T11-L7: Medical Liver Diseases

Question 1

What is bilirubin combined with in the liver to become conjugated?

Answer 1

Glucuronic acid

• Once conjugated it is excreted in bile and bacteria act on the bilirubin to conjugate it again so that it cannot be absorbed and so excreted into bile. Some however a small amount is not unconjugated again and along with bile acids forming part of the enterohepatic circulation.

Question 2

Give prehepatic causes of jaundice.

Answer 2

In this case these is a rise in unconjugated bilirubin

• Haemeolysis
• Gilbert’s syndromes- this is a harmless deficiency that leads to the build up of bilirubin in times of stress

Question 3

Give hepatic causes of jaundice.

Answer 3

This leads to a build up of The kidneys can excrete it leading to dark urine and yellow eyes/skin. Causes include:
Few functioning hepatocytes e.g. in acute liver injury, end stage liver disease and inborn errors of metabolism.

Question 4

Give post-hepatic causes of jaundice.

Answer 4

This leads to a build up of conjugated bilirubin leading to dark urine (as it is soluble), yellow eyes/skin and pale stools (as bilirubin is not passed into faeces).

Question 5

Give liver function tests.

Answer 5

• Albumin levels - low in liver disease
• Clotting factor levels through INR
• Aminotransferases - ALT and AST
• Blood tests

In addition to the LFTs we can also use ultrasound and biopsy to test for the cause of liver damage.

Question 6

What effects do we see in the liver as bile accumulates?

Answer 6

• Portal Tract Expansion
• Oedema
• Ductular reaction - proliferation of the ductules around the portal tracts
• Bile salts which are toxic build up (cause itchy skin). The copper cannot get out. These accumulate in the liver and skin.

Question 7

What is the aetiology of acute hepatitis?

Answer 7

• Viruses
• Drugs
• Autoimmune
• Unknown (seronegative)

Question 8

What do we see histologically on acute hepatitis?

Answer 8

Loss of hepatocytes. All that remains is collagen and vascular stature - known as pan acing encores,

Question 9

What is the comment cause of hepatitis in the UK? Give their modes of transmission.

Answer 9

Viral hepatitis A, B and C

Hepatitis A - food and water borne
Hepatitis B and C - parenteral rout - most common is maternal and through IVDU (and through blood products)

These a can progress to chronic infection - 70% in Hepatitis C and 10% in Hepatitis B.

Other causes include EBV and CMV in the immunocompromised.

Question 10

What does Hepatitis D require to survive?

Answer 10

Hepatitis B

Question 11

What is alcoholic steatohepatitis?

Answer 11

Fat deposition and inflammation. When cells cannot cope with the oxidative stress due to the fat accumulation they undergo cell damage with ballooning - breakdown of the cytoskeleton and hydronic enlargement. Mallory bodies are also seen - these are pink condense cytoplasm with an inflammatory infiltrate.

Question 12

What is the fastest growing case fo liver disease in the Western World?

Answer 12

Non-Alcoholic Fatty Liver Disease (NAFLD)

Question 13

What is the type of liver injury that occurs when you overdose in a drug?

Answer 13

Intrinsic

Question 14

What is the antidote for paracetamol overdose?

Answer 14

N-acteylcysteine

Question 15

Which hepatocytes are destroyed first in instrinc hepatic injury?

Answer 15

Those furthest from the portal tracts. They produce the toxic metabolite and are first to undergo necrosis.

Question 16

What is Haemochromatosis?

Answer 16

An inborn error of metabolism that leads to an accumulation of iron. This leads to cirrhosis, diabetes, pigmented skin, arthritis and cardiomyopathy. The treatment is venesection to deplete iron stores.

Question 17

What is Wilson’s disease?

Answer 17

An inborn error of metabolism that leads to the accumulation of Copper. This leads to cirrhosis, Kayser-Fleischer rings (dark rings that surround the iris) in the eye and ataxia.

Question 18

What is Alpha-1-AntiTripsin disorder?

Answer 18

Anti-trypsin is an abnormal and so cannot be exported from hepatocytes and others cells of the body. The protease therefore accumulates in the liver and injures them causing cirrhosis. It is also therefore insufficient in blood and so failures to inactivate neutrophil enzymes leading to emphysema

Question 19

Give examples of autoimmune liver disease.

Answer 19

• Autoimmune hepatitis
• Primary Sclerosing Cholangitis
• Primary Biliary Cholangitis

Question 20

What is Primary biliary cholangitis?

Answer 20

Definition: This is an autoimmune inflammation of the biliary tree.

Epidemiology: It mainly effects middle aged women.

Aetiology: Autoimme

Pathogenesis: Characterised by anti-mitochondrial antibodies. Bile duct granulomas are produced at an early stage and surrounded by Kupffer cells.

Clinical features: This leads to an elevated phosphate. The destruction of the cells can lead to ductopenia (loss of the bile duct) and cirrhosis.

Question 21

What is Primary Sclerosing Cholangitis?

Answer 21

Definition: A long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladder.

It presents with high ALP and biliary features such as a ‘pruned tree - a narrowing in biliary untagging. There is periductal “onion skin” fibrosis seen around the duct.

It is associated with ulcerative colitis.

Long term, it can lead to ductopenia and cirrhosis.

Question 22

Give causes of cirrhosis.

Answer 22

• Alchohol
• Drugs
• Virus - Hepatitis B and C
• Autoimmune
• Metabolic - e.g. iron, copper and A1AT deficiency

Question 23

What are complications of cirrhosis?

Answer 23

In cirrhosis there is widespread fibrosis and scarring. there is loss of the architecture leading to nodal repair. The liver cells are bypassed as the blood travels to the portal vein.

Consequences include:

• Loss of detoxification of drugs and hormone - can lead to encephalopathy
• Clotting problems and so bruising
• Malnutrition due to vitamin loss
• Oedema due to lack of albumin
• Ascites
• Muscle wasting
• Susceptibility to infection - antibodies not produced
• Failure to excrete bile and bile salts leading to jaundice and itchy skin respectively
• Portal hypertension (oesophageal varies)

Question 24

How does a patient with chronic liver disease present?

Answer 24

• Ascites
• Muscle wasting
• Bruising
• Gynaecomastia
• Spider naevi
• Varices, Caput medusae = variceal umbilical vein collaterals