Introduction 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 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) gout : more chronic process; can see granulomatous inflammation associated with tophi This form alone is rare, although it is the most frequent type in psittacines Crystal formation is rare in all other mammals as they have uricase and therefore excrete allantoin as their primary nitrogenous waste compound
Causes Impaired excretion- severe dehydration, severe renal disease, postrenal obstruction, nephrotoxic drugs, ochratoxicosis , viral infections including astroviruses and nephropathogenic infectious bronchitis virus Over production excessive dietary protein, inherited enzyme defects
Pathogenesis In birds, reptiles, and humans/great apes, uric acid is normally eliminated by a combination of glomerular filtration, secretion, reabsorption , and post- secretory reabsorption impaired excretion or overproduction 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
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
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
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
Radiating urate crystals surrounded by heterophilic inflammation and necrotic tubules Gouti tophus composed of radiating uric acid crystals surrounded by heterophilic inflammation.