Histopathology - Liver pathology

Question 1

What changes occur during liver injury?

Answer 1

Loss of hepatocyte microvilli

Activated stellate cells

Deposition of scar matrix

Loss of fenestrae

Kupffer cell activation

Question 2

Definition of cirrhosis

Answer 2

1. whole liver involved
2. fibrosis
3. nodules of regenerating hepatocytes
4. distortion of liver vascular architecture:

intra- (blood goes through the liver but doesn’t get filtered) and extra- hepatic (e.g. gastro-oesophageal -> varices) shunting of blood

Question 3

How is cirrhosis classified?

Answer 3

According to nodule size: micronodular or macronodular

According to aetiology: fatty liver disease (alcohol/insulin resistance) or viral hepatitis

*Alcohol tends to produce a micronodular cirrhosis whereas viral hepatitis tends to cause macronodular cirrhosis*

Question 4

Complications of cirrhosis

Answer 4

Portal hypertension

Hepatic encephalopathy

Liver cell cancer

Question 5

Is cirrhosis reversible?

Answer 5

Potentially (recent discovery) - if the aetiology is aggressively treated

Question 6

Difference between acute and chronic hepatitis

Answer 6

Less than 6 months vs more than 6 months

Acute is caused by viruses (including A and E) and drugs

Chronic is caused by viruses (excluding A and E), drugs and autoimmune disease

Question 7

Histological feature of acute hepatitis

Answer 7

Spotty necrosis

Question 8

What is the grade and stage of chronic hepatitis?

Answer 8

Grade = severity of inflammation

Stage = severity of fibrosis

Like cancer, the stage is more important than the grade for assessing prognosis

Question 9

Histological features of chronic hepatitis

Answer 9

Piecemeal necrosis (actually apoptosis), hepatocyte necrosis, fibrosis, nodules of regenerating hepatocytes

Portal inflammation -> interface inflammation -> lobular inflammation -> bridging from portal vein to central vein (critical stage for evolution of hepatitis into cirrhosis)

Question 10

What is the difference between portal and interface inflammation?

Answer 10

Interface inflammation involves damage to the hepatocytes

Cannot see the border between portal tract and parenchyma

Question 11

What are the stages of alcoholic liver disease?

Answer 11

Fatty liver (reversible)

Alcoholic hepatitis

Cirrhosis (micronodular)

Question 12

Features of alcoholic hepatitis

Answer 12

Ballooning (+/- Mallory Denk Bodies - balloon cells containing Mallory hyaline)

Fat

Pericellular fibrosis

Mainly seen in Zone 3 (centrilobular)

Question 13

Characteristics of NAFLD

Answer 13

NAFLD includes NASH

Histologically looks like alcoholic liver disease

Due to insulin resistance associated with high BMI and diabetes

Question 14

Characteristics of PBC

Answer 14

Now called primary biliary CHOLANGITIS (many patients don’t actually have cirrhosis)

F > M

Bile duct loss associated with chronic inflammation (may be granulomatous destruction)

Diagnostic test is detection of anti-mitochondrial antibodies

Question 15

Characteristics of PSC

Answer 15

Primary sclerosing cholangitis (sclerosing means increasing thickness)

M > F (small difference)

Periductal bile fibrosis leading to loss

Associated with UC

Increased risk of cholangiocarcinoma

Diagnostic test is bile duct imaging

Question 16

Characteristics of haemochromatosis

Answer 16

Genetically determined increased gut iron absorption

Gene on chromosome 6 affected (HFe)

Parenchymal damage to organs secondary to iron deposition - bronzed diabetes

Question 17

What is haemosiderosis?

Answer 17

Iron accumulates in macrophages

Not a genetic condition -> it’s caused by blood transfusions

*Unlike hepatocytes, macrophages/Kupffer cells know how to store iron so there isn’t really liver damage*

Question 18

Characteristics of Wilson’s disease

Answer 18

Accumulation of copper due to failure of excretion by hepatocytes into the bile

Assessed by biopsy or biochemistry

Genes on chromosome 13

Accumulates in the liver and CNS (hepato-lenticular degeneration)

Kayser-Fleishcer rings in the eyes

Question 19

Which stain is used for copper to diagnose Wilson’s disease?

Answer 19

Rhodanine stain

Question 20

Characteristics of autoimmune hepatitis

Answer 20

F>M

Active chronic hepatitis with plasma cells

Anti-smooth muscle actin antibodies in the serum

Responds to steroids

Question 21

Characteristics of alpha-one anti-trypsin deficiency

Answer 21

Failure to secrete alpha-one antitrypsin

Intra-cytoplasmic inclusions due to misfolded protein

Hepatitis and cirrhosis

Question 22

What types of liver disease can be caused by drugs

Answer 22

Any type - hepatocellular and/or cholestatic

*May be dose-related or idiosyncratic*

Question 23

Causes of hepatic granulomas

Answer 23

Specific causes: PBC, drugs

General causes: TB, Sarcoid etc

Question 24

What are the benign liver tumours?

Answer 24

1) liver cell adenoma 2) bile duct adenoma 3) haemangioma

Question 25

What are the malignant liver tumours?

Answer 25

1) secondary tumours
2) primary tumours:

hepatocellular carcinoma

hepatoblastoma

cholangiocarcinoma

haemangiosarcoma

Question 26

What are the causes of liver cell cancer?

Answer 26

Usually associated with cirrhosis, especially in the West

Question 27

What are the risk factors for cholangiocarcinoma?

Answer 27

Associated with:

PSC

Worm infections

Cirrhosis

Can arise from:

intrahepatic ducts

extrahepatic ducts (including gall bladder)

Question 28

Most common carcinoma seen in the liver

Answer 28

Metastatic adenocarcinoma (from stomach, colon etc.)

Question 29

Which of the following cause fatty changes to the liver?

Alcohol

Diabetes

Hepatitis B

Hepatitis C

Answer 29

Alcohol and diabetes