Canine Biliary Disease - Gallbladder mucocoeles, Cholangitis, Extrahepatic bile duct obstruction

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CANINE BILIARY DISEASEGallbladder mucocoeles, Cholangitis, Extrahepatic bile duct obstruction

Dr Dave Collins, BVSc FANZCVS

dcollins@sashvets.com

www.sashvets.com

Biliary disease

Clinical Signs: abdominal pain, jaundice, vomiting, lethargy, +/-pyrexia

Lab: elevated liver enzymes, bilirubin, +ve snap cPL, neutrophilia

DDx: GI, Pancreatitis

Hepatitis/cholangiohepatitis: infectious, drugs, toxic

Cholangitis

Pancreatitis – cyst, abscess, neoplasia

Biliary disease: cholangitis, cholecystitis, biliary mucocoele, cholelithiasis, neoplasia, EHBDO

Ultrasound findings

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Biliary tree

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Gallbladder Mucocoeles

Progressive accumulation of tenacious mucin-laden bile

May extend into cystic, hepatic & common bile ducts variable EHBDO

Consequences: GB ischaemic necrosis, bile peritonitis +/- opportunistic infection

IBD much more prevalent in dogs with GB mucocoele

Clinical Signs: vomiting, inappetance, lethargy, PU/PD, diarrhoea; severity of signs relating to degree of EHBDO, rupture or infection

Physical examination: Abdominal pain, icterus, pyrexia

Laboratory Findings: ALP elevation, hyperbilirubinaemia 60%, mature neutrophilia, monocytosis

Diagnosis: ultrasonographic appearance, clinical signs, clin path

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Gallbladder Mucocoeles – Risk factors

Breed :Shetland Sheepdog (ABCB4 mutation) , mixed, Bichon, poodles, WHWT, Dachsund, GSD, Cocker Spaniels, Miniature Schnauzers

Age: average 11 years, no gender predisposition

Endocrinopathies: hyperA, hypoT, diabetes mellitus

Pancreatitis

Gallbladder dysmotility

High fat diet

Protein losing nephropathy

Gallbladder neoplasia

Hyperlipidaemia

Glucocorticoid treatment in predisposed dogs

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Gallbladder Mucocoeles

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Gallbladder Mucocoeles

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Gallbladder Mucocoele

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Gallbladder rupture Bile peritonitis

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Canine Bacterial Cholangitis

Cholangitis: inflammation of the intrahepatic bile ducts and ductulesrestricted to the portal areas

Bacterial cholangitis rarely reported in the dog, cholecystitis also uncommon

Is canine and feline bile sterile in the absence of biliary tree pathology??

Potential bacterial invasion via: ascension from duodenum; haematogenousvia hepatic portal venous blood

Biliary defense mechanisms:

mechanical (biliary stasis and increased biliary pressure predispose an animal to biliary infection)

immunological (enteric bacteria normally gain entry to portal circulation and are extracted by hepatic Kupffer cells)

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Canine Bacterial Cholangitis

Limited reports in literature, few single case reports, case series of 4 (4/95 cases with chronic hepatopathy Bristol)

Inclusion criteria: positive bile culture, concurrent liver histopathology demonstrating periportal neutrophilic infiltrate

May occur much more frequently than reported

190 dogs Madison-Wisconsin: 28% biliary cultures, 5% hepatic cultures positive

Positive bile cultures may occur in health or may be secondary to other chronic hepatopathy

Aetiopathogenesis: ascending gut infection or translocation from portal circulation

May be concurrent cholangitis in cases of cholecystitis or biliary mucocoele

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Canine Bacterial Cholangitis - Clinical

Older animals (8-10), no sex predilection

Vomiting, icterus, inappetance, lethargy, diarrrhoea +/- pyrexia

Marked liver enzyme elevation and hyperbilirubinaemia in most

Inflammatory leukogram with mature neutrophilia typical

Ultrasonography: thickening, increased echogenicity of gallbladder wall +/-diffuse changes in hepatic parenchyma; (may be concurrent choleliths, mucocoeles; concurrent cholecystitis common)

Diagnosis: neutrophilic infiltrate in periportal areas, positive hepatobiliarybacteriological culture (anaerobic & aerobic), bile more sensitive

4-6 weeks antimicrobials based on C & S, repeat culture post therapy

+/- UDCA, cholecystectomy

Good prognosis

Other Differentials

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Emphysematous cholecystitis

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Emphysematous cholecystitis

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Cholelith

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13 FN Chihuahua cross

Pyrexia 40.4, abdominal pain

Blirubin 128 umol/L (0-7); ALP 5546 IU/L (1-150)

AST 715 IU/L (18-80); ALT 1601 IU/L (16-90) Cholesterol 14.3 mmol/L (3.5-9.0);

Neutrophilia 18x10^9/L (3.5-12); Canine Pancreas Specific Lipase 627 ug/L (<200) Elevated APTT 168 (72-102) with normal PT.

IVF, ampicillin, enrofloxacin, metronidazole, methadone, vitamin K

24 hours APTT 99, 48 hours (pre-surgery) bilirubin 60 umol/L (0-7)

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Gallbladder

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CBD

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13 FN Chihuahua cross

Day 2: ex-lap, flush bile duct, cholecystectomy

72 hours ALT 108 ALP 2992 bilirubin 36

Discharged 6 days after admission, appetite starting by day 5

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13 FN Chihuahua cross

HISTOPATHOLOGY REPORT

Moderate to marked chronic-active cholecystitis (frequently suppurative and with presumed ischemic necrosis of mucosa and marked fibroplasia)

Moderate to marked chronic-active (frequently suppurative) cholangiohepatitis with marked cholestasis.

MICROBIOLOGY REPORT

Liver and bile

CULTURE (Blood agar, aerobic, 37C ; cooked meat medium, 37C)

No bacteria isolated aerobically.

Clostridium perfringens was isolated in cooked meat medium from both the liver biopsy and the bile (only very light growth from the bile).

Treatment: 4 weeks of amoxiclav and enrofloxacin

Antimicrobials

Enterococcus*

Strep* Staph E Coli* Pasteurella Enterobacter

Pseudom/Klebsiella

Clostridia sp.*

Bacteroides*

Penicillin - +++ - to + - to ++ +++ - - +++ -

Ampicillin - +++ - to + - to ++ +++ - - ++ -

Amoxicillin/clavulunate

+ to

++++++ + to

+++- to ++ +++ - -/+ ++ +++

Ticarcillin/clavulanate

++ +++ - to

+++- to ++ +++ +++ + to +++ +++ +++

Enrofloxacin - to + - to + - to + +++ +++ +++ ++/+++ - to + -

Cefazolin - +++ - to + ++ +++ - -/+++ - to +++ -

Metronidazole - - - - - - - +++ +++

Clindamycin - ++ - to

+++- - - - +++ +/-

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Supportive medications

Vitamin K 0.5 -1.5mg/kg SC q12h x 3

Vitamin E 10-15U/kg PO q24h (Value Plus Vitamin E Equine powder 52U/g)

UDCA 7.5mg/kg PO q12h with food

SAMe 20-40mg/kg PO q24h empty stomach (Denamarin??)

Silibinin 2-5mg/kg PO q24h (Nature’s Own, Blackmores 84mg tablets)

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Extrahepatic bile duct obstruction

(EHBDO)

EHBDO in 200 dogs (Cornell)

- 42% pancreatitis

- 14% gallbladder mucocoele

- 13% cholelithiasis

- 12% neoplasia eg adenocarcinoma,mural/extramural ductal or GB neoplasia

- trauma causing common bile duct (CBD) stenosis

- cholecystitis

Ultrasonographic features (of EHBDO):

- Distended gallbladder, cystic duct 24hrs

- Common bile duct 48hrs (<4mm)

- Extrahepatic ducts 72hrs

- Intrahepatic ducts 5-7d

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Biliary tree

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Extrahepatic bile duct

obstruction (EHBDO)

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Extrahepatic bile duct

obstruction (EHBDO)

EHBDO intrahepatic accumulation of potentially toxic bile acids hepatocyte necrosis, apoptosis, biliary fibrosis & cirrhosis

Profound acute increases in ALT, AST, ALP, GGT that progressively rise in first 2 weeks; modest/marked increases in cholesterol

After 4 to 6 weeks of EHBDO enzyme levels improve due to hepatic cirrhosis

Within 8 weeks acquired portosystemic shunting develops

Coagulopathies develop in around 18% of dogs (more common in cats)

PT elevation in 11%, APTT elevation in 8.6%, give vitamin K anyway

May actually be hypercoagulable

BMBT more predictive of intraoperative haemorrhage

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EHBDO due to pancreatitis

Recommend decompression if 7 -10 days (surgical advice) of hyperbilirubinaemia and ultrasound evidence of GB distension, earlier if evidence of systemic compromise, or if not resolving in 3 weeks (medical advice)

Surgical complications:

Systemic endotoxaemia often resistant hypotension

Haemorrhage, stricture, anastomosis breakdown, ascending cholangiohepatitis, gastric ulceration

Surgery may exacerbate pancreatitis

Short term choledochal stenting, 3.5F-12F red rubber catheters with fenestrations

Cholecystostomy tubes: percutaneous endoscopic, laparoscopic; cholecystocentesis

Biliary-enteric anastomoses: cholecystoduodenostomy, cholecystojejunostomy: survival 36-72%. May have reflux post anastomoses, often E Coli. Cyclic illnesses, elevated liver enzymes, fever, leukocytosis

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10 FN Kelpie Cross: Nala

One month history of weight loss, inappetance

Elevated liver enzymes ALP 9137, ALT 1845

Bilirubin 155, neutrophilia 10.8, abnormal cPL

Treatment: IVF, metronidazole, clavulox, enrofloxacin

Abdominal ultrasound: distended gallbladder, distended CBD, cholecystitis, thickened pancreas

4 days later clinically stable but no improvement in bilirubin

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Cholecystitis

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Distended CBD

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Pancreatopathy

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10 FN Kelpie Cross: Nala

Surgery: Bile aspirated submitted for C & S

mild distension of common bile duct and left hepatic bile ducts duodenotomy, major duodenal papilla flushed some biliary sludge, expressed gallbladder

Grossly abnormal liver liver biopsies

After a few days appetite improved, bilirubin dropped to 160

Discharged on enrofloxacin, clavulox, UDCA

Lab results: E Coli from liver tissue culture and bile aspirates resistant to enrofloxacin (which was discontinued)

Liver: chronic cholangiohepatitis, pancreas: normal

6 weeks post operatively bilirubin 51, ALT 900, ALP 7000

Still on clavulox UDCA, SAMe

May need repeat cultures

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13 MN Standard Schnauzer: Henry

Vomiting 6 weeks ago resolved with clavulox

Represented 5 days before with vomiting, inappetance, icterus

T bil 261 (0-7), ALP 13225 (1-150), ALT 2896 (16-90), Chol 21.5 (3.5-9)

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CBD distension

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Pancreatic pseudocyst

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Henry

Surgery: flushing and stenting of bile ducts (with difficulty)

Cholecystitis, septicaemia Enterococcus sp. cultured from blood

2 days later bilirubin 51, 12 days later bilirubin 21, some appetite, discharged

Discharged on: Amoxicillin, Metronidazole, SAMe , UDCA,

4 months later, vomiting, inappetance, no EHBDO

Abdominal carcinomatosis – pts on the table

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