Liver Path 3 - SRS Flashcards
Autoimmune hepatitis involves injury to normal hepatocytes by infiltrating T cells and plasma cells leading to fibrosis/cirrhosis. Lab tests for what characteristic antibodies are useful?
In addition to the antibodies, what else can you look for?
- Anti-nuclear antibodies
- Anti-smooth (actin) muscle antibodies
Also, look for high levels of polyclonal IgG
Autoimmune hepatitis is a chronic disease but is typicaly highly responsive to what two drugs?
Immunosuppression by prednisone and azathioprine
Are antimitochondrial antibodies found in autoimmune hepatitis?
Not usually.
These are more often seen in primary biliary cirrhosis.
In what patients is autoimmune hepatitis most common?
Is there a genetic association?
Young women.
Yes, HLA-DR in caucasians
What are the two types of autoimmune hepatitis?
Type 1
Type 2
What is the typical population affected by type 1 autoimmune hepatitis?
What antibodies are associated with type 1?
- Middle-aged women
- Antibodies include
- Antinuclear (ANA)
- Anti-smooth muscle (actin) antibodies (ASMA)
- pANCA
What is the typical population affected by type 2 autoimmune hepatitis?
What antibodies are associated with type 2?
–children or teenagers (mostly female)
–associated with anti-liver kidney microsomal antibodies (anti-LKM1)
Autoimmune hepatitis shares patterns of injury with acute or viral chronic hepatitis.
What are the features considered typical of autoimmune hepatitis?
–Extensive interface hepatitis
–Plasma cell predominance in the mononuclear inflammatory infiltrates
What do you see here in this sample?
What is going on with this patient?
Autoimmune hepatitis
Active interface hepatitis with numerous plasma cells in the portal inflammatory infiltrate and extending into the adjacent hepatic parenchyma are shown.
In both types of autoimmune hepatitis either an indolent or aggressive course may occur. What is the likely outcome in untreated?
Liver fails
What is a major component of the inflammatory infiltrate seen in autoimmune hepatitis?
plasma cells
What is the most common cause of acute liver failure in the US?
Tylenol
What are some examples of drug induced liver injuries?
- Bile duct injury
- Steatosis and steatohepatitis
- Vascular injury/veno-occlusive disease
- Neoplasms
What are three mechanisms by which drugs/chemicals can cause hepatic injury?
- Direct toxicity
- Hepatic conversion to a toxic form
- Immune mechanisms - agent acts as hapten
What are two common patterns of drug/toxin mediated hepatic injury?
Periportal region
pericentral region
If the periportal region is damaged, what processes are impaired?
Gluconeogenesis
Cholesterol synthesis
Urea synthesis
If the pericentral region is damaged, what are processes suffer as a result? 5
- Glycolysis
- bile acid synthesis
- glutamine synthesis
- drug metabolism
- p450-dependent bioactivation
What zone is the periportal zone?
Zone 1
What else is zone 3 called?
Perivenular region
What zone is the most common for zonal necrosis to occur?
Identify the toxins that are associated with this.
Zone 3
Acetaminophen
Bromobenzene
CCL4
CHCL3
copper salts
pyrrolizidine alkaloids
tannic acid
amanita phalloides toxins
What are some agents that characteristically produce periportal necrosis?
phosphorous
ferrous sulfate
Concentrated acetic acid
proteus vulgaris endotoxin
halothane
Except in rare cases of drug induced chronic hepatitis, the liver injury subsides and disappears after what?
Cessation of exposure/treatment to/with offending drug
What drug is particularly associated with hepatocellular injury?
Acetaminophen
What drug is associated with autoimmune hepatocellular injury?
halothane hepatitis
What drug is associated with cholestatic liver injury?
Estrogen
Acetaminophen is now the most common cause of acute liver failure necessitating transplantation in the United States.
What is the toxicity from?
What greatly enhances the toxicity?
Metabolic by-product (NAPQI)
Concurrent ETOH consumption