Cirrhosis Flashcards
What is cirrhosis?
When the liver does not function properly due to long term damage
The damage is irreversible and involves scarring and nodules
What are the causes of cirrhosis?
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
How does alcohol cause cirrhosis?
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
What is non-alcoholic fatty liver disease (NAFLD)?
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
What causes NAFLD?
Insulin resistance: diabetes mellitus
Obesity
Genetics
Poor nutrition: drinking lots of soft drinks
Some drugs: amiodarone, methotrexate
How do you diagnose NAFLD?
Biospy: to look for fatty deposits and scarring
How do you treat NAFLD?
Control risk factors: lose weight, control diabetes
No drug available
Transplant
What’s the link between NAFLD and cirrhosis?
NAFLD can lead to cirrhosis
What is the pathogenesis of cirrhosis?
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
What is the role of the stellate cells in cirrhosis?
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
What do stellate cells usually do?
They store vitamin A
Cirrhosis can present with symptoms that occur as a result of the failure of liver cells.
Describe the symptoms and why they occur?
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
Why does cirrhosis cause a rise in oestrogen levels?
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
Why does cirrhosis cause raised bilirubin?
When healthy, the liver clears bilirubin from the bloodstream.
If the liver is impaired it won’t be able to clear it
What is bilirubin?
Breakdown product of haem
Haem is released by old rbcs
It is yellow
What causes the yellow colour in jaundice?
Bilirubin
Liver failure means it can’t be cleared by the liver so it builds up causing yellow skin etc.
What is portal hypertension? Why does it occur in cirrhosis?
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
Cirrhosis can present with symptoms that occur as a result of portal hypertension.
Describe the symptoms and why they occur?
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
What occurs in advanced cirrhosis?
Coagulopathy: bruising + bleeding
Problems clotting due to decreased production of coagulation factors
Encephalopathy: neurological problems such as confusion, coma
Hepatocellular carcinoma
Why does cirrhosis cause encephalopathy?
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.
Investigations of cirrhosis?
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
What are the liver function tests?
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
Management of cirrhosis?
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
