Histo: Liver Flashcards
What is the average weight of a liver?
1500 g
Describe the blood supply to the liver.
Dual blood supply: hepatic artery and hepatic portal vein
NOTE: this means that the liver does not tend to get affected by ischaemia
List the main cell types of the liver.
- Hepatocytes
- Bile ducts (cholangiocytes)
- Blood vessels
- Endothelial cells
- Kupffer cells
- Stellate cells
How is the arrangement of endothelial cells in the liver different from other parts of the body?
The endothelial cells do not sit on a basement membrane and the endothelium is discontinuous (there are no tight junctions)
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)
outline the arrangement of structures within a normal liver, and what are the zones
- There will be portal tracts consisting of a branch of the hepatic artery, a branch of the portal vein and a bile duct
- Blood will flow from the portal tract to the central vein
- There is a ring of collagen around the portal tract called the limiting plate
- There are three zones of hepatocytes in between the portal tract and the central vein
- Zone 3 is closest to the central vein and contains the most metabolically active enzymes
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 sinusoids
- Kupffer cells are found within the sinusoids
- Blood can easily get through the spaces in the endothelial cells in the space of Disse where they are exposed to hepatocytes
Describe how the cell arrangements change in liver disease.
- 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
What are the 4 key features of cirrhosis?
- The whole liver is involved
- There is extensive fibrosis
- nodules of regenerating hepatocytes
- Shunting occurs (intra and extrahepatic)
Name and describe the two types of shunting that occur in cirrhosis.
- Extra-hepatic: blood never reaches the liver because it backlogs into sites of porto-systemic anastamosis
- Intra-hepatic: blood goes through the liver but it does not come into contact with hepatocytes (so the blood is unfiltered)
How can cirrhosis be classified?
- According to nodule size (old system): micro- or macronodular
- According to aetiology: alcohol/insulin resistance or viral hepatitis
Does viral and alcoholic cirrhosis cause micro or macronodular cirrhosis?
Alcoholic tends to be micronodular
Viral tends to be macronodular
List some complications of cirrhosis.
- Portal hypertension
- Hepatic encephalopathy
- Hepatocellular carcinoma
NOTE: cirrhosis may be reversible
What causes acute hepatitis?
- Hepatitis virus (A and E)
- drugs
What is a common histological feature of all acute hepatitis?
Spotty necrosis
What are some causes of chronic hepatitis?
- Viral hepatitis
- Drugs
- Autoimmune
How can the histology in chronic hepatitis be used to grade and stage the disease?
- Severty of inflammation = grade (how bad does it look)
- Severity of fibrosis = stage (how far has it spread)
What is interface hepatitis?
- Aka piecemeal hepatitis
- Inflammation crosses the limiting plate making it difficult to distinguish where the portal tract ends and the hepatocytes begin
- Seen in chronic hepatitis
What are the three histological patterns of alcoholic liver disease?
- Fatty liver - accumulation of fat droplets (steatosis), which is fully reversible if alcohol is avoided
- Alcoholic hepatitis - seen acutely after a night of heavy drinking. Ranges from asymptomatic to fulminant liver failure
- Cirrhosis - micronodular cirrhosis
NOTE: these may co-exist (they are not distinc entities)
List some histological features of alcoholic hepatitis.
- Ballooning - cell swell and may contain pink depositis within cells (Mallory Denk bodies/Mallory hyaline)
- Apoptosis
- Pericellular fibrosis
In which part of the liver do the histological features of alcoholic hepatitis tend to be seen and why?
- Zone 3
- Alcohol is not toxic, but acetaldehyde is toxic
- Zone 3 cells contain the most alcohol dehydrogenase thereby producing the most acetaldehyde
- Furthermore, by the time blood reaches zone 3 (after passing zones 1 and 2) it is relatively hypoxic making the cells in zone 3 even more vulnerable to damage
Describe the histological appearance of non-alcoholic fatty liver disease.
- Looks like alcoholic hepatitis - hepatocyte ballooning + mallory denk bodies
NOTE: caused by insulin resistance associated with a raised BMI and diabetes
How is NAFLD distinguished from alcoholic liver disease?
Based on the history
AST:ALT ratio <2 in NAFLD but >2 in ALD
What is primary biliary cholangitis?
Autoimmune conditions characterised by bile duct loss associated with chronic inflammation (with granulomas)
Intrahepatic! + slow development of cirrhosis over years
What is the diagnostic test for PBC?
- Anti-mitochondrial antibodies (AMA) (>90% positive)
What is the histological appearance of PBC?
Bile ducts surrounded by epithelioid macrophages, suggestive of chronic granulomatous destruction of bile ducts
What is primary sclerosing cholangitis?
- Autoimmune condition characterised by periductal bile duct fibrosis leading to loss of bile ducts, extrahepatic and intrahepatic
NOTE: in PBC, bile duct loss is aused by inflammation, whereas in PSC it is caused by fibrosis
NOTE: PSC is associated with ulcerative colitis and is associated with an increased risk of cholangiocarcinoma
What is the diagnostic test for PSC?
- Bile duct imaging by ERCP
What causes haemochromatosis and which gene is implicated?
- Caused by increased gut iron absorption
HFe gene on chromosome 6
NOTE: women tend to present later because they have naturally lower iron levels
What is haemosiderosis?
Type of iron overload characterised by the accumulation of iron in macrophages
Usually occurs as a result of receiving blood transfusions
What is Wilson’s disease?
Characterised by an accumulation of copper due to the failure of excretion of copper by hepatocytes into the bile
Responsible gene (ATP7B) is found on Chr13
How does Wilson’s disease lead to movement disorders?
Accumulation of copper in the lentiform nucleus of the basal ganglie leads to movement disorders
How is the severity of disease in autoimmune disease different from viral hepatitis?
- Autoimmune hepatitis is very active with lots of plasma cells
- The degree of inflammation is usually worse than in viral hepatitis
How is autoimmune hepatitis diagnosed?
Anti-smooth muscle antibodies (ASMA)
How is autoimmune hepatitis treated?
Steroids (responds very well)
Describe the levels of alpha-1 antitrypsin in the blood and liver in a patient with alpha-1 antitrypsin deficiency.
- The mutation means that the protein cannot fold properly and cannot exit hepatocytes
- This leads to the alpha-1 antitrypsin forming globules within hepatocytes which causes damage leading to chronic hepatitis
- An inability to exit the liver leads to a deficiency of alpha-1 antitrypsin elsewhere in the body which leads to an increased risk of emphysema (as A1AT usually protects the lung from damage by e.g. smoke)
Why is the liver so susceptible to drug-related injury?
It is the main site of drug transformation
It is also where toxic drug metabolites are formed
List some causes of hepatic granulomas.
- Specific: PBC, drugs
- General: TB, sarcoidosis
List the main types of benign liver tumour. State which is most common.
- Liver cell adenoma
- Bile duct adenoma
- Haemangioma (MOST COMMON)
What is the most common type of malignant liver tumour?
Secondary tumours
List some types of primary liver tumour.
- Hepatocellular carcinoma
- Hepatoblastoma (in children)
- Cholangiocarcinoma
- Haemangiosarcoma
What are some risk factors for cholangiocarcinoma?
- PSC
- Worm infections
- Cirrhosis
Why is the liver such a common site for secondary tumours?
- It is supplied by the hepatic artery so tumour cells from the systemic circulation could reach the liver
- It is also supplied by the portal artery meaning that tumours from the stomach, bowels and pancreas will reach the liver before any other part of the body
Most common cause of chronic liver disease in the west?
NAFLD / MAFLD
most common benign lesion of the liver?
haemangioma
what liver tumour is associated with OCP?
Hepatic adenoma
what is the commonest carcinoma seen in the liver?
metastatic adenocarcinoma (from other places!)
commonest primary malignant tumour of the liver?
HCC
Describe zone 1, zone 2 and zone 3 of the liver?
Zone 1 - closest to portal triad. Periportal hepatocytes are affected first in viral hepatitis
Zone 2 - midzone
Zone 3 - closest to terminal central vein. Perivenular hepatocytes are the most metabolically active (thus most sensitive to metabolic toxins e.g. drugs and alcohol)
What happens as a result of extrahepatic shunting?
Blood pools in portosystemic anastamoses (oesophageal varices, caput medusae, anorectal varices)
AST:ALT ratio in alcoholic liver disease vs NAFLD
> 2 in ALD
<2 in NAFLD
Major causes of cirrhosis? (+ genetic causes + drugs)
NAFLD
ALD
Hepatitis (BCD)
Autoimmune
PSC, PBC
Haemochromatosis
Wilson’s
A1AT
Galactosaemia (cannot convert galactose -> glucose so it builds up in liver)
Glycogen storage disease (cannot break down glycogen, so it builds up in the liver)
Drugs - methotrexate
What score for prognosis in liver cirrhosis?
Modified child’s pugh score
Macroscopic characteristics of the three liver pathologies in alcohol-related liver disease?
Hepatic steatosis/fatty liver - large, pale, yellow greasy liver
Alcoholic hepatitis - large fibrotic liver
Cirrhosis - looks cirrhotic
What conditions make up NAFLD
Simple steatosis
NASH = steatosis + hepatitis. Can progress to cirrhosis
What gene and antibodies are associated with autoimmune hepatitis?
HLA-DR3
Antinuclear antibody, anti-smooth muscle antibody
anti-LKM antibody (anti liver kidney microsomal antibody)
What is seen on histology with autoimmune hep?
plasma cells
Histology shows bile duct loss with granulomas - diagnosis?
Primary biliary cholangitis
Blood tests for PBC?
raised ALP, raised cholesterol, raised IgM (as autoimmune)
Treatment for PBC and PSC
ursodeoxycholic acid +/- liver transplant
PSC vs PBC - in terms of male and female prevelence?
PBC - F>M
PSC - M>F
What diseases is PSC associated with, and what antibody?
IBD - esp UC and increased risk of cholangiocarcinoma (PBC is not)
p-ANCA antibody
What would USS show of PBC vs PSC?
PBC - no dilatation of bile ducts (as being closed)
PSC - dilatation of bile ducts
histology of PSC?
onion skinning fibrosis
inheritance pattern of haemochromatosis, wilson’s and A1AT?
haemo and wilsons - autosomal recessive
A1AT - autosomal dominant
what stain for iron
Prussian blue
what stain for copper
rhodanine stain
what rings in eyes for wilson’s
kayser fleischer rings
two benign tumours of the liver?
hepatic adenoma and haemangioma (most common)
Ix for HCC?
AFP!!!!! (also raised in yolk sac tumours), USS
