Liver Histopathology Flashcards
What is the dual blood supply to the liver?
Does the liver get affected by ischaemic diseases?
Hepatic portal vein
Hepatic artery
Because of dual blood supply the liver does NOT tend to get affected by ischaemic diseases
Cells of the liver (6)
Hepatocytes
Bile ducts (cholangiocytes)
Blood vessels
Endothelial cells
- In the liver, the endothelial cells do NOT sit on a basement membrane
- The endothelium is discontinuous (there are no tight junctions)
Kupffer cells: resident macrophages of the liver
Stellate cells
- In most people, these cells don’t do much other than store vitamin A
- When activated, they become myofibroblasts and lay down collagen
- They are responsible for most of the scarring in liver disease
what is in the portal triad and what surrounds it
zone 1-3 which is the most metabolically active
hepatic artery, portal vein, bile duct
ring of collagen around portal triad (limiting placte)
zone 33 cells more metabolically active enzymes
Where can you find Kupffer cells?
Where can you find stellate cells?
sinusioids
space of Disse = between endothelial cells and hepatocytes
Changes in liver injury
Endothelial
Kupffer
Stellate
Hepatocytes
Kupffer cells activated (inflammatory response)
endothelial cells stick together (harder for blood to make way through)
BM-type collages secreted into the space of Disse by activated stellate cells
hepatocytes lose microvilli
–> hard for blood to diffuse into hepatocytes
Cirrhosis
liver scarring = fibrosis and deposition of collagen
nodules of regenerating hepatocytes (clusters of fibrous tissue around the nodules)
distortion of liver vascular architecture: intra- and extra-hepatic shunting of blood
- extrahepatic shunting is shunting of blood to sites of porto-systemic anastomosis (e.g. gastro-oesophageal junction)
WHOLE liver invlved
Shunting explained
Normally, blood comes from intestines, is filtered through liver and comes out via hepatic vein
- Extrahepatic Shunting: blood never reaches the liver because it backlogs into the sites of porto-systemic anastomosis
- Intrahepatic Shunting: blood comes through the liver but it does NOT come into contact with hepatocytes (so the blood is unfiltered and toxic)
Major functional reason why patients with advanced liver disease have functional abnormalities
Classification of cirrhosis
According to nodule size (old method): micronodular (< 2 mm) or macronodular (> 2 mm)
According to aetiology:
- Alcohol/insulin resistance – both produce fatty changes
- Viral hepatitis – chronic causes of viral hepatitis: hepatitis B, C and D
There is some overlap between these two forms of classification:
- Micronodular tends to be associated with alcoholism
- Macronodular tends to be associated with viral infections
Complications of cirrhosis
portal hypertension
hepatic encephalopathy
liver cell cancer
NB: cirrhosis may be reversible if you actively treat the underlyign cause
Acute hepatitis ; aetiology and histology
Aetiology: viruses (mainly hepatitis A and E) and drugs
Histology: spotty necrosis
- Common histological feature of all types of acute hepatitis (regardless of aetiology)
Chronic hepatitis: aetiology and histology
Aetiology: viral hepatitis, drugs and autoimmune
Histology:
- Severity of inflammation = GRADE (‘how bad does it look’)
- Severity of fibrosis i.e. scarring = STAGE (‘how far has it spread’)
What 3 types of inflammation can you see in chronic hepatitis?
portal inflammation, interface hepatitis and lobular inflamamation
Portal inflammation
- Within limiting plate
Interface hepatitis (left)
- Used to be called ‘piecemeal hepatitis’
- It is difficult to see where the portal tract begins and where the hepatocytes end
- This is because the inflammation crosses the limiting plate
Lobular inflammation (right)
Colour of fibrosis in stain
fibrosis between portal tract and central vein - what does it lead to? (RIGHT IMAGE)
This fibrosis will lead to intrahepatic shunting
Instead of going through the hepatocytes, blood will go straight from the portal tract to the central vein without being filtered
Progression of liver disease
Patients will develop fibrosis, which gets progressively worse
Eventually they will get cirrhosis
Once you have cirrhosis, you could become decompensated – might need a liver transplant
what is cirrhosis a risk factor for
Cirrhosis is also a risk factor for HCC
NOTE: HCC is becoming increasingly common in non-cirrhotic livers
Features of alcoholic hepatitis (3+.5)
Alcohol is NOT toxic, acetaldehyde IS toxic (cells that get damaged the most are the oens that contain the most alcohol dehydrogenase thereby have the greatest capacity to produce acetaldehyde)
Ballooning (w/wo Mallory Denk bodies)
- swelling of cells
- bodies: pink deposits found within the cells (‘Mallory hyaline’)
Apoptosis
Pericellular fibrosis (fibrosis around individual cells)
- prominent in zone 3
- zone 3 cells blood by the time it reaches there is relatively hypoxic so vulnerable to damage
PBC
F>M
Bile duct loss associated with chronic inflamamtion (with granulomas)
- often see granulomatous inflammation
Diagnostic test: anti-mitochondrial antibodies (AMA) serological hallmark of PBC
Histology: epithelioid macrophages surround bile duct (sugegsts granulomatous destruction of bile duct)
PSC
M>F
Periductal bile duct fibrosis leading to loss
- PBC bile duct loss is caused by inflammation, in PSC it is caused by fibrosis
- onion skin fibrosis
Associated with UC and increased risk of cholangiocarcinoma
Diagnostic test: bile duct imaging of biliary tree (ERCP/MRCP)
Haemochromatosis
Genetically determined increased in gut iron absorption
Women tend to have lower iron levels than men -> present with haemochromatosis later
The implicated gene (HFe) is located on chromosome 6
Iron deposition in parenchymal cells -> organ damage
- E.g. iron deposits in the hepatocytes -> liver damage (and ‘chocolate brown’ liver)
- It can deposit in the heart leading to cardiomyopathy and in the testes leading to infertility
- It is sometimes referred to as ‘bronzed diabetes’ because iron deposits in the skin give a tanned complexion and iron deposition in the pancreas leads to diabetes
SKIN, HEART, PANCREAS, LIVER, TESTES
Haemosiderosis
This is a type of iron overload
- It is characterised by the accumulation of iron in macrophages
Macrophages are good at handling iron -> causes very few problems
This usually occurs as a result of receiving blood transfusions
Haemosiderosis occurs when excess iron from blood transfusions is taken up by macrophages
Wilson’s disease
Accumulation of copper due to the failure of excretion of copper by hepatocytes into the bile
Assessed by biopsy or biochemistry
Responsible genes are found on chromosome 13
Copper accumulates in the liver and CNS (sometimes referred to as hepato-lenticular degeneration) and iris (Kayser-Fleischer rings)
Accumulation in the lentiform nucleus of the basal ganglia leads to movement disorders
AIH
F>M
Very active form of chronic hepatitis with lots of plasma cells
degree of inflammation often much worse than in viral hepatitis
antibodies: anti-smooth muscle antibodies (ASMA)
mx: steroids (important in diagnosis)
Alpha-1 Antitrypsin Deficiency
failure to secrete alpha-1 antitrypsin
The deficiency of alpha-1 antitrypsin is in the BLOOD
There is, in fact, a gross excess of alpha-1 antitrypsin in the hepatocytes
This is because the protein sequence is wrong -> can’t fold properly -> cannot exit hepatocytes
This leads to the alpha-1 antitrypsin forming globules within the hepatocytes which damages them and leads to chronic hepatitis (and then eventually, cirrhosis)
A deficiency of alpha-1 antitrypsin in the rest of the body leads to increased risk of emphysema
Drug-related liver injury
paracetamol overdose
ANY type of liver disease can be caused by a drug
could look hepatocellular or cholestatic
dose-related or idiosyncratic (doesn’t happen in most individuals)
liver = main site of drug transformation -> main site where toxic metabolites are formed
zone 3 worst affected in paracetamol overdose (where most NAPQI is formed)
Hepatic granulomas: specific causes and general causes
Specific: PBC and drugs
General causes: TB and sarcoidosis
Tumours in the liver
Why is the liver such a common site for secondary tumours?
The liver is supplied by the hepatic artery
Hepatic artery: branch of the aorta
Tumour cells that have circulated in the systemic circulation have a good chance of reaching liver
Furthermore, the liver is a big organ that is very susceptible to forming metastases
In addition, all blood from portal circulation comes to the liver (i.e. for all tumours from stomach, small bowel, large bowel and pancreas, the liver will be the first capillary bed that they see)
