JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1952605): Crowned pigeon
HISTORY: Tissue from a very thin common crowned pigeon found down in its cage. At necropsy, the bird had no subcutaneous fat stores, and there were white crystalline deposits on serosal surfaces throughout the coelomic cavity.
HISTOPATHOLOGIC DESCRIPTION: Kidney (3 sections): Multifocally and randomly, expanding and replacing tubules and extending into the adjacent cortical interstitium are colorless to basophilic radiating, sharp, acicular, crystalline deposits (urate tophi) up to 150 microns in diameter which are often surrounded by low to moderate numbers of viable and degenerate heterophils, fewer macrophages, and small amounts of eosinophilic cellular and karyorrhectic debris (necrosis), hemorrhage and fibrin, which extend into the adjacent interstitium. Tubules exhibit one or more of the following changes: mild ectasia with attenuated epithelium; swollen epithelial cells with indistinct cell borders and microvacuolated cytoplasm (degeneration); hypereosinophilic epithelial cytoplasm and pyknotic nuclei (necrosis); or hypertrophic, crowded epithelial cells with prominent nuclei that have coarse chromatin and rare mitotic figures (regeneration). Multifocally, tubular lumina contain sloughed necrotic epithelial cells admixed with heterophils and cellular debris (cellular casts), and affected tubules often have disruption of the tubule basement membrane (tubulorrhexis). Randomly, the interstitium contains an infiltrate of few heterophils and occasional macrophages.
Liver (2 sections): Multifocally and randomly, there are few previously described urate tophi surrounded by heterophils and macrophages.
Spleen: There are rare urate tophi as previously described.
Kidney: Urate tophi with mild heterophilic and histiocytic interstitial nephritis, cellular casts, and tubular degeneration, necrosis, and regeneration, common crowned pigeon (Goura cristata), avian.
Liver: Few urate tophi.
Spleen: Rare urate tophi.
CONDITION: Visceral gout (Visceral urate deposition); renal gout in chickens may also be referred to as urolithiasis, nephrosis and caged layer nephritis
- Gout is a disease characterized by urate crystal deposition on articular/synovial surfaces of joints and/or serous surfaces of viscera in birds, reptiles and humans
- Visceral gout or a mixed visceral-articular form is seen most commonly in birds and is more of an acute process compared to articular gout; these tophi incite little to no inflammatory response as compared to the inflammation seen in articular gout
- Synovial (articular) gout alone is rare, although it is the most frequent type in psittacines; it is a chronic process that results in deposition of urates and a resulting granulomatous inflammation in the joint spaces
- Catabolism of purines in mammals occurs by conversion to allantoin:
- Adenine > inosine > hypoxanthine > xanthine > uric acid > allantoin
- Guanine > xanthine > uric acid > allantoin
- Humans and higher apes, birds, and reptiles lack the enzyme uricase to convert uric acid to allantoin
- Uric acid is normally eliminated by a combination of glomerular filtration, secretion, reabsorption, and post-secretory reabsorption
- Gout is mainly due to impaired excretion by the kidneys (severe dehydration, severe renal disease, postrenal obstruction, nephrotoxic drugs, infections such as avian nephritis virus or nephrotoxoic infectious bronchitis virus ochratoxicosis) or overproduction (excessive dietary protein or calcium, inherited enzyme defects) of uric acid > elevation of plasma uric acid concentration (hyperuricemia) > precipitation of monosodium urate crystals (tophi) on many visceral and/or articular surfaces > phagocytosis of tophi by macrophages > activation of caspase 1 > release of IL-1beta > recruitment of granulocytes > release of leukotriene B4, prostaglandins, free radicals and lysosomal enzymes from granulocytes > chronic inflammation and fibrosis
- In mammals, the solubility of uric acid is modulated in joints by temperature (lower temp, lower solubility > peripheral joints favor precipitation) and in the kidney by pH (lower pH in tubules, lower solubility)
- In birds, development of gout is influenced by exposure to cold, dampness, excessive dietary protein, vitamin A or B12 deficiency, dehydration, nephrotropic strains of infectious bronchitis virus, avian nephritis virus (astrovirus), and Type A influenza
TYPICAL CLINICAL FINDINGS:
- Birds may appear alert but progressively weaken until death
- Birds with articular gout are restless and have difficulty flying and perching; toes become swollen, warm, and rigid
TYPICAL GROSS FINDINGS:
- Visceral: White/gray chalky patches are present on serous membranes: pericardium, liver, mesentery, and peritoneum; in liver and kidney, deposits may be interstitial and subcapsular
- Kidneys alone may be affected (renal gout); the kidneys are enlarged, tubules are streaky due to urate distension, and the ureters may be obstructed and dilated with thick gray-white cords or cylindrical concretions surrounded by thick mucus
- Articular: Swollen joints and tendon sheaths contain white deposits that are frequently visible through the skin; the joints of the extremities are most commonly affected; synovial membranes are swollen and hyperemic, many epithelial cells are desquamated, and the surface is covered with fibrin and embedded urate deposits; swellings may rupture, and heal poorly
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Tophi are pathognomonic: Clusters of sharp acicular, birefringent, radiating, basophilic or colorless (ghost) crystals surrounded by a variable inflammatory reaction of neutrophils or heterophils, macrophages and giant cells
- Crystals may not be birefringent on histologic sections due to degradation of crystals during tissue processing
- Articular gout: Tophi and associated inflammation in articular surfaces, joint capsule or adjacent tissues
- Renal and visceral gout: Tophi and associated inflammation in tubules and ureters; various serous surfaces covered with finely crystalline or granular material that does not stain
- Renal gout: Tubular degeneration, dilation, atrophy and dilated ureters “upstream” of the site of uretral obstruction; compensatory hypertrophy of undamaged portions of kidney
ADDITIONAL DIAGNOSTIC TESTS:
- Formalin fixation results in leaching of most urate deposits since they are water-soluble; collection in absolute ethyl alcohol is preferable
- Light microscopic examination of deposits for characteristic crystalline architecture is a practical diagnostic method; crystals appear as sharp, acicular (needle-like), clear to basophilic, radiating spicules
- Tophi stain with Gomori's methenamine silver (GMS) and Von Kossa's stain for calcium
- Chondrocalcinosis (pseudogout) - Crystals other than sodium urate, such as calcium pyrophosphate crystals are deposited in joints; clinical and radiographic features resemble articular gout; this has been described in a dog and in macaques
- Reptiles: Both articular and visceral forms are found; the visceral form is commonly associated with unexpected death without premonitory signs; gout may develop in the absence of primary renal disease; hyperuricemia is present; gentamicin is recognized as a cause of nephrotoxic gout in snakes and has been suggested as a model for gout in reptiles; renal constipation in reptiles may occur due to dehydration, slowing urate clearance and leading to similar histological lesions; lower ambient temperature decreases renal tubule function and clearance of drugs, which may predispose animals to development of gout
- Dogs: Dalmatians have two hereditary defects predisposing to urate urolithiasis; dalmatians cannot oxidize uric acid to allantoin due to a defect in hepatocellular urate oxidase (uricase); dalmations poorly reabsorb uric acid in renal proximal tubules and they secrete excessive uric acid compared to other breeds, resulting in hyperuricosuria; uric acid is poorly soluble in urine and precipitates out in the urinary bladder as the monohydrate
- Mink: Urate nephrolithiasis due to an inherited defect in uric acid metabolism
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