3. Liver Disease

Question 1

How is alcohol metabolised?

Answer 1

ethanol oxidised to acetaldehyde by alcohol dehydrogenase

acetaldehyde converted into acetate by acetaldehyde dehydrogenase

acetate is used by the peripheral tissues as part of cellular respiration

Question 2

How are alcohol units calculated?

Answer 2

(volume of drink x ABV) ÷ 1000

Question 3

A deficiency of what contributes to neurological manifestations of alcohol excess?

Answer 3

thiamin

Question 4

1. What drug is given to reduce alcohol withdrawal symptoms?

2. What drug is given to help maintain alcohol abstinence?

Answer 4

1. chlordiazepoxide

2. acamprostate

Question 5

1. What do phase I reactions involve?

2. What do phase II reactions involve?

Answer 5

1. oxidation/hydrolysis/reduction, facilitated by CP450 enzymes
2. conjugation to make drugs more water soluble

Question 6

What is hepatic clearance of oral drugs dependent on? (4)

Answer 6

• efficiency of metabolising enzymes
• hepatic blood flow
• intrinsic clearance
• protein binding

Question 7

Name 5 risk factors for impaired hepatic drug metabolism

Answer 7

• hepatocellular failure
• decreased hepatic blood flow
• decreased enzyme function
• decreased protein binding
• reduced bile production

Question 8

Name 5 CP450 Inducers

Answer 8

CRAPS out drugs
Carbamazepine
Rifampicin
barbituates
phenytoin
St John's Wort

Question 9

Name 8 CP450 Inhibitors

Answer 9

some certain silly compounds annoyingly inhibit enzymes, grrr

Sodium valproate
Ciprofloxacin
Sulphonamide
Cimetidine
Antifungals; amiodarine
Isoniazind
Erythromycin
Grapefruit

Question 10

When is jaundice clinically detectable (i.e. visualised?

Answer 10

Bilirubin >50

Question 11

Describe how jaundice is classified

Answer 11

PREHEPATIC - haemolysis; defects in conjugation
HEPATIC - liver disease, drugs, toxins
POST-HEPATIC - obstruction of billiary tree

Question 12

What is Gilbert’s Syndrome?

Answer 12

• familial conjugated hyperbilirubinaemia
• asymptomatic
• mutations in enzyme responsible for bilirubin conjugation

Question 13

What’s the difference between acute and chronic hepatits?

Answer 13

acute - resolves in ≥6 months

chronic - lasts ≥6 months

Question 14

What are the clinical features of:

1. acute hepatitis
2. fulminant hepatitis
3. Chronic hepatitis

Answer 14

1. prodromal, non-specific flu like symptoms + jaundice, RUQ pain and hepatomegaly
2. signs of acute hepatitis + coagulopathy + encephalopathy
3. Signs of acute hepatitis + systemic inflammatory symptoms. Chronic onset

Question 15

Describe the route of transmission and prognosis of the following types of viral hepatitis

1. A
2. B
3. C
4. D
5. E

Answer 15

1. faecal oral; never progresses to chronic disease
2. transmitted via body fluids. can cause both acute and chronic hepatitis
3. blood borne; becomes chronic in 70% of those infected (but remains asymptomatic for long periods)
4. only occurs with hep B infection
5. faecal oral; mostly acute. can be fulminant in pregnant women

Question 16

1. What is NAFLD?

2. What can it progress to?

Answer 16

1. accumulation of fat (steatosis) in the liver due to causes other than alcohol
2. NAFLD → non-alcoholic steatohepatitis → cirrhosis

Question 17

Name 3 investigations which can be performed for ?NAFLD

Answer 17

1. ultrasound - demonstrates steatosis
2. liver biopsy (for disease stage)
3. elastography - used to evalulate the degree of fibrosis

Question 18

Briefly describe the pathogenesis of alcoholic liver disease

Answer 18

1. metabolism of alcohol increases the NADH/NAD ratio in the liver; this alters the redox potential which drives hepatic fatty acid synthesis and decreased fatty acid oxidation. This results in the hepatic accumulation of fatty acid

Question 19

Describe the 3 stages of alcoholic liver disease

Answer 19

1. steatosis - reversible with abstinence from alcohol
2. alcoholic hepatitis - infiltration of leucocytes and hepatocyte necrosis
3. cirrhosis - fibrosis (which disrupts hepatic blood flow); irreversible

Question 20

Name the complications of cirrhosis (6) which patients typically present with

Answer 20

1. ascities
2. oesophageal varices
3. hepatic encephalopathy
4. hepatorenal syndrome
5. hepatopulmonary syndrome
6. Hepatocellular carcinoma

Question 21

Investigations for Alcoholic Liver Disease (5)

Answer 21

1. LFTs
2. ultrasound
3. CT
4. Liver biopsy and histology
5. elastography

Question 22

How is alcoholic liver disease managed? (4)

Answer 22

1. abstience from alcohol
2. bed rest
3. high protein diet and vitamin supplimentation
4. liver transplant for cirrhosis

Question 23

What scoring system is used to assess severity of Cirrhosis?

Answer 23

Child’s-Pugh Classification

Question 24

1. What should be avoided in patients with cirrhosis? (3)
2. What screening should people with cirrhosis undergo?
3. What diet is recommended for patient’s with cirrhosis?

Answer 24

1. alcohol, NSAIDs, aspirin
2. 6 monthly ultrasound to detect early hepatocellular carcinoma
3. reduced salt

Question 25

1. What is the eligibility criteria for liver transplantation? 2. Name 4 contraindications for liver transplant

Answer 25

1. must be abstinent from alcohol for 6+ months and/or must not be continuing to use intravenous drugs 2. active sepsis outside the hepatobiliary tree malignancy outside the liver liver mets lack of psychological commitment on the part of the patient

Question 26

1. What is budd-chiari syndrome? | 2. Name 4 causes of budd chiari syndrome

Answer 26

1. obstruction to the venous outflow of the liver because of hepatic vein occlusion 2. idiopathuc hypercoagulability thrombophillia occlusion of the hepatic vein secondary to tumours