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834 Small Animal Clinical Nutrition
Table 39-1. Common characteristics of canine purine uroliths. ETIOPATHOGENESIS AND RISK FACTORS
VetBooks.ir Chemical names Formulas 4 2 Applied Biochemistry: Uric Acid Metabolism
C H N O NH •H O
Ammonium acid urate
5 3 4 3
Sodium acid urate
2
5 3 4 3
Uric acid C H N O Na•H O Uric acid is one of several biodegradation products of purine
C H N O •2H O
5 4 4 3
2
Xanthine C H N O nucleotide metabolism (Figure 39-1) (Foreman, 1984; Gut-
5 4 4 2
Some variations in mineral composition
Ammonium urate only man, 1964; Greene et al, 1969; Williams and Wilson, 1990;
Sodium calcium urate Wyngaarden and Holmes, 1978). Purines are made up of three
Sodium urate only groups of compounds: 1) oxypurines (hypoxanthine, xanthine,
Uric acid only
Xanthine only uric acid and allantoin), 2) aminopurines (adenine, guanine)
Ammonium urate mixed with variable quantities of sodium and 3) methylpurines (caffeine,theophylline and theobromine).
urate, or sodium and calcium urate, magnesium ammonium In most dogs and cats, allantoin is the major metabolic end
phosphate and/or calcium oxalate
Sodium and calcium oxalate product, and it is the most soluble of the purine metabolic
Xanthine and uric acid products excreted in urine (Bartges et al, 1992; Cohen et al,
Physical characteristics 1965; Giesecke and Stangassinger, 1990; Roch-Ramel and
Color: Light or dark brown, brown-green
Shape: Variable. Usually round or ovoid in urinary bladder, may Peters, 1978). Whereas uric acid provides a means for nitrogen
assume shape of renal pelvis (funnel shaped), may assume excretion in some animals (reptiles, birds, etc.), mammals
jackstone appearance. Usually smooth, occasionally irregular excrete nitrogen in the form of urea (ureotelics). Because peo-
or rough.
Nuclei: Nuclei and concentric laminations are common. ple and apes lack the enzyme uricase (urate oxidase), they can-
Density: Usually dense and brittle. Radiographically, purine not metabolize uric acid into allantoin. It has been estimated
uroliths have marginal radiodensity compared with soft tissue. that the serum uric acid level of people is up to 100 times
Some may be radiolucent.
Number: Single or multiple greater than serum creatinine concentrations in other mammals
Location: May be located in kidneys, ureters, urinary bladder (Rafey et al, 2003).
(most common) and/or urethra. The serum concentration of uric acid is derived from two
Size: Usually small (1 mm to 1 cm in diameter), occasionally
large (more than 1 cm) sources: 1) exogenously from food and 2) endogenously from de
Prevalence novo purine biosynthesis, involving nucleic acid turnover and
Approximately 5 to 6% of all canine uroliths. Approximately production from non-purine precursors. Purine synthesis occurs
13% of canine nephroliths.
May be recurrent. in the liver and involves recycling of guanine and hypoxanthine.
Characteristics of affected canine patients In people, excess nucleotides are converted to xanthine and then
In Dalmatian dogs, most common in males. uric acid via xanthine oxidase (Asplin, 1996). In most dogs and
Mean age at diagnosis is four years (range <1 to >17 years).
Most commonly observed in Dalmatian dogs, English bulldogs, cats, excess uric acid is converted to allantoin via the hepatic
miniature schnauzers, Yorkshire terriers and Shih Tzus. enzyme uricase. Allantoin is highly soluble in urine, whereas
uric acid and xanthine are not. Therefore, people are at greater
risk for uric acid urolithiasis than most dogs and cats (Cameron
and Sakhaee, 2007).Tissue catabolism or consumption of foods
calcium urate uroliths; however, these uroliths were primarily high in purine content may increase purine catabolism. In peo-
encountered in Dalmatians (92%) and English bulldogs (4%). ple, consumption of high-purine foods can cause as much as a
Six different breeds had uric acid uroliths; Dalmatians were 50% increase in urinary excretion of uric acid compared to con-
affected most commonly (80%). Five different breeds had xan- sumption of a purine-free diet (Fellstrom et al, 1983).
thine uroliths, including Dalmatians (56%) and English bull- In people, it has been estimated that approximately one-third
dogs (35%). Ammonium urate (97%), sodium and calcium of excess uric acid is eliminated by way of the intestinal tract
urate (96%), uric acid (100%) and xanthine (94%) uroliths were (Sorensen, 1965). The kidneys eliminate the remainder.
more commonly removed from the lower urinary tract than the Although the mechanisms involved in glomerular filtration,
upper urinary tract. renal tubular absorption and renal tubular secretion of uric acid
Ammonium urate, sodium and calcium urate and uric acid have not yet been completely defined, it appears that all three
uroliths typically appear as multiple, small, smooth, hard, mechanisms are involved (Cameron and Sakhaee, 2007). It has
round or ovoid structures with a characteristic brown-green been proposed that glomeruli freely filter uric acid. The proxi-
color (Table 39-1). However, the physical appearance of mal tubules actively reabsorb approximately 99% of filtered uric
urate uroliths may vary depending on the presence and quan- acid. Subsequently, the renal tubules secrete approximately 50%
tity of different mineral components, the quantity of matrix of the filtered uric acid, followed by 40% postsecretory reab-
they contain, the site(s) of their formation and growth and sorption. The final uric acid excretion is approximately 10%
whether or not they are associated with concurrent urinary (Cameron and Sakhaee, 2007).
tract disorders. Rarely, they form jackstones. Examination of Uric acid is a weak organic acid with an ionization constant
º
º
cross sections of urate uroliths frequently reveals concentric (pKa) of 5.5. At a temperature of 37 C (98.6 F), human urine
laminations and nuclei located in the geographic center of has a pKa of 5.35. Uric acid is less soluble than its base (urate)
the urolith. (Cameron and Sakhaee, 2007).