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Flashcards in Liver & Biliary Overview Deck (118)
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1

B - non-alcoholic steatohepatitis

 

  • she has type II diabetes, is obese and consumes alcohol regularly
    • these are all risk factors

 

  • simvastatin can be hepatotoxic, but she has only been taking this for 2 years so it is unlikely 

2

A - full recovery

 

  • HBsAg shows that they have a current infection 
    • this could be acute or chronic

 

  • Anti-HBcAg IgM (IgM core antibody) shows that they must currently have an acute infection

 

  • someone with an acute hep b infection is most likely to make a full recovery

3

D - IV cefotaxmine and oral lactulose

 

  • the patient has encephalopathy

 

  • they also have spontaneous bacterial peritonitis 
    • fever
    • worsening abdominal tenderness / distenstion
    • high neutrophil count

 

  • IV cefotaxime is an antibiotic that will treat the SBP

 

  • lactulose reduces ammonia production in the gut to prevent encephalopathy from getting worse 

4

What is the underlying cause of jaundice?

it is caused by an increased concentration of bilirubin in the blood

 

(hyperbilirubinaemia)

5

What are the steps involved in the bilirubin metabolism pathway?

  • old RBCs are broken down in the spleen 

 

  • the haemoglobin from RBCs produces iron and unconjugated bilirubin

 

  • the unconjugated bilirubin travels in the blood, bound to albumin, to the liver

 

  • in the liver it is conjugated by UDPGT enzyme

 

  • conjugated bilirubin then enters the biliary system and forms part of the bile

 

  • conjugated bilirubin enters the duodenum in the bile via the common bile duct

 

  • here it is converted to urobilinogen and stercobilinogen
    • urobilinogen is excreted in the urine
    • stercobilinogen is excreted in the faeces and gives them a dark colour

6

What causes pre-hepatic jaundice?

 

What type of hyperbilirubinaemia is present?

  • caused by excessive RBC breakdown 
    • or impaired uptake of RBCs by the liver 

 

  • this overwhelms the liver's ability to conjugate bilirubin

 

  • there is an unconjugated hyperbilirubinaemia

 

  • any bilirubin that is conjugated will be excreted normally, but the excess unconjugated bilirubin will remain in the bloodstream to cause jaundice 

7

What are the 2 major causes of pre-hepatic jaundice?

 

Why do these lead to jaundice?

Haemolysis:

  • increased RBC breakdown leads to an increase in unconjugated bilirubin concentration

 

  • the liver cannot conjugate the bilirubin fast enough, leading to an increase in unconjugated bilirubin in the blood
    • there is nothing wrong with the liver, there is just a massive excess of bilirubin

 

Gilbert's Syndrome:

  • this is a deficiency of the UDPGT enzyme

 

  • UDPGT enzyme is not working as well as it would in a healthy person, so when this individual becomes stressed / gets an infection they can appear jaundiced

8

What causes hepatocellular (intrahepatic) jaundice?

 

What type of hyperbilirubinaemia is produced here?

  • caused by dysfunction of the hepatic cells

 

  • the liver loses some of its ability to conjugate bilirubin, however this is not the main problem

 

  • if the liver becomes cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction
    • the conjugated bilirubin cannot get into the biliary system

 

  • this produces a mixed conjugated and unconjugated hyperbilirubinaemia
    • it is mainly conjugated hyperbilirubinaemia

9

What are the main causes of hepatocellular jaundice?

Caused by anything that damages the hepatocytes:

 

  • alcoholic liver disease / cirrhosis 

 

  • hepatitis
    • viral, autoimmune

 

  • hepatocellular carcinoma / liver mass

 

  • haemochromatosis

 

  • iatrogenic e.g. medication

10

What causes post-hepatic jaundice?

 

What type of hyperbilirubinaemia is produced?

  • this is jaundice caused by obstruction of biliary drainage 

 

  • the liver is still functioning and conjugating bilirubin as normal

 

  • the conjugated bilirubin cannot get into the duodenum, so it enters the bloodstream instead

 

  • this produces a conjugated hyperbilirubinaemia 

11

How can the causes of post-hepatic jaundice be divided into 3 categories? 

Intra-luminal causes:

  • gallstones 

 

Mural causes:

  • strictures 
  • cholangiocarcinoma
  • drug-induced cholestasis
  • PSC / PBS

 

Extra-mural causes:

  • pancreatic cancer
  • abdominal masses (e.g. lymphomas)

12

How can looking at the urine determine what kind of hyperbilirubinaemia might be present?

  • conjugated bilirubin is water soluble and so can be excreted in the urine

 

  • unconjugated bilirubin cannot be excreted in the urine

 

  • dark ("coca-cola") urine occurs in conjugated or mixed hyperbilirubinaemia
    • hepatocellular or post-hepatic jaundice

 

  • normal urine is seen in unconjugated hyperbilirubinaemia
    • pre-hepatic jaundice 

13

In what type of jaundice do the stools appear different?

 

Why does this occur?

  • in post-hepatic jaundice the stools will appear paler

 

  • this occurs when there is an obstructive picture as there are reduced levels of stercobilin entering the GI tract
    • this normally colours the stool

 

  • there will also be dark urine and pruritis 
    • itching is caused by bile salts, as the blockage affects the drainage of bile salts into the duodenum

14

What blood tests should anyone presenting with jaundice have?

  • liver function tests

 

  • coagulation studies
    • prothrombin time can be used as a marker of liver synthetic function

 

  • FBC
    • anaemia, raised MCV and thrombocytopenia can all be seen in liver disease

 

  • U&Es

15

What tests are included in a liver screen?

 

What does each of these things measure?

Bilirubin:

  • quantifies the degree of suspected jaundice

 

Albumin:

  • marker of liver synthetic function

 

Transaminases - ALT & AST:

  • markers of hepatocellular injury
    • AST : ALT ratio > 2 means likely alcoholic liver disease
    • AST : ALT ratio = 1 means viral hepatitis more likely 

 

Alkaline phosphatase (ALP):

  • raised in biliary obstruction
    • as well as during pregnancy, bone disease and certain malignancies

 

Gamma-GT:

  • more specific for biliary obstruction than ALP

16

What results would you expect to see for each type of jaundice on LFTs?

Pre-hepatic:

  • raised bilirubin only 

 

Hepatocellular:

  • there is damage to hepatocytes so you would expect to see raised AST & ALT

 

Post-hepatic:

  • there is an obstruction / bile duct damage so you would expect to see raised ALP / GGT

17

What is meant by hepatitis?

 

What are the possible causes of this?

  • hepatitis is inflammation of the liver 

 

  • it presents with raised AST and ALT

 

  • causes can be acute or chronic and include:
    • alcoholic hepatitis
    • non-alcoholic steatohepatitis (NASH)
    • viruses
    • drugs
    • autoimmune 

18

How does hepatitis tend to present?

  • all types of hepatitis tend to present with similar symptoms

 

  • RUQ pain
  • jaundice (hepatocellular)
  • hepatomegaly
  • joint pain
  • nausea
  • fatigue
  • dark urine

19

How long does hepatitis have to persist for to become chronic?

 

What are the possible outcomes of acute and chronic hepatitis?

  • acute hepatitis resolves within 6 months
    • it becomes chronic if it lasts for longer than 6 months

 

  • acute hepatitis can resolve on its own, progress to chronic hepatitis or (rarely) result in acute liver failure

 

  • chronic hepatitis may progress to cirrhosis, liver failure and hepatocellular carcinoma

20

What are the 3 conditions that make up the spectrum of alcoholic liver disease?

  • steatosis occurs after a few days of heavy drinking 
    • this is completely reversible

 

  • alcoholic hepatitis (inflammation) occurs after long term alcohol use (not a binge)
    • this is reversible, especially if mild

 

  • if alcohol consumption is continued this can cause cirrhosis
    • this is IRREVERSIBLE as it involves scarring of the liver

 

21

What are the symptoms of mild and severe alcoholic hepatitis?

Mild:

  • nausea
  • anorexia
  • weight loss 
  • hepatomegaly

 

Severe:

  • fever
  • jaundice
  • tachycardia
  • tender hepatomegaly
  • bruising 
  • encephalopathy
  • ascites

22

What causes the inflammation associated with alcoholic hepatitis?

  • alcohol metabolism requires NAD+

 

  • when there is excessive alcohol consumption, there is not enough NAD+ available for glycolysis

 

  • this promotes fatty infiltration into the liver, leading to inflammation

23

What would a full blood count show in someone with chronic high alcohol intake?

macrocytic anaemia

 

  • this presents as low haemoglobin and high mean cell volume (MCV)

24

What would liver function tests show in someone with chronic high alcohol consumption?

  • AST : ALT ratio > 2
    • remember "alcohol then toAST"

 

  • increased bilirubin

 

  • decreased albumin

 

  • ALP may be normal or raised

 

  • GGT is raised in someone who drinks a lot of alcohol over long periods of time
    • raised GGT indicates biliary damage, but also chronic alcohol consumption

25

What would a clotting screen show in someone with chronic alcohol consumption?

  • clotting screen is a functional assessment that tells you how well the liver is working

 

  • the liver makes clotting factors, so clotting time increases when the liver is damaged

 

  • increased prothrombin time is a sensitive marker of significant liver damage 

26

What imaging is performed in alcoholic liver disease?

 

What would a liver biopsy show?

  • hepatic ultrasound scan is performed

 

  • liver biopsy is diagnostic, but rarely needed

 

the presence of Mallory bodies indicates hepatitis 

  • these are damaged intermediate filaments within the hepatocytes

 

there may also be ballooning degeneration of hepatocytes

  • this is a form of liver parenchymal cell death

27

What is involved in the management of alcoholic liver disease?

  • alcohol abstinence 

 

  • diazepam may be given in hospital to manage alcohol withdrawal
    • this prevents withdrawal symptoms and seizures

 

  • nutrition 
    • enteral preferred - calories and vitamins - alcoholics are often malnourished

 

  • weight loss / smoking cessation

 

  • steroids are given in severe alcoholic hepatitis 

28

What is meant by non-alcoholic fatty liver disease (NAFLD) and how can this progress?

  • the presence of a fatty liver in those who do not consume alcohol in amounts generally considered harmful to the liver 

 

  • steatosis is completely reversible

 

  • this progresses to steatohepatitis (NASH), which involves inflammation
    • this is reversible, especially if it is mild

 

  • this progresses to cirrhosis, which is irreversible

29

What are the risk factors associated with NAFLD?

  • obesity (truncal)

 

  • insulin resistance / type II diabetes

 

  • hyperlipidaemia

 

  • hypertension

 

  • metabolic syndrome

 

  • short bowel syndrome

 

  • total parenteral nutrition (TPN)

30

What additional symptoms may someone with NAFLD present with?

  • they may have signs of insulin resistance

 

  • polyuria

 

  • polydipsia

 

  • acanthosis nigricans