Histopath 8: Liver Pathology Flashcards by D J

What direct does blood and bile flow in the liver?

Blood = Zone 1 -\> zone 3 
Blie = zone 3 -\> zone 1

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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)

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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

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What is acute hepatitis caused by?

Viral (Hep A-E)

Drugs

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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

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What is chronic hepatitis caused by?

Viral (Not Hep A or E)

Drugs

PBC, PSC, Wilson, hemochromatosis

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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)

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What is cirrhosis?

Abnormality of liver architecture – interferes with liver function and blood flow

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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

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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

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Complications of liver cirrhosis?

Portal hypertension

Hepatic encephalopathy

Hepatocellular carcinoma

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What are the 3 main histological pattens of alcoholic liver disease?

Hepatic steatosis

Alcoholic hepatitis

Alcoholic cirrhosis

IMPORTANT TO REMEMBER THESE CAN CO-EXIST

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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

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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

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What are the main features of Alcoholic cirrhosis?

Shrunken brown organ

Buzzwords:
- Micronodular cirrhosis

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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

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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