Pathology of the Liver Flashcards
What are the causes of acute hepatitis?
- Viral (hepatitis A, B, E)
- Drug-induced liver injury
- Autoimmune hepatitis
- No cause can be identified = seronegative
What are some infectious agents that cause hepatitis?
- HAV, HBV and HCV
- Cytomegalovirus
- Epstein-Barr virus
- Herpes simplex virus
What can acute hepatitis progress to?
- Recovery in most cases
- Fulminant hepatitis in rare cases
What can chronic hepatitis progress to?
- Recovery
- Cirrhosis and/or hepatocellular carcinoma
What are the microscopic findings for acute hepatitis?
- Lobular inflammation: Liver lobules are infiltrated by inflammatory cells.
- Hepatocyte injury: swelling (‘ballooning’) or shrinkage and pyknosis (acidophil bodies).
- Severe cases show confluent areas of hepatocyte necrosis.
Describe fulminant hepatitis.
- Rapid progression of acute liver failure.
- > 50% of cases are caused by viral hepatitis.
- Other causes include drugs and toxins
- Characterised by massive liver necrosis, causing jaundice and mental status changes.
List some causes of fulminant hepatitis.
- Acute viral hepatitis
- Drug induced hepatitis
- Circulatory collapse - heart failure, shock (circulatory/septic) with or without DIC
- Rare diseases e.g autoimmune hepatitis
Give some examples of bridging necrosis in hepatitis.
BRIDGING NECROSIS FROM
- Central vein to central vein
- Portal tract to portal traact
- Central vein to portal tract
What are some common causes of chronic hepatitis?
- Chronic Hepatitis B, C and D
- Autoimmune and drug-induced hepatitis
- Cryptogenic hepatitis
- Wilson’s disease
Describe macroscopic and microscopic findings of chronic hepatitis.
- MACROSCOPIC - Liver feels firm due to fibrosis
- Portal inflammation mostly lymphocytes.
- Interface hepatitis (‘piecemeal necrosis’) extension of portal inflammation into hepatocytes at the limiting plate.
- Mild lobular inflammation.
- Fibrosis is a marker of how advanced the disease is.
Describe disease progression of hepatitis.
- ACUTE INFECTION
- ACUTE HEPATITIS
- Most recover - but some develop chronic hepatitis
- Less than 2% recover and 30% return to a healthy carrier state.
- 12-20% have cirrhosis of which some progress to hepatocellular carcinoma
Describe steatosis.
- Fatty change reversible with abstinence.
- Gross appearance: enlarged, yellow, greasy liver.
- Microscopically, the liver initially shows steatosis (reversible) that can progress to fibrosis around the central vein (irreversible)
- Continued exposure leads to cirrhosis and severe exposure leads to hepatitis.
Name the 3 steps of alcoholic liver disease.
- Hepatic steatosis
- Alcoholic hepatitis
- Alcoholic cirrhosis
Describe pathogenesis of alcoholic liver disease.
- Alcohol metabolism in the liver generates high levels of NADH which stimulates fatty acid synthesis and production of triglycerides, leading to steatosis.
- In some individuals, oxidative stress from metabolism of alcohol leads to hepatocyte injury and necro-inflammatory activity (ASH).
- Ongoing necro-inflammatory activity causes liver fibrosis which may progress to cirrhosis.
Describe macroscopic findings of alcoholic liver disease.
- Steatosis causes an enlarged soft greasy liver.
- Alcoholic steatohepatitis may cause a firm texture due to fibrosis in the liver.
- Cirrhosis causes diffuse nodularity of the liver.
Describe microscopic appearances of alcoholic liver disease. PART 1
- Steatosis shows large droplets of fat in hepatocytes, which displace the nucleus to one side (macrovesicular steatosis).
- ASH shows ballooned hepatocytes which may contain Mallory’s hyaline (clumps of dense pink material) and an inflammatory infiltrate rich in neutrophils.
Describe microscopic appearances of alcoholic liver disease. PART 2
- Fibrosis in ASH is typically perivenular.
- Cirrhosis shows diffuse replacement of the liver by nodules of regenerating hepatocytes surrounded by fibrous bands.
Describe pathogenesis of cirrhosis.
- Activation of stellate cells into myofibroblast-like cells induced by alcohol
Define cirrhosis.
- End-stage liver disease
- Characterized by disruption of the liver architecture by bands of fibrosis
- Bands divide the liver into nodules of regenerating liver parenchyma.
List some causes of cirrhosis.
- Alcohol
- Chronic hepatitis - autoimmune, viral or drug-induced
- Biliary diseases e.g extrahepatic biliary obstruction
- Metabolic diseases e.g glycogen storage or Wilson disease
- Cryptogenic causes
Describe cirrhosis pathogenesis.
- Liver cell necrosis
- Inflammation and hepatocyte regulation
- FIBROSIS occurs
- Destruction of normal liver architecture - leading to nodule formation
What are the types of cirrhosis?
MACRONODULAR
MICRONODULAR
MIXED
Describe microscopic appearance of cirrhosis.
- Entire liver replaced by nodules of regenerating hepatocytes surrounded by fibrous bands.
- Bands contain a variable inflammatory infiltrate and reactive bile ductular proliferation.
What can cirrhosis progress to?
- Portal hypertension - leading to ascites, congestive splenomegaly and portosystemic shunts
- Reduced detoxification - leading to reduced osterogen metabolism leading to hyperestrogenima leading to gynecomastia, spider angioma and palmar erythema
What factors can lead to ascites?
- Portal hypertension induced by cirrhosis
- Reduced protein synthesis induced by cirrhosis - hypoalbuminemia and reduced plasma osmotic pressure leading to transudation
- Splanchnic vasodilation - reduced RBF and RAAS activates leading to H2O and Na+ retention
