Histopathology 8: Liver pathology Flashcards
Aspergillus produces …………. which causes hepatocellular carcinoma
Aflatoxin
Which tumour marker indicates hepatocellular carcinoma ?
alphaFP
List 5 causes of hepatocellular carcinoma (liver cell carcinoma)?
- Hepatitis B or C
- Alcoholic cirrhosis
- Haemochromatosis
- Aflatoxin (from asprgillus)
- NAFLD
Associated with cirrhosis in the West and viral infections in developing countries
Which syndrome is associated with cholangiocarcinoma ?
Lynch syndrome type II
What are the macrophages in the liver called ?
Kupffer cells
Where do stellate cells reside in the liver ?
Space of disse (this is the space between the endothelial cells and hepatocytes)
Is alcoholic cirrhosis micronodular or macronodular ?
Micronodular
Is cirrhosis due to viral hepatitis micronodular or macronodular ?
Macronodular
List 3 histological features of alcoholic liver disease ?
Features of alcoholic hepatitis (NB this leads to scarring)
- Fatty liver
- Alcoholic hepatitis (fatty liver hepatitis)
- Cirrhosis
- Ballooning +/- Mallory Denk bodies (ballooning = cell swelling, Mallory Denk = pink deposits in cells)
- Apoptosis
- Pericellular fibrosis
What causes NAFLD ?
How do you distinguish from alcoholic liver disease?
Insulin resistance e.g due to diabetes or obesity
Not under microscope - based on alcohol Hx
What is the characteristic histological features of PBC ?
Granulomatous destruction of bile ducts secondary to chronic inflammation
Which auto antibody is associated with Primary Biliary Cholangitis?
anti-mitochondrial antibodies (HALLMARK)
Describe the characteristic histological features of PSC ?
- Periductal bile duct cirrhosis leading to bile duct loss
- “Onion skinning”
Which disease is associated with PSC ?
Ulcerative colitis
Is cirrhosis due to biliary tract disease micronodular or macronodular ?
Micronodular
List 5 genetic causes of liver cirrhosis ?
- haemochromatosis
- wilson’s disease
- alpha 1 antitrypsin deficiency
- galactosaemia
- glycogen storage disease
What is the most common benign liver tumour ?
Haemangioma (endothelial cells)
Which zone in liver lobules is the first to be affected by alcoholic liver disease ?
Zone 3 (these are most metabolically active)
Which HLA is associated with autoimmune hepatitis ?
HLA-DR3
List 3 auto antibodies seen in autoimmune hepatitis ?
ANA
Anti-Smooth muscle antibodies
Anti-LKM (anti-liver-kidney microsomal antibody)
ERPC shows beading of bile ducts.
Most likely diagnosis ?
PSC (Primary Sclerosing Cholangitis)
What is Budd-Chiari syndrome ?
Compression/ Occlusion of the hepatic vein
Which stain is used to identify copper in Wilson’s disease “
Rhodanine stain (sees copper accumulating in the hepatocytes)
What happens to Caeruloplasmin levels in Wilson’s disease ?
They are reduced
Which genetic disease causes both Emphysema and liver cirrhosis ?
Alpha 1 antitrypsin deficiency
(so lung and liver problem, think this)
Which auto-immune disease is associated with PBC ?
Sjogrens
What is the triad for PBC ?
Jaundice
Xanthelasma
Pruritus
What is haemosiderosis
Main cause of haemosiderosis
Iron overload: accumulation of iron in macrophages
Blood transfusions
describe the dual blood supply of the liver
hepatic portal vein
hepatic artery
Hence why liver does not tend to get affected by ischaemic diseases
what are stellate cells
- store vitamin A
- when activated - become myofibroblasts and lay down collagen
- responsible for most of the scarring in liver disease
which liver zone has the most metabolically active enzymes
3 (closest to central vein)
describe the process of stellate activation
Normal:
- normal hepatocytes have microvilli
- endothelial cells have no BM and have spaces between
- stellate cells sit in the space between endothelial cells (space of disse)
- blood gets through the endothelial cells
Liver injury:
- kupffer cells (macrophages) activate
- endothelial cells stick together
- hepatocytes lose their microvilli
- stellate cells secrete BM type collagen into space of disse
- All this means blood finds it hard to diffuse into the hepatocytes (liver disease)
what is cirrhosis
- fibrosis of liver
- NB whole liver involvement
- get intra- and extra-hepatic shunting of blood
- intrahepatic shunting = blood comes through liver but not in contact with hepatocytes
- extrahepatic = blood backlogs into porto-systemic anastamoses (so it is totally unfiltered and toxic)
3 complications of cirrhosis
portal hypertension
hepatic encephalopathy
liver cell cancer
causes of acute hepatitis (2)
Feature on histology
- hep A and E mainly
- drugs
Histology: spotty necrosis
causes of chronic hepatitis (3)
viral hepatitis
drugs
AI
features of NASH
- hepatitis resulting from NAFLD
- caused by insulin resistance associated with raised BMI and diabetes
- one of commonest causes of liver disease ww
Aetiology of Primary Biliary Cholangitis (NB not called cirrhosis anymore since not always cirrhotic)
Which gender is more common?
Mx
Autoimmune (Characterised by bile duct loss secondary to chronic inflammation)
Female
Urso
Aetiology of Primary Sclerosing Cholangitis
Characterised by periductal bile duct fibrosis leading to loss
Aetiology of haemochromatosis
- genetically determined increased gut iron absorption
- HFe gene on chr 6
- iron deposition in parenchymal cells -> organ damage -> cirrhosis and HCC
Presentation of haemochromatosis
- Sx of liver damage
- deposit in the heart, leading to cardiomyopathy
- in the testes leading to infertility
- bronzed diabetes: tanned complexion and in the pancreas leading to diabetes
So all in all: hepatomegaly, micronodular cirrhosis, pseudogout, hypogonadism, DM, cardiomyopathy
what is haemosiderosis
iron overload
accumulation of iron in macrophages
result of blood transfusions
what is wilsons disease
accumulation of copper due to failure of excretion of copper by hepatocytes into bile
chr 13
accumulates in liver and CNS and iris (KF rings)
antibodies in AI hepatitis
anti-smooth muscle antibodies (ASMA)
responds to steroids
what is alpha-1 antitrypsin deficiency
failure to secrete alpha- 1 antitrypsin
deficiency in the blood, excess in hepatocytes
chronic hepatitis
emphysema
causes of hepatic granulomas
specific - PBC, drugs
general - TB, sarcoidosis
list benign liver tumours
liver cell adenoma
bile duct adenoma
haemangioma
list malignant liver tumorus
secondary (most common)
hepatocellular carcinoma
hepatoblastoma
cholangiocarcinoma (associated with PSC, worm infections, cirrhosis)
hemangiosarcoma
What happens to liver of someone who drinks and is this reversible?
- Get fatty changes (white parts = fat droplets)
- REVERSIBLE
Cancer at increased R in Primary Sclerosing Cholangitis
cholangiocarcinoma
Marker that increases in Primary Sclerosing Cholangitis
pANCA
Primary Sclerosing Cholangitis vs Primary Biliary Cholangitis - key difference in aetiology
in PBC, the bile duct loss is caused by inflammation, whereas in PSC, it is caused by fibrosis
Mx of haemochromatosis
Venesection, iron chelation with desferrioxamine
Stain for haemochromatosis
Prussian Blue
Diagnostic lesion for PBC
bile duct is surrounded by epithelioid macrophages suggestive of granulomatous destruction of bile ducts
Liver colour in cirrhosis
Type of cirrhosis in terms of size
Pale (+ fatty change)
micronodular cirrhosis
Most characteristic immune cell seen in alcoholic hep
neutrophil polymorph
Alcohol vs acetaldehyde in terms of toxicity
alcohol is NOT toxic, but acetaldehyde IS TOXIC
the cells that get damaged are the ones that contain the most alcohol dehydrogenase, thereby having the greatest capacity to produce acetaldehyde
3 histological patterns in alcoholic liver disease
- Fatty liver
- Alcoholic hepatitis (fatty liver hepatitis)
- Cirrhosis
Grade vs stage meaning in chronic hepatitis
- Severity of inflammation = GRADE (how bad does it look)
- Severity of fibrosis (scarring) = STAGE (how far is the patient from cirrhosis)
Can cirrhosis be reversible?
Yep - If the underlying cause is treated i.e. alcoholism (which is tricky) or viral hepatitis (which is easily done with new medications), then it can reverse the cirrhosis
Micro vs macronodular in terms of cause
- Micronodular (< 3mm): tends to be associated with alcoholism and insulin resistance (producing fatty change) as well as biliary tract disease
- Macronodular (> 3mm): tends to be associated with viral infections (these tend to be causes of chronic viral hepatitis, B C, D) + Wilson’s disease and a1-antitrypsin
What is the portal triad
hepatic artery, portal vein and bile duct
Name of ring of collagen surrounding portal triad
limiting plate
What colour does the collagen in the liver stain?
Blue (distinct from purple of rest of liver)
What is bridging fibrosis?
CRITICAL feature for intra-hepatic shunting:
Blood comes into the portal tract and instead of trickling past the hepatocytes and into the central vein, it takes a short cut from the portal tract straight into the central vein (NOT coming into contact with hepatocytes)
Aetiology of Wilson’s disease
accumulation of copper in liver due to the failure of excretion of copper by hepatocytes into the bile
Where does the copper in Wilson’s deposit, there what is presentation?
Liver, CNS, iris
- Liver: acute hepatitis, fulminant liver failure or cirrhosis
- CNS: parkinsonism, dementia, psychosis
- Iris: Kayser-Fleischer rings
Mx of Wilson’s
penicillamine
Degree of inflammation in autoimmune hep vs viral hep
degree of inflammation is much more marked in autoimmune hep
Mx of autoimmune hep
Steroids
Aetiology of alpha-1 antitrypsin def
- failure to secrete a1-antitrypsin from hepatocytes
- NB deficiency of a1 anti-trypsin in the BLOOD but there is a gross excess in the liver
- Therefore you get a1-antitrypsin forming globules within the hepatocytes, damaging them and resulting in chronic hepatitis and cirrhosis
Which zones are mainly affected in paracetamol toxicity?
Zone 2, but mainly 3 (so furthest away from portal triad on histology, you’ll get paler parts on the outside which are the parts that have been damaged)
Cause of caseating granuloma in liver
Cause of non-caseating
TB/Sarcoidosis
PBC
Hepatic adenomas are associated with what?
oral contraceptive pill use
Most common tumours in liver
Secondary: from the GIT, breast or bronchus
Tumours of primitive hepatocytes which mainly Occur in childhood
Hepatoblastoma
adenocarcinoma arising from the bile ducts called?
What 3 things is it associated with?
Cholangiocarcinoma
PSC, Worm infections, Cirrhosis
Why is the liver such a common site for secondary tumours?
liver is supplied by the hepatic artery which is a branch of the aorta, so tumours cells that have circulated in the systemic circulation have a good chance of getting to the liver
all the blood from the portal circulation comes to the liver (i.e. for all tumours from the stomach, small bowel, large bowel and pancreas, the liver will be the first capillary bed that they see)
Which is the commonest carcinoma seen in the liver?
Metastatic adenocarcinoma
Which hep is not associated with fatty change in liver?
Hep B
