Histopath 8: Liver Pathology Flashcards
What direct does blood and bile flow in the liver?
Blood = Zone 1 -\> zone 3 Blie = zone 3 -\> zone 1
What are the 3 different zones of a liver lobule known as
Z1 - Periportal - closest to portal triad
Z2 - Mid Zone
Z3 - Periventricular - most mature hepatocytes (least oxygenated - most sensitive to ischaemia)
What part of the liver lobule is most likely to be affected by:
- Viral hepatitis and toxic substance ingestion
- Metabolic toxins
Viral hepatitis and toxic substance ingestion:
Periportal / Z1 (closest to portal triad)
Metabolic toxins (ethanol, paracetamol): Perventricular / Z3 = Most liver enzymes: most sensitive to metabolic toxins (ethanol, paracetamol)
NB - alcohol isnt toxic however Z3 has the most alcohol dehydrogenase hence makes a lot of acetaldehyde which is the issue
What is acute hepatitis caused by?
Viral (Hep A-E)
Drugs
Histopathological features of acute hepatitis?
Spotty necrosis - Small foci of inflammation and necrosis with inflammatory infiltrates
This usually concentrates around portal triad + smaller v what is seen in chronic hep
What is chronic hepatitis caused by?
Viral (Not Hep A or E)
Drugs
PBC, PSC, Wilson, hemochromatosis
Histopathological features of chronic hepatitis?
Piecemeal necrosis/interface hepatitis
- Loss of the border between the portal tract and the surrounding parenchyma (lot more widespread compared to spotty necrosis)
Bridging fibrosis from portal triad → central vein: Signals evolution to cirrhosis (this means blood cant come into close contact w/ liver enzymes)
What is cirrhosis?
Abnormality of liver architecture – interferes with liver function and blood flow
What are the key features of cirrhosis?
Hepatocyte necrosis
Nodules of regenerating hepatocytes
- Micronodular: alcoholic hepatitis
- Macronodular: alpha-1, Wilson’s, viral hepatitis
Distortion of vascular architecture
Fibrosis
Difference between extra- and intra-hepatic shunting as seen in cirrhosis?
Extrahepatic shunting – Blood backlogs into the sites of porto-systemic anastomosis -> Esophageal varices, anorectal varices, caput medusae
Intrahepatic shunting – Blood goes through liver but does not contact hepatocytes/is not filtered
Complications of liver cirrhosis?
Portal hypertension
Hepatic encephalopathy
Hepatocellular carcinoma
What are the 3 main histological pattens of alcoholic liver disease?
Hepatic steatosis
Alcoholic hepatitis
Alcoholic cirrhosis
IMPORTANT TO REMEMBER THESE CAN CO-EXIST
What are the main features of Hepatic steatosis?
Fully reversible if alcohol is avoided
Large, pale, yellow greasy liver
Buzz words:
- Fat droplets in hepatocytes
What are the main features of Alcoholic hepatitis?
Large, fibrotic liver
80% also cirrhotic
Buzzwords:
- Hepatocyte ballooning (when hepatocytes die due to alcohol)
- Mallory Denk Bodies (bits of hyaline - stains blue)
- Mainly zone 3 damage (most metabolic active site)
- Neutrophil polymorphs
- Fibrosis
What are the main features of Alcoholic cirrhosis?
Shrunken brown organ
Buzzwords:
- Micronodular cirrhosis
What are the main features of NAFLD? Cause?
Histologically similar to alcoholic liver disease (ballooning, mallory denk etc)
Distinguished based on history
Cause: insulin resistance associated with raised BMI and diabetes
What are the main features of Primary Sclerosing Cholangitis? who is it more common in? what is it associated w/? which antibody is imporant?
More common in males
Fibrotic process: Periductal bile duct fibrosis
Associated with UC and increased risk of cholangiocarcinoma
pANCA
What are the main features of Primary Biliary Cholangitis? who is it more common in? what is it associated w/? which antibody is imporant?
More common in females, associated with other autoimmune conditions
Inflammatory process: Bile duct chronic inflammation with granulomas
Anti-mitochondrial antibodies
What are the main features of Autoimmune Hepatitis? who is it more common in? what is it associated w/? which antibody is imporant?
Young/post-menopausal females with other autoimmune conditions
Anti-smooth muscle antibodies and anti-liver-kidney-microsomal Ig
What are some genetic conditions that affect the liver? What is the inheritance?
Haemochromatosis (AR) - HFe gene on chr 6
Wilson’s Disease (AR) - ATP7B gene on chr 13
Alpha-1 Antitrypsin Deficiency (AD)
What are the main features of Haemochromatosis? + What stain is used?
- Increased gut iron absorption
- Iron deposits in the hepatocytes leading to liver damage
- Bronzed diabetes - browned skin
Histology: Prussian Blue stain
What are the main features of Wilson’s diease? + What stain is used?
- Copper accumulation: liver, CNS (movement disorders), iris (Kaiser-Fleischer rings)
- Failure of excretion by hepatocytes to bile
Histology: Rhodanin stain
What are the main features of Alpha-1 Antitrypsin deficiency? + What stain is used?
- Failure to secrete alpha-1 antitrypsin (in blood)
- Gross excess of alpha-1 antitrypsin in the hepatocytes → forms globules within hepatocytes → chronic hepatitis
Histology: Periportal red hyaline globules using PAS (periodic-acid schiff) stain
Questions - may also refer to resp issues
Why is alpha-1 antitrypsin important?
Alpha-1 antitrypsin: enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase
What are the different benign liver malignancies?
Haemangioma- Most common
Liver Cell Adenoma - Associated with OCP
Bile Duct Adenoma
What are the different malignant liver cancers + which is most common?
Secondary mets = MOST COMMON (usually from breast or GI system)
Cholangiocarcinoma
Hepatocellular carcinoma
What is the tumour marker for HCC + what is it associated w/?
Tumor marker: AFP
Linked with:
viral hepatitis,
alcoholic cirrhosis
NAFLD
haemochromatosis
aflatoxin (WEED KILLER - banned in UK so Qs may refer to immigrants),
What is cholangiocarcinoma associated w/ + main histological finding?
Associated with PSC
Histology – capillary ingrowth
A 36 year old woman with a history of hypothyroidism was seen in clinic following abnormal routine LFTs.
Liver biopsy revealed loss of bile ducts with granulomas.
What characteristic serological marker is likely to be raised?
Anti-smooth muscle antibodies
pANCA (anti-myeloperoxidase antibodies)
Anti-mitochondrial antibodies
Anti-liver-kidney-microsomal Ig
Anti-Jo1
C) Anti-Mitochonrial antibodies
Woman + Loss of bile ducy + Granulomas - Suggestive of PBC
PBC:
- Females 9:1
- Granulomas = inflammatory
Hence Anti-Microbial antibodies are useful
Which of the following is the inheritance of genetic haemochromatosis?
X-linked recessive
X-linked dominant
Polygenic
Autosomal recessive
Autosomal dominant
Autosomal recessive
Hemochromatosis and Wilson’s are autosomal recessive
Anti-alpha1 antitrypsin is autosomal dominant
What is the best indicator for portal hypertension? what are the other features caused by?
Splenomegaly
Hepatomegaly
Spider naevi in the distribution of the SVC
Jaundice
Liver flap
Splenomegaly - due to increased pressure in portal system
Other answers:
Hepatomegaly – after the portal vein, cirrhosis leads to small scarred liver
Spider naevi in the distribution of the SVC – due to oestrogen
Jaundice – due to high bilirubin
Liver flap – due to ammonia in blood
List the main cell types of the liver
Hepatocytes
Bile ducts (cholangiocytes)
Blood vessels
Endothelial cells
Kupffer cells
Stellate cells
What is the role of stellate cells and what could happen to them when activated?
Storage of vitamin A
When activated, they become myofibroblasts that lay down collagen (this is responsible for scarring in liver disease)
Describe the arrangement of hepatocytes, endothelial cells, stellate cells and Kupffer cells in a normal liver
There are spaces in between endothelial cells and there is a gap in between the endothelial cells and the hepatocytes (space of Disse)
Stellate cells sit within the space of Disse
Kupffer cells are found within the sinusoids
Blood can easily get through the spaces in the endothelial cells into the space of Disse where they are exposed to hepatocytes
Describe how these arrangements change in liver disease (hepatocytes, endothelial cells, stellate cells and Kupffer cells )
Kupffer cells become activated (inflammatory response)
Endothelial cells stick together so blood finds it more difficult to get into the space of Disse
Stellate cells become activated and secrete basement membrane-type collagens into the space of Disse
Hepatocytes lose their microvilli
All these changes make it difficult for blood to be exposed to hepatocytes
How can the histology in chronic hepatitis be used to grade and stage the disease?
Severity of inflammation = grade (how bad does it look)
Severity of fibrosis = stage (how far has it spread)
Difference in cause of duct loss in PBC and PSC?
In PBC, bile duct loss is caused by inflammation
PSC it is caused by fibrosis
How does Wilson’s disease lead to movement disorders?
Accumulation of copper in the lentiform nucleus of the basal ganglia leads to movement disorders
List some causes of hepatic granulomas
Specific: PBC, drugs
General: TB, sarcoidosis
How is autoimmune hepatitis treated?
Steroids (usually responds well)
Which hepatobiliary pathology is associated w finding of beading of bile ducts during ERCP?
Primary Sclerosing Cholangitis
