Pathology of the Liver Flashcards
4 causes of acute liver failure and acute onset of jaundice?
Alcohol
Viruses
Drugs
Bile duct obstruction
Outcomes of acute liver failure?
Complete regeneration
Chronic liver disease
Death from liver failure
Classifications of jaundice by site and causes?
Pre-hepatic (increased requirement of haem breakdown increases bilirubin) - causes include haemolysis, of any type, and haemolytic anaemias; there is unconjugated bilirubin
Hepatic (injury/necrosis of hepatocytes) - causes include acute liver failure, alcoholic hepatitis, decompensated cirrhosis, bile duct loss (atresia, PBC, PSC), pregnancy
Post-hepatic (obstructive) - causes include congenital biliary atresia (no bile duct), gallstones in CBD, strictures and tumours of the head of the pancreas
Classifications of jaundice by type?
Conjugated - has been conjugated in the liver; causes are post-hepatic and hepatic
Unconjugated - has not been conjugated in the liver; causes are pre-hepatic and hepatic (problem with the conjugating capacity of the liver)
What is liver cirrhosis?
Bands of fibrosis separate regenerating nodules of hepatocytes; this is irreversible and a common end-point for liver disease
Complications of cirrhosis?
Portal hypertension (oeosphageal varices at the porto-caval anastamoses, caput medusae)
Ascites (accumulation of fluid in the peritoneal cavity due to raised hydrostatic pressure and hypoalbuminaemia)
Liver failure
What are other causes of portal hypertension?
Budd-chiari syndrome - narrowing and occlusion of the hepatic veins
Portal vein thrombosis
Portal fibrosis in sarcoidosis
Explain the causes of CLD clinical features?
Oedema - hypoalbuminaemia; ascites arises with portal hypertension as well
Haematemesis - ruptured oesophageal varices, due to portal hypertension
Spider naevi and gynecomastia - hyperoestrogenemia
Purpure and haemorrhaging - reduced clotting factor synthesis
Coma (hepatic encephalopathy) - failure to eliminate toxic gut bacterial metabolites
Infection - reduced Kupffer cell number and function
Pathogenesis of alcoholic liver disease?
Increased peripheral release of fatty acids and increased synthesis of fatty acids and triglycerides within the hepatocyte; acetaldehyde causes hepatocyte injury
Increased collagen synthesis by fibroblasts
How does the duration of alcohol consumption affect the prognosis?
2-3 days causes a fatty liver - steatosis is infiltration of hepatocytes with fat (reversible)
4-6 weeks causes hepatitis (reversible)
Months-years causes fibrosis (irreversible)
Years causes cirrhosis (irreversible)
Histopathological features of alcoholic fatty liver?
Fat vacuoles appear clear in the hepatocytes
Histopathological features of alcoholic hepatitis?
Hepatocyte necrosis and a neutrophil infiltrate
Mallory bodies (inclusions within cells) and pericellular fibrosis
Histopathological features of alcoholic fibrosis?
Collagen laid down around cells
Histopathological features of alcoholic cirrhosis?
Bands of fibrosis separate regenerating nodules of hepatocytes
What is non-alcoholic steatohepatitis (NASH)?
Caused by fat deposition in hepatocytes, due to a reason other than alcohol consumption; it is pathologically identical to alcoholic steatohepatitis
Risk factors for NASH?
Diabetes, obesity, hyperlipidaemia
What is viral hepatitis?
Inflammation of hepatocytes due to viral infection with Hep A-E, EBV, herpes simplex virus and CMV
Describe hepatitis A
Spread by faecal-oral route and it has a short incubation period
The virus kills hepatocytes DIRECTLY
There is no carrier state and it usually causes a mild illness
Describe hepatitis B
Spread via blood, blood products, intercourse and in utero; it has a long incubation period
There is a carrier state
Bystander hepatocyte damage due to anti-viral immune response
Describe hepatitis C
Spread by blood, blood products and (possibly) via intercourse; it has a short incubation period and is often asymptomatic
The disease is dynamic (comes and goes) and tends result in carriers or chronic disease
Histopathological findings in chronic viral hepatitis?
Dense portal chronic inflammation
Interface hepatitis (dense portal and peri-portal lymphocyte and plasma cell infiltrate that disrupts the parenchymal limiting plate)
Lobular inflammation
Fibrosis and cirrhosis
Outcomes of Hep B infection?
Asymptomatic (carrier - unaffected but able to transmit the infection)
Chronic hepatitis
Cirrhosis
Hepatocellular carcinoma
Fulminant hepatic failure
Outcomes of Hep C infection?
Chronic hepatitis
Cirrhosis
What are the autoimmune diseases of the liver?
Primary biliary cirrhosis (PBC)
Autoimmune hepatitis
Primary sclerosing cholangitis
What is primary biliary cirrhosis (PBC)?
A rare autoimmune disease; it is assoc. with auto-antibodies to mitochondria (AMA - anti-mitochondrial)
Aetiology of PBC?
Unknown aetiology but majority of cases are in females (90%)
Histopathology of PBC?
Progressive damage and loss of interlobular bile ducts
Progressive chronic granulomatous inflammation on biopsy
What is autoimmune hepatitis (AIH)?
Attack to hepatocytes that mimics chronic hepatitis; there may be a trigger, e.g: a drug
Antibodies in autoimmune hepatitis?
Assoc. with production of auto-antibodies to smooth muscle, anti-nuclear antibodies and anti-LKM (liver, kidney, microsomal) antibodies
What is chronic drug-induced hepatitis?
Features similar to that of chronic hepatitis and may trigger autoimmune hepatitis; this can be caused by numerous drugs
What is primary sclerosing cholangitis (PSC)?
Chronic inflammation and onion-skin PERI-DUCTAL FIBROSIS; appearance of “beads on a string”
Aetiology of
More commonly affects males and is assoc. with UC; there is an increased risk of malignancy of the bile duct and of the colon
What are 3 liver storage diseases?
Haemochromatosis
Wilson’s disease
α1-antitrypsin deficiency
What is haemochromatosis?
Excess iron within the liver
Causes of haemochromatosis?
Primary - genetic condition increasing Fe absorption
Secondary - Fe overload from diet, transfusions and iron therapy
What is primary haemochromatosis?
Autosomal recessive condition that leads to excess Fe absorption from the intestine and abnormal Fe metabolism; it is worse in homozygotes and in males (do not have menstrual excretion of Fe)
After menopause, women will be just as susceptible as males
Pathogenesis of primary haemochromatosis?
Deposited in portal connective tissue and leads to fibrosis and cirrhosis
It predisposes to carcinoma and can cause diabetes, cardiac failure, impotence and haemosiderin deposition in the skin
What is Wilson’s disease?
Inherited autosomal recessive disorder of Cu metabolism; Cu accumulates in the liver and brain (basal ganglia)
It can cause chronic hepatitis and neurological deterioration
Signs of Wilson’s disease?
Kayser-Fleischer rings (dark rings around iris)
Low serum caeruloplasmin
What is α1-antitrypsin deficiency?
Inherited autosomal recessive disorder of production of anti-trypsin (anti-protease); causes emphysema, in non-smokers, and cirrhosis
Histopathology of α1-antitrypsin deficiency?
Cytoplasmic globules of unsecreted protein globules remain in liver cells
Tumours of the liver?
Primary (rare):
Hepatocellular adenoma
Hepatocellular carcinoma
Secondary (common):
Multiple metastases from colon, pancreas, stomach, breast, lung, etc
Describe hepatocellular adenoma
Benign and most common in females; they can rupture and bleed but most remain assymptomatic
Describe hepatocellular carinoma
Assoc. with HBV, HCV and cirrhosis
Presentation of hepatocellular carcinoma
Usually presents as a mass, pain and obstruction; often advanced on finding
