination
in rats increases the number and size of parathyroid cells. of dietary restriction of phosphorus and administration
This is important because some percentage of each cell’s of phosphate binders. 11,49
secretion is autonomous, and parathyroid hyperplasia In contrast to findings in early chronic renal failure,
means that there is a greater amount of nonsuppressible hyperphosphatemia is typical in acute renal failure
PTH secretion. Chronically increased PTH concentra- because of insufficient time for compensatory
tion leads to bone demineralization and other toxic mechanisms to develop. Hyperphosphatemia also occurs
effects of uremia (e.g., bone marrow suppression, uremic in uroabdomen or urethral obstruction because of urine
encephalopathy). In addition, uremia decreases the num- reabsorption from the peritoneal cavity or decreased GFR
ber of parathyroid gland calcitriol receptors, which subse- caused by increased intratubular pressure resulting from
quently decreases the responsiveness of parathyroid urinary tract obstruction. 26,54
glands to the inhibitory effect of calcitriol on PTH Hypoparathyroidism in people causes mild hyperphos-
release. 21,90,110,162 Thus, both decreased calcitriol phatemia because renal reabsorption of phosphate is
production and decreased numbers of parathyroid gland increased in the absence of PTH. Mild hyperphos-
calcitriol receptors promote development of renal phatemia also occurs in dogs with hypoparathyroidism
secondary hyperparathyroidism. but is overshadowed by the effects of hypocalcemia
Renalsecondaryhyperparathyroidismcanbeprevented (e.g., muscle tremors, tetany, seizures, ataxia, behavioral
or reversed in dogs with experimentally induced chronic aberrations). 24,25,111,153 Hyperphosphatemia has also
renal disease by reducing dietary phosphorus intake in been reported in cats with hypoparathyroidism. 130
proportion to the decrease in GFR. 83,157,159 Early in the Acromegalic people may develop hyperphosphatemia
course of chronic renal disease, decreased phosphorus because of growth hormone’s effects on renal tubular
intake stimulates renal 1a-hydroxylase activity, which phosphate reabsorption. Mild hyperphosphatemia has
increases calcitriol production. Increased calcitriol been reported in some acromegalic dogs and
52,126,128,129
enhances intestinal calcium absorption, increases serum cats. Thyroxine increases renal tubular phos-
ionized calcium concentration, and decreases PTH secre- phate reabsorption, which contributes to the increased
tion. Late in the course of chronic renal disease, the serum phosphorus concentrations observed in hyperthy-
kidneys are unable to produce sufficient calcitriol to pro- roid cats. 127,167,170 Hyperphosphatemia was reported in
motenormalintestinalabsorptionofcalcium.Phosphorus 21% of hyperthyroid cats in one study. 127
restriction in advanced renal disease still decreases PTH
secretion by unknown mechanisms independent of serum TREATMENT OF
ionized calcium or calcitriol concentrations. 162 These HYPERPHOSPHATEMIA
observations form the basis for restricting phosphorus in Volume expansion with saline dilutes ECF phosphate and
the medical management of chronic renal failure. enhances renal phosphate excretion in dehydrated
Phosphorus restriction also may prevent renal disease patients. Increasing GFR by volume expansion increases
progression by minimizing renal interstitial mineraliza- the filtered load of phosphate, and natriuresis impairs
3
tion. In rats with experimentally induced chronic renal proximal tubular phosphate reabsorption. Administra-
failure, detrimental histologic changes (e.g., interstitial tion of glucose (and insulin if necessary) may temporarily