Cirrhosis

Question 1

What is cirrhosis?

Answer 1

When the liver does not function properly due to long term damage

The damage is irreversible and involves scarring and nodules

Question 2

What are the causes of cirrhosis?

Answer 2

Chronic alcohol abuse

Hepatitis B + C

Metabolic disorders such as haemochromatosis, Wilson’s disease, alpha1-antitrypsin deficiency

Hepatic vein problems

Non-alcoholic fatty liver disease

Autoimmune conditions

Long term use of some drugs

Question 3

How does alcohol cause cirrhosis?

Answer 3

Alcohol is oxidised to acetaldehyde in the liver

It blocks the normal metabolism of proteins, fats and carbohydrates

This leads to injury of the liver

Which leads to scarring and fibrosis = cirrhosis

Question 4

What is non-alcoholic fatty liver disease (NAFLD)?

Answer 4

Fat builds up in the hepatocytes causing inflammation.
This leads to scar tissue and fibrosis and eventually cirrhosis

It is the same as alcoholic liver disease, except they don’t have a history of alcohol

Question 5

What causes NAFLD?

Answer 5

Insulin resistance: diabetes mellitus

Obesity

Genetics

Poor nutrition: drinking lots of soft drinks

Some drugs: amiodarone, methotrexate

Question 6

How do you diagnose NAFLD?

Answer 6

Biospy: to look for fatty deposits and scarring

Question 7

How do you treat NAFLD?

Answer 7

Control risk factors: lose weight, control diabetes

No drug available

Transplant

Question 8

What’s the link between NAFLD and cirrhosis?

Answer 8

NAFLD can lead to cirrhosis

Question 9

What is the pathogenesis of cirrhosis?

Answer 9

No matter what the cause is cirrhosis involves:

Development of scar tissue that replaces the normal lung parenchyma

The scar tissue impedes the blood flow through the liver, disturbing its function

Question 10

What is the role of the stellate cells in cirrhosis?

Answer 10

They are activated by the inflammation caused by the damage to liver parenchyma

They increase the production of fibroblasts

And secretes cytokines which lead to proliferation of connective tissue

Also secrete cytokines that prevent proteins from breaking down the fibrotic material

Question 11

What do stellate cells usually do?

Answer 11

They store vitamin A

Question 12

Cirrhosis can present with symptoms that occur as a result of the failure of liver cells.

Describe the symptoms and why they occur?

Answer 12

Spider naevi: occur due to an increase in oestrogen

Palmar erythema: increased oestrogen

Gynecomastia: increase in breast gland size due to increased oestrogen

Hypogonadism:

Ascites: due to low albumin

Jaundice: due to increased bilirubin

Question 13

Why does cirrhosis cause a rise in oestrogen levels?

Answer 13

In liver disease there is an increased production of androstenedione in the adrenal glands

Androstenedione is converted to oestrogen

The liver is less able to clear oestrogen from the blood

So more oestrogen in blood stream

Question 14

Why does cirrhosis cause raised bilirubin?

Answer 14

When healthy, the liver clears bilirubin from the bloodstream.

If the liver is impaired it won’t be able to clear it

Question 15

What is bilirubin?

Answer 15

Breakdown product of haem

Haem is released by old rbcs

It is yellow

Question 16

What causes the yellow colour in jaundice?

Answer 16

Bilirubin

Liver failure means it can’t be cleared by the liver so it builds up causing yellow skin etc.

Question 17

What is portal hypertension? Why does it occur in cirrhosis?

Answer 17

Raised pressure in the portal venous system

Occurs because cirrhosis causes scarring that impedes blood flow through the liver

This causes resistance in the liver

So blood starts to back-log into the portal system

Raising the pressure of the portal system

Question 18

Cirrhosis can present with symptoms that occur as a result of portal hypertension.

Describe the symptoms and why they occur?

Answer 18

Splenomegaly

Oesophageal varices: vessels of oesophagus enlarge due to raised pressure causing varices

Caput medusa: dilated periumbilical veins, because they are higher pressure than usual due to portal hypertension

Question 19

What occurs in advanced cirrhosis?

Answer 19

Coagulopathy: bruising + bleeding
Problems clotting due to decreased production of coagulation factors

Encephalopathy: neurological problems such as confusion, coma

Hepatocellular carcinoma

Question 20

Why does cirrhosis cause encephalopathy?

Answer 20

Because liver can’t remove ammonia and other nitrogenous substances they go to the brain

Here they affect brain function, causing forgetfulness, trouble concentrating, unresponsiveness etc.

Question 21

Investigations of cirrhosis?

Answer 21

Tests for liver dysfunction

• liver function tests
• low platelets
• low albumin

Establish the cause:

• autoantibodies
• antibodies against hep viruses
• other signals

Liver USS:

• show a distended or shrunken liver
• shows splenomegaly

Ascitic tap:
- collect some fluid from ascites to sample

Liver biopsy:
- look for cell damage

Question 22

What are the liver function tests?

Answer 22

AST: Aspartate aminotransferase
- an enzyme that is raised in liver damage

ALT: Alanine aminotransferase
- enzyme, raised indicates liver damage

ALP: Alkaline phosphate
- raised levels indicate bone or liver damage

GGT: Gamma-glutamyl transferase
- Shows whether raised ALP is down to liver or bone disease

Bilirubin

Question 23

Management of cirrhosis?

Answer 23

Prevention of further damage:

• abstain from alcohol
• good nutrition
• avoid liver metabolised drugs
• vaccinate against hep B+C

Treatment specific to cause

Screen for hepatocellular carcinoma

Transplantation