Hepatic Disease Flashcards by Poppy Ballantine

What is the precursor to bilirubin?

Haemoglobin
(Haemoglobin > heme > biliverdin > bilirubin)

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Where does haemoglobin metabolism occur?

Liver

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Where does conjugated bilirubin go?

Enters biliary tree then GI tract at duodenal papilla

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What do colonic bacteria deconjugate bilirubin into? (Give faeces and urine their colour)

Urobilin (wee-bilin)
Stercobilin (poo-bilin)

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Is excess haemoglobin/heme a pre-hepatic, hepatic or post-hepatic problem?

Pre-hepatic

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Pre-hepatic differentials for bilirubin excess (3)

Haemolytic anaemia (many causes, most important are primary immune mediated diseases and secondary immune mediated disease e.g. neoplasia)
Internal haemorrhage
Severe myolysis (myoglobin)

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Two hepatic causes of increased bilirubin

Hepatic disease
Proximal biliary disease (cholangitis/cholangiohepatitis)

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Degenerative hepatic diseases (3)

Amyloidosis
Lipidosis (cats)
Cirrhosis

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Cholangitis

Inflammation of the intrahepatic biliary ducts

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Cholangiohepatitis

When cholangitis leads to secondary inflammation of the surrounding hepatic parenchyma

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What occurs in all post-hepatic causes of bilirubin excess?

Extrahepatic bile duct obstruction (EHBDO)

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Intraluminal differentials for EHBDO (5)

Cholelithiasis (stones)
Gall bladder mucocele (Border Terrier)
Inspissated (thickened) bile
Gall bladder polyps
Cysts (cats)

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Mural differentials for EHBDO

Inflammation (cholangitis/cholecystitis/choledochitis)
Neoplasia

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Extramural differentials for EHBDO

Pancreatic disease (pancreatitis/neoplasia of pancreas head)
Duodenal disease (infectious/inflammatory/neoplastic)
Porta hepatitis stricture (local inflammation/infectious/neoplasm)

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Should there be bile acids in the peripheral circulation?

No, never

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Tests for pre-hepatic causes of jaundice

Haematology (look for anaemia)
Blood smear (spherocytes/autoagglutination)
Gross serum colour (red)
Infectious disease screening
History (toxins?)
Imaging (neoplasia)

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What can cause elevations in AST other than liver damage?

Muscle damage (concurrent CK elevation)
(Restraining animal for venepuncture?)

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Which are the important biochemistry measures for liver function?

ALT
ALP

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How do urea values reflect hepatic dysfunction?

Low
(Urea is the end product of protein metabolism and ammonia production, however can drop for a number of reasons e.g. anorexia)

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How do ammonia values reflect hepatic dysfunction?

High
(Labile so need point of care testing)

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What clinical sign is caused by elevated ammonia?

Hepatic encephalopathy (neurological signs)

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How does albumin reflect hepatic dysfunction?

Low
(Produced by liver, <15g/L there will be failure of endothelial glycocalyx and therefore oedema/ascites)

What is a bile acid stim test used to assess?

Liver function
Biliary flow

Excellent test of liver function/biliary tract disease but poor at differentiating between hepatic and post hepatic jaundice

How is a bile acid stim test done?

Take a sample for baseline bile acids, feed patient and take another sample

Use of ultrasound when diagnosing hepatic dysfunction

Cannot make a diagnosis but it may indicate a problem

Main risk of liver biopsy when testing for hepatic dysfunction and how to manage it

Risk of bleeding (the liver produces clotting factors so risk increased as patients with liver disease likely to have a coagulopathy) Test clotting time and give fresh frozen plasma transfusion before the biopsy if there is a prolonged clotting time

What is the cholestatic marker in biochemistry?

ALP

When biochemistry shows elevated liver values how can you differentiate hepatic causes from post hepatic causes of jaundice?

Post-hepatic: liver function retained so liver function markers are normal (urea, albumin and clotting times)

Test used in dogs/cats for pancreatitis (as a post-hepatic cause of jaundice)

cPLI/fPLI (canine/feline Pancreatic Lipase Immunoreactivity)

Liver blood supply

Double blood supply: ~30% hepatic artery ~70% hepatic portal vein

How are infectious/toxic substances drained from the GI tract to the liver?

Hepatic portal vein

Functions of the liver

Digestion/metabolism/storage of nutrients (triglycerides, protein, glycogen, cholesterol, vitamins and minerals) Waste management (NH3, bilirubin) Protein metabolism (albumin synthesis) Production and activation of clot factors Drug metabolism Immunoregulation (Kupffer cells)

What percentage of liver function must be lost before there are clinical signs of chronic liver failure?

70%

In acute liver disease are clinical signs seen before there is 70% loss of functional liver mass and why?

Yes, because there is last time for adaptation by surviving hepatocytes

Which direction does blood flow in?

From portal triad to central vein (zone 1 to 3)

Where is bile made and which direction does it flow in?

Made in zone 3 cells Flows towards bile duct (opposite direction to blood flow)

Disease in which zone causes jaundice earliest?

Zone 3

Non-specific clinical signs in liver disease

Depression/lethargy Anorexia Weight loss Vomiting/diarrhoea PUPD

Clinical signs suggestive of liver disease (although can occur with other disease)

Jaundice Hepatic encephalopathy Ascites Drug intolerance Coagulopathy

Why do GI signs occur with liver disease?

Portal hypertension leads to vascular stasis and venous congestion which has an adverse effect on the GI tract (Also increased risk of GI ulceration)

Mechanism of ascites in liver disease (two causes)

Portal hypertension Hypoalbuminaemia

What presents in the following way: Waxing and waning Non-localising on neurological exam Hyperactive and/or depressed Circling/pacing Central blindness Salivation Seizures/coma

Hepatic encephalopathy

Enzymatic markers of hepatocellular injuries (3)

ALT/alanine aminotransferase AST/aspartate aminotransferase GLDH/glutamate dehydrogenase

Where is the liver enzyme (AST) also found and how do you differentiate liver damage as the source?

Muscle In muscle inflammation CK is also present in biochemistry. In liver disease ALT will be elevated

In which species is a small increase in levels of ALT always significant

Cats (low reference range due to short half life in circulation)

Enzymatic markers of cholestasis

ALP/alkaline phosphatase GGT/gamma glutamyl transferase

Difference in ALP half life between dogs and cats

Long in dogs (66 hours), short in cats (6 hours)

Causes of ALP increase

Cholestasis Iatrogenic (corticosteroids and anti-convulsants in dogs) Secondary 'reactive hepatopathies' (hyperthyroidism and DM in cats, bone lesions and young animals as it is a bone isoenzyme of ALP)

After hepatic insult, does ALP or ALT rise more slowly?

ALP (must be synthesised before release)

Which enzyme will rise alongside ALP in cholestasis but will not increase with bone lesions?

GGT

Causes of increased bile acids (3)

Hepatic dysfunction Cholestasis Portosystemic shunt

What level of bilirubinuria is abnormal in dogs and cats?

Any level is abnormal in cat ++ in dog

Is USG increased or decreased in liver disease?

Decreased