Bile duct dysplasia and congenital hepatic fibrosis associated with polycystic kidney (Caroli syndrome) in a rat

Hepatic fibrosis with bile duct ectasia and hyperplasia associated with polycystic kidney disease, analogous to Caroli syndrome in humans, was observed in a rat used as a control in a subchronic toxicity study. Light microscopy of liver sections showed multiple cystic and segmental saccular dilatations and hyperplasia of the intrahepatic bile ducts associated with overgrowth of portal connective tissue; the kidneys had diffuse cystic dilatation of cortical renal tubules. The lesions resembled those of human cases of the fibropolycystic disease termed as Caroli syndrome, which is thought to be the result of a pathologic developmental process known as ductal plate malformation. Recently, an animal model of Caroli syndrome has been described in mutant rats from a colony that constantly showed renal and hepatic cysts and an autosomal recessive mode of inheritance. The finding in our case of identical hepatorenal lesions suggests that the same mutation has occurred incidentally in a standard colony.     

Congenital hepatic fibrosis and cystic bile duct formation in Swiss Freiberger horses

Congenital hepatic fibrosis with autosomal recessive or dominant inheritance has been described in humans, cats, piglets, and dogs. In horses, only two cases of congenital hepatic fibrosis have been previously reported. This retrospective study of records from the Institute for Animal Pathology, University of Berne, identified 30 foals with liver lesions compatible with congenital hepatic fibrosis. Anamnestic data revealed clinical signs of severe liver injury in most affected animals. Pathologic examination showed severely enlarged, firm livers with thin-walled cysts. Histologically, the livers showed diffuse porto-portal bridging fibrosis with many small, irregularly formed and sometimes cystic bile ducts. All foals belonged to the Swiss Freiberger breed. Pedigree analysis revealed that the diseased animals could be traced back to one stallion. These results strongly suggest that congenital hepatic fibrosis in Swiss Freiberger horses is a recessively inherited autosomal genetic defect.     

Congenital dilatation of the bile ducts (Caroli's disease) in young dogs

We describe 8 young dogs with congenital dilatation of the intra- and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed-breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids: increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra- and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein-restricted diet.     

Choledochal cyst with secondary cholangitis,choledochitis, duodenal papillitis,and pancreatitis in a young domestic shorthair cat

Choledochal cysts, congenital segmental dilations of the common bile duct, have been reported in few cats, and histologic characterization is lacking. A 20-mo-old spayed female domestic shorthair cat was presented because of vomiting and weight loss. There was progressive elevation of liver enzyme activity (ALT > ALP, GGT) and hyperbilirubinemia. Diagnostic imaging identified focal cystic dilation of the common bile duct, dilation and tortuosity of adjacent hepatic ducts, and a prominent duodenal papilla. A choledochal cyst was suspected, and the animal was euthanized. On postmortem examination, there was a 2-cm, firm, thickened, cystic dilation of the common bile duct, patent with adjacent ducts. Histologically, the cyst wall was expanded by fibroblasts, collagen, and lymphoplasmacytic inflammation. Adjacent bile ducts were markedly dilated and tortuous, with lymphoplasmacytic inflammation and papillary mucosal hyperplasia that extended to the major duodenal papilla. There was chronic neutrophilic cholangitis, suggesting bacterial infection and/or disturbed bile drainage, extrahepatic obstruction, and lymphoplasmacytic pancreatitis with ductular metaplasia. Prominent lymphoid follicles within biliary ducts and duodenum suggested chronic antigenic stimulation. Choledochal cysts can be associated with chronic neutrophilic cholangitis, extrahepatic obstruction, choledochitis, duodenal papillitis, and pancreatitis, and should be a differential for increased hepatic enzymes and hyperbilirubinemia in young cats.     

Primary infundibular stenosis and pedigree analysis in three Golden Retriever littermates

Three eight-week-old Golden Retriever puppy littermates were evaluated because of left basilar systolic murmurs and were diagnosed with primary infundibular stenosis. Pedigree analysis in this line was also performed to identify a mode of inheritance. All dogs were asymptomatic at the time of diagnosis; two of the three had congenital lesions in addition to primary infundibular stenosis. Two additional affected dogs were identified in the line, and pedigree analysis suggested an autosomal recessive mode of inheritance. Another, unrelated golden retriever was also identified with isolated infundibular stenosis in the record database. Primary infundibular stenosis should be considered in the differential diagnoses for golden retriever dogs with a left basilar systolic murmur, and is often associated with complex congenital cardiac disease. Primary infundibular stenosis may worsen in severity with time, and in this line of dogs an autosomal recessive pattern of inheritance is likely.     

Mesenchymal hamartoma of the liver in a late-term equine fetus

Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract development. During the necropsy of a late-term equine fetus, a markedly enlarged liver of more than two times normal weight was found. Light microscopic review revealed that the normal hepatic parenchyma had been obliterated, replaced, and expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion was diagnosed as a mesenchymal hamartoma. Small portions of the liver had bridging septa of fibrosis and proliferations of small-caliber abnormal bile ducts, resembling another congenital biliary abnormality termed congenital hepatic fibrosis.     

ULTRASONOGRAPHIC EVALUATION OF BILIARY CYSTADENOMAS IN CATS

The purpose of this study was to describe the ultrasonographic appearance of biliary cystadenomas in cats and compare the findings to a similar rare form of liver tumor in humans. Biliary cystadenomas are uncommon, benign liver tumors of older cats that may occur as focal or multifocal cystic lesions within the liver. The records of 10 cats which had abdominal ultrasonography and histologic diagnosis of biliary cystadenoma were reviewed. The average age of affected cats was 13.3 years (range 10-16 years). Eight cats were neutered males and two were neutered females. In three cats, the tumors were not seen ultrasonographically due to their small size or from being obscured by near-field reverberation echoes. The remaining seven cats had solitary (4 cats) or multifocal (3 cats) masses corresponding to variable ultrasonographic patterns: multilocular masses containing thin-walled cysts, hyperechoic masses with cystic components, or masses of mixed echogenicity with cystic components. The masses had variable ultrasonographic patterns when multifocal disease was present. Recognizable cysts were evident somewhere within the tumors seen ultrasonographically, although sometimes the cysts appeared very small. The biliary cystadenomas were thought to be clinically silent. Although liver enlargement or a cranial abdominal mass was palpable in 4 cats, no consistent trend of clinical signs, CBC or serum biochemical abnormalities could be directly attributed to biliary cystadenoma. The treatment of choice is surgical resection of the tumor, as continued growth may compress adjacent vital structures within the liver. The differential diagnosis of biliary cystadenomas from other cystic liver lesions such as hepatic cysts, hematomas, abscesses, parasitic cysts, or other liver tumors is discussed.     

Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep. METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopathological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions. RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation. CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.     

Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep.

METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopath- ological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions.

RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation.

CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.     

Experimental biliary cryptosporidiosis in broiler chickens

Biliary cryptosporidiosis was studied by inoculation of 2 x 10(5) Cryptosporidium baileyi oocysts (AU-B1 isolate) into the gall bladders of ten 6-day-old broiler chickens. Clinical signs of disease were not seen. Three of the 10 chickens developed biliary tract infections, based on histologic examination of tissue sections. Lesions seen in the gall bladders of these birds included epithelial hyperplasia and infiltration of the underlying connective tissue with mononuclear leukocytes. One of these birds also had involvement of the hepatic bile ducts. The bile ducts were mildly dilated and contained lesions similar to those seen in the gall bladder. Few to many cryptosporidia were present in the gall bladders and bile ducts of infected birds. Chickens may be of use in the study of biliary cryptosporidiosis, a common sequel to enteric infection in humans with human immunodeficiency virus infection.     

Pathogenesis of aleutian mink disease. VII. Chronic hepatitis with bile duct proliferation]

Aleutian disease is a chronic persistent viral infection of mink characterized by hypergammaglobulinema, generalized plasmacytosis, sclerosing glomerulonephritis, polyarteritis, and plasma cell hepatitis with bile duct proliferation. The development of hepatic lesions was studied both light- and electron-microscopically in mink experimentally infected with Aleutian disease virus. Fifteen normal and 99 mink experimentally infected with Aleutian disease virus were used. Experimental mink were killed in intervals from 3 weeks to 23 months after infection, and liver sections were processed for both light- and electron-microscopic studies. Experimentally infected mink developed portal and intralobular lymphocytic and plasmacytic infiltrates in the liver 3 weeks after infection. Four to five weeks after infection there was evidence of early bile duct proliferation that began as an outgrowth of the portal bile ducts. Three to five months after infection a marked bile duct proliferation was present in some of the portal triads and adjacent liver lobules; but there was no tendency of these lesions to progress into biliary cirrhosis. Ultrastructural characteristics of proliferating bile duct cells were marked deformation, formation of multiple cell layers, reduction in the number of microvilli and desmosomes, and infiltration of the epithelial cells by lymphoid cells and plasmacytes. The hepatic lesions either develop by direct virus stimulation or by the deposition of virus-antibody complexes.     

Extrahepatic biliary atresia in a border collie

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.     

Congenital cystic disease of the liver and kidney in a pygmy goat.

A 1-month-old pygmy goat was presented with abdominal distension and hematuria. Anemia, leukocytosis, and increased bilirubin and blood urea nitrogen levels suggested renal and hepatic disease. Radiographs revealed bilateral renomegaly, and ultrasound confirmed bilateral hydronephrosis. Necropsy findings determined that the renomegaly was due in part to edema and marked cystic tubular distension. Similarly, intrahepatic bile ducts were ectatic. The character and distribution of the gross and histologic lesions were consistent with a polycystic disorder, presumably congenital, affecting the liver and the kidney.     

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.     

A case of alveolar hydatid disease in a dog: domestic animals as rare incidental intermediate hosts for Echinococcus multilocularis

A 2-years old male Labrador retriever dog was presented with intermittent therapy-resistant diarrhoea, accompanied by vomiting, inappetence, apathy, and mild fever. The blood analysis showed an anaemia, neutrophilia, eosinophilia, and increased liver enzymes. Abdominal palpation was slightly painful. X-rays and echography revealed a severely enlarged liver with multiple cavernous structures. Histopathologic examination of liver biopsies showed a severe chronic granulomatous hepatitis with numerous parasitic cysts. Morphology of the cysts was compatible with the metacestode stage of Echinococcus multilocularis. The dog was only 2-years old at the time of diagnosis. Although alveolar hydatid disease of the liver is rare in dogs, it should be envisaged as a possible differential diagnosis in cases of space-occupying processes in the liver, even in young animals, as the incubation period of this disease in the dog can be considerably shorter than in humans.     

Cornification defect in the golden retriever: clinical, histopathological, ultrastructural and genetic characterisation

Veterinarians have recognised a nonpruritic skin disease in the Golden retriever breed characterised by excessive scaling of large, variably pigmented flakes of skin in otherwise healthy dogs. This prospective case series describes clinical, histopathological, ultrastructural and genetic features of this cornification defect in 17 affected dogs. The condition affects young dogs of either sex and is characterised by symmetrical, predominantly ventro-lateral scaling and hyperpigmentation of the trunk. Histopathological and ultrastructural changes of the stratum corneum are suggestive of delayed degradation of corneodesmosomes. A genetic aetiology is proposed and a single-trait autosomal recessive mode of inheritance discussed.     

Congenital polycystic kidney in a white-tailed deer (Odocoileus virginianus).

Polycystic kidney and liver disease was seen in a stillborn white-tailed deer (Odocoileus virginianus) fawn. Bilaterally enlarged kidneys were characterized by severe dilatation of all renal tubules. Glomeruli were sparse, small, and located within a dilated Bowman's capsule. The liver was characterized by marked periportal fibrosis, biliary hyperplasia, and bile duct ectasia with dilated ducts containing inspissated bile. The presentation and morphology of this case are most similar to autosomal recessive polycystic disease in humans.     

Quantitative hepatobiliary scintigraphy as a measure of bile flow in dogs with cholestatic disease

In 25 dogs with spontaneous cholestatic disease, the hepatobiliary dynamics were evaluated by use of scintigraphy and a 99mTc-labeled iminodiacetate (IDA) derivative. Hyperbilirubinemia existed in all dogs, with serum total bilirubin concentration ranging from 6 to 262 mumol/L. An appropriate compartmental model was used to characterize the liver time-activity curves. Model-dependent variables for hepatic uptake and biliary excretion of radiolabeled IDA were found to reliably represent the underlying physiologic processes. Measurements directly derived from the liver time-activity curves of IDA, representing the moments of accumulation of 50 and 95% of the maximal hepatic activity did not accurately represent the hepatic uptake by being significantly influenced by biliary excretion and by competition of renal excretion. The time-interval between 95% and 50% of the maximal activity in the excretory phase proved to be a quantitative characteristic of bile flow in all instances. Compartmental analysis of 99mTc-IDA excretory scintigraphy characterized bile flow quantitatively in clinically normal dogs and in dogs with cholestasis. The method permitted the clinical evaluation of cholestasis based on quantitative, instead of the usual qualitative, and on functional, instead of phenomenologic, criteria.     

Anatomicopathological study of vascular and biliary systems using cast samples of Fasciola-infected bovine livers

In 117 livers with fascioliasis, this study was focused on the number of Fasciola, the number and intrahepatic localization of affected hepatic ducts and bile ducts, and the degree of fibrosis in the hepatic segments and bile ducts. The degree of pathological changes in bile ducts caused by fascioliasis was classified into five levels. The site of Fasciola habitation was most often the hepatic ducts of the porta hepatis: it was the left hepatic duct in 101 livers and the right hepatic duct in 88 livers. Casts were prepared by infusing synthetic resin into the hepatic arterial, portal, hepatic venous and biliary systems of 15 bovine livers with fascioliasis and then examined. In the left lobe, quadrate lobe, and caudate process where atrophic fibrosis was noted, the bile ducts became rod-shaped by losing branches, and the samples resembled dead branches of liver. Portal branches were thinned or completely terminated with marked fibrosis. Fine and irregular newly formed bile ducts not parallel with portal branches were observed in livers with markedly chronic fascioliasis. Distal portal branches in the right lobe, caudate lobe, and papillary process showed hypertrophic proliferative changes. The arterial system was generally well developed in thickened walls of bile ducts and formed vascular beds, and surrounded the bile ducts as tubes. In livers with severe fibrosis, capillaries were markedly developed and resembled glass cotton.     

SONOGRAPHIC EVALUATION OF EXPERIMENTAL BILE DUCT LIGATION IN THE DOG

The common bile duct was surgically ligated in five normal adult dogs. Ultrasonographic examinations of the gallbladder and biliary system were performed after duct ligation at intervals of 24 hours. The sequence of biliary system dilation was from the common duct to the peripheral intrahepatic ducts. Common duct enlargement was evident in 24–48 hours, while peripheral biliary duct dilation was recognized by five to seven days after obstruction. When compared with hepatic and portal veins, dilated biliary ducts were more tortuous and had irregular branching patterns. Gross pathologic changes were correlated with ultrasonographic findings at seven, 14, 15, 18 and 21 days after obstruction.