Mechanisms of Liver Disease 1 and 2

Question 1

What reversible types of hepatocellular injury?

Answer 1

Ballooning degeneration
Steatosis
Cholestasis

Question 2

What is ballooning degeneration? What is it indicative of?

Answer 2

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

Question 3

What is steatosis?

Answer 3

Reversible hepatocellular injury

Accumulation of fat triglyceride droplets in hepatocytes

Question 4

Differentiate between macrosteatosis and microsteatosis

Answer 4

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

Question 5

What’s causing the damage in cholestasis? The bilirubin or bile salts?

Answer 5

BILE SALTS

Bilirubin just causes the yellow discoloration of the skin (jaundice)

Question 6

What is kernicterus?

Answer 6

Severe complication of UNCONJUGATED hyperbilirubinemia

Free bilirubin crosses blood brain barrier and deposits in basal ganglia

Question 7

What is “feathery degeneration” of hepatocytes and what is it indicative of?

Answer 7

Feathery degeneration is ballooning of hepatocytes caused by bile salt accumulation seen in cholestasis and its related disorders

Question 8

What are the three key features seen in obstructive/mechanical cholestasis?

Answer 8

Portal expansion

Bile duct proliferation

Bile plugs

Question 9

What are irreversible types of hepatocellular injury?

Answer 9

Necrosis

Apoptosis

Question 10

What are the types of necrosis in hepatocellular injury

Answer 10

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

Question 11

What is the difference between confluent necrosis and zonal necrosis?

Answer 11

Confluent = death of GROUPS of adjacent hepatocytes

Zonal = confluent necrosis that exhibits a zonal distribution in the lobule (Zone 3 vs Zone 1, etc.)

Question 12

What lab tests are indicative of hepatocyte integrity?

Answer 12

AST, ALT, LDH

Question 13

What lab tests are indicative of biliary function?

Answer 13

Bilirubin
Bile Acids
Cancalicular enzymes: GGT, alk phos

Question 14

What cells in the liver cause fibrosis?

Answer 14

Stellate cells

Question 15

What are the most common causes of ACUTE liver failure?

Answer 15

Viral hepatitis (worldwide)

Acetaminophen overdose (USA)

Question 16

What are the most common causes of CHRONIC liver failure?

Answer 16

Chronic Hepatitis B and C

Non-alcoholic Fatty Liver Disease (NAFLD)

Alcoholic Liver Disease

Question 17

What is the defining difference between acute and chronic hepatitis in terms of structural change?

Answer 17

Acute: changes are primarily within the lobule

Chronic: changes are primarily within the portal tract (fibrosis!)

Question 18

If you see chronic hepatitis on histology, what 4 things should be on the differential?

Answer 18

Chronic Viral Hepatitis

Autoimmune Hepatitis

Metabolic Diseases

Drugs

Question 19

Define the terminology used for describing chronic hepatitis

Answer 19

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

Question 20

What are the five mechanisms of liver disease?

Answer 20

Steatosis

Iron Overload

Cholestatic Diseases

Vascular Diseases

Nodules and Tumors

Question 21

What are the main causes of steatosis?

Answer 21

Alcoholic liver disease

Non-alcoholic liver disease (NAFLD)

Ischemia

Inherited Disorders

Question 22

What are the key histologic features of alcoholic liver disease?

Answer 22

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

Question 23

What zone is most affected in many of the causes of steatosis?

Answer 23

ZONE 3

Question 24

List the main inherited disorders that can cause steatosis?

Answer 24

Fatty Acid Oxidation Defect

Cystic Fibrosis

Question 25

What are the main causes of iron overload leading to liver disease?

Answer 25

Hereditary Hemochromatosis Hemosiderosis (secondary hemochromatosis)

Question 26

What is the difference between Hereditary Hemochromatosis and Hemisiderosis?

Answer 26

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

Question 27

What is the main histologic difference between hereditary hemochromatosis and hemosiderosis?

Answer 27

HH - iron accumulation occurs in hepatocytes Hemosiderosis - iron accumulation in Kupffer cells

Question 28

Is neonatal hemochromatosis a hereditary hemochromatosis or is it hemosiderosis?

Answer 28

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.)

Question 29

What causes neonatal hemochromatosis?

Answer 29

in-utero alloimmune reaction of mother with formation of anti-liver antibodies that destroy the liver

Question 30

What are the main causes of INTRAHEPATIC cholestasis?

Answer 30

Primary biliary Cirrhosis (PBC) Biel duct paucity (aka ductopenia)

Question 31

What are the main causes of EXTRAHEPATIC cholestasis?

Answer 31

Primary Sclerosing Cholangitis Bile duct stones Malignancy of head of pancreas Strictures Biliary atresia (neonatal)

Question 32

What is the histologic duct lesion in PBC vs. PSC?

Answer 32

PBC - inflammatory destruction of interlobular bile ducts +/- granulomas PSC - "onion-skin" inflammation and fibrosis and on ERCP you'll see BEADING

Question 33

What are the main serologic differences between PBC and PSC?

Answer 33

PBC = AMA+ PSC = ANCA+

Question 34

What are the characteristic histologic signs of extrahepatic/obstructive cholestatic disease?

Answer 34

Enlarged portal ducts Bile duct proliferation Bile plugging

Question 35

What is characteristic histology of inflow obstruction (hepatic infarction)

Answer 35

Coagulative type necrosis with a hyperemic rim Super rare because you would need to occlude both the portal vein and the hepatic artery

Question 36

What is Budd-Chiari syndrome

Answer 36

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)

Question 37

What are benign tumors and tumor-like lesions of liver

Answer 37

Cysts Mesenchymal tumors Cholangiocellular Hepatocellular

Question 38

What are the main types of benign cysts found in liver?

Answer 38

Echinococcal (major) Simple cysts and polycystic liver disease

Question 39

What are the main types of benign mesenchymal tumors found in liver?

Answer 39

Adult: Hemangioma (common, benign) Child: Infantile hemandioendothelioma (

Question 40

What are the main types of benign hepatocellular tumors of the liver?

Answer 40

Adenoma (highly associated with OCPs) Focal nodular hyperplasia

Question 41

What is fibrolamellar carcinoma?

Answer 41

Type of hepatocellular carcinoma Better outcome and occurs at younger age