JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

December 2023

U-M08

 

 

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 amphophilic to lightly basophilic radiating, sharp, acicular, crystalline deposits (urate tophi) up to 150 µm 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) with 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.  

 

MORPHOLOGIC DIAGNOSIS: 

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, common crowned pigeon (Goura cristata), avian.

 

Spleen: Rare urate tophi, common crowned pigeon (Goura cristata), avian.

 

CONDITION: Visceral gout (Visceral urate deposition); renal gout in chickens may also be referred to as urolithiasis, nephrosis and caged layer nephritis

 

 

GENERAL DISCUSSION: 

• Gout is a disease characterized by urate crystal deposition on articular/synovial surfaces of joints and/or serous surfaces of viscera in birds, reptiles, great apes (including humans) 
• Visceral (acute) gout or a mixed visceral-articular form: seen most commonly in birds and is more of an acute process; tophi incite little to no inflammatory response 
• Articular (synovial; ‘chronic’) gout: more chronic process; can see granulomatous inflammation associated with tophi
• Birds, reptiles, and humans/great apes lack the enzyme uricase (enzyme that oxidizes uric acid to allantoin)
  1. Crystal formation is rare in all other mammals as they have uricase and therefore excrete allantoin as their primary nitrogenous waste compound 

 

PATHOGENESIS:

• Catabolism of purines (adenine, guanine) occurs by oxidation of uric acid to allantoin by uricase 
• In birds, reptiles, and humans/great apes, uric acid is normally eliminated by a combination of glomerular filtration, secretion, reabsorption, and post-secretory reabsorption

• Birds/reptiles: Uric acid excreted in feces as dry matter
• Humans/great apes: Uric acid excreted in the urine 

• Gout is mainly due to impaired excretion by the kidneys (severe dehydration, severe renal disease, postrenal obstruction, nephrotoxic drugs, ochratoxicosis, viral infections including astroviruses and nephropathogenic infectious bronchitis virus) 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 (inflammasome) > 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)

• Peripheral joints have decreased temperature (increased likelihood of precipitation) whereas follow up inflammation increases temperature and likely assists in resolution/dissolution seen in recurrent bouts

• In birds, development of gout is influenced by exposure to cold, dampness, excessive dietary protein and/or calcium, vitamin A or B12 deficiency, dehydration, mycotoxins, nephrotropic strains of infectious bronchitis virus, avian nephritis virus (astrovirus)

 

TYPICAL CLINICAL FINDINGS:

• Birds may appear alert but progressively weaken until death; may also reflect decreased production/performance
• 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. Kidneys are typically grossly normal.

 

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
  1. 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
• Monosodium urate stones are radiolucent, but when combined with calcium species (e.g. oxalates and/or phosphates) they are radiodense

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:

• Goose Astrovirus (GAstrV): novel astrovirus that emerged in China in 2015; causes visceral gout with high morbidity and mortality in 4-16 day old goslings; exact pathogenesis is currently unclear (Wankun, et. al, Poult Sci, 2020)
• 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
  1. Some reptiles excrete uric acid as their primary nitrogenous waste while others (crocodiles and some chelonians) utilize ammonia and/or urea. These latter species are still susceptible to gout during fasting periods when metabolism shifts or due to diet (protein overload). Herbivorous reptiles are also more susceptible. 
• Dogs: Dalmatians have two hereditary defects predisposing to urate urolithiasis
  1. Dalmatians cannot oxidize uric acid to allantoin due to a defect in uricase
  2. 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

 

REFERENCES: 

1. Albasan H, Lulich JP, Osborne CA, Lekcharoensuk C. Evaluation of the association between sex and risk of forming urate uroliths in Dalmatians. J Am Vet Med Assoc. 2005;227:465-9.
2. Conley KJ, Shilton CM. Crocodilia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:850-851.
3. Crespo R. Developmental, metabolic, and other noninfectious disorders. In: Swayne DE, ed. Diseases of Poultry. 14th ed. Ames, IA: John Wiley & Sons, Inc; 2020:1308-1310. 
4. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Colubriformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:743.
5. Fenton H, McManamon R, Howerth EW. Chapter 29: Anseriformes, Ciconiiformes, Charadriiformes, and Gruiformes. In: Terio KA, McAloose D, St. Leger J, ed. Pathology of Wildlife and Zoo Animals, Cambridge, MA Academic Press; 2018: 695-696. 
6. Graham EA, Burns RE, Ossiboff RJ. Depositional Diseases. In: Garner MM, Jacobsen ER, eds. Noninfectious Diseases and Pathology of Reptiles. Vol 2. Boca Raton, FL: CRC Press; 2021: 107-110.
7. Horvai A. Bones, joints, and soft-tissue tumors. In: Kumar V, Abbas AK, , Aster JC, Turner JR eds. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia, PA: Elsevier; 2021:1204-1207.
8. Ilha MR, Rajeev S. Pathology in practice. Mycotic dermatitis and gout in an American alligator.  J Am Vet Med Assoc. 2015 Mar 15;246(6):609-11.
9. Divers SJ, Innis CJ. Gout. In: Divers SJ, ed. Reptile Medicine and Surgery. 3rd ed. St. Louis, MO: Saunders Elsevier; 2019:642-644.
10. Sellers H, Ojkic DViral diseases. In: Boulianne M, ed. Avian Disease Manual. 8^th ed. Jacksonville, FL: The American Association of Avian Pathologists; 2019:33.
11. Olson EJ, Dykstra JA, Armstrong AR, Carlson CS. Bones, joints, tendons, and ligaments. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1087.
12. Ossiboff RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:897. 
13. Reavill DR, Dorrestein G. Psittacines, Coliiformes, Musophagiformes, Cuculiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:772-773.
14. Rodriguez CE, Duque AMH, Steinberg J, Woodburn DB. Chelonia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:826-827.
15. Shivaprasad HL. Fungal diseases. In: Boulianne M, ed. Avian Disease Manual. 8^th ed. Jacksonville, FL: The American Association of Avian Pathologists; 2019:122.
16. Shivaprasad HL. Miscellaneous diseases. In: Boulianne M, ed. Avian Disease Manual. 8^th ed. Jacksonville, FL: The American Association of Avian Pathologists; 2019:222-223.
17. Tripathi NK, Gregory CR, Latimer KS. Urinary system. In: Latimer KS, ed. Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology. 5th ed. Ames, IA: Wiley-Blackwell; 2011:278.
18. Trupkiewicz J, Garner MM, Juan-Salles C. Passeriformes, Caprimulgiformes, Coraciiformes, Piciformes, Bucerotiformes, and Apodiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:795.
19. Wankun Wu, Rong Xu, Yingjun Lv, Endong Bao. Goose astrovirus infection affects uric acid production and excretion in goslings. Poult Sci. 2020;99(4):1967-1974.
20. Wunschmann A, Armien AG, Hofle U, Kinne J, Lowenstine LL, Shivaprasad HL. Birds of Prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:718

 

 

Click the slide to view.

---