CS8 - Cirrhosis and Paracetamol Overdose

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

- Hepatic artery

- 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

Define acute liver injury:

An overwhelming assault of the liver that causes a significant proportion of hepatocytes to die at 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 of paracetamol overdose:

1) Abdominal pain

2) Clotting disturbance

3) Acidotic blood

4) Renal failure

5) LFTs deranged (high transaminases)

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?

Gluthionine

How does apoptosis occur in the liver?

Holes between cells appear with the presence of acidophil bodies

What are acidophilic bodies?

Pink, eosinophilic regions

How does acute liver failure affect enzyme release?

Aspartate transaminase (AST) and alanine transaminase (ALT) are released into the blood

How does acute liver failure affect bilirubin metabolism?

Metabolism fails, causing hyperbilirubinaemia and so jaundice

How does acute liver failure affect detoxification of nitrogenous compounds?

Detoxification fails, causing circulation of excitatory amino acids and potentially hepatic encephalopathy (coma)

How does acute liver failure affect blood clotting?

Failure to synthesise clotting factors II, VII, IX and X causing bleeding tendencies

How does acute liver failure affect t the kidneys?

Shock causes low glomerular filtration, leading to renal failure

Give 2 drugs used to treat paracetamol overdose:

1) Activated charcoal

2) N-acetyl cysteine

How does activated charcoal help treat a paracetamol overdose?

Prevents absorption in the gut

How does N-acetyl cysteine help treat paracetamol overdose?

Increases glutathione stores

In which zone do toxic metabolites build up in hepatocytes?

Zone 3

What is chronic liver disease?

Any disease that causes persistent and ongoing/repetitive inflammation of the liver

- Results in increasing amounts of fibrosis

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

Liver biopsy

What is cirrhosis?

Significant fibrosis of the liver with nodularity of parenchyma

What is parenchyma?

Functional tissue of an organic

What is repair of the liver?

Formation of scar tissue

What is regeneration of the liver?

Labour and stable cells regenerate

Give 4 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 2 main effects of increased portal hypertension?

1) Oesophageal varices

2) Acites

How does liver cirrhosis cause ascites?

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