SA Hepatobiliary and Pancreatic

4 exocrine pancreas functions

Enzymes
Bicarbonate
Intrinsic factor
Antimicrobial proteins

Acute pancreatitis: pathogenesis (detailed)

Lysosomes and zymogen granules fuse \= activation of trypsin \= rupture of vacuoles \= pancreatic autodigestion

Defences against acute pancreatitis

Enzymes synthesised in inactive form (activated by enzymes in SI)
Zymogens packaged in granules
Hydrolases packaged into lysosomes
Systemic plasma anti-proteases

Risk factors for acute pancreatitis in dogs

Hypertriglyceraemia
Genetics (mini schnauzer, Yorkshire terrier)
Drugs (e.g. KBR)
Hypertension/ischemia/trauma
Hypercalcaemia
Neoplasia

Risk factors for acute pancreatitis in cats

Biliary tract disease
Inflammatory bowel disease
Ischemia
Infection (e.g. FIP, Toxoplasmosis)
OP toxicity
Trauma

Signs of acute pancreatitis

Anorexia
Lethargy
Vomiting
Cranial abdominal pain
Dehydration
Less obvious in cats

Acute pancreatitis: diagnosis

Haematology - inflammatory leukogram
Serum biochemistry - increased ALT, ALP, bilirubin, calcium, azotaemia
Increased serum amylase and lipase
Trypsin-like immunoreactivity (TLI)
*Pancreas-specific lipase (PLI)*
Radiography - loss of serosal detail
Ultrasound
Biopsy and cytology

Acute pancreatitis: treatment

No definitive treatment
Fluids and electrolytes
Analgesia
Anti-emetics and anti-ulcer medications
Nutritional support

Acute pancreatitis: potential sequelae

Pancreatic abscess
Necrotic masses
Pancreatic pseudocysts
Duodenal perforation \= septic peritonitis
Biliary tract obstruction

Chronic pancreatitis: clinical signs

Intermittent, low-grade signs
Recurrent acute pancreatitis
Exocrine pancreatic insufficiency

Chronic pancreatitis: diagnosis

Biopsy

Chronic pancreatitis: management

Treat acute episodes as acute pancreatitis (supportive)
Analgesia
Low fat diet
B12 if required
Appetite stimulants
Treat concurrent conditions if required

Cause of exocrine pancreatic insufficiency

Pancreatic acinar atrophy
Aplasia (young)
Chronic pancreatitis

Exocrine pancreatic insufficiency (EPI): clinical signs

Diarrhoea
Steatorrhea
Increased appetite
Weight loss
Poor coat
Flatulence

Exocrine pancreatic insufficiency (EPI): diagnosis

Trypsin-like immunoreactivity (TLI)

Exocrine pancreatic insufficiency (EPI): management

Enzyme supplementation
Low fibre, moderate fat diet
Cobalamin supplementation

Ddx for secondary hepatopathies

Hypoxia/hypotension
Shock
Surgery
Seizures
Anaemia
Endocrinopathies
Cushing's/Addison's
Diabetes mellitus
Hyperthyroidism (cats)/hypothyroidism (dogs)
Hyperlipidaemia
Non-hepatic inflammation
GI disease
Pancreatitis
Sepsis
Toxaemia
Drugs
Glucocorticoids
Phenobarbital
Misc.
R CHF
Pericardial effusion
Metastasis

Signs of liver disease

Variable
Anorexia/weight loss
Depression/lethargy
PUPD
Vomiting/diarrhoea
Jaundice
Ascites
Coagulopathies

Ddx for chronic liver disease in dogs

Chronic hepatitis
Neoplasia
Chronic progression of acute hepatopathies
Copper storage disease
Chronic cholangitis
Congenital disease

Ddx for chronic liver disease in cats

Chronic cholangitis
Hepatic lipidosis
Neoplasia
Infectious (FIP, toxoplasmosis)
Congenital portosystemic shunts
Amyloidosis

DDx for acute hepatic disease

Drugs
NSAIDs
Paracetamol
Azathioprine
TMPS antibiotics
Diazepam
Lomustine
Carbimazole/methimazole
Infectious
Leptospirosis
CAV-1
Clostridium
Acute neutrophilic cholangitis
Metabolic
Hepatic lipidosis
Toxins
Xylitol
Mycotoxins/aflatoxins
Amonita mushrooms
Blue-green algae
Neoplasia (lymphoma)
Idiopathic

Biochemistry indicators of liver damage

ALT (liver specific but not indicative of severity)
AST (not liver specific but indicates greater damage)

Biochemistry markers of cholestasis

ALP/ALKP (not liver specific)
GGT
Bilirubin

Biochemistry markers of liver function

Bile acids
Ammonia
Bilirubin
Glucose, urea, albumin and cholesterol (GUAC)

Types of jaundice

Pre-hepatic
Hepatic
Post-hepatic

Indicators of pre-hepatic jaundice

Increased liver enzymes
Low PCV

Diagnosis of hepatic jaundice

Increased liver enzymes
Biopsy
Rule out pre- and post-hepatic jaundice

Indicators of post-hepatic jaundice

Increased liver enzymes
ALP and GGT \> ALT and AST
Increased cholesterol

What is the most specific liver function parameter

Bile acids

What causes increased bile acids

Decrease in hepatocellular mass
Impaired hepatocellular function
Disruption of blood flow to liver
Obstruction of biliary flow

Ddx for increased bile acids

Portosystemic shunt
Diffuse hepatic disease
Biliary stasis

Causes of hyperammonaemia

Abnormal portal blood flow
Hepatic dysfunction
Urea cycle abnormality

Causes of ascites

Imbalanced Starling's forces
Increased hydrostatic pressure (portal hypertension)
Decreased oncotic pressure (hypoalbuminaemia)
Organ or vessel leakage
Inflammation

Diagnosis/investigation of ascites

Abdominocentesis

Ddx for portal hypertension

Ascites
Hepatic encephalopathy
Portosystemic shunts
GI ulceration

Classification of portal hypertension

Pre-hepatic
Hepatic (pre-sinusoidal, sinusoidal and post-sinusoidal)
Post-hepatic

Determining classification of portal hypertension

Analysis of ascitic fluid:
Low protein transudate \= pre-hepatic or pre-sinusoidal
High protein transudate \= sinusoidal, post-sinusoidal, post-hepatic

What should be checked before liver biopsy

Coags and platelets

Biliary disease: clinical signs

non-specific signs
Jaundice
Pale faeces

Ddx for biliary disease

Pancreatitis (causing duct obstruction)
Cholecystitis
Gallbladder mucocele
Neoplasia
Cholelithiasis

Characteristic appearance of gallbladder mucocele on ultrasound

'Kiwi'

GAllbladder mucocele: treatment

Surgical removal of gallbladder

Bile peritonitis: diagnosis

Abdominocentesis - bilirubin 2x serum level

Cholangitis

Inflammation of biliary ducts
Can be neutrophilic or lymphocytic

Neutrophilic cholangitis

Ascending infection from intestines (usually E. coli)
Usually cats due to the anatomy of their bile ducts

Lymphocytic cholangitis

Immune-mediated biliary duct inflammation

Critical liver functions

Metabolism of bilirubin, bile acids, CHO, lipids, xenobiotics
Protein (albumin, globulin, clotting factors) production
Immune function

Types of portosystemic shunts

Congenital extrahepatic shunts (portal vein to cd. vena cava or azygous vein)
Congenital intrahepatic shunts (patent ductus venosus)
Congenital hepatoportal microvascular dysplasia
Acquired shunts due to chronic liver disease
Primary portal vein hypoplasia

Primary portal vein hypoplasia: aetiology

portal hypertension \= development of multiple collateral shunts

Histological features of portosystemic shunts

Hepatocellular atrophy
Closely and unevenly spaced portal triads
Portal triads with attenuated/absent portal veins
Proliferation of portal arterioles
Bile duct proliferation

Portosystemic shunts: clinical signs

Congenital:
Failure to thrive
Neurological signs due to hepatic encephalopathy
Acquired:
Chronic liver disease
Increased liver enzymes
Ascites

Canine infectious hepatitis cause

Canine Adenovirus 1 (CAV-1)

Canine infectious hepatitis: signs

Fever
Vomiting and melaena
Abdominal pain
Corneal opacity (if chronic)

Canine infectious hepatitis: gross pathology

Serosal surfaces appear granular
Petechiae
Enlarged, friable liver
Fibrin strands on liver (especially between lobules)
Gallbladder wall thickening
Variable haemorrhage in other organs

Chronic hepatitis in dogs: causes

Viruses/bacteria
Toxins (including copper)
Idiopathic/breed related

Chronic hepatitis in dogs: pathogenesis

Inflammatory infiltrates
Hepatocellular necrosis and loss
Progression to parenchymal collapse and fibrosis

Chronic hepatitis in dogs: Signs

Non-specific systemic signs (lethargy, weight loss, vomiting/diarrhoea, polydipsia)
Icterus
Hyperthermia
Ascites
Abdominal pain

Chronic hepatitis in dogs: blood work/biochem findings

Increased WBC
increased ALT and ALP
Increased AST, GGT, bilirubin, bile acids
(sometimes decreased albumin, urea and increased PT and PTT)

Chronic hepatitis in dogs: histopath

Portal and parenchymal inflammation
Hepatocellular necrosis
Periportal to bridging fibrosis
Cu accumulation in periportal region (secondary to cholestasis)

Copper-associated liver disease: breed associations

*Bedlington terrier*
Dobermann
WHWT
Skye terrier
Dalmatian
Labrador

Copper-associated liver disease: diagnosis

Cu levels in fresh liver sample (\>1800-2000ug/g)
Histopathology (specialised stain \= Rhodanine)

Copper-associated liver disease: pathophysiology

Centrilobular hepatitis and Cu accumulation

Causes of toxic liver disease in dogs

Xylitol
Drugs - trimethoprim-sulfonamide, mebendazole, anticonvulsants, carprofen
Amanitin
Blue-green algae

Steroid-induced hepatopathy

Iatrogenic or exogenous (Cushing's)
Marked hepatocellular hypertrophy/vacuolation
Normal liver function maintained (but increase in ALP)

Suppurative cholangitis/cholangiohepatitis: signalment

Older cats (11-15)

Suppurative cholangitis/cholangiohepatitis: pathogenesis

Biliary tract inflammation associated with ascending bacterial infection (commonly E. coli)

Lymphocytic cholangitis/cholangiohepatitis: signalment

Cats \>4yrs

Lymphocytic cholangitis/cholangiohepatitis: pathogenesis

Inflammation \= fibrosis, cholestasis and icterus
Possibly immune mediated

Which histological stain is used for fibrosis

Masson's Trichrome

Gallbladder mucocele: pathogenesis

Accumulation of mucoid secretions \= gallbladder distension
Extension into cystic, hepatic and common bile ducts \= extrahepatic bile obstruction
Ischemia and necrosis

Gallbladder mucocele: histopathology

Hyperplasia of mucous secreting glands
Formation of mucous-filled cysts

Juvenile pancreatic atrophy: breed associations

GSDs, Rough Collies, English Setters

Juvenile pancreatic atrophy: pathophysisology

Pancreatic atrophy preceded by inflammatory cell infiltration

Exocrine pancreatic insufficiency: signs

Diarrhoea
Chronic weight loss despite good appetite
Steatorrhea
Malassimilation of nutrients

Exocrine pancreatic insufficiency: diagnosis

Serum trypsin-like immunoreactivity (TLI)

Acute pancreatic necrosis: pathogenesis

Activation of trypsin within pancreas \= activation of pancreatic enzymes \= autodigestion of pancreas
Causes activation of kinin system, coagulation cascade, fibrinolytic system and complement \= systemic inflammation, hypovolaemic shock and DIC

Acute pancreatitis

Inflammation of pancreas with ductal and lobar distribution
Dogs \= reflux of bacteria and enzymes from intestines
Cats \= systemic toxoplasmosis

Chronic pancreatitis

Extension of inflammatory process from ducts
Due to: ascending infection from intestines, fluke or strongyle migration

Biomarkers for pancreatitis

Canine pancreas-specific lipase (cPSL)
Canine pancreas elastase-1 (cPE-1)

Triaditis

Inflammation of the pancreas, liver and SI in cats
Will see: increased liver enzymes, bilirubin and pancreatic lipase

and decreased cobalamin, folate and albumin

General approach to managing acute hepatopathies

Supportive care - fluids, antioxidants, antiemetics
Treat cause if known
Steroids are contraindicated

General approach to managing chronic hepatopathies

Aim \= slow down progression
Supportive
Specific therapy based on biopsy
Need to consider medications carefully due to hepatic metabolism

Nutraceuticals

Dietary supplementation with medicinal benefits
Little information on purity, dosage, safety or efficacy
Commonly used

Common nutraceuticals used in liver disease

Anti-oxidants (SAMe, Vit. E, Silymarin)
Zinc

Ursodeoxycholic acid (UDA)

Synthetic hydrophilic bile acid
Increased glutathione production in hepatocytes
Promotes bile flow (contraindicated if biliary obstruction present)

Hepatic fibrosis: pathogenesis

Fibrosis \= impedes blood flow \= portal hypertension
Can progress to cirrhosis
Bridging fibrosis causes permanent hepatic distorsion

Indications for steroid use in hepatopathies

Biopsy reveals inflammation and infection has been ruled out

Contraindications for steroid use in hepatopathies

Infection
Hepatic encephalopathy
Portal hypertension
Gastric ulceration
Ascites
Advanced, bridging fibrosis
Acute hepatopathies

Side effects of steroid use

PUPD
Polyphagia
Alopecia
Lethargy
Hepatomegaly

Differentiation of primary vs secondary copper storage disease

Primary - Cu accumulates in zone 3
Secondary - Cu accumulates in zone 1

Copper storage disease: treatment

D-penacillamine (or trientine) - chelating agents
Dietary - low Cu, high zinc

Leptospirosis: disease

Causes acute kidney injury +/- acute hepatic disease

Leptospirosis: diagnosis

Microscopic agglutination test (several weeks apart, looking for 4x increase)

Leptospirosis: treatment

Barrier nurse - zoonotic
Supportive care
Antibiotics (Doxycycline or penicillin)

Ascites: treatment

Diuretics (spironolactone +/- furosemide)
Abdominocentesis - only if patient is uncomfortable

GI ulceration: treatment

Proton pump inhibitors
H2 antagonists
Mucosal cytoprotectants
Small frequent meals

Treatment for hepatic encephalopathy due to liver disease

Small frequent meals with lower protein (but not too low - plant/dairy protein is best)
Antibiotics to decrease intestinal microflora
Lactulose to acidify the gut and trap ammonia as ammonium
If severe - fluids (not lactated), gastroprotectants, treat seizures

Types of congenital portosystemic shunts

Extrahepatic (esp. small dogs)
Intrahepatic (esp. larger dogs)
Microscopic portal vein hypoplasia

Treatment of portosystemic shunts

Congenital macroscopic \= ligation
Congenital microscopic \= medical management
Acquired \= medical management