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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).
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