HISTO: Liver pathology Flashcards
How much does the liver weigh? What is the dual blood supply of the liver?
1.5kg
Prortal vein and hepatic artery
What are the cells of the liver?(6)
- Hepatocytes
- Bile ducts
- Blood vessels
- Endothelial cells
- Kupffer cells
- Stellate cells
Where are stellate cells located? What is the function of stellate cells in the liver?
Stellate cells sit in the space of Disse between the endothelial cells and hepatocytes.
They become myofibroblasts if there is damage and inflammation
What are the defining signs of liver cirrhosis?
- whole liver involved
- fibrosis
- nodules of regenerating hepatocytes
- distortion of liver vascular architecture: intra- and extra- hepatic (e.g. gastro-oesophageal) shunting of blood
Given picture one, what does picture two show?
1) whole liver involved in fibrosis in cirrhosis
s) nodules of regenerating hepatocytes in cirrhosis
What are the two classifications of cirrhosis?
a) according to nodule size: micronodular or macronodular
b) according to aetiology:
1) alcohol / insulin resistance
2) viral hepatitis etc.
What kind of shunting is found in liver cirrhosis?
Both intra- and extra-hepatic shunting
List 3 complications of cirrhosis.
- Portal hypertension
- Hepatic encephalopathy – lack of filtration
- Liver cell cancer – most important factor for this is cirrhosis
What is this complication of liver cirrhosis?
Streaky vessels = varices which can easily rupture
What is this complication of liver cirrhosis?
Spleen 3x normal size
What is this complication of liver cirrhosis?
Liver cancer
Can liver cirrhosis be reversible?
Yes it may be, if you aggressively treat the aetiology of the cirrhosis
What are the durations defining acute and chronic hepatitis?
Acute hepatitis <6 months duration (Hep AE, drugs)
Chronic >6 months
Name 2 causes of acute hepatitis.
Viruses
Drugs
What is spotty necrosis?
Spotty necrosis – inflammation between where the blood is coming in and going out. Can be seen in both drug and virus induced acute hepatitis.
What are 3 causes of chronic hepatitis?
- viral hepatitis (BCD hep)
- drugs
- auto-immune
How do you characterise severity of chronic hepatitis?
Stage is more important than grade in cancer, in chronic hepatitis it is the opposite
severity of inflammation = grade
severity of fibrosis = stage
What are the 3 types of alcoholic liver disease (ALD)?
1) fatty liver
2) alcoholic hepatitis
3) cirrhosis
What is this type of ALD? Describe where you would also see this other than ALD.
Fatty liver - can also be seen in marasmus so not specific for ALD
This is a reversible metabolic process
What are the main features of alcoholic hepatitis?
KEY: Ballooning ( +/- Mallory Denk Bodies – collapsed cytoskeleton of hepatocytes )
- Fat
- Apoptosis
- Pericellular fibrosis
- Mainly seen in Zone 3
What is shown here in ALD?
Balloon hepatocytes shown with surrounding fibrosis - seen in alcoholic hepatitis.
What type of ALD is seen here?
Cirrhosis
What is NAFLD and NASH caused by? What is the epidemiology worldwide?
Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH)
- Histologically looks like alcoholic liver disease
- Due to insulin resistance associated with raised BMI and diabetes
- Becoming recognised as one of the commonest causes of liver disease, world-wide
What is the epidemiology of primary biliary cholangitis? (PBC)
- Previously primary biliary cirrhosis – not as many patients have cirrhosis as previously thought
- F> M - ~10:1
What happens to bile ducts in PBC?
Bile duct loss associated with chronic inflammation (with granulomatous destruction of these ducts – HALLMARK)
What antibodies are detected in PBC?
- Diagnostic test is detection of anti-mitochondrial antibodies (anti-M2 antibodies)
What disease is PSC (primary sclerosing cholangitis) associated with?
Ulcerative colitis
Associated with increased risk of cholangiocarcinoma.
What is the pathophysiology of PSC? What is the epidemiology of PSC? What is seen in the picture below in PSC?
- M > F
- Periductal bile duct fibrosis leading to loss
- Diagnostic test is bile duct imaging
Picture: Onion skin fibrosis (not granulomatous destruction like in PBC)
What is the aetiology of haemochromatosis?
- Genetically determined increased gut iron absorption
- Gene on chromosome 6 (HFe)
- Parenchymal damage to organs secondary to iron deposition (bronzed diabetes)
What is show below and what condition is this?
Iron is INSIDE hepatocytes – seen as brown on this slide. This is haemochromatosis.
What is the difference between this and haemochromatosis? What can cause this?
Haemosiderosis
- Compared to previous, iron is INSIDE MACROPHAGES not hepatocytes like in haemochromatosis.
- Blood transfusion causes haemosiderosis
- Kupffer cells
What is the aetiology of Wilson’s disease?
- Accumulation of copper due to failure of excretion by hepatocytes into the bile – normally bile ducts excrete copper
- Assessed by biopsy or biochemistry
What are the genetics of Wilson’s disease?
- Genes on chromosome 13
What clinical features would you see in Wilson’s disease in the liver and eyes?
Accumulates in the liver and CNS (hepato-lenticular degeneration) including Kayser-Fleishcer rings
What is shown below?
Rhodanine stain for copper – copper becomes golden brown against blue counterstain. This is Wilson’s disease.
What sex is more affected by autoimmunse hepatitis?
Females > males
What is the pathophysiology of autoimmune hepatitis? What antibodies are found in the serum? Does it respond to steroids?
- Active chronic hepatitis with plasma cells
- Anti-smooth muscle actin antibodies in the serum
- Responds to steroids
What is the pathophysiology of alpha-1 antitrypsin deficiency? What is seen histologically?
- Failure to secrete alpha-one antitrypsin – they make it but it cannot be secreted into the blood. In respiratory medicine, this antielastase would usually stop inflammation so without it you get emphysema and inflammation.
- Intra-cytoplasmic inclusions due to misfolded protein
- Hepatitis and cirrhosis
How can alpha-1 antitrypsin present in the neonatal period?
Giant cell hepatitis
What is liver disease caused by drugs called?
Drug related liver injury - any kind of liver disease can be caused by drugs
May be overdose related of idiosyncratic
What % of drug reactions involve the liver?
10%
What zone of the liver does paracetamol toxicity affect?
Paracetamol is converted to a toxic metabolite in the liver.
Causes zone 3 damage because this is where most cells involved in drug metabolism are located.
What are 4 causes of hepatic granulomas?
Specific causes:
- PBC
- drugs
General causes
- TB
- Sarcoid etc
What does this picture show in the liver?
Granuloma = organised collection of activated macrophages. Can be caused by sarcoid, TB, PBC or drugs.
Name 3 benign liver tumours.
1) liver cell adenoma
2) bile duct adenoma
3) haemangioma
When are benign liver tumours common?
Common in women (menopause/reproductive years). Sharp demarcated edges seen on histology.
What are the most common malignant tumours of the liver?
- secondary tumours e.g. pancreatic will spread here quietly
- primary tumours
Describe the portal venous system of the liver.
E.g. pancreatic cancer can spread; usually adenocarcinomas make glands and secrete mucin.
What are the malignant primary tumours of the liver?
- hepatocellular carcinoma
- hepatoblastoma
- cholangiocarcinoma
- haemangiosarcoma
What precursor liver pathology is liver cell cancer associated with?
Cirrhosis; seen especially in the West
What are cholangiocarcinomas associated with?
Associated with:
- PSC
- Worm infections
- Cirrhosis
Where can cholangiocarcinomas arise from?
- intrahepatic ducts
- extrahepatic ducts (including gall bladder)
Can cause potential obstruction.
Which of these is not associated with fatty change in the liver?
- Diabetes
- Hepatitis B
- Hepatitis C
- Alcohol
Hep B or C
Diabetes and alcohol are almost ALWAYS associated with fatty liver change
