Pathology of the Liver Flashcards by Aliya Hussain

4 causes of acute liver failure and acute onset of jaundice?

Alcohol
Viruses
Drugs
Bile duct obstruction

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Outcomes of acute liver failure?

Complete regeneration
Chronic liver disease
Death from liver failure

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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

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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)

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What is liver cirrhosis?

Bands of fibrosis separate regenerating nodules of hepatocytes; this is irreversible and a common end-point for liver disease

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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

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What are other causes of portal hypertension?

Budd-chiari syndrome - narrowing and occlusion of the hepatic veins

Portal vein thrombosis

Portal fibrosis in sarcoidosis

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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

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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

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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)

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Histopathological features of alcoholic fatty liver?

Fat vacuoles appear clear in the hepatocytes

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Histopathological features of alcoholic hepatitis?

Hepatocyte necrosis and a neutrophil infiltrate

Mallory bodies (inclusions within cells) and pericellular fibrosis

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Histopathological features of alcoholic fibrosis?

Collagen laid down around cells

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Histopathological features of alcoholic cirrhosis?

Bands of fibrosis separate regenerating nodules of hepatocytes

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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

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Risk factors for NASH?

Diabetes, obesity, hyperlipidaemia

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What is viral hepatitis?

Inflammation of hepatocytes due to viral infection with Hep A-E, EBV, herpes simplex virus and CMV

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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

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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