Congenital Disorders of the Canine and Feline Biliary Tree

Transcription

1 Congenital Disorders of the Canine and Feline Biliary Tree John M. Cullen VMD PhD DACVP FIATP 1 Annual Seminar of the French Society of Veterinary Pathology

2 2 Embryonic Liver

3 3 Cytokeratin 7 Ductal Plate In utero AND later

4 4 Hepatic Artery ECM Ductal Plate

5 5 Still-born Arab foal Mesenchymal Hamartoma Vet Pathol 44: (2007) Mesenchymal Hamartoma of the Liver in a Late-Term Equine Fetus D. L. BROWN, M. ANDERSON, AND J. M. CULLEN

6 Human Cystic Biliary Disorders 6 Polycystic Liver Disease ADPKD Kidney Liver Pancreas isolated PCLD No kidney involvement Fibropolycystic diseases Congenital hepatic fibrosis Caroli s disease ARPKD

7 Genetics of Human Biliary Cystic 7 Disorders All involve primary cilia function Modulation of Ca ++ ER glycoprotein traffic ADPKD: polycystin 1, 2 Isolated polycystic liver disease: hepatocytstin Fibropolycystic diseases: fibrocystin

8 Primary Cilia in Biliary Epithelium 8 Non motile Sense Flow Composition Osmolatilty LaRusso, Dig Dis 2011;29:6 12

9 9

10 10

11 11 Strazzabosco, Gastroenterology 2011;140:

12 With ectasia 12 Ductal Plate Malformations ADPKD Polycystic Liver Disease With involution von Meyenburg Complexes ARPKD Cong. Hepatic Fibrosis Caroli Disease Caroli Syndrome Modified from Desmet, V. Hepatology, 2009

13 13 Ductal Plate Malformations With involution von Meyenburg Complexes Cong. Hepatic Fibrosis Caroli Syndrome Modified from Desmet, V. Hepatology, 2009

14 14 von Meyenburg Complex Lemur

15 Ductal Plate Malformations: With involution 15 von Meyenburg Complexes Congenital. Hepatic Fibrosis Caroli Syndrome Modified from Desmet, V. Hepatology, 2009

16 CONGENITAL HEPATIC FIBROSIS: CAT 16 Courtesy Dr. T. van den Ingh

17 17 Congenital Hepatic Fibrosis: Feline

18 Canine Congenital Hepatic Fibrosis 18 Congenital Hepatic Fibrosis in 5 Dogs Brown, Vet Pathol 2010

19 Swiss Freiberger 19 Horses Van den Ingh et al.

20 Swiss Freiberger Horses Gender: male Age: 2 months Weight: 84 kg History: Runt, apathic, big abdomen Ultrasound: liver with variable texture and cysts, Blood: high numbers of leucocytes, high liver values Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne

21 Necropsy Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne

22 Autopsy Christine Gopfert Inst. Swiss Vet. Annual Meeting, Berne

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24 Thoroughbred, Pennsylvania, USA

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26 Case Example 4 yo Domestic Short Hair, Male, 26 castrated Clinical signs Diffusely enlarged, inhomogenous liver on ultrasound, Elevated ALT/AST, Slightly low albumin, Ascites, Toxic neutrophilia.

27 27 Clinical Context

28 28 Differential diagnoses Extra-hepatic obstruction Vascular anomalies with biliary proliferation Portosystemic shunts Portal vein hypoplasia Fibrous variant A-V fistula

29 29 Ductal Plate Malformations ADPKD Polycystic Liver Disease With ectasia ARPKD Caroli Disease Modified from Desmet, V. Hepatology, 2009

30 Solitary Biliary Cyst: Dog 30 T. Van den Ingh

31 31 Polycystic Hepatic Disease Cats: PDK1 Autosomal dominant Persian Siamese Dogs Cairn Terriers West Highland White

32 Feline Polycystic 32 Disease Fel Kidneys Polycystic Disease

33 33 When are a lion and a cat the same? Wallpaperswide.com Cattime.com

34 34

35 35 Polycystic Disease: PCK Rat Sprague-Dawley Pkhd1

36 36 Ductal Plate Malformations ADPKD Polycystic Liver Disease ARPKD With ectasia Caroli Disease Modified from Desmet, V. Hepatology, 2009

37 37 Caroli s disease Fusiform and saccular dilatation of the large bile ducts Patent Vater s papilla Kidneys: diffusely affected with radially arranged elongated cysts

38 Caroli s disease 38 Dog T. van den Ingh Last, RD, J S Afr Vet Assoc 77: 2006

39 39 Differential: Obstruction *

40 40 Differential Diagnosis: What is a Biliary Adenoma? Rare Localized metaplasia? Distended von Meyenburg complexes? Biliary cystadenoma Benign Biliary Proliferation

41 41 Differentiation

42 42 Metaplastic example

43 43 Biliary Adenoma? Dedifferentiation and re-differentiation?

44 44 Segmental abnormalities Biliary Atresia: Canine Dr. M. Stalker, U. of Guelph

45 Biliary Atresia 45

46 46 Gallbladder Mucocoele Cholelithiasis Cystic mucinous hyperplasia Cholecystitis Lymphoplasmacytic and Follicular cholecystitis. Gall bladder Mucocele Gall bladder infarcts

47 47 Canine Gall Bladder Mucocoele Rare 10 years ago Common biliary disorder today ~20% mortality with surgery

48 Cause(s) 48 Breed association Shetland Sheepdogs Miniature Schnauzers Transporter mutation? ABCB4 (mdr-3) insertion mutation No homozygous mutants Micelle formation Phosphatidylcholin e flippase Drug exposure? Evaluated 88 dogs Roughly equal distribution of insertion in affected and normal dogs. Complex pathogenesis Mealey, Comparative Hepatology 2010, 9:6

49 49 Causes Endocrine status? Cushing s Disease 29-fold increased risk Hyperlipidemia Diet? Other steroids Therapeutic drugs? M. L. L. MESICH, Journal of Small Animal Practice (2009) 50,

50 Dog 1 Dog 2 50 Mucocoele: Dog

51 51 Histologic change Loss of portal vein profiles. Fuzzy Portal vein Ménage à foie

52 Veterinary Congenital Biliary Tree 52 Diseases Congenital Ductal Plate anomalies Congenital cystic diseases Acquired metaplastic ductular changes Adenomas Acquired Gall Bladder Mucocoele Parenchymal effects