What is cirrhosis?
End Stage Chronic Liver Disease
Diffuse loss of normal liver structure with replacement by nodules of hepatocytes & fibrous tissue
What causes cirrhosis?
All sorts:
- Alcohol
- Hepatitis B & C
- Immune conditions
- Metabolic disorders
- Obesity (Diabetes Mellitus)
- Cryptogenic
Name some immune conditions that cause cirrhosis?
Auto-immune hepatitis
Primary Biliary Cholangitis
Name some metabolic disorders that cause cirrhosis?
Excess iron (primary haemochromatosis) Excess copper (Wilson's Disease)
What is cryptogenic Cirrhosis?
Cirrhosis of unknown cause
What are the effects of cirrhosis?
It can lead to:
- Weakness/Fatigue
- Loss of appetite -> Weight Loss
- Bruising
- Jaundice
- Pruritis
- Nausea -> Vomiting
Complications:
- Liver Failure
- Portal Hypertension
- Increases risk of hepatocellular carcinoma
- Ascites & ankle oedema
What are the common causes of acute liver injury?
Anything causing hepatitis:
- Viruses
- Alcohol
- Drugs
Or Bile Duct Obstruction causing bile build up to &
kill liver cells
What are the possible outcomes of acute liver injury?
- Resolves
- Liver Failure
- Chronic hepatitis & cirrhosis
What is alcoholic liver disease?
Response to excess alcohol, it disrupts metabolism of fats causing an accumulation in the liver. The liver cells look more like fat droplets than hepatocytes down the microscope.
What are the consequences of alcholic liver disease (acute & Chronic)?
Acute -> Inflammation -> Liver cell death -> Liver Failure
Chronic -> Cirrhosis -> Liver Failure
What is Jaundice?
An increase in circulating bilirubin due to an altered bilirubin metabolism.
What are the types of jaundice?
Pre- hepatic
Hepatic
Post Hepatic
Define the stages of bilirubin metabolism
Pre-Hepatic:
- Haemoglobin -> Haem & Globin in the spleen
- Haem -> Bilirubin which is released into blood
Hepatic:
- Hepatocytes take up bilirubin from blood
- Conjugate it then excrete into the biliary system
Post-Hepatic:
- Transported in bile to duodenum
- Bilirubin-conjugate broken down in intestine
- Some bilirubin eliminated in faeces/urine and some reabsorbed through entero-hepatic circ.
What causes pre-hepatic jaundice?
Excess haemoglobin release from RBC’s. Haemolysis.
Often down to infection or genetic conditions
What are the causes of hepatic and obstructive jaundice?
Hepatic:
- Viral Hep
- Alcoholic Hep
- Liver Failure
- Drugs
- Liver Cancer
- Wilsons/haemochromatosis
- PBC/PSC if involving intra-hepatic ducts
Obstructive Cholestasis
- Primary Biliary Cholangitis
- Primary Sclerosing Cholangitis
- Pancreatic cancer
- Cholangiocarcinoma
- Gallstones
- Cholecystitis
What are the types of drug induced cholestasis?
Therapeutic vs Recreational
Predictable (dose related) vs Unpredictable (non-dose related)
What types of liver tumours are there?
Hepatocellular carcinoma - malignancy of hepatocytes
Cholangiocarcinoma - Malignancy of bile duct epithelium
Metastases from other cancers
Define Primary Biliary Cholangitis?
An auto-immune condition primarily occurin in women
Unknown environmental trigger + genetic predisposition for loss of immune tolerance to self mitochondrial proteins (i.e. production of auto-mitochondrial antibodies)
Leads to chronic granulomatous inflammation of bile ducts -> Loss of intra-hepatic bile ducts -> Cirrhosis
Define Primary Sclerosing Cholangitis? (PSC)
Progressive cholestasis due to bile duct inflammation & fibrous stricture formation, mainly in men.
Eventually obliterates intra-hepatic bile ducts and leads to cirrhosis
How do we test for PSC?
pANCA (neutrophil antibodies)
MRCP (MR Cholangiopancreatography)
What other conditions are associated with PSC?
IBD & Cholangiocarcinoma
How do we treat PSC?
Biliary Stents or a liver transplant
What are the risk factors for cholelithiasis?
Obesity & Diabetes
What types of gall bladder disease cause post-hepatic jaundice?
Acute or chronic cholecystitis Often due to: - Gall stones - Empyema - Perforation - Biliary Peritonitis
What are the effects of a common bile duct obstruction?
- Post-hepatic Jaundice
- Lack of bile in duodenum -> Pale stools
- Ascending Cholangitis (when infected bile is proximal to the obstruction)
- Secondary Biliary Cirrhosis if the obstructions belonged
