EXAM #2: LIVER PATHOLOGY III Flashcards
Draw the liver acinus and label the zones. What zone of the liver (acinus) is usually affected by drug injury?
Zone 3
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?
- 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
What are the two types of drugs that cause liver injury?
1) Intrinsic
2) Idiosyncratic
What is an intrinsic drug reaction?
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.
What is an idiosyncratic drug reaction?
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.
What is the morphology of the liver injury seen with Tetracycline?
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.
What is the morphology of the liver injury seen with Methothrexate?
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.
What is the morphology of the liver injury seen with Acetaminophen?
Necrosis
*Note that this is the leading cause of drug-induced acute liver failure
What is the morphology of the liver injury seen with Isoniazid?
Hepatitis
What is the morphology of the liver injury seen with Halothane?
Hepatitis
What is the morphology of the liver injury seen with Amiodarone?
Fibrosis
What is the morphology of the liver injury seen with Steroids?
Cholestasis
What is the morphology of the liver injury seen with Erythromycin?
Cholestasis
How much chronic alcohol consumption is required to induce alcoholic liver disease?
Males= more than 80g/day (six drinks)
Females= more than 40 g/day (three drinks)
What is the first pathologic change in the progression toward alcoholic liver disease with simple exposure?
Steatosis i.e. fat accumulation in hepatocytes
What is the first pathologic change in the progression toward alcoholic liver disease with severe exposure (binge drinking)?
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
Is fatty change or steatosis of the liver in alcoholic liver disease reversible?
Yes
What are Mallory Bodies?
Damaged intermediate filaments, or “alcoholic hyalin” acute alcoholic hepatitis
What are the histologic markers of chronic alcoholic liver disease?
Necrosis and fibrosis
*Note that this is long-term, chronic alcohol induced liver damage
What are the morphologic markers of alcoholic cirrhosis?
Extensive fibrosis and regenerative nodules
What cell mediates the inflammatory process seen in alcoholic hepatitis?
Neurtophils
What stain is used to demonstrate fibrosis in alcoholic hepatitis?
Trichrome stain
What are the clinical manifestations of Alcoholic Steatohepatitis?
- Fever
- Leukocytosis
- Jaundice
- AST/ALT elevation
What ratio of AST: ALT is indicate of continued drinking?
2:1 or greater
List the most common causes of death in chronic alcoholism.
1) Hepatic coma
2) Massive GI hemorrhage
3) Infection
4) Hepatorenal Syndrome
What is the alternate name for Nonalcoholic Steatohepatitis? How can you tell this apart from alcohol-related liver disease?
Non-alcoholic fatty liver disease
- ALT will be higher than AST
- Patients commonly asymptomatic
What causes Nonalcoholic Steatophepatitis?
1) Insulin resistance/ metabolic syndrome
2) Drug hepatotoxicity
3) Pregnancy
What two drugs can induce Nonalcoholic Steatohepatits?
Tamoxifen
Nifedipine
What are the symptoms of hepatic vein outflow obstruction?
Ascites Hepatomegaly Abdominal pain AST/ALT elevation Jaundice
*Note that this is what is seen in Budd-Chiari Syndrome
What are the symptoms of impaired intrahepatic blood flow?
Ascites
Esophageal varices
Hepatomegaly
AST/ALT elevation
*Note that this is what is seen in cirrhosis
What are the symptoms of impaired blood inflow to the liver?
Esophageal varices
Splenomegaly
Intestinal congestion
*Note that this is what is seen in hepatic artery compromise or portal vein obstruction.
What are the common etiologies of liver infarct?
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
What causes ischemic hepatitis/ shock liver/ hypoxic hepatitis??
- Left sided heart failure
- Heart surgery
- Shock
What are the manifestations of ischemic hepatitis?
- Centrilobular coagulative necrosis
- ASt/ALT elevation
- Jaundice
What are the extrahepatic etiologies of Portal Vein Thrombosis?
1) Abdominal infection
2) Hypercoaguability
3) Surgery
What are the intrahepatic etiologies of Portal Vein Thrombosis?
1) Cirrhosis
2) Malignancy e.g. HCC
3) Stasis
4) Pregnancy
5) Idiopathic
What are the clinical manifestations of portal vein thrombosis?
1) Abdominal pain
2) Portal HTN
- Esophageal varices
- Splenomegaly
- Ascites
3) Bowel Infarction
What are the etiologies of Hepatic Vein Obstruction?
- Cardiac related
1) Venous congestion
2) Centrolobular hemorrhage
3) Cardiac sclerosis - Budd-Chiari Sydrome
What causes Hepatic Passive Congestion?
- Right heart failure
- Constrictive pericarditis
- Congenital heart disease
What is Budd-Chiari Syndrome?
Thrombosis of the hepatic vein or IVC–prevents the liver from draining
What are the etiologies of Budd-Chiari Syndrome?
1) HCC
2) Abdominal cancer
3) Myeloproliferative disorder
4) PNH
5) Hypercoagulability
6) Pregnancy
7) Contraceptives
What are the clinical features of acute Budd-Chiari Syndrome?
- Abdominal pain
- Hepatomegaly
- Ascites
- Jaundice
- Liver failure
What are the clinical features of chronic Budd-Chiari Syndrome?
- Portal HTN
- Cirrhosis
- Obliterative Hepatocavopathy
What is an Obliterative Hepatocavopathy?
IVC obstruction at its hepatic portion
*Note that this is endemic in Nepal and is suspected to have an infectious etiology
What is Veno-Occlusive Disease of the liver?
Complication following bone marrow transplant or ingestion of plant alkaloids (Jamaican)
- Vasculitis causes sinusoid obstruction
