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Congenital Disorders of the Canine and Feline Biliary TreeJohn M. Cullen VMD PhD DACVP FIATP
Annual Seminar of the French Society of VeterinaryPathology
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Embryonic Liver2
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Ductal Plate
Cytokeratin 7
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In utero AND later
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Hepatic ArteryECMDuctal Plate
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Still-born Arab foal5
Vet Pathol 44:100–102 (2007)Mesenchymal Hamartoma of the Liver in a Late-Term Equine FetusD. L. BROWN, M. ANDERSON, AND J. M. CULLEN
Mesenchymal Hamartoma
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Human Cystic Biliary Disorders
� Polycystic Liver Disease� ADPKD
�Kidney�Liver�Pancreas
� “isolated” PCLD�No kidney
involvement
� Fibropolycystic diseases
�Congenital hepatic fibrosis
�Caroli’s disease� ARPKD
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Genetics of Human Biliary Cystic Disorders
� All involve primary cilia function
� Modulation of Ca++
� ER glycoprotein traffic
�ADPKD: �polycystin 1, 2
� Isolated polycystic liver disease:�hepatocytstin
�Fibropolycystic diseases: �fibrocystin
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Primary Cilia in Biliary Epithelium
� Non motile� Sense�Flow�Composition�Osmolatilty
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LaRusso, Dig Dis 2011;29:6–12
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Strazzabosco, Gastroenterology 2011;140:1855–1859
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ARPKD
ADPKD
Polycystic Liver Disease
von Meyenburg Complexes
Cong. Hepatic Fibrosis
Caroli Syndrome
Caroli Disease
Ductal Plate Malformations
Modified from Desmet, V. Hepatology, 2009
With ectasia With involution12
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von Meyenburg Complexes
Cong. Hepatic Fibrosis
Caroli Syndrome
Ductal Plate Malformations
Modified from Desmet, V. Hepatology, 2009
With involution13
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von Meyenburg Complex14
Lemur
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von Meyenburg Complexes
Congenital. Hepatic Fibrosis
Caroli Syndrome
Ductal Plate Malformations: With involution
Modified from Desmet, V. Hepatology, 2009
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CONGENITAL HEPATIC FIBROSIS: CAT
Courtesy Dr. T. van den Ingh
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Congenital Hepatic Fibrosis: Feline
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Canine Congenital Hepatic Fibrosis18
Congenital Hepatic Fibrosis in 5 DogsBrown, Vet Pathol 2010
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Swiss FreibergerHorses
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Van den Ingh et al.
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Swiss Freiberger Horses
� Gender: male� Age: 2 months� Weight: 84 kg
� History:Runt, apathic, big abdomenUltrasound: liver with variable texture and cysts, Blood: high numbers of leucocytes, high liver values
Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne
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Necropsy
Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne
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Autopsy
Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne
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Thoroughbred, Pennsylvania, USA
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Case Example4 yo Domestic Short Hair, Male, castrated�Clinical signs� Diffusely enlarged,
inhomogenous liver on ultrasound,
� Elevated ALT/AST,
� Slightly low albumin,
� Ascites,
� Toxic neutrophilia.
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Clinical Context27
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Differential diagnoses
� Extra-hepatic obstruction
� Vascular anomalies with biliary proliferation� Portosystemic shunts� Portal vein hypoplasia
�Fibrous variant� A-V fistula
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ARPKD
ADPKD
Polycystic Liver Disease
Caroli Disease
Ductal Plate Malformations
Modified from Desmet, V. Hepatology, 2009
� With ectasia
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Solitary Biliary Cyst: Dog
T. Van den Ingh
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Polycystic Hepatic Disease
� Cats: PDK1� Autosomal dominant
� Persian� Siamese
� Dogs�Cairn Terriers�West Highland White
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Feline Polycystic Disease32
Fel 08-1291 Kidneys Polycystic Disease
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When are a lion and a cat the same?33
Wallpaperswide.com
Cattime.com
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Polycystic Disease: PCK RatSprague-DawleyPkhd1
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ARPKD
ADPKD
Polycystic Liver Disease
Caroli Disease
Ductal Plate Malformations
Modified from Desmet, V. Hepatology, 2009
�With ectasia
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Caroli’s disease
� Fusiform and saccular dilatation of the large bile ducts
� Patent Vater’s papilla
� Kidneys: diffusely affected with radially arranged elongated cysts
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Caroli’s disease
T. van den Ingh
Last, RD, J S Afr Vet Assoc 77: 2006Gorlinger, S et al. JVIM 17:2003
Dog38
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Differential: Obstruction39
*
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Differential Diagnosis: What is a Biliary Adenoma?� Rare
� Localized metaplasia?
� Distended von Meyenburg complexes?
� Biliary cystadenoma
� “Benign Biliary Proliferation”
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Differentiation 41
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Metaplastic example42
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Biliary Adenoma?
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Dedifferentiation and re-differentiation?
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Segmental abnormalitiesBiliary Atresia:
Canine
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Dr. M. Stalker , U. of Guelph
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Biliary Atresia45
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Gallbladder Mucocoele
Cholelithiasis
Cystic mucinous hyperplasia
Cholecystitis
Lymphoplasmacytic and Follicular cholecystitis.
Gall bladder Mucocele
Gall bladder infarcts
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Canine Gall Bladder Mucocoele� Rare 10 years ago
� Common biliary disorder today
� ~20% mortality with surgery
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Cause(s)� Breed association
� Shetland Sheepdogs�Miniature Schnauzers
� Transporter mutation?�ABCB4 (mdr-3)
insertion mutation�No homozygous
mutants�Micelle formation
�Phosphatidylcholine flippase
� Drug exposure?
� Evaluated 88 dogs
� Roughly equal distribution of insertion in affected and normal dogs.
�Complex pathogenesis
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Mealey, Comparative Hepatology2010, 9:6
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Causes
� Endocrine status?� Cushing’s Disease
� 29-fold increased risk
� Other steroids
� Hyperlipidemia
� Diet?
� Therapeutic drugs?
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M. L. L. MESICH, Journal of Small Animal Practice (2009)50, 630–635
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Mucocoele: Dog
Dog 1 Dog 2
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Histologic change
� Loss of portal vein profiles.
� “Fuzzy” Portal vein
� Ménage à foie
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Veterinary Congenital Biliary Tree Diseases
� Congenital
� Ductal Plate anomalies� Congenital cystic diseases
� Acquired metaplastic ductular changes� Adenomas
� Acquired
� Gall Bladder� Mucocoele
� Parenchymal effects
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