Abstract
Amyloidosis is a condition that affects humans and a large number of animal species. It is characterized by the abnormal deposition of extracellular fibrillar proteins in wide range of tissues. Amyloid can be classified based on its constituent chemical fibrils (e.g., AL, AA, Aβ), distribution pattern (systemic vs. localized), or based on association with other diseases (primary vs. secondary). Reactive systemic or secondary, amyloidosis is associated with chronic inflammation.1 Amyloidosis has been reported in captive and free-ranging wildlife and is often associated with severe inflammatory disease.6,8,9 Among marine mammal species, amyloidosis has been reported in several stranded bottlenose dolphins.2 Although severe inflammatory diseases are relatively common in stranded pinnipeds,3 amyloidosis has not been previously reported. The purpose of this study was to describe the pathologic features of amyloidosis in stranded California sea lions (Zalophus californianus) and to identify any predisposing conditions associated with amyloid deposition.
Between 1983 and 2004 a total of 20 sea lions were diagnosed with amyloidosis via histopathologic examination of necropsy specimens by the Pathology Service of the Veterinary Medical Teaching Hospital, University of California, Davis, CA. All animals stranded live along the central California coast and were brought to The Marine Mammal Center (Sausalito, CA) for rehabilitation. Sixteen of the twenty sea lions diagnosed with amyloidosis died or were euthanatized within three days of stranding. In the remaining four sea lions, time in rehabilitation ranged from seven to 30 days. Antemortem blood work was available for five animals. Abnormal blood values in these sea lions included leukocytosis (5/5) and hyperglobulinemia (4/5). All animals were determined to be sexually mature adults, based on standard length, weight, tooth development, and presence of a sagittal crest in males.7 Eighteen animals were females and two were males.
The most common organs affected were, in order of decreasing frequency, kidney (18/20), blood vessels (19/20), thyroid gland (13/20), gastric and intestinal mucosa (3/20), and liver (2/20). In all affected kidneys amyloid deposition was found in the peritubular interstitium, particularly in a distinct band along the outer medulla adjacent to the corticomedullary junction. Glomerular amyloid deposits were found in 16 of 18 affected kidneys and deposits were present in the walls of small and medium muscular arteries or arterioles in 17 of 18 affected kidneys. Amyloid deposits within glomeruli consisted of segmental or nodular deposits expanding the mesangium and capillary basement membrane. Glomerular and interstitial amyloid deposits were often seen in conjunction in affected kidneys. In affected thyroid glands, large deposits of amyloid were present in the interstitium separating thyroid follicles. Deposition of amyloid in extrarenal blood vessels occurred in 15 of 20 sea lions. Blood vessels most commonly affected were arterioles in the spleen, pancreas, heart, and adrenal gland. In five of these animals, amyloid deposits were also detected in arterioles within the brain, meninges, and choroid plexus. In the two affected livers, amyloid deposits were within the space of Disse lining hepatic cords. Localized amyloid deposits were restricted to blood vessels of the penis and prepuce of one adult male sea lion with severe balanoposthitis.
Confirmation of amyloid deposition in affected organs was accomplished through examination of Congo red-stained sections. Amyloid stained pale red-orange with Congo red and exhibited characteristic apple green birefringence under polarized light. Pretreatment with potassium permanganate abolished Congo red staining, suggesting that the amyloid fibrils were type AA.10
Underlying inflammatory conditions were common in most of the sea lions diagnosed with amyloidosis. Ten of twenty sea lions with amyloidosis had concurrent metastatic carcinoma of presumed urogenital origin.5 In many affected tissues, the neoplastic masses contained large central regions of necrosis with widespread areas of inflammation. Moderate to severe interstitial nephritis was observed in four of 20 sea lions with amyloidosis. Two sea lions had severe bronchopneumonia associated with metastrongyloid lungworm and bacterial infection. Two animals had lesions in the hippocampus and amygdala consistent with domoic acid toxicosis. One animal had chronic osteomyelitis and myositis, two animals had chronic abscesses, and one animal had severe granulomatous hepatitis associated with trematode infection. Other inflammatory diseases diagnosed concurrently with amyloidosis included enterocolitis (9/20), gastritis or gastric ulceration (8/20), and cholecystitis (7/20). Stress has been proposed as a primary factor in amyloidosis in other species.4,6 Ten of the twenty animals with amyloidosis had adrenal cortical hyperplasia identified histologically. The significance of this finding is unknown, however, as normal weight ranges for adrenal glands and normal values for plasma cortisol have not been established for California sea lions.
The pattern of amyloid distribution in the sea lions in this study is similar to that described in other species with reactive secondary amyloidosis. The predilection for amyloid deposition in the outer cortex and corticomedullary junction was an unexpected finding; however, a similar pattern was also noted in bottlenose dolphins with renal amyloidosis.2 The results of this study indicate that amyloidosis can be a significant cause of morbidity and mortality in stranded adult California sea lions and is often secondary to underlying inflammatory disease.
Acknowledgments
We thank the staff of The Marine Mammal Center for submission of the cases and the anatomic pathology residents for initial review of cases.
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