Mechanisms of Liver Disease 1 and 2 Flashcards
What reversible types of hepatocellular injury?
Ballooning degeneration
Steatosis
Cholestasis
What is ballooning degeneration? What is it indicative of?
Reversible hepatocellular injury
Depletion of cellular ATP with loss of volume control (influx of electrolytes and water)
It is present in many different causes of liver injury
What is steatosis?
Reversible hepatocellular injury
Accumulation of fat triglyceride droplets in hepatocytes
Differentiate between macrosteatosis and microsteatosis
Macrosteatosis - large droplets replacing the nucleus; more common, seen in numerous conditions
Microsteatosis - small droplets that do not replace the nucleus; more rare, seen in pregnancy, Reye’s syndrome
BOTH CAN BE PRESENT IN ONE PATIENT
What’s causing the damage in cholestasis? The bilirubin or bile salts?
BILE SALTS
Bilirubin just causes the yellow discoloration of the skin (jaundice)
What is kernicterus?
Severe complication of UNCONJUGATED hyperbilirubinemia
Free bilirubin crosses blood brain barrier and deposits in basal ganglia
What is “feathery degeneration” of hepatocytes and what is it indicative of?
Feathery degeneration is ballooning of hepatocytes caused by bile salt accumulation seen in cholestasis and its related disorders
What are the three key features seen in obstructive/mechanical cholestasis?
Portal expansion
Bile duct proliferation
Bile plugs
What are irreversible types of hepatocellular injury?
Necrosis
Apoptosis
What are the types of necrosis in hepatocellular injury
Cytolytic - IRREVERSIBLE ballooning of hepatocytes due to defective osmotic regulation –> cell swelling and death
Coagulative - architecture of dead tissue is preserved; results from ischemic damage
What is the difference between confluent necrosis and zonal necrosis?
Confluent = death of GROUPS of adjacent hepatocytes
Zonal = confluent necrosis that exhibits a zonal distribution in the lobule (Zone 3 vs Zone 1, etc.)
What lab tests are indicative of hepatocyte integrity?
AST, ALT, LDH
What lab tests are indicative of biliary function?
Bilirubin
Bile Acids
Cancalicular enzymes: GGT, alk phos
What cells in the liver cause fibrosis?
Stellate cells
What are the most common causes of ACUTE liver failure?
Viral hepatitis (worldwide)
Acetaminophen overdose (USA)
What are the most common causes of CHRONIC liver failure?
Chronic Hepatitis B and C
Non-alcoholic Fatty Liver Disease (NAFLD)
Alcoholic Liver Disease
What is the defining difference between acute and chronic hepatitis in terms of structural change?
Acute: changes are primarily within the lobule
Chronic: changes are primarily within the portal tract (fibrosis!)
If you see chronic hepatitis on histology, what 4 things should be on the differential?
Chronic Viral Hepatitis
Autoimmune Hepatitis
Metabolic Diseases
Drugs
Define the terminology used for describing chronic hepatitis
Limiting plate = hepatocytes at junction of portal tract and lobule
Interface activity (piecemeal necrosis) = inflammation and hepatocellular injury at limiting plate i.e. death of hepatocytes at the junction of portal tract and lobule
Grade = severity of portal and lobular inflammation and cellular injury
Stage = extent of fibrosis
What are the five mechanisms of liver disease?
Steatosis
Iron Overload
Cholestatic Diseases
Vascular Diseases
Nodules and Tumors
What are the main causes of steatosis?
Alcoholic liver disease
Non-alcoholic liver disease (NAFLD)
Ischemia
Inherited Disorders
What are the key histologic features of alcoholic liver disease?
Steatosis with pericentral sinusoidal (“arachnoidal,” “chicken wire”) fibrosis
Mallory-Denk bodies (characteristic but not exclusively seen in alcoholic liver disease) - just eosinophilic looking hyaline in hepatocytes
What zone is most affected in many of the causes of steatosis?
ZONE 3
List the main inherited disorders that can cause steatosis?
Fatty Acid Oxidation Defect
Cystic Fibrosis
What are the main causes of iron overload leading to liver disease?
Hereditary Hemochromatosis
Hemosiderosis (secondary hemochromatosis)
What is the difference between Hereditary Hemochromatosis and Hemisiderosis?
Hereditary hemochromatosis is due to a genetic defect/inherited disorder
Hemochromatosis is iron accumulation due to iron overload, ineffective erythropoiesis, increased oral iron intake, chronic liver disease
What is the main histologic difference between hereditary hemochromatosis and hemosiderosis?
HH - iron accumulation occurs in hepatocytes
Hemosiderosis - iron accumulation in Kupffer cells
Is neonatal hemochromatosis a hereditary hemochromatosis or is it hemosiderosis?
It is a subset of hemosiderosis but it presents a lot like HH: does not have any mutations but fibrosis extends to other parts of the body (heart, lungs, etc.)
What causes neonatal hemochromatosis?
in-utero alloimmune reaction of mother with formation of anti-liver antibodies that destroy the liver
What are the main causes of INTRAHEPATIC cholestasis?
Primary biliary Cirrhosis (PBC)
Biel duct paucity (aka ductopenia)
What are the main causes of EXTRAHEPATIC cholestasis?
Primary Sclerosing Cholangitis
Bile duct stones
Malignancy of head of pancreas
Strictures
Biliary atresia (neonatal)
What is the histologic duct lesion in PBC vs. PSC?
PBC - inflammatory destruction of interlobular bile ducts +/- granulomas
PSC - “onion-skin” inflammation and fibrosis and on ERCP you’ll see BEADING
What are the main serologic differences between PBC and PSC?
PBC = AMA+
PSC = ANCA+
What are the characteristic histologic signs of extrahepatic/obstructive cholestatic disease?
Enlarged portal ducts
Bile duct proliferation
Bile plugging
What is characteristic histology of inflow obstruction (hepatic infarction)
Coagulative type necrosis with a hyperemic rim
Super rare because you would need to occlude both the portal vein and the hepatic artery
What is Budd-Chiari syndrome
Caused by outflow obstruction that spares caudate lobe of the liver
Hepatomegaly, ascites and liver dysfunction
Necrosis of Zone 3 (sometimes 2 but spares 1)
What are benign tumors and tumor-like lesions of liver
Cysts
Mesenchymal tumors
Cholangiocellular
Hepatocellular
What are the main types of benign cysts found in liver?
Echinococcal (major)
Simple cysts and polycystic liver disease
What are the main types of benign mesenchymal tumors found in liver?
Adult: Hemangioma (common, benign)
Child: Infantile hemandioendothelioma (
What are the main types of benign hepatocellular tumors of the liver?
Adenoma (highly associated with OCPs)
Focal nodular hyperplasia
What is fibrolamellar carcinoma?
Type of hepatocellular carcinoma
Better outcome and occurs at younger age
