Lecture 23 - Hepato-biliary Pathology

Question 1

What are the functions of the liver?

Answer 1

Protein synthesis
Metabolism of fat and carbs
Detoxification of drugs and toxins, including alcohol

Question 2

What pathologies can affect the liver?

Answer 2

Liver failure
Jaundice
Intra-hepatic bile duct obstruction 
Cirrhosis
Tumours

Question 3

How might pathology affect the extra-hepatic ducts?

Answer 3

By obstructing them

Question 4

Liver failure is caused by which two types of liver injury?

Answer 4

Acute liver injury
Chronic liver injury, e.g. cirrhosis
The two are usually quite separate

Question 5

What are some common acute liver injuries and what cause each?

Answer 5

Hepatitis (inflammation of the liver) caused by viruses, alcohol and other toxins and drug use
Bile duct obstruction - if you can’t expose of bilirubin properly it can be very toxic to the liver

Question 6

What types of hepatitis can you contract?

Answer 6

Hepatitis A, B, C, E (D is a parasite of B)

nb. other viruses can also cause liver disease

Question 7

Describe the general pathology of viral hepatitis

Answer 7

Inflammation of the liver and loss of lots of liver cells leading to liver failure
Outcome of acute inflammation
Resolution - return to normal, no long-term consequences in Hep A and E
Liver failure if severe damage to the liver in Hep A, B and E
Progression to chronic hepatitis and cirrhosis in Hep B and C

Question 8

What are the modes of transmission in viral hepatitis?

Answer 8

Hep A - faecal-oral
Hep B and C - blood borne
Hep E - consumption of infected pork

Question 9

What is alcoholic liver disease?

Answer 9

A response of the liver to excess alcohol involving a fatty change leading to alcoholic hepatitis (acute inflammation –> liver cell death –> liver failure –> cirrhosis)

Question 10

What is jaundice? What causes it?

Answer 10

Increased circulating bilirubin which causes a yellowish/green-sh pigmentation of the skin and sclera of the eye

It is caused by altered metabolism of bilirubin

Question 11

What are the three pathways involved in bilirubin metabolism?

Answer 11

Pre-hepatic
Hepatic
Post-hepatic

Question 12

What is bilirubin?

Answer 12

The result of the breakdown of haemoglobins

Question 13

Describe the pre-hepatic phase of bilirubin metabolism

Answer 13

Breakdown of Hb in spleen to form harm and global (protein component)
Haem converted to bilirubin
Release of bilirubin into circulation

Question 14

Is it normal for bilirubin to be travelling about in the bloodstream?

Answer 14

Yes, it is physiological for a small amount of bilirubin to circulate in the body without causing symptoms of jaundice

Question 15

Describe the hepatic phase of bilirubin metabolism

Answer 15

Uptake of bilirubin by hepatocytes where it is processed
Conjugation of bilirubin (make it more water soluble and more easily excreted) in hepatocytes
Excretion of conjugated bilirubin into the biliary system (into the bile canaliculi)

Question 16

Describe the post-hepatic phase of bilirubin metabolism

Answer 16

Transportation of conjugated bilirubin in biliary system
Breakdown of bilirubin conjugate in intestine
Re-asborption of bilirubin via the entero-hepatic circulation

Question 17

Where can some bilirubin be stored?

Answer 17

In the gallbladder

Question 18

What is the enter-hepatic circulation?

Answer 18

The circulation of biliary acids, bilirubin, drugs and other substances from the liver to the bile, followed by entry into the small intestine

Question 19

What are the three classifications of causes of jaundice? Give examples of diseases that come under these headings

Answer 19

Pre-hepatic jaundice - increased release of haemoglobin from red cells (haemolysis)
Hepatic - cholestasis, intra-hepatic bile duct obstruction
Post-hepatic jaundice - cholelithiasis (gallstones), disease of gallbladder, extra-hepatic duct obstruction

Question 20

What is cholestasis?

Answer 20

Accumulation of bile within hepatocytes or bile canaliculi

Question 21

What can cause cholestasis?

Answer 21

Viral hepatitis (bile canaliculi/ducts can swell blocking release of bile)
Alcoholic hepatitis
Liver failure
Drugs (therapeutic, recreational)

Question 22

Drug induced cholestasis can be predictable or unpredictable, explain what this means?

Answer 22

If you know a drug has a risk of liver damage, it is ‘predictable drug-induced cholestasis’ and this is dose related

If a drug you don’t suspect to cause liver harm, causes liver harm it is ‘unpredictable drug-induced cholestasis’ and it is not dose related

Question 23

What things can cause intra-hepatic bile duct obstruction?

Answer 23

Primary biliary cholangitis
Primary sclerosing cholangitis
Tumours of the liver

Question 24

What kinds of tumours might you get obstructing the intra-hepatic bile duct?

Answer 24

Hepatocellular carcinoma
Tumours of intra-hepatic bile ducts
Metastatic tumours

Question 25

What is primary biliary cholangitis?

Answer 25

Organ specific auto-immune disease mainly affecting females (9:1) Causes granulomatous inflammation involving the bile ducts and loss of intra-hepatic bile ducts (obstructing bile secretion) Diffuse process leading to cirrhosis

Question 26

How can you diagnose primary biliary cholangitis?

Answer 26

Anti-mitochondrial auto-antibodies in serum | Raised serum alkaline phosphatase very helpful in diagnosis

Question 27

What is primary sclerosing cholangitis?

Answer 27

Chronic inflammation and fibrous obliteration of bile ducts leading to loss of intra-hepatic bile ducts Progression to cirrhosis

Question 28

What disease is PSC strongly associated with?

Answer 28

Inflammatory bowel disease

Question 29

What are PSC patients at higher risk of? What is done to try to combat this?

Answer 29

Developing cholangiocarcinoma | Regular screening of patients with PSC to allow early intervention on any suspicious masses

Question 30

What is hepatic cirrhosis?

Answer 30

Liver dysfunction due to long-term damage, leading to the replacement of healthy liver with fibrotic tissue - END STAGE of CHRONIC LIVER DISEASE

Question 31

What are the causes of cirrhosis?

Answer 31

Alcohol - recurrent episodes of alcoholic hepatitis Hep B and C Immune mediated liver disease (e.g. auto-immune hepatitis, PBC, PSC) Metabolic disorders (genetically determined) - e.g. primary haemochromatosis, Wilson's disease Obesity (DM, fatty liver disease) Most commonly cryptogenic

Question 32

What is primary haemochromatosis?

Answer 32

Excess iron in the liver which is toxic to the liver Primary - genetic Secondary - developed

Question 33

What is Wilson's disease?

Answer 33

Autosomal recessive disorder of Cu metabolism, characterised by excessive Cu deposition in several organs, including the liver Can be fatal

Question 34

Which part of the liver does cirrhosis affect?

Answer 34

It is a diffuse process, affecting the whole liver leading to loss of normal liver structure

Question 35

What does a cirrhotic liver look like?

Answer 35

It is replaced by noodles of hepatocytes separated by broad bands of fibrotic tissue It looks shrunken, nodular and fibrosed

Question 36

What are the main complications of cirrhosis?

Answer 36

Altered liver function (liver failure) Abnormal blood flow - portal hypertension leading to varices (more difficult for venous blood to pass through liver, so creates pressure leading to back up of blood) - pressure rising in splenic vein can cause splenomegaly (--> haematological consequences and more susceptible to trauma and a BIG bleed) Increased risk of hepatocellular carcinoma

Question 37

What is a hepatocellular carcinoma?

Answer 37

A malignant tumour of hepatocytes

Question 38

What is a cholangiocarcinoma?

Answer 38

A malignant tumour of bile duct epithelium

Question 39

What kind of cancer often affects the liver?

Answer 39

Metastatic disease

Question 40

What are the risk factors for gallstones?

Answer 40

4 Fs - fat, female, fertile, forty | and also diabetes

Question 41

What are the local effects of gallstones?

Answer 41

They cause inflammation of the gallbladder (cholecystitis) - can be acute cholecystitis or chronic cholecystitis or a mixture of both

Question 42

What is acute cholecystitis? And what are its complications?

Answer 42

Acute inflammation of the gallbladder If severe and long lived can lead to empyema (pus filling the gallbladder), perforation of the gallbladder, or biliary peritonitis (release of bile and infective contents into the peritoneum causing inflammation of the peritoneum) Can also progress to chronic inflammation

Question 43

What is chronic cholecystitis?

Answer 43

Chronic inflammation and fibrosis of the gallbladder wall and dysfunction (thin, muscle wall replaced by fibrosis)

Question 44

What are the causes of common bile duct obstruction?

Answer 44

Gallstones (move from gallbladder into cystic or bile duct) Bile duct tumours Benign strictures (e.g. as a result of PSC) External compression, e.g. tumours (esp. tumours of the head of the pancreas)

Question 45

What are the effects of common bile duct obstruction?

Answer 45

Jaundice No bile excreted into duodenum Infection of bile proximal to obstruction (ascending cholangitis) Secondary biliary cirrhosis if obstruction prolonged