Liver Pathology Flashcards
What is the classical liver lobule?
Unit drained by central vein
What is the portal lobule?
Unit supplied and drained by portal triad
What is the central acinus?
Unit supplied and drained by terminal branches of portal triad
What are the three acinar zones?
1 - Most nutrients and oxygen - Most toxic metabolites 2 3 - Least nutrients and oxygen - Most susceptible to ischaemic change
What causes ascites?
HTN in portal tract
Low albumin levels
Which liver function tests tell you about liver synthesis function?
Albumin Prothrombin time (INR)
Which liver function tests tell you about hepatocellular damage?
ALT
AST
Which liver function tests tell you about bile duct damage?
ALP
GGT
Which liver function tests tell you about hepatic bile secretion?
Bilirubin
What are albumin levels like in acute and chronic liver disease?
Normal in acute liver damage, due to 20-day half-life
Slow decline in chronic disease
What governs the decline of prothrombin time?
Short half-life of coagulation factors
Where are GGT and ALP located?
Bile canaliculi
Sinusoids
Secondary to what conditions are GGT and ALP induced?
Cholestasis
EtOH > GGT
- Good test in alcoholics to determine if abstaining from alcohol
Where else in the body is ALP found, other than the liver?
Bone
Which of the transaminases is more liver specific?
ALT
Which of the transaminases is relatively higher in chronic liver disease?
AST, especially in alcoholic hepatitis
How long does it take for transaminases to rise after hepatic injury?
24 hours
Where are the transaminases located?
Predominantly in periportal hepatocytes
What form of bilirubin rises in prehaptic hyperbilirubinaemia?
Unconjugated
What form of bilirubin rises in intrahepatic hyperbilirubinaemia?
Conjugated
Unconjugated
What form of bilirubin rises in post-hepatic hyperbilirubinaemia?
Conjugated
What are common alcoholic liver diseases?
Steatosis
Alcoholic steatohepatitis (ASH)
Cirrhosis
What is the histology of steatosis?
Microvesicular and macrovesicular fat
What is the histology of ASH?
Steatosis
Ballooning degeneration
Mallory’s hyaline
PMN satellitosis
What are the clinical features of alcoholic steatohepatitis?
Generally unwell Low fever Tender hepatomegaly Often icteric \+/- diarrhoea \+/- nausea and vomiting Transaminases may be greatly elevated
What is non-alcoholic steatohepatitis?
Histologically similar to ASH
Usually less severe
Hepatic manifestation of metabolic syndrome
Thought to be most common cause of idiopathic cirrhosis
What are the prehepatic causes of portal hypertension?
Portal vein thrombosis
Stenosis
Compression
What are the intrahepatic causes of portal hypertension?
Perivenular fibrosis Cirrhosis Schistosomiasis Severe steatosis Sarcoidosis
What are the post-hepatic causes of portal hypertension?
Hepatic vein obstruction
Severe right heart failure
Constrictive pericarditis
Of which condition is perivenular fibrosis a feature?
Alcoholic steatohepatitis
What are common benign liver neoplasms?
Hepatic adenoma
Focal nodular hyperplasia (FNH)
Bile duct hamartoma = von Meyenburg complex
Bile duct adenoma = prebiliary gland hamartoma
Cavernous haemangioma
What are common malignant liver neoplasms?
Hepatocellular carcinoma
Cholangiocarcinoma
Angiosarcoma
Metastases
What is the histopathology of hepatocellular carcinoma?
Abnormal architecture - Trabeculae >3 cells thick - Abnormal bile canalicular architecture 50% or less alpha-foetal protein +ve in immunostains Bile production in some
What are the causes of chronic hepatitis?
Chronic viral hepatitis Autoimmune hepatitis (AIH) Drug induced Metabolic - Wilson's disease - Alpha-1 antitrypsin deficiency Idiopathic
What are the causes of acute viral hepatitis?
HAV
HBV
HCV (rare)
HEV
What is the pattern of damage in acute viral hepatitis?
Predominantly lobular inflammation
Hepatocellular injury
What are the causes of chronic viral hepatitis?
HBV
HCV
HDV
What is the pattern of damage in chronic viral hepatitis?
Predominantly portal inflammation
What defines chronic viral hepatitis?
More than 6 months with hepatitis, due to viral infection
What is the clinical presentation of chronic viral hepatitis?
Chronic fatigue
Generally unwell
Poor appetite
Low level nausea
What are the pathological findings in chronic viral hepatitis?
Low level elevation of transaminases
Periportal +/- lobular hepatocellular inflammation and necrosis
Portal fibrosis > cirrhosis
Nodular regeneration
What are some of the complications of chronic viral hepatitis?
Portal HTN
Liver failure
Hepatocellular carcinoma
How is AIH diagnosed?
AutoAbs
Which antibodies are positive in type 1 AIH?
Smooth muscle Abs (SMA) Antinuclear Abs (ANA)
Which antibodies are positive in type 2 AIH?
Liver-kidney microsomal Abs (LKM1)
Which antibodies are positive in type 3 AIH?
Antisoluble liver Ag/liver pancreas Abs (anti-SLA/anti-LP)
What is the treatment for autoimmune hepatitis?
Steroid therapy > good response
What is the histology of autoimmune hepatitis?
Dense periportal inflammation with plasma cells
Lymphocytic piecemeal/bridging necrosis
Milder forms often seen
What is primary biliary cirrhosis?
Non-suppurative autoimmune cholangitis characterised by
- Increased ALP and GGT
- Antimitochondrial Abs (AMA)
- Increased IgM
- Typically affects middle aged females
What is the treatment for primary biliary cirrhosis?
Ursodeoxycholic acid
Poor response to steroids
What is the pathophysiology of primary biliary cirrhosis?
Immune attack on small bile ducts Chronic cholestasis and loss of small bile ducts Variable periportal hepatitis Progression to cirrhosis Overlap syndrome with AIH exists
What is primary sclerosing cholangitis?
Fibrosing and lymphocytic cholangitis > irregular stenoses and strictures
Usually involves intrahepatic and extrahepatic bile ducts
Overlap syndrome with AIH exists
How is primary sclerosing cholangitis diagnosed?
Cholangiography - Irregular strictures and beading - +/- diverticula - Pruned tree Liver biopsy when cholangiography non-diagnostic
What are the histological features of primary sclerosing cholangitis?
Onion skin periductular fibrosis
Loss of bile ducts
What gene defect causes haemochromatosis?
HFE gene defect on ch 6
How is haemochromatosis diagnosed?
Raised serum ferritin Raised serum transferrin saturation Genetic testing: C282Y, H63D Hepatic iron index (HII) Hepatic dry weight iron Liver biopsy
What are the features of a liver biopsy from someone with haemochromatosis?
Fibrosis > cirrhosis
Fe overload in hepatocytes
Hepatocellular carcinoma/precursors may be detected
Negligible inflammation/necrosis
What are common causes of hepatic granulomas and granulomatous hepatitis?
Sarcoidosis
Primary biliary cirrhosis
TB
Drugs
