Clinical symposium 8: Paracetamol overdose and cirrhosis

Question 1

What is the largest solid organ in the body?

Answer 1

Liver

Question 2

What vessels make up the dual blood supply of the liver?

Answer 2

1) hepatic artery

2) hepatic portal vein

Question 3

Give 8 functions of the liver:

Answer 3

1) chemical detoxification

2) carbohydrate metabolism

3) coagulation factor synthesis

4) fat metabolism

5) bile production and excretion

6) protein metabolism and synthesis

7) hormone metabolism

8) vitamin storage

Question 4

How does a healthy liver look? (3)

Answer 4

1) reddish (due to abundance of iron)

2) shiny

3) smooth capsules

Question 5

How do portal and hepatic vein branches appear under a microscope?

Answer 5

irregular and distended

Question 6

How do hepatic artery branches appear under a microscope?

Answer 6

thicker and more circular

Question 7

Define acute liver injury:

Answer 7

an overwhelming assault of the liver causes a significant proportion of hepatocytes to die and once but most eventually regenerate

Question 8

Define chronic liver injury:

Answer 8

persistent ongoing damage and injury causing a chronic inflammatory response that leads to fibrosis and regeneration and eventually cirrhosis

Question 9

Give 5 clinical signs for paracetamol overdose:

Answer 9

1) abdominal pain

2) clotting disturbance

3) acidotic blood

4) renal failure

5) liver tests markedly deranged (high transaminases)

Question 10

True or false: people differ in the way they metabolise drugs

Answer 10

True

Question 11

What is the term used to describe liver damage caused by a rare, unpredictable reaction of a drug?

Answer 11

idiosyncratic hepatotoxicity

Question 12

What term is used to describe liver damage caused by high doses of drugs?

Answer 12

intrinsic hepatotoxicity

Question 13

Give the minor pathway of paracetamol metabolism:

Answer 13

P450 enzymes break paracetamol down, forming NAPQI which glutathione metabolises

Question 14

What molecule is depleted in paracetamol metabolism following an overdose?

Answer 14

glutathione

Question 15

How does apoptosis in the liver appear?

Answer 15

holes between cells with presence of acidophil bodies

Question 16

What are acidophil bodies?

Answer 16

pink, eosinophilic regions

Question 17

How does acute liver failure affect enzyme release?

Answer 17

aspartate transaminase and alanine transaminase are released into the blood

Question 18

How does acute liver failure affect bilirubin metabolism?

Answer 18

bilirubin metabolism fails, causing hyperbilirubinaemia and jaundice

Question 19

How does acute liver failure affect detoxification of nitrogenous compounds?

Answer 19

detoxification of nitrogenous compounds fails resulting in the circulation of excitatory amino acids and possibly hepatic encephalopathy (coma)

Question 20

How does acute liver failure affect blood clotting

Answer 20

there is failure to synthesis clotting factors II, VII, IX and X causing bleeding tendencies

Question 21

How does acute liver failure affect the kidneys?

Answer 21

shocks causes low glomerular filtration, leading to renal failure

Question 22

Give two drugs used to treat paracetamol overdose:

Answer 22

1) activated charcoal

2) N-acetyl cysteine

Question 23

How does activated charcoal help treat paracetamol overdose?

Answer 23

it prevents absorption in the gut

Question 24

How does N-acetyl cysteine help treat paracetamol overdose?

Answer 24

it increases glutathione levels

Question 25

In which zone do toxic metabolites build up in in hepatocytes?

Answer 25

Zone 3

Question 26

What is the only reliable method of assessing fibrosis of the liver?

Answer 26

liver biopsy

Question 27

What is cirrhosis?

Answer 27

significant fibrosis with nodularity of parenchyma

Question 28

What is the only cure for end stage liver disease?

Answer 28

transplantation

Question 29

How does cirrhosis appear under a microscope?

Answer 29

regenerative nodules of hepatocytes will be surrounded by sheets of fibrous tissue

Question 30

Give 4 core consequences of cirrhosis of the liver:

Answer 30

1) portal hypertension 2) risk of infection 3) ascites 4) carcinogenesis

Question 31

How does liver cirrhosis cause portal hypertension?

Answer 31

the stiff, scarred liver puts pressure on the portal venous system

Question 32

What are the two main effects of increased portal hypertension?

Answer 32

1) oesophageal varices 2) ascites

Question 33

How does liver cirrhosis increase risk of infection?

Answer 33

alterations in the immune system leads to an increased risk of sepsis

Question 34

Describe how ascites comes about:

Answer 34

back pressure from portal hypertension increases blood pressure in the kidneys, activating the renin-angiotensin system (causing H2O and Na+ retention) - albumin isn't synthesised so the osmotic gradient is lost causing fluid to leak into the peritoneum