Pathology of the liver Flashcards
What are the two concepts of microanatomical units in the liver?
The lobular concept and the acinar concept
Which acinar zones are used to describe patterns of liver injury?
Which cells are most vulnerable do injury?
Zone 1: periportal
Zone 2: Mid acinar
Zone 3: Pericentral
Zone 3 cells are most vulnerable to injury
Are all liver cells capable of regeneration?
Yes
Do liver cells replicate frequently?
No, they are stable and only replicate infrequently.
However if the liver is injured nearly all surviving hepatocytes can enter the cell cycle and rapidly replace destroyed hepatocytes.
What is the late stage of all chronic liver diseases?
Cirrhosis
What is cirrhosis defined as?
What effects does it have on the liver?
It is defined anatomically by the presence throughout the liver of fibrous septa that subdivide the parenchyma into nodules.
Perfusion of sinusoids is inefficient, liver cell function is impaired, and intraheptic pressure is increased.
What are the possible outcomes of acute liver failure?
complete recovery
chronic liver disease
death from liver failure
Are all patients with severe liver disease jaundiced?
No, there are many who are not.
The liver has a massive reserve and can handle a build up of bilirubin with just a third of the cells.
How is jaundice classified?
By site and type
Pre-hepatic
Intra-hepatic
Post-hepatic
Conjugated
Unconjugated
What causes pre-hepatic jaundice?
What type of bilirubin causes the jaundice?
Haemolysis of any type.
Unconjugated bilirubin
What causes hepatic jaundice?
Liver cells that are injured or dead. e.g. Alcoholic hepatitis Cirrhosis (decompensated) Bile duct loss (atresia, PBC, PSC) Pregnancy
What causes post hepatic jaundice?
Bile cannot escape into the bowel E.g. Congenital biliary atresia Gallstones block CBDuct Strictures of CBDuct Tumours (Ca head of pancreas)
Is cirrhosis reversible or irreversible?
Irreversible
What are features of cirrhosis?
There is alteration of hepatic microvasculature and many hepatocytes now have a compromised blood supply
There is loss of hepatic function
The liver is nodular, hard and craggy
How is cirrhosis classified?
Morphologically:
classified by the average size of the regenerative nodules
micronodular- nodules up to 3mm in diameter
macronodular- nodules greater than 3mm in diameter
Aetiologically
What are the major complications of cirrhosis?
Liver failure
Portal hypertension
Infection
Liver cell carcinoma
What are common causes of cirrhosis?
Alcohol
Hep B and C
Iron overload
Is liver failure a manifestation of compensated or decompensated cirrhosis?
Decompensated
What causes hepatic encephalopathy?
Failure of the liver to eliminate toxic nitrogenous products of gut bacteria
What other type of failure may also occur with hepatic failure?
Renal failure (hepato-renal syndrome)
What does failure to eliminate endogenous steroid hormones result in?
Secondary hyperaldosteronism, causing sodium and water retention
In the male, it causes loss of secondary sexual characteristics and gynaecomastia due to hyperoestrogenism.
What are results of portal hypertension?
Oesophageal varices
Caput medusa
Haemorrhoids
Ascites
Is cirrhosis the only cause of portal hypertension?
No
What is the reason for oedema in chronic liver disease?
Reduced albumin synthesis resulting in hypoalbuminaemia
What is the reason for ascites in chronic liver disease?
Hypoalbuminaemia
Secondary hyperaldosteronism
Portal hypertension
What is the cause of haematemesis in chronic liver disease?
Ruptured oesophageal varices due to portal hypertension
What is the cause of spider naevi and gynaecomastia in chronic liver disease?
Hyperoestrogenism
What is the cause of purpura and bleeding in chronic liver disease?
Reduced clotting factor synthesis
What is the cause of coma in chronic liver disease?
Failure to eliminate toxic gut bacteria metabolites (false neurotransmitters)
What is the cause of infection in chronic liver disease?
Reduced Kuppfer cell number and function
What is the commonest cause of chronic liver disease in the UK?
Alcohol liver disease
What is the spectrum of alcohol liver injury which can be seen in liver biopsies?
Fatty change/steatosis:
fat globules in the cytoplasm of liver cells
a disturbance of energy metabolism which on its own is reversible when alcohol consumption stops
Alcoholic steatohepatitis:
A combination of fatty change with cell swelling. This is reversible, but can lead to liver cell death and fibrosis which is not reversible.
Progressive architectural damage ranging from pericellular fibrosis to cirrhosis.
Outline the stages of fatty liver disease, when they occur in terms of duration of drinking, and whether or not they are reversible.
2-3 days drinking: fatty liver- reversible
4-6 weeks drinking: hepatitis- reversible
months-years: fibrosis- irreversible
Years: cirrhosis- irreversible
Outline the pathogenesis of alcoholic liver disease
Alcohol metabolism disturbs other metabolic pathways, such as carbohydrate and fat metabolism, so fat accumulates in the liver cells
Acetaldehyde, the main product of alcohol metabolism, binds to liver cell proteins, resulting in injured hepatocytes and an inflammatory reaction
Alcohol stimulates collagen synthesis in the liver, leading to fibrosis and eventually cirrhosis.
How does non-alcoholic steatohepatitis compare pathologically to alcohol liver disease?
It is identical
Which patients get non-alcoholic steatohepatitis?
Patients with diabetes, hyperlipidaemia and obesity
What can non-alcohol steatohepatitis lead to?
In a proportion of patients it can progress to cirrhosis
How does Hep A cause liver damage?
It is directly cytopathic
It is possible to have Hep A carriers?
No
is it possible to have Hep B carriers?
yes
What are the different outcomes of Hep B infection?
Fulminant acute infection (Death) Chronic hepatitis Cirrhosis Hepatocellular carcinoma Assymptomatic (Carrier)
What are the different outcomes of Hep C infection?
Chronic Hepatitis
Cirrhosis
Is autoimmune hepatitis more common in males or females?
Females
What can autoimmune hepatitis cause?
it can cause acute liver failure
Without treatment, it can progress rapidly to cirrhosis
How is autoimmune hepatitis characterised histologically?
Extensive interface hepatitis
Numerous plasma cells and rosette-like arrangements of swollen liver cells
There may be bridging and panacinar necrosis
Which autoimmune liver disease is associated with antibodies to mitochondria?
Primary biliary cirrhosis
What causes primary biliary cirrhosis?
Unknown
What is the indication for biopsy in primary biliary cirrhosis?
To stage the disease
What may be seen on biopsy of the liver in primary biliary cirrhosis?
Granulomas
Bile duct loss
What are clinical features of primary biliary cirrhosis?
Pruritis
Xanthelasmas
What is the pathogenesis of primary biliary cirrhosis if untreated?
Bile duct loss leads to cholestasis, liver injury, inflammation, fibrosis and cirrhosis.
What autoantibodies are present in autoimmune hepatitis?
Auto-antibodies to:
Smooth muscle antigen (SMA)
Nuclear DNA (anti-nuclear antibody, ANA)
Liver-kidney microsomal (LKM) antigens
What could be a potential trigger for autoimmune hepatitis?
Some drugs
What may chronic drug-induced hepatitis trigger?
Autoimmune hepatitis
Which drugs can damage the liver?
Innumerable
What can cause the damage to the liver by drugs?
It may be dose related, or idiosyncratic (unpredictable)
What harmful effects can drugs have on the liver?
Hepatitis Granulomas Fibrosis Necrosis Failure Cholestasis Cirrhosis
Which liver diseases can drug induced liver injury mimic?
Any
What is primary sclerosing cholangitis?
An autoimmune disease that results in a chronic inflammatory process, causing damage and destruction of bile ducts
It affects intrahepatic and/or extrahepatic bile ducts, often in a patchy way.
What does primary sclerosing cholangitis lead to?
Periductal fibrosis
Duct destruction
Jaundice
Fibrosis
What other inflammatory disease is primary sclerosing cholangitis linked to?
Ulcerative colitis
Are males or females more affected by primary sclerosing cholangitis?
Males
What is there an increased risk of in primary sclerosing cholangitis?
Malignancy in bile ducts and colon
Name some storage diseases of the liver
Haemochromatosis
Wilsons disease
Alpha-1-antitrypsin deficiency
What is the body’s main storage site for iron?
Hepatocytes
What can large amounts of iron in the liver cause?
Liver damage
What is haemochromatosis?
Excess iron within the liver
What is primary haemochromatosis?
A genetic condition
There is iron overload due to a failure to switch off intestinal absorption of iron and abnormal iron metabolism
What can cause secondary haemochromatosis?
Iron overload from the diet
Transfusions
Iron therapy
How is primary haemochromatosis inherited?
It is an autosomal recessive condition
What protects younger women from the effects of primary haemochromatosis?
Menstruation
Describe how primary haemochromatosis progresses
Iron is deposited in the liver- the patient is asymptomatic for years
Eventually iron is deposited in the portal connective tissue which stimulates fibrosis
If not treated, it can lead to cirrhosis
What does primary haemochromatosis predispose to?
Carcinoma
What other conditions does haemochromatosis cause?
Diabetes
Cardiac failure
Impotence
Which stain on a biopsy confirms iron in hepatocytes?
Perl’s stain
this stains iron blue
What factors does the outcome of haemochromatosis depend on?
genetics
therapy (venesection)
cofactors such as alcohol
What are possible outcomes of haemochromatosis?
Cirrhosis
Hepatocellular carcinoma
What is Wilson’s disease?
Inherited autosomal recessive disorder of copper metabolism
Where does copper accumulate in Wilson’s disease?
The liver and the basal ganglia of the brain
How does Wilson’s disease manifest in the eyes?
Kayser-Fleischer rings (dark rings around the iris)
What is there a low serum concentration of in Wilson’s disease?
Ceruloplasmin
What does Wilson’s disease cause?
Causes chronic hepatitis and neurological deterioration
What is alpha-1 antitrypsin deficiency?
Inherited autosomal recessive disorder of production of an enzyme inhibitor that is produced in the liver
What does alpha 1 antitrypsin deficiency cause?
Injury to hepatocytes which results in progressive fibrosis and cirrhosis
It also predisposes to pulmonary emphysema due to the unopposed actions of neutrophil enzymes damaging the alveolar walls.
What happens to the abnormal protein in alpha 1 antitrypsin deficiency?
The protein is misfolded and it cannot be secreted from the hepatocyte
It accumulates in the periportal hepatocytes where it can be visualised as globular inclusions
Is the risk of liver cell carcinoma greater in macronodular or micronodular cirrhosis?
Macronodular
What are the tumours of the liver?
Primary- rare
Hepatocellular adenoma
Hepatocellular carcinoma (hepatoma)
Secondary- common
multiple
metastases from colon, pancreas, stomach, breast, lung, others
What is a hepatocellular adenoma?
A benign, well-differentiated neoplasm of hepatocytes.
Is hepatocellular adenoma more common in males or females?
Females
What can hepatocellular adenomas cause?
They can become big
They can rupture and bleed
However most remain asymptomatic
Is hepatocellular carcinoma rare or common in Europe?
Rare
What is hepatocellular carcinoma associated with?
HBV
HCV
Cirrhosis
How does hepatocellular carcinoma usually present?
As a mass, pain or obstruction
It can also present as decompensation of cirrhosis due to replacement of liver by the cancer
What is a diagnostic marker of hepatocellular carcinoma?
Raised alpha-fetoprotein, although it is not usually detectable in early or well differentiated HCC
What is cholangiocarcinoma?
Adenocarcinoma arising in bile ducts
