9-year-old, female, Egyptian fruit bat (Rousettus aegyptiacus)Animal from a zoological collection found deceased in its enclosure.

Gross Description:  

The liver was very small and firm with loss of lobular contours, and contained numerous 1-3 mm diameter nodules, consistent with cirrhosis.

Histopathologic Description:

Liver: There is cirrhosis, evidenced by streams of fibrous connective tissue dissecting between regenerative nodules of hepatocytes. Numerous small bile ducts and hemosiderophages are present within the fibrous connective tissue. A Prussian blue stain also reveals moderate to large amounts of hemosiderin within Kupffer cells, and a variable amount of hemosiderin within many hepatocytes and biliary epithelial cells. There are multifocal areas of hepatocellular necrosis, sometimes involving entire nodules or several adjacent nodules, and sometimes involving small clusters of hepatocytes within nodules. There are rare individual necrotic hepatocytes near the margin of lobules adjacent to regions of fibrosis and increased hemosiderin deposition. There is moderate to marked, multifocal cholestasis.

Morphologic Diagnosis:  

1. Hemochromatosis, liver: Marked hemosiderin deposition within macrophages, biliary epithelial cells and hepatocytes, with bridging fibrosis, nodular hyperplasia, and rare individual hepatocyte necrosis, liver.
2. Moderate, multifocal, acute hepatocellular necrosis.
3. Moderate to marked, multifocal cholestasis, liver.



Contributor Comment:  

In veterinary cases, hemochromatosis refers to excessive iron deposition with associated tissue damage (fibrosis and/or necrosis), and hemosiderosis refers to increased iron deposition without associated tissue damage. In human cases, the term hemochromatosis is generally reserved for genetic causes of iron overload, and all other cases are referred to as secondary iron overload.

Hemochromatosis has been described in numerous exotic species, including Egyptian fruit bats, hyraxes, mynahs, ramphastids and lemurs.(4) These appear to be diseases of captivity, and thus are believed to be related to husbandry. Some species of animals which are affected consume materials in the wild which are high in tannins, which are iron binders. Wild lemurs consume several plants that are high in tannins.(8) If these animals have adapted to a low level of available iron in their diet, they may absorb iron very efficiently. In a captive situation, with an iron-replete diet which contains no binders, excessive absorption of iron occurs. Iron homeostasis is principally controlled at the level of absorption, as there is no physiologic mechanism for excretion.(5)

Iron is typically bound to transferrin while it is in circulation and ferritin when it is stored. Iron bound to these proteins cannot participate in chemical reactions, as free iron can.(6) In iron overload, however, it is presumed that the storage capacity for iron is overwhelmed, and free iron is then available to participate in the generation of free radicals, either through the Fenton or Haber-Weiss reactions.(7) Free radicals can damage DNA, proteins and lipids. The organs damaged in many humans with iron overload are the liver, pancreatic beta (β) cells and heart, which are organs with high mitochondrial activity.(3) Approximately 1-2% of electrons in the mitochondrial electron transport chain are leaked into reactive oxygen species, such as H2O2 and O2-.(3)

High vitamin C concentrations in the captive diet of these frugivorous bats may also contribute to iron overload and associated damage, as vitamin C enhances the absorption of dietary non-heme iron1 and may exacerbate free radical damage from excess stored iron.(6)

The large areas of necrosis identified in this case are not consistent with hemochromatosis. In cases of hemochromatosis, hepatocyte necrosis is typically limited to individual hepatocytes, often bordering regions of fibrosis and increased iron deposition. A specific cause for the larger areas of necrosis was not identified in this case.

JPC Diagnosis:  

Liver: Hepatocellular degeneration, necrosis, loss and nodular regeneration, diffuse, marked, with bridging fibrosis and biliary hyperplasia (cirrhosis), marked bile stasis, and hemosiderosis (hemochromatosis).

Conference Comment:  

Conference participants were impressed by the level of hepatocellular damage and cirrhotic changes, which precipitated a discussion of whether the hemochromatosis preceded cirrhosis or vice versa. Cirrhosis is considered one of the three primary morphologic changes in hereditary hemochromatosis in humans. The authors of Robbins and Cotran Pathologic Basis of Disease note that, in addition to the toxic effects of free radical formation, iron also induces hepatic stellate cell activation with subsequent deposition of collagen.(2) They provide an overview of the pathogenesis of this disease in humans. Briefly, iron accumulation begins in periportal hepatocytes and as the iron load increases, more of the hepatic lobule becomes involved, including biliary epithelium and Kupffer cells. Fibrous septae slowly form, resulting in micronodular patterns of cirrhosis.(2)

The contributor provides a concise, informative overview of hemochromatosis as it pertains to veterinary species.


1. Cook JD, Watson SS, Simpson KM, Lipschitz DA, Skikne BS. The effect of high ascorbic acid supplementation on body iron stores. Blood. 1984;64:721-726.

2. Crawford JM, Liu C. Liver and biliary tract. In: Kumar V, Abbas AK, Fausto N, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia, PA: Elsevier Saunders; 2009:861-863.

3. Eaton JW, Qian M. Molecular bases of cellular iron toxicity. Free Rad Biol Med. 2002;32:833-840.

4. Farina LL, Heard DJ, LeBlanc DM, et al. Iron storage disease in captive Egyptian fruit bats (Rousettus aegyptiacus): relationship of blood iron parameters to hepatic iron concentrations and hepatic histopathology. J Zoo Wildl Med. 2005;36:212-221.

5. Fleming MD, Andrews NC. The liver and iron. In: Arias IM, ed. The Liver: Biology and Pathobiology. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2001:345-359.

6. Herbert V, Shaw S, Jayatilleke E. Vitamin C-driven free radical generation from iron. J Nutr. 1996;126(Suppl): 1213-1220.

7. Kadiiska MB, Burkitt MJ, Xiang Q, Mason RP. Iron supplementation generates hydroxyl radical in vivo. J Clin Invest. 1995;96:1653-1657.

8. Spelman LH, Osborn KG, Anderson MP. Pathogenesis of hemosiderosis in lemurs: role of dietary iron, tannin and ascorbic acid. Zoo Biol. 1989;8:239-251.

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