L34. Patterns of Liver Injury 1: Acute Hepatitis

Question 1

What is the clinical definition of acute hepatitis?

Answer 1

Elevation of serum transaminase enzymes (ALT) for a period of less than 6 months duration

Question 2

What are some clinical signs of acute hepatitis?

Answer 2

Malaise
Nausea
Jaundice
With hepatic profile of abnormal liver biochemistry

Question 3

Are biopsies normally done for patients with acute hepatitis?

Answer 3

No

Unless - severe, uncertain cause or concern of a flare up of chronic liver disease

Question 4

What are the three possible underlying pathology of clinical acute hepatitis?

Answer 4

Acute hepatitis
Chronic liver disease (including alcoholic liver disease)
Diffuse malignant infiltration (rare)

Question 5

What is the pathological definition of acute hepatitis?

Answer 5

Pathological changes in the liver that resemble (and include) acute viral hepatitis

Question 6

Acute hepatitis is a NON-SPECIFIC PATTERN of liver injury shared by many different causes (look similar under the microscope). What are these causes?

Answer 6

Acute viral hepatitis: A, B, E 
Drug induced liver injury
"Natural" remidies
Autoimmune hepatitis
Idiopathic

Question 7

What are the hallmark features of acute inflammation?

Answer 7

Death of hepatocytes (by BOTH necrosis and apoptosis)
Diffuse injury (no acute polymorph inflammation)
Regeneration of hepatocytes
Absence of fibrosis

Question 8

What zones do hepatocellular insults preferentially affect?

Answer 8

Zone 3 is the vulnerable zone

- caused by hypoxia, metabolic disorders, toxins, drugs and inflammatory conditions

Question 9

describe the reversible vs. irreversible stages of acute hepatocellular injury

Answer 9

Reversible: swelling (ballooning, hydrophobic degeneration), impaired excretion of bile (cholestasis)

Irreversible: necrosis and apotosis

Question 10

How is there both apoptosis and necrosis in hepatocellular injury?

Answer 10

Single death is by apoptosis (apoptotic bodies) while death of groups of adjacent hepatocytes is necrosis

Question 11

What are the four steps of acute hepatitis hepatocellular injury?

Answer 11

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

Question 12

Is the necrosis in acute hepatitis coagulative?

Answer 12

NO

Question 13

How is necrosis in the liver occurring? What can be seen?

Answer 13

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

Question 14

Describe the macroscopic changes in the liver seen in acute hepatitis

Answer 14

reddish brown areas of necrosis and collapsed liver
yellow nodules showing regenerating groups of hepatocytes
wrinkled capsules

Question 15

What is lobular disarray seen in acute hepatitis?

Answer 15

Disruption of the hepatocelular plates and hepatocyte swelling

Question 16

What is cholestasis and how are they generally formed?

Answer 16

Bile accumulates in bile canilliculi

Usually formed by swelling of hepatocytes causing strictures and obstructions in the bile ducts

Question 17

What are the major sequelae [3] of acute hepatitis?

Answer 17

1. Resolution with restoration
2. Massive hepatic necrosis (death or transplant)
3. Chronic hepatitis

Question 18

Paracetamol induced liver necrosis produces what kind of necrosis?

Answer 18

Zonal necrosis rather than pan-lobular changes of acute hepatitis

Question 19

How does paracetamol cause liver hepatocyte damage?

Answer 19

Paracetamol has a toxic metabolite NAPQI which directly injures hepatocytes and causes depletion of a natural anti-oxidant (glutathione)

Question 20

Why does paracetamol induced necrosis prefentially occur in zone three?

Answer 20

Because the enzyme CYP2E1 is located here and is what breaks down the toxin

Question 21

Is lobular disarray seen in paracetamol induced liver necrosis?

Answer 21

No mainly only necrosis or hepatocytes involving zone three.

Question 22

Is necrosis coagulative in paracetamol induced liver necrosis?

Answer 22

Yes

Question 23

Is inflammation present in paracetamol induced liver necrosis?

Answer 23

It is minimal compared with acute hepatitis