** Histopath : Liver Pathology Flashcards
What is the weight of the liver
• Weight: 1500 g
What is the liver’s blood supply
- Hepatic portal vein
- Hepatic artery
Does the liver tend to be affected by ischaemic diseases?
because of dual blood supply the liver does NOT tend to get affected by ischaemic diseases
Which cells are present in the liver?
• Hepatocytes
• Bile ducts (cholangiocytes)
• Blood vessels
• Endothelial cells
• Kupffer cells
• Resident macrophages
• Stellate cells
What is the function of the stellate cells in the liver?
- 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
Describe the structure of the endothelial cells in the liver
- In the liver, the endothelial cells do NOT sit on a basement membrane
- The endothelium is discontinuous - there are no tight junctions
What does this show?
liver
- The portal tract is at the bottom left and the central vein is at the top right
- The blood will flow from the portal tract to the central vein
What does the portal tract consist of?
- : portal triad = hepatic artery (branch), portal vein (branch) and bile duct
How many zones are there in the liver?
THREE zones in the liver: 1, 2 and 3
- The cells look the same but they are functionally very different
- ‘They begin life in zone 1, grow up in zone 2 and retire in zone 3’
- Therefore, cells in zone 3 have more metabolically active enzymes
Describe the normal structure of the liver
- normal hepatocytes have microvilli
- REMEMBER: endothelial cells in the liver have NO basement membrane and have spaces between them
- Kupffer cells are found within the sinusoids
- Stellate cells sit in the space between the endothelial cells and the hepatocytes, known as the space of Disse
- Blood can easily get through the spaces between endothelial cells and come into contact with hepatocytes
What are the changes that happen to the liver’s microstructure during liver injury?
-
Changes in Liver Injury
- Kupffer cells become activated (typical inflammatory response)
- Endothelial cells stick together so blood finds it hard to make it through
- IMPORTANT: in liver injury, basement membrane-type collagens are secreted into the space of Disse by activated stellate cells
- Hepatocytes lose their microvilli
- Because of all of these changes, blood finds it hard to diffuse into the hepatocytes
Define cirrhosis
- WHOLE liver is involved
- Fibrosis
- Nodules of regenerating hepatocytes
- Distortion of liver vascular architecture: intra- and extra-hepatic shunting of blood
What is extra-hepatic shunting?
extra-hepatic shunting is referring to the shunting of blood to sites of porto-systemic anastomosis (e.g. gastro-oesophageal junction)
What is the difference between intra-hepatic and extra-hepatic shunting?
- Normally, blood comes from the intestines, is filtered through the liver and comes out via the hepatic vein
- Extrahepatic Shunting - the blood never reaches the liver because it backlogs into the sites of porto-systemic anastomosis
- Intrahepatic Shunting - the blood comes through the liver but it does NOT come into contact with hepatocytes (so the blood is unfiltered and toxic)
How is cirrhosis classified?
-
According to NODULE SIZE (old method)
- Micronodular
- Macronodular
-
According to AETIOLOGY
- Alcohol/insulin resistance
- Viral hepatitis
- 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
What are the complications of cirrhosis?
-
Complications of Cirrhosis
- Portal hypertension
- Hepatic encephalopathy
- Liver cell cancer
Is cirrhosis reversible?
cirrhosis may be REVERSIBLE
What is the aetiology of acute hepatitis?
- Viruses (mainly hepatitis A and E)
- Drugs
What does this show?
Acute hepatitis
- A common histological feature of all types of acute hepatitis (regardless of aetiology) is spotty necrosis
What is the aetiology of chronic hepatitis?
- Viral hepatitis
- Drugs
- Autoimmune
How is chronic hepatitis classified?
- Severity of inflammation = GRADE (‘how bad does it look’)
- Severity of fibrosis = STAGE (‘how far has it spread’)
What does this show?
Interface Hepatitis
- Used to be called ‘piecemeal hepatitis’
- It is difficult to see where the portal tract ends and the hepatocytes begin because the inflammation crosses the limiting plate
What does this show? What is the blue structure?
normal portal tract
blue = collagen
What does this show?
- there is a lot of fibrosis in between the portal tract and the central vein
What is a consequence of fibrosis between the portal tract and the central vein?
- 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
How does liver disease progress?
- Liver disease will progress in a sequence
- Patients will develop fibrosis, which gets progressively worse
- Eventually they will get cirrhosis
- Once you have cirrhosis, you could become decompensated and you might need a liver transplant
- Cirrhosis is also a risk factor for HCC
- NOTE: HCC is becoming increasingly common in non-cirrhotic livers
What are the 3 patterns of Alcoholic Liver Disease?
- Fatty liver
- Alcoholic hepatitis
- Cirrhosis
NOTE: they may co-exist, they are not distinct entities
Is fatty liver changes reversible?
- anyone that drinks in excess will undergo some fatty change but this is reversible
What does this show?
Alcoholic Hepatitis
-
Ballooning (with or without Mallory Denk bodies)
- This is when the cells swell
- Mallory Denk bodies are pink deposits found within the cells (sometimes referred to as ‘Mallory hyaline’)
- Apoptosis
- Pericellular fibrosis
These changes are mainly seen in ZONE 3, where we find the most metabolically active cells in the liver
The cells in which zone are most vulnerable to changes seen in alcoholic hepatitis?
zone 3
- alcohol is NOT toxic, acetaldehyde IS toxic - so, the cells that get damaged are the ones that contain the most alcohol dehydrogenase, thereby having the greatest capacity to produce acetaldehyde
- Furthermore, by the time the blood has gone past zones 1 and 2 and reached zone 3, it is relatively hypoxic
- This means that cells in zone 3 are particularly vulnerable to damage
What type of hepatitis is found in NAFLD?
- Non-alcoholic steatohepatitis is the hepatitis that results from NAFLD
How do you distinguish between NAFLD and alcoholic liver disease histologically?
- Histologically looks a lot like alcoholic liver disease
- It is distinguished from alcoholic liver disease based on the history
What is the cause of Non-Alcoholic Fatty Liver Disease (NAFLD)?
- Caused by insulin resistance associated with raised BMI and diabetes
What is Primary Biliary Cholangitis?
- Characterised by bile duct loss associated with chronic inflammation (with granulomas)
- More common in FEMALES
What is the diagnostic test for What is Primary Biliary Cholangitis?
- Diagnostic Test: anti-mitochondrial antibodies (AMA)
What does this show?
Primary Biliary Cholangitis
- The bile duct is surrounded by epithelioid macrophages, suggestive of granulomatous destruction of bile ducts
- This is the diagnostic lesion for PBC
What is Primary Sclerosing Cholangitis?
- Characterised by periductal bile duct fibrosis leading to loss
- More common in MALES
What is the difference between primary biliary cholangitis and primary sclerosing cholangitis?
in PBC, bile duct loss is caused by inflammation, whereas in PSC it is caused by fibrosis
Which conditions is Primary Sclerosing Cholangitis associated with?
- Associated with ulcerative colitis
- Associated with an increased risk of cholangiocarcinoma
What is the diagnostic test for Primary Sclerosing Cholangitis?
- Diagnostic Test: bile duct imaging
What does this show?
Primary Sclerosing Cholangitis
What is Haemochromatosis?
- Genetically determined increased in gut iron absorption
- As women tend to have lower iron levels than men, they tend to present with haemochromatosis LATER
What is the genetics of haemachromatosis?
- The implicated gene (HFe) is located on chromosome 6
What are the complications of haemachromotosis?
- Iron deposition in parenchymal cells leads to organ damage (e.g. iron deposits in the hepatocytes leading to liver damage)
- It can deposit in the:
- heart → cardiomyopathy
- testes → infertility
- pancreas → diabetes
What is Haemosiderosis?
- This is a type of iron overload
- It is characterised by the accumulation of iron in macrophages
What is the most common cause of haemosiderosis?
- This usually occurs as a result of receiving blood transfusions
What does this show?
Haemochromatosis
What is Wilson’s Disease?
- Characterised by an accumulation of copper due to the failure of excretion of copper by hepatocytes into the bile
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What are the Ix for ?wilson’s disease?
- Assessed by biopsy or biochemistry
What are the genetics behind Wilson’s disease?
- Responsible genes are found on chromosome 13
What are the complications of Wilson’s disease?
- Copper accumulates in the
- liver + CNS (sometimes referred to as hepato-lenticular degeneration)
- iris (Kayser-Fleischer rings)
- Accumulation in the lentiform nucleus of the basal ganglia leads to movement disorders
What is Autoimmune Hepatitis?
- This is a very active form of chronic hepatitis with lots of plasma cells
- The degree of inflammation is often much worse than in viral hepatitis
- More common in FEMALES
Which antibodies are implicated in Autoimmune Hepatitis?
- Antibodies: Anti-smooth muscle antibodies (ASMA)
How is the diagnosis of autoimmune hepatitis confirmed?
- Responds to STEROIDS (important to confirm the diagnosis)
What is Alpha-1 Antitrypsin Deficiency?
- Characterised by a failure to secrete alpha-1 antitrypsin from hepatocytes into the blood
Summarise the pathophysiology of Alpha-1 Antitrypsin Deficiency
- Alpha-1 antitrypsin is made in hepatocytes
- Protein sequence is wrong so it CANNOT fold properly and cannot exit the hepatocytes
- → alpha-1 antitrypsin forms globules within the hepatocytes which damages them and leads to chronic hepatitis
- → deficiency of Alpha-1 antitrypsin in the blood
What are the complications of Alpha-1 Antitrypsin Deficiency?
- A deficiency of alpha-1 antitrypsin in the rest of the body leads to increased risk of emphysema
What does a Drug-Related Liver Injury picture look like?
- ANY type of liver disease can be caused by a drug (i.e. it could look like a hepatocellular problem or a cholestatic problem)
- NOTE: because the liver is the main site of drug transformation, it is also the main site where toxic metabolites are formed
- E.g. zone 3 is worst affected in paracetamol overdose because that is where the most NAPQI is formed
What does this show?
Hepatic Granulomas
What are the causes of hepatic granulomas?
Specific causes:
- PBC
- drugs
General causes:
- TB
- Sarcoidosis
Name some benign liver tumours
- Liver cell adenoma
- Bile duct adenoma
- Haemangioma (MOST COMMON)
Name some malignant liver tumours
- Secondary tumours (MOST COMMON)
- Primary tumours
- Hepatocellular carcinoma
- Hepatoblastoma
- Cholangiocarcinoma
- Haemangiosarcoma
What is hepatocellular carcinoma associated with?
- Associated with cirrhosis in the West, and
- associated with viral infections in developing countries
What is cholangiocarcinoma associated with?
- Associated with:
- PSC
- Worm infections
- Cirrhosis
Which structures can cholangiocarcinomas arise from?
- Can arise from:
- Intrahepatic ducts
- Extrahepatic ducts (including gallbladder)
