Liver and Biliary Disease Flashcards
How much does the liver weigh and where does it get it’s blood supply from?
1500g
Portal vein and hepatic artery
What issues may arise in gall bladder surgery?
Anatomy is very variable - surgeons may accidentally tie off both sources of blood
Name 6 different cell types of the liver and their roles
hepatocytes
bile ducts
blood vessels
endothelial cells - line sinusoids, unique cells
kupffer cells - resident macrophages, clear debris and endotoxin
stellate cells - store vitamin A in healthy individuals. when activated, these become myofibroblasts and produce collagen - involved in liver scarring and diseases involving fibrosis.
What is the arrangement of the liver?
Arranged in hexagonal lobules. Hepatic vein at the centre connected to sinusoids.
At each corner lies the portal triad - hepatic artery, portal vein and bile duct.
Blood flows from triads, through sinusoids and into hepatic vein
What are the zones of the liver?
1 - periportal - closest to portal triad, rich O2 supply
2 - mid zonal - between 1 and 3
3 - perivenular - surrounding hepatic vein, poor O2 supply
Different diseases occur in different zones
How do stellate cells become activated?
Lie between endothelial cells and hepatocytes.
Endothelial cells don’t sit on a BM and are discontinuous.
Blood flows between endothelial cells to get to hepatocytes. When the liver is injured, kupffer cells activated. Endothelium becomes continuous and secretes a BM. Stellate cells become activated to become myofibroblasts and then there is collagen int the space of disse. Microvilli are lost from hepatocytes. - reduced function of the liver.
Reduced contact with blood for homeostasis and own nutrition is impaired.
Define cirrhosis
End-stage liver disease, regardless of cause.
Whole liver is involved, there is fibrosis and nodules of regenerating hepatocytes with distortion of liver vascular architecture (intra and extra-vascular shunting of blood).
What is seen histologically in liver cirrhosis?
hepatocytes surrounded by fibrous tissue
How can cirrhosis be classified?
1) according to nodule size - micro, macro (>3mm) or mixed
2) according to aetiology - alcohol or insulin resistance (secondary to T2DM) - tends to be micronodular
If you drink a weekends, nodules become macronodular as have time to recover
viral hepatitis - tends to be macronodular
What are the complications of cirrhosis?
portal hypertension, hepatic encephalopathy, liver cell cancer, splenic congestion
What are the causes of acute hepatitis?
What does histology show?
Viruses - Hep A, B, C, D, E
Drus
Spotty necrosis
Define chronic hepatitis
What are the causes of chronic hepatitis?
hepatitis for 6 months or more Viruses - Hep B, C or D - D only occurs in patients with B. Either already present or acquired together. Drugs Autoimmune Idiopathic
What does histology show?
Grade: severity of inflammation
Stage: severity of fibrosis - risk of developing acutal cirrhosis
Piecemeal necrosis - line between portal tract and hepatocytes - limiting plate.
Interface hepatitis - along this line
Actually apoptosis and not necrosis
Can also get lobular inflammation
Fibrosis in histology = closer to developing cirrhosis
lymphocytic
How do viral hepatitises progress?
All start acutely - chronic - cirrhosis - liver cell cancer
What are the three categories of Alcoholic Liver disease?
Fatty liver disease
Alcoholic hepatitis
Cirrhosis
Fatty liver disease features
pale, yellow and greasy liver
Histology - fat droplets visible throughout
REVERSIBLE as fatty changes are metabolic
Alcoholic hepatitis features
Fatty change, damage and inflammatory cells present (neutrophilic)
Mallory-denk bodies
Alcohol not toxic, acetaldehyde binds to lysine residues and cross-links cytoskeleton leading to clumps
Ballooning of hepatocytes due to loss of cytoskeleton. Get fibrosis around individual cells - pericellular fibrosis
Cirrhosis features…
Alcoholic cirrhosis - pale, yellow, greasy and fatty. Usually micronodular.
Non-alcoholic fatty liver disease
histologically looks like alcoholic liver disease
due to insulin resistance associated with increased BMI and diabetes
Most important liver disease in western countries.
Primary Biliary Cirrhosis
Bile duct loss associated with chronic inflammation (with granulomas)
Anti-mitochondrial antibodies are diagnostic
May develop cirrhosis
Destruction of bile ducts by granulomas
Liver biopsy - bile duct surrounded by granuloma (organised collection of activated macrophages, for secretion, not phagocytosis).
Portal tract looks inflamed with absence of bile duct.
Primary Sclerosis Cholangitis
Sclerosing = fibrosis Damage of ducts due to scarring (not inflammation). Periductal bile duct fibrosis Associated with UC Increased risk of cholangiocarcinoma Dx via ERCP
Histology: bile duct surrounded by fibrosis - squeezed until leads to disappearing bile duct syndrome disease
Haemochromatosis
Genetically determined increased gut iron absorption
Gene on chromosome 6
Parenchymal damage to organs secondary to iron deposition
iron overload in hepatocyes
catalysis of oxidation reactions
affects many other parts of the body e.g. pancreas and skin (pigmentation).
Present at birth but takes until middle-age to see liver damage
Histology: iron in hepatocytes.
Chocolatey brown liver, accumulates in all organs
Haemosiderosis
Accumulation of iron in macrophages
Due to excessive blood transfusion
Most commonly seen in those with SCD and Beta thalassaemia, who are awaiting BM transplantation
Phagocytosis of RBCs - macrophages accumulate iron
Biopsy shows - scattered iron accumulation in liver macrophages
Wilson’s disease
Accumulation of copper due to failure to excrete by hepatocytes in bil
Genes on chromosome 13
Accumulates in liver and CNS
Becomes multi-organ disease
Psychiatric patients - abnormal LFT (?Wilson’s disease)
Rhodanine stain - copper accumulation in hepatocytes
KF rings
