Flashcards in L34. Patterns of Liver Injury 1: Acute Hepatitis Deck (23)
What is the clinical definition of acute hepatitis?
Elevation of serum transaminase enzymes (ALT) for a period of less than 6 months duration
What are some clinical signs of acute hepatitis?
With hepatic profile of abnormal liver biochemistry
Are biopsies normally done for patients with acute hepatitis?
Unless - severe, uncertain cause or concern of a flare up of chronic liver disease
What are the three possible underlying pathology of clinical acute hepatitis?
Chronic liver disease (including alcoholic liver disease)
Diffuse malignant infiltration (rare)
What is the pathological definition of acute hepatitis?
Pathological changes in the liver that resemble (and include) acute viral hepatitis
Acute hepatitis is a NON-SPECIFIC PATTERN of liver injury shared by many different causes (look similar under the microscope). What are these causes?
Acute viral hepatitis: A, B, E
Drug induced liver injury
What are the hallmark features of acute inflammation?
Death of hepatocytes (by BOTH necrosis and apoptosis)
Diffuse injury (no acute polymorph inflammation)
Regeneration of hepatocytes
Absence of fibrosis
What zones do hepatocellular insults preferentially affect?
Zone 3 is the vulnerable zone
- caused by hypoxia, metabolic disorders, toxins, drugs and inflammatory conditions
describe the reversible vs. irreversible stages of acute hepatocellular injury
Reversible: swelling (ballooning, hydrophobic degeneration), impaired excretion of bile (cholestasis)
Irreversible: necrosis and apotosis
How is there both apoptosis and necrosis in hepatocellular injury?
Single death is by apoptosis (apoptotic bodies) while death of groups of adjacent hepatocytes is necrosis
What are the four steps of acute hepatitis hepatocellular injury?
1. Single cell apoptosis
2. Zonal necrosis (staring in zone 3 around the central vein)
3. Bridging necrosis (from the central vein to portal triads)
4. Multi-acinar necrosis
Is the necrosis in acute hepatitis coagulative?
How is necrosis in the liver occurring? What can be seen?
Severe, osmotic failure and bursting (lysis) - we don't normally see the necrotic cells themselves; rather see the aftermath (collapse of liver reticulin framework) and presence of scavenger macrophages
Describe the macroscopic changes in the liver seen in acute hepatitis
reddish brown areas of necrosis and collapsed liver
yellow nodules showing regenerating groups of hepatocytes
What is lobular disarray seen in acute hepatitis?
Disruption of the hepatocelular plates and hepatocyte swelling
What is cholestasis and how are they generally formed?
Bile accumulates in bile canilliculi
Usually formed by swelling of hepatocytes causing strictures and obstructions in the bile ducts
What are the major sequelae  of acute hepatitis?
1. Resolution with restoration
2. Massive hepatic necrosis (death or transplant)
3. Chronic hepatitis
Paracetamol induced liver necrosis produces what kind of necrosis?
Zonal necrosis rather than pan-lobular changes of acute hepatitis
How does paracetamol cause liver hepatocyte damage?
Paracetamol has a toxic metabolite NAPQI which directly injures hepatocytes and causes depletion of a natural anti-oxidant (glutathione)
Why does paracetamol induced necrosis prefentially occur in zone three?
Because the enzyme CYP2E1 is located here and is what breaks down the toxin
Is lobular disarray seen in paracetamol induced liver necrosis?
No mainly only necrosis or hepatocytes involving zone three.
Is necrosis coagulative in paracetamol induced liver necrosis?