Paracetamol Overdose and Cirrhosis

What is the largest solid organ in the body?

liver

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

1) hepatic artery

2) hepatic portal vein

Give 8 functions of the liver:

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

How does a healthy liver look? (3)

1) reddish (due to abundance of iron)

2) shiny

3) smooth capsules

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

irregular and distended

How do hepatic artery branches appear under a microscope?

thicker and more circular

Define acute liver injury:

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

Define chronic liver injury:

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

Give 5 clinical signs for paracetamol overdose:

1) abdominal pain

2) clotting disturbance

3) acidotic blood

4) renal failure

5) liver tests markedly deranged (high transaminases)

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

true

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

idiosyncratic hepatotoxicity

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

intrinsic hepatotoxicity

Give the minor pathway of paracetamol metabolism:

P450 enzymes break paracetamol down, forming NAPQI which glutathione metabolises

What molecule is depleted in paracetamol metabolism following an overdose?

glutathione

How does apoptosis in the liver appear?

holes between cells with presence of acidophil bodies

What are acidophil bodies?

pink, eosinophilic regions

How does acute liver failure affect enzyme release?

aspartate transaminase and alanine transaminase are released into the blood

How does acute liver failure affect bilirubin metabolism?

bilirubin metabolism fails, causing hyperbilirubinaemia and jaundice

How does acute liver failure affect detoxification of nitrogenous compounds?

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

How does acute liver failure affect blood clotting

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

How does acute liver failure affect the kidneys?

shocks causes low glomerular filtration, leading to renal failure

Give two drugs used to treat paracetamol overdose:

1) activated charcoal

2) N-acetyl cysteine

How does activated charcoal help treat paracetamol overdose?

it prevents absorption in the gut

How does N-acetyl cysteine help treat paracetamol overdose?

it increases glutathione levels

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

zone 3

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

liver biopsy

What is cirrhosis?

significant fibrosis with nodularity of parenchyma

What is the only cure for end stage liver disease?

transplantation

How does cirrhosis appear under a microscope?

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

Give 4 core consequences of cirrhosis of the liver:

1) portal hypertension

2) risk of infection

3) ascites

4) carcinogenesis

How does liver cirrhosis cause portal hypertension?

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

What are the two main effects of increased portal hypertension?

1) oesophageal varices

2) ascites

How does liver cirrhosis increase risk of infection?

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

Describe how ascites comes about:

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

True or false: cirrhosis of the liver increases the risk of hepatocellular carcinoma

true