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.
- 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 and hepatocytes 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
Oxygenation: Zone 1 has the highest oxygen supply, followed by Zone 2, with Zone 3 having the least.
Functions:
Zone 1: Gluconeogenesis, oxidative metabolism, detoxification.
Zone 2: Intermediate functions.
Zone 3: Glycolysis, lipogenesis, drug metabolism.
Susceptibility to Damage:
Zone 1: More resistant to ischemia but susceptible to toxins.
Zone 2: Intermediate susceptibility.
Zone 3: Highly susceptible to ischemia and certain toxins/metabolic by-products. (less susceptible to toxins than zone 1 as it is most metabolically active)
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 in the space of Disse where they are exposed to hepatocytes
- NOTE: normal hepatocytes have microvilli
- REMEMBER: endothelial cells in the liver have NO basement membrane and have spaces between them
Describe how these 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 key features of cirrhosis?
- The whole liver is involved
- There is extensive fibrosis and nodules of regenerating hepatocytes
- Shunting occurs
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
How do these two classications of cirrhosis overlap?
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
What are the three histological patterns of alcoholic liver disease?
- Fatty liver
- Alcoholic hepatitis
- 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
NOTE: caused by insulin resistance associated with a raised BMI and diabetes
How is NAFLD distinguished from alcoholic lver disease?
Based on the history
AST:ALT ratio <2 in NAFLD
What is primary biliary cholangitis?
Autoimmune conditions characterised by bile duct loss associated with chronic inflammation (with granulomas)
What is the diagnostic test for PBC?
- Anti-mitochondrial antibodies (AMA)
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
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
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
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
- 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
The portal tract is made up of three different vessels. What is the name of the vein found in the portal tract?
Hepatic portal vein
A 50 year old homeless alcoholic is admitted to A+E after an alcohol binge, where he reportedly drank two litres of vodka in 24 hours. His past medical history includes gallstones.
He also reported trying intravenous drugs with a needle shared with someone known to have hepatitis C 2 days prior.
He reports pain in his right upper quadrant which comes and goes.
Blood tests show ALT 2x upper limit of normal, AST 5x upper limit of normal, ALP 1.5x upper limit of normal and bilirubin in the normal range.
What is the likely cause of his hepatic derangement?
Alcoholic hepatitis
What is the typical inheritance pattern of hereditary haemochromatosis?
Autosomal recessive
What liver enzyme may be measured in the blood and, if raised to a level >10x the upper limit of normal is suggestive of viral hepatitis?
Alanine Aminotransferase ALT
A 40 year old man has routine bloods done for yearly statin monitoring at his GP. His monitoring blood tests last year were normal
One week prior he broke his ankle falling off his bike.
Blood tests show a normal ALT, raised ALP, normal AST, normal bilirubin.
What is the likely explanation for his deranged liver function?
Fracture
Give an example of a blood test that may be used to monitor hepatic synthetic function
INR
What histochemical stain would reveal the presence of iron in a liver biopsy with a patient with haemachromatosis?
Prussian blue
What is the inheritance pattern of Wilson’s disease?
Autosomal recessive
What histochemical stain would reveal the presence of copper in a liver biopsy with a patient with Wilson’s disease?
Rhodanine
A 42 year old woman with Type 1 Diabetes Mellitus is investigated for fatigue and pruritus.
She has an elevated serum ALP and an elevated anti mitochondrial antibody titre.
An ultrasound of the biliary tree shows no gross dilatation.
What is the likely diagnosis?
Primary Biliary Cholangitis
What is the first line treatment for severe haemachromatosis?
Therapeutic phlebotomy
Other than zinc, what is the first line pharmacological treatment for Wilson’s disease?
Trientine
A liver biopsy from a patient with chronic hepatitis B shows areas of fibrosis and hepatocyte necrosis. There are visible nodules of regenerating hepatocytes.
An upper GI endoscopy reveals the presence of large, dilated veins in the oesophagus.
What diagnosis is likely responsible for the increase in portal venous pressure?
Cirrhosis
Which tumour marker is used in the diagnosis of hepatocellular carcinoma?
Alpha-fetoprotein
Which hepatobilary pathology is classically associated with an elevated p-ANCA?
Primary Sclerosing Cholangitis
What liver enzyme may be measured in the blood and, if raised, is suggestive of biliary obstruction?
Alkaline Phosphatase (ALP)
Which common medication are hepatic adenomas associated with?
Oral Contraceptive Pill
Kayser Fleischer rings represent the deposition of what substance in the cornea?
Copper
Give an example of a biomarker that suggests the presence of hepatic ischaemia
Alanine Aminotransferase
Which hepatobiliary condition may be described as: fibrosis of bile ducts throughout the biliary tree with associated stricture formation?
Primary Sclerosing Cholangitis
Which hepatobillary condition may be described as a slow, insidious process of autoimmune destruction of intrahepatic bile ducts, associated with cholestasis?
Primary Biliary Cirrhosis
Which form of inflammatory bowel disease is associated with Primary Sclerosing Cholangitis?
Ulcerative colitis
Which hepatobiliary pathology is associated with the finding of “beading” of bile ducts during an endoscopic retrograde cholangiopancreatogram (ERCP)?
Primary Sclerosing Cholangitis
Which hepatobiliary pathology, associated with a positive antimitochondrial antibody, may show the presence of granulomas on biopsy?
Primary Biliary Cirrhosis
A 45 year old diabetic man is investigated for heart failure.
A panel of blood tests shows an elevated serum ferritin in the absence of a fever, with a low total iron binding capacity and elevated transferrin saturation. He recalls that his brother has something wrong with iron in his body.
What is the diagnosis?
Hereditary Haemochromatosis
A 16 year old body is investigated for liver failure. He has markedly increased transaminases.
His mother, aunt and grandmother are all smokers and have COPD.
Blood tests show a low serum copper and low serum caeruloplasmin.
What is the likely diagnosis?
Wilson’s disease
A 20 year old man with liver failure and parkinsonism is a classical history of what condition?
Wilson’s disease
In which liver condition will cytoplasmic Mallory Denk Bodies most commonly be found on biopsy?
Alcoholic hepatitis
