Small animal hepatobiliary disease

• Liver blood supply

  Abundant and double blood supple:

  • Hepatic artery (~30%)
  • Hepatic portal vein (~70%).

  Hepatic portal vein can drain infectious agents and toxic substances absorbed from gastrointestinal tract to the liver.

  The liver is a highly efficient and effective processing plant.
• Classic liver lobule

  Hepatocytes are organised in radial cords forming a six-sided polyhedral prism with portal triads at each of the corners and a single central vein.

  Portal triads = portal venule (from portal veins) and arteriole of hepatic artery.

  
• Liver diseases - overview

  Massive structural and functional reserve

  Clinical signs not seen until >70% of functional liver mass lost -> liver failure.

  Signs seen earlier in acute disease because less time for adaptation by surviving hepatocytes.

  Significant capacity to regenerate.
• Clinical signs of liver disease

  Lethargy, anorexia, weight loss, PUPD, vomiting and diarrhoea.

  Jaundice, drug tolerances, hepatic encephalopathy, ascites, coagulopathy.

  Portal hypertension.
• Portal hypertension

  Increased intrahepatic resistance to portal blood flow.

  Portal hypertension

  • Splanchnic pooling (spleen/ GIT)
  • Reduction in effective circulating volume, activation RAAS, fluid retention/ ascites.
  • Portosystemic collateral vessel formation
  • Development of an acquired PSS
• Why do we see certain clinical signs with liver disease - vomiting and diarrhoea

  Can be due to metabolic derangements or due to portal hypertension.

  Portal hypertension leads to vascular stasis and venous congestion and oedema -> adverse effect on GI tract.

  Increases the risk of GI ulceration.
• Why do we see certain clinical signs with liver disease - PUPD

  Decreased urea production -> decreased medullary solute gradient -> impaired renal concentration mechanism -> dilute urine and compensatory polydipsia.

  Psychogenic component? Linked to hepatic encephalopathy.

  Reduced hormone metabolism e.g. cortisol.
• Why do we see certain clinical signs with liver disease - Ascites

  Mechanisms include: portal hypertension - activation of RAAS and fluid retention.

  Hypoalbuminaemia (rarely the cause)

  • Has to be significantly low e.g. serum albumin < approximately 15g/l
• What causes clinical signs of pre-hepatic jaundice?

  Due to haemolytic anaemia; bilirubin production exceeds the livers capacity to excrete it.
• What causes clinical signs of hepatic jaundice?

  Decreased uptake, conjugation and excretion of bilirubin.
• What causes clinical signs of post-hepatic jaundice?

  Obstruction of the biliary tree; prevention of excretion via faeces e.g. pancreatitis, cholelith, duodenal or bile duct mass obstructing the bile duct.
• Hepatic encephalopathy - overview

  Encephalopathic toxins - e.g. ammonia - originate in the GI tract.

  • Normal situation: detoxified in the liver.
  • Abnormal -> detoxification fails for several reasons:
  • Congenital portosystemic shunts (cPSS) - toxins bypass the processing plant of the liver.
  • Acute liver disease - detoxification processes in the liver compromised and overwhelmed.
  • Acquired portosystemic shunts - chronicn fibrotic/cirrhotic liver disease leads to multiple tortuous anastomotic vessels opening up to divert blood from the hepatic portal vein to bypass the liver.
• Hepatic encephalopathy - clinical signs

  Waxing and waning; non-localising on neuro exam.

  May be associated with feeding.

  Hyperactive &/or depressed/ dull/ clumsy.

  Cicrling, pacing, central blindness.

  Salivation, especially cats

  Seizures leading to comas.
• Diagnosing liver problems - urinalysis

  Urine specific gravity

  • Often decreased due to various mechanisms causing PU/PD.

  Bilirubinuria:

  • Normal to find some bilirubin in dog urine but can be increased.
  • Always abnormal in cat urine.

  Sediment analysis:

  • Ammonium biurate crystals sometimes seen with PSS.
  • Identifies dogs at risk of urate urolithiasis.
• Diagnosing liver problems - radiography

  Poor sensitivity for detection of liver disease

  Some information about liver size i.e. normal if:

  • Contained within the costal arch
  • The caudal border appears angular
  • Stomach axis is parallel to the ribs.

  Might see:

  • Choleliths
  • Mineralisation

  Consider thoracic radiography if worried about neoplasia
• Diagnosing liver problems - ultrasound

  Poor sensitivity for detection of liver disease unless:

  • Mass lesion
  • Nodular disease
  • Significant change in echo texture.

  Gives some information about liver i.e. normal if:

  • Moderately and uniformly echoic
  • Coarsely granular parenchyma
  • Uniform texture
• Diagnosing liver problems - CT

  Not perfect, but better structural detail.

  Can still be challenging to differentiate benign and malignant changes.

  • Positive indicators of malignancy in dogs are:
  • Size (>4.5cm)
  • Post contrast enhancement pattern.
• Secondary hepatopathies

  GI disease

  Pancreatitis

  Endocrine disease

  • Hyperadrenocorticism (very rare in cats).
  • Diabetes mellitus

  Right-sided congestive heart failure.

  Hypoxia e.g. secondary to shock, trauma, anaemia.

  Sepsis/ bacteraemia

  Drug induced in in dogs e.g. corticosteroids, phenobarbitone.
• Primary hepatopathies - acute toxin/drug induced

  Acute toxic hepatitis.

  • Phenonarnitone
  • NSAID e.g. Carprofen
  • TMPS
  • Azathioprine
  • Paracetemol
  • Xylitol
  • Environmental toxins e.g. blue green algae, mushrooms.
• Primary hepatopathies - acute infection

  Infectious hepatitis

  • Leptosporosis
  • Viruses: CAV-1, neonatal canine herpes virus.
  • Bacteria from the GI tract
  • Tyzzers disease (clostridium piliforms).
• Primary hepatopathies - acute congenital

  Portosystemic shunt

  Primary portal vein hypoplasia.
• Primary hepatopathies - acute metabolic

  Glycogen storage disease

  Heptaic amyloidosis
• Primary hepatopathies - acute sepsis/ endotoxaemia

  May be part of progression of sepsis to SIRS and MODS.
• Management of liver disease - supportive

  Intravenous fluid supports; avoid LRS as liver can not metabolise lactate as the buffer.

  Monitor serum potassium and supplement in IV fluids as necessary.

  Monitor blood glucose regularly and supplement if necessary.

  Control vomiting:

  • Maropitant: may need to use with caution die to hepatic metabolism]Consider CRI metoclopramide.

  Treat any gastrointestinal ulceration:

  • GI bleeding can be aggravated by coagulopathy.
• Management of liver disease - treat the causes

  Antibiotids for leptosporosis

  Stop hepatotoxic drugs if you are sure they are implicated.

  N-acetylcysteine for paracetamol toxicity, may help with xylitol toxicity too.
• Management of liver disease - manage coagulopathy as necessary

  Fresh frozen plasma

  Vitamin K therapy might help.
• Management of liver disease - liver support

  Ursodeoxycholic acid; choleretic effects anti inflammatory/ immune modulating properties

  Anti-oxidants (SAMe, silymarin).
• Management of liver disease - diet

  Protein:

  • Adequate, good quality protein as typically in negative energy balance; 15-30% for dogs; 30-45% for cats.
  • If HE - limit dietary protein to reduce ammonia production.

  Decreased glycogen storage and decreased gluconeogenesis - often have fasting hypoglycaemia.

  Lipids augment fat-soluble vitamin absorption and make food more palatable, be careful in the case of cholestasis though.

  Vitamin K supplementation of cholestasis or increased clotting times.

  Consider feeding tube.
• Management of liver disease - prognosis

  Difficult to predict because varies with extent of damage.

  Full recovery is possible but can progress to chronic disease (hepatitis, fibrosis and cirrhosis).

  Severe cases can required a high level of intensive care

  • Refer to a specialist centre if possible.

  Negative prognostic indicators include presence of:

  • Ascites and splenomegaly
  • Suggest portal hypertension has developed.
• Chronic liver and biliary disease - clinical signs

  Long-standing, chronic, recurrent or waxing-waning signs.

  Non-specific clinical signs including:

  • Inappetence and weight loss; poor body condition.
  • Vomiting +/- haematemesis if GI ulceration
  • Diarrhoea +/- melaena
  • PU/PD
  • Lethargy, depression -> true neuro signs/ hepatic encephalopathy.

  Slightly more specific:

  • Jaundice - have to rule out IMHA as well.
  • Ascites.
• Chronic liver and biliary disease - Laboratory testing

  Prolonged elevation, often progressive liver enzyme levels.

  Reduced hepatic function with associated markers;

  • Coagulation parameters, albumin, cholesterol, glucose

  Generally over time liver parameters will get worse. Involves you doing repeat tests
• Chronic liver and biliary disease, common differentials - idiopathic chronic hepatitis

  Most common liver disease in dogs.

  Cause unknown:

  • Rule out chronic infectious/ toxic disease as much as possible.
  • Several breed dispositions.
• Chronic liver and biliary disease, common differentials - copper-associated liver disease

  Associated with some specific breeds

  Labrador retriever, Dalmatian, Sky terrier, Doberman pinscher

  True copper storage disease:

  • Bedlington terriers.
• Chronic liver and biliary disease, common differentials - congenital vascular disease

  Usually occurs in young animals, 3-6 months, but can be diagnosis 4/5 years old.

  E.g. congenital portosystemic shunts (cPSS).
• Chronic liver and biliary disease, common differentials - neoplasia

  There are tumours that are primarily affect the liver but are most commonly metastases.

  Primary

  • Hepatocellular carcinoma
  • Lymphoma

  Secondary:

  • Very common for metastases
  • Can be clinically silent
  • Can be haemorrhage e.g. met from splenic haemangiosarcoma.
• Chronic liver and biliary disease, common differentials - biliary tract disease

  Biliary mucoceles

  Neutrophillic cholangitis

  Extra-hepatic bile duct obstruction.

  Bile duct rupture.
• Portosystemic shunt - clinical signs

  Anomalous connection between the portal and systemic venous systems.

  Neurological:

  • Lethargy, ataxia, obtundation, pacing, circling, blindness, seizures, coma.

  Gastrointestinal

  • Vomiting, diarrhoea, anorexia, pica, melaena, haematemesis.

  Urianry:

  • Ammonium urate crystals, haematuria, stranguria, pollakiuria, urethral obstruction.
• Portosystemic shunt - diagnosis

  Laboratory clues; maybe low BUN, low albumin, low glucose.

  Raised liver enzymes, but not always as liver is small.

  Low USG +/- ammonium biurate crystals.

  Raised fasting and post-prandile bile acids, increased ammonia.

  Ultrasound, Porto gram (radiograph/fluoroscopy), contrast CT.
• Portosystemic shunt - surgical occlusion

  Surgical treatment offers significantly greater survival times.

  Surgical ligation:

  • Complete attenuation has a bad prognosis as animals dont cope well with a major change.

  Ameroid ring:

  • Ring of casein surrounded by stainless steel.
  • Hygroscopic substance that swells after absorbing fluid.
  • Incites a fibrous tissue reaction.

  Cellophane banding:

  • Clear non-medical grade cellophane.
  • Titanium clips used to hold in place.
  • Fibrous tissue reaction leading to gradual occlusion.
• Why do a liver biopsy?

  Need to find out more as it will change how you treat. No point in knowing what it is if the owner doesn’t want to do anything. Type of biopsy depends on the mass. Liver bleeds a lot.