EXAM #2: LIVER PATHOLOGY III

Question 1

Draw the liver acinus and label the zones. What zone of the liver (acinus) is usually affected by drug injury?

Answer 1

Zone 3

Question 2

Why is the centrilobular region (center of the liver lobule, i.e. the central vein) or zone 3 the most affected by toxic drug effects?

Answer 2

• Drug biotransformation occurs in the mitochondria of the liver acinus/lobule
• Mitochondria require oxygen
• Zone 3 has the lowest oxygen content as it is farthest from the portal triad carrying incomin-oxygenated blood

Question 3

What are the two types of drugs that cause liver injury?

Answer 3

1) Intrinsic

2) Idiosyncratic

Question 4

What is an intrinsic drug reaction?

Answer 4

This is a predictable drug reaction that occurs in response to sufficient quantity of a hepatotoxic agent e.g. Tylenol

Note that this type of reaction is dose-dependent and acute.

Question 5

What is an idiosyncratic drug reaction?

Answer 5

This is an unpredictable drug reaction that is dependent on the genetic susceptibility of the host.

Note that this type of reaction is dose-independent and has a variable (though commonly subacute) onset.

Question 6

What is the morphology of the liver injury seen with Tetracycline?

Answer 6

Microsteatosis

This is the abnormal retention of lipids within a cell. Micro simply refers to the fact that the lipid filled vesicles that accumulate do NOT distort the nucleus.

Question 7

What is the morphology of the liver injury seen with Methothrexate?

Answer 7

Macrosteatosis

This is the abnormal retention of lipids within a cell. Macro simply refers to the fact that the lipid filled vesicles that accumulate DO distort the nucleus.

Question 8

What is the morphology of the liver injury seen with Acetaminophen?

Answer 8

Necrosis

*Note that this is the leading cause of drug-induced acute liver failure

Question 9

What is the morphology of the liver injury seen with Isoniazid?

Answer 9

Hepatitis

Question 10

What is the morphology of the liver injury seen with Halothane?

Answer 10

Hepatitis

Question 11

What is the morphology of the liver injury seen with Amiodarone?

Answer 11

Fibrosis

Question 12

What is the morphology of the liver injury seen with Steroids?

Answer 12

Cholestasis

Question 13

What is the morphology of the liver injury seen with Erythromycin?

Answer 13

Cholestasis

Question 14

How much chronic alcohol consumption is required to induce alcoholic liver disease?

Answer 14

Males= more than 80g/day (six drinks)

Females= more than 40 g/day (three drinks)

Question 15

What is the first pathologic change in the progression toward alcoholic liver disease with simple exposure?

Answer 15

Steatosis i.e. fat accumulation in hepatocytes

Question 16

What is the first pathologic change in the progression toward alcoholic liver disease with severe exposure (binge drinking)?

Answer 16

Hepatitis–results from chemical injury to hepatocytes

*Note that the toxic effects of alcohol on the liver are specifically mediated by the toxic metabolite, acetaldehyde

Question 17

Is fatty change or steatosis of the liver in alcoholic liver disease reversible?

Answer 17

Yes

Question 18

What are Mallory Bodies?

Answer 18

Damaged intermediate filaments, or “alcoholic hyalin” acute alcoholic hepatitis

Question 19

What are the histologic markers of chronic alcoholic liver disease?

Answer 19

Necrosis and fibrosis

*Note that this is long-term, chronic alcohol induced liver damage

Question 20

What are the morphologic markers of alcoholic cirrhosis?

Answer 20

Extensive fibrosis and regenerative nodules

Question 21

What cell mediates the inflammatory process seen in alcoholic hepatitis?

Answer 21

Neurtophils

Question 22

What stain is used to demonstrate fibrosis in alcoholic hepatitis?

Answer 22

Trichrome stain

Question 23

What are the clinical manifestations of Alcoholic Steatohepatitis?

Answer 23

• Fever
• Leukocytosis
• Jaundice
• AST/ALT elevation

Question 24

What ratio of AST: ALT is indicate of continued drinking?

Answer 24

2:1 or greater

Question 25

List the most common causes of death in chronic alcoholism.

Answer 25

1) Hepatic coma 2) Massive GI hemorrhage 3) Infection 4) Hepatorenal Syndrome

Question 26

What is the alternate name for Nonalcoholic Steatohepatitis? How can you tell this apart from alcohol-related liver disease?

Answer 26

Non-alcoholic fatty liver disease - ALT will be higher than AST - Patients commonly asymptomatic

Question 27

What causes Nonalcoholic Steatophepatitis?

Answer 27

1) Insulin resistance/ metabolic syndrome 2) Drug hepatotoxicity 3) Pregnancy

Question 28

What two drugs can induce Nonalcoholic Steatohepatits?

Answer 28

Tamoxifen | Nifedipine

Question 29

What are the symptoms of hepatic vein outflow obstruction?

Answer 29

``` Ascites Hepatomegaly Abdominal pain AST/ALT elevation Jaundice ``` *Note that this is what is seen in Budd-Chiari Syndrome

Question 30

What are the symptoms of impaired intrahepatic blood flow?

Answer 30

Ascites Esophageal varices Hepatomegaly AST/ALT elevation *Note that this is what is seen in cirrhosis

Question 31

What are the symptoms of impaired blood inflow to the liver?

Answer 31

Esophageal varices Splenomegaly Intestinal congestion *Note that this is what is seen in hepatic artery compromise or portal vein obstruction.

Question 32

What are the common etiologies of liver infarct?

Answer 32

This is rare b/c of the livers dual blood supply, but when it does happen it is caused by: 1) Liver transplant 2) Chemoembolism 3) Polyarteritis nodosa 4) Surgery

Question 33

What causes ischemic hepatitis/ shock liver/ hypoxic hepatitis??

Answer 33

- Left sided heart failure - Heart surgery - Shock

Question 34

What are the manifestations of ischemic hepatitis?

Answer 34

- Centrilobular coagulative necrosis - ASt/ALT elevation - Jaundice

Question 35

What are the extrahepatic etiologies of Portal Vein Thrombosis?

Answer 35

1) Abdominal infection 2) Hypercoaguability 3) Surgery

Question 36

What are the intrahepatic etiologies of Portal Vein Thrombosis?

Answer 36

1) Cirrhosis 2) Malignancy e.g. HCC 3) Stasis 4) Pregnancy 5) Idiopathic

Question 37

What are the clinical manifestations of portal vein thrombosis?

Answer 37

1) Abdominal pain 2) Portal HTN - Esophageal varices - Splenomegaly - Ascites 3) Bowel Infarction

Question 38

What are the etiologies of Hepatic Vein Obstruction?

Answer 38

- Cardiac related 1) Venous congestion 2) Centrolobular hemorrhage 3) Cardiac sclerosis - Budd-Chiari Sydrome

Question 39

What causes Hepatic Passive Congestion?

Answer 39

- Right heart failure - Constrictive pericarditis - Congenital heart disease

Question 40

What is Budd-Chiari Syndrome?

Answer 40

Thrombosis of the hepatic vein or IVC--prevents the liver from draining

Question 41

What are the etiologies of Budd-Chiari Syndrome?

Answer 41

1) HCC 2) Abdominal cancer 3) Myeloproliferative disorder 4) PNH 5) Hypercoagulability 6) Pregnancy 7) Contraceptives

Question 42

What are the clinical features of acute Budd-Chiari Syndrome?

Answer 42

- Abdominal pain - Hepatomegaly - Ascites - Jaundice - Liver failure

Question 43

What are the clinical features of chronic Budd-Chiari Syndrome?

Answer 43

- Portal HTN - Cirrhosis - Obliterative Hepatocavopathy

Question 44

What is an Obliterative Hepatocavopathy?

Answer 44

IVC obstruction at its hepatic portion *Note that this is endemic in Nepal and is suspected to have an infectious etiology

Question 45

What is Veno-Occlusive Disease of the liver?

Answer 45

Complication following bone marrow transplant or ingestion of plant alkaloids (Jamaican) - Vasculitis causes sinusoid obstruction