Page 910 - Small Animal Clinical Nutrition 5th Edition

942 Small Animal Clinical Nutrition

excretion (Yu and Gross, 2005). However, the effects of vitamin
Box 46-3. Urinary pH, Ammonium and
VetBooks.ir Anionic Phosphate. C supplementation have not been studied in cats at risk for cal-
cium oxalate urolithiasis. A large part of the metabolic pool of

Normal urinary concentration of total phosphate ions is high and glyoxylate is transaminated to glycine by the enzyme alanine
glyoxylate aminotransferase, which requires pyridoxine (vita-
not subject to great variation by dietary manipulation. Although min B ) as a cofactor (Menon and Koul, 1992). Pyridoxine
6
complexes are formed between phosphate ions and calcium and deficiency has been associated with increased oxalate produc-
magnesium ions, these complexes do not markedly decrease tion and urinary excretion in cats but has not been associated
free phosphate ion concentration. The urinary variable that has with calcium oxalate uroliths in cats (Bai et al, 1989, 1991).
the greatest impact on trivalent phosphate ion concentration is
urinary pH. Urinary pH influences formation of struvite precipi- Primary hyperoxaluria, due to reduced activity of hepatic D-
tates because it influences the amount of total urinary phospho- glycerate dehydrogenase, has been recognized in a family of
rus present as the free trivalent phosphate ion. Concentration of cats; however, the role of primary hyperoxaluria in cats with cal-
the free trivalent ion depends on the position of the acid-base cium oxalate uroliths is unknown (McKerrell et al, 1989).
equilibria of the two principal phosphate species that exist in the Urinary oxalate is an important determinant of urinary calci-
–
normal urinary pH range: HPO 4 2– and H PO . As urinary pH um oxalate saturation because small increases in oxalate excre-
4
2
increases, concentration of free trivalent ions increases, as tion profoundly influence the activity product ratio. Oxalate
monobasic and dibasic phosphates are deprotonated. forms a number of complexes and salts in solution; the calcium
salt is relatively insoluble and pH does not influence its solubil-
H PO 4 – = HPO 4 2– + H + ity over the physiologic range.The calcium salt of oxalate is just
2
HPO 4 2– = PO 4 3– + H + as insoluble in the luminal content of the intestinal tract as in
other complex solutions. Consequently, dietary calcium is an
important determinant of oxalate availability and intestinal
According to the above equations, an increase in hydrogen ion
concentration will shift both equilibria to the left, resulting in lower absorption. Sufficiently available dietary calcium in the intes-
concentrations of free trivalent phosphate (PO 4 3– ). Decreasing tinal lumen combines with oxalate to form insoluble complex-
urinary pH from 8.5 to 5.5, the approximate physiologic range for es of calcium oxalate. This phenomenon reduces intestinal
cats, results in a 14,000-fold decrease in free trivalent ion con- absorption and subsequently less renal excretion of calcium
centration, with no change in total urinary phosphate. oxalate. In contrast, if dietary calcium is reduced without a con-
Urinary pH also influences concentration of ammonium ions. comitant reduction in dietary oxalate, intestinal absorption and
Ammonia generated by urease enzymes provides necessary ions urinary excretion of oxalate may increase.
that react with available hydrogen ions to increase urinary pH:
Urine normally contains substances that modify and inhibit
+
NH + H = NH 4 + nucleation, growth and aggregation of crystals. This likely ex-
3
plains, in part, why urine of most human beings is continuous-
ly saturated with calcium oxalate, yet only a small percentage of
Reduction in urinary pH from the upper to the lower end of the
physiologic range changes the ratio of NH 4 + to NH from 3.4:1 the human population will form calcium oxalate uroliths dur-
3
to 3,400:1. Thus, foods that produce moderately acidic urine ing their lifetime. Inhibitors such as citrate, magnesium and
increase urinary ammonium concentration. However, because the pyrophosphate can form soluble complexes with calcium or
effect on free trivalent phosphate ion concentration is greater, the oxalic acid, making them unavailable to form insoluble salts
net effect of moderate urinary acidification is a reduced likelihood such as calcium oxalate (Khan et al, 1993). Low concentrations
of struvite precipitation. of urinary citrate are common in human patients with calcium
oxalate uroliths and some recurrent urolith formers may have
The Bibliography for Box 46-3 can be found at defective inhibitory substances (Hess et al, 1991; Parks and
www.markmorris.org.
Coe, 1986). Magnesium is a potent inhibitor of calcium oxalate
crystallization in vitro. Low excretion of magnesium in urine
cats and were confirmed to be calcium oxalate (Midkiff et al, has been suggested as a possible risk factor for development of
2000). In another study of 71 cats with hypercalcemia, eight of calcium-containing uroliths. In an experimental study in rats,
11 had calcium oxalate uroliths; nine of the 11 cats with uroliths administration of magnesium oxide prevented renal deposition
also had chronic kidney disease (Savary et al, 2000). The role of of calcium oxalate crystals in hyperoxaluric rats (Khan et al,
hypercalcemia in the pathogenesis of calcium oxalate uroliths 1993). Magnesium presumably increased urinary pH and
requires further study; it is appropriate to screen patients for excretion of citrate and decreased urinary oxalate excretion.
hypercalcemia and, when possible, manage the underlying cause. This effect of magnesium depends on which specific salt is used
Hyperoxaluria may result from increased dietary intake or (e.g., magnesium oxide has an alkalinizing effect, whereas mag-
endogenous production of oxalate from metabolism of ascorbic nesium sulfate has an acidifying effect). Other substances such
acid (vitamin C), glycine, glyoxylate or other substances. A as mucoproteins (e.g., Tamm-Horsfall mucoprotein), nephro-
study in healthy cats fed differing amounts of vitamin C rang- calcin and osteopontin (uropontin) also may inhibit crystal
ing from 40 to 193 mg vitamin C/kg of food for approximate- nucleation, growth and/or aggregation; however, their role in
ly one month found no significant change in urinary oxalate preventing calcium oxalate uroliths in cats has not been evalu-