Liver pathology

Question 1

Zones of liver and diseases affecting each zone

Answer 1

1. Periportal: viral hepatitis
2. Midzonal: yellow fever
3. Centrilobular:
   • alcohol
   • acetaminophen toxicity
   • CVC
   • ischemia
   • Budd Chiari syndrome

Question 2

Zones of liver most susceptible to toxin induced & ischemic damage respectively

Answer 2

To toxin induced damage: zone 1 
 Periportal area (like viral hepatitis)

To ischemic damage: zone 3
(Centrilobular area)

Question 3

Space of Disse

Answer 3

Space between hepatocytes and lining of sinusoids

1. Vitamin A storage
2. Ito cells/ Stellate cells- fibrosis in cirrhosis
3. Amyloid is first seen here

Question 4

Canals of Herring

Kupffer cells

Answer 4

Present between hepatocytes
Contain oval cells/stem cells of liver
Kupffer cells (macrophages) are located in the sinusoids

Question 5

Cirrhosis

Answer 5

End stage liver disease
Characterised by:
1. Disruption of liver architecture
2. Regenerating parenchymal nodules
3. Bridging fibrous septae 
Types: 3mm
1. Micronodular
2. Macronodular

Question 6

Micronodular cirrhosis

Answer 6

<3 mm

1. Early ALD
2. Hemochromatosis
3. 1° biliary cirrhosis
4. Indian childhood cirrhosis

Question 7

Macronodular cirrhosis

Answer 7

> 3 mm

1. Late ALD
2. Wilson’s disease
3. α-1 antitrypsin deficiency
4. Viral hepatitis
5. Drugs and toxins

Question 8

Causes of cirrhosis

Answer 8

1. Alcoholic liver disease
2. Non-alcoholic steatohepatitis NASH
3. Metabolic disorders:
   • α-1 antitrypsin deficiency
   • Wilson’s disease
   • Hemochromatosis
4. Viral hepatitis
5. Autoimmune hepatitis
6. Drugs and chemicals
7. Biliary diseases

Question 9

Pathogenesis of cirrhosis

Answer 9

Hallmark: capillarisation of sinusoids
Normal liver:
Type 1 and 3 collagen - periportal and centrilobular area
Type 4 collagen - space of Disse
In cirrhosis: type 1 and 3 collagen occupies space of Disse ➡️
loss of fenestrations of sinusoids ➡️
capillarisation of sinusoids

Question 10

Minimum amount of alcohol that can cause alcoholic liver disease

Answer 10

60-80 ml/day for 10 years

Question 11

Alcoholic liver disease gross features

Answer 11

Soft, yellow, greasy

Question 12

Manifestations of alcoholic liver disease

Answer 12

1. Steatosis
• Fatty liver
• Reversible
• starts in centrilobular area (zone-3)
• micro or macrovesicular
2. Hepatitis
3. Cirrhosis:
• Irreversible
• Fibrosis seen

Question 13

Features of hepatitis of alcoholic liver disease

Answer 13

1. Hepatocyte swelling ➡️
2. Ballooning degeneration
3. Neutrophilic infiltrate
4. Mallory hyaline bodies
5. Some fibrosis

Question 14

Laennac cirrhosis

Answer 14

End stage of alcoholic liver disease

Liver is reduced to a fibrotic scar

Question 15

Mallory hyaline bodies
Mallory deny bodies
composed of

Answer 15

Composed of intermediate filaments like CK8, CK18

Question 16

Mallory denk bodies or
Mallory hyaline bodies
are seen in

Answer 16

New. NASH
Indian. childhood cirrhosis
W. Wilson’s disease
A. Alcoholic liver disease
T. Tumours like HCC
C. Cirrhosis, 1° biliary
H. Hyperplasia, focal nodular 
Not present in: hemochromatosis and 1° sclerosing cholangitis

Question 17

Microvesicular steatosis is seen in

Answer 17

D. Drugs and toxins
A. Acute fatty liver of pregnancy 🤰
R. Reye’s syndrome
E. Early alcoholic liver disease

Question 18

Macrovesicular steatosis is seen in

Answer 18

C. Chronic hepatitis C
L. Late alcoholic liver disease
O. Obesity 
N. NASH
E. PEM

Question 19

NASH

Non Alcoholic Steatohepatitis

Answer 19

Features similar to ASH, except no history of alcohol
Seen in:
1. Obesity
2. Metabolic syndrome
3. Insulin resistance

Question 20

Differences between alcoholic steatohepatitis and NASH

Answer 20

ASH has prominent Mallory hyaline bodies and inflammation (with neutrophils) compared to NASH
Macrophages are predominant in NASH
Perisinusoidal damage is predominant in ASH, unlike periportal damage in NASH

Question 21

Reye’s syndrome

Answer 21

Rare disorder
When children suffering from viral illness is treated with aspirin ➡️ severe mitochondrial dysfunction
On H&E, extensive microvesicular steatosis
Clinically, 
1. Rash
2. Vomiting 🤮 
3. Hypoglycaemia
4. Hepatic encephalopathy

Question 22

Haemochromatosis

Answer 22

Excessive iron overload
M/C metabolic cause of liver cirrhosis 
Autosomal recessive
Common pathogenesis:
1. Mutation of HPE gene on chr 6p
2. Decreased hepcidin
3. Increased iron
Treatment: phlebotomy
DoC: Desferoxamine (chelator)

Question 23

Causes of hemochromatosis

Answer 23

Hereditary:
1. HFE gene mutation on chr 6p
2. HAMP gene
3. HJV juvenile hemochromatosis
Secondary:
1. Repeated blood transfusions
2. Bantu siderosis (iron 🍽)

Question 24

Hemochromatosis

clinical features

Answer 24

Clinical triad: 
1. Liver: micronodular cirrhosis (M/C and earliest organ affected)
2. Pancreas: DM
3. Skin: brown due to melanin (> hemosiderin)
Bronze diabetes, 2. and 3. together
4. Restrictive or dilated cardiomyopathy
5. Testicular abnormalities
6. Joint involvement
7. Risk of HCC

Question 25

Lab diagnosis of hemochromatosis

Answer 25

1. Serum iron increases 2. Serum ferritin increases 3. Serum transferrin saturation increases 4. Serum TIBC decreases Liver biopsy: 1. Brownish pigmentation-hemosiderin 2. Micronodular cirrhosis 3. On Prussian blue, bluish iron deposits can be seen

Question 26

Wilson’s disease | pathogenesis

Answer 26

Excessive copper accumulation Autosomal recessive Pathogenesis: 1. Mutation of ATP7B gene on chr 13q 2. Defect in incorporation of copper into ceruloplasmin 3. Increased accumulation of copper in tissues 4. Wilson’s disease

Question 27

Wilson’s disease | clinical manifestations

Answer 27

1. Liver - cirrhosis 2. Eye 👁: Kayser Fleisher ring Brownish discolouration of Descemet’s membrane of cornea 3. Brain 🧠: putamen and basal ganglia are affected ➡️ neuropsychiatric manifestations

Question 28

Wilson’s disease | diagnosis and treatment

Answer 28

1. Increased copper levels 2. Decreased ceruloplasmin Liver biopsy: • Stain for Cu: Rhodamine, Rubeanic acid • Stain for ceruloplasmin: orcein Most sensitive: increased urinary Cu excretion Treatment: copper chelators

Question 29

α1-Antitrypsin deficiency | basics and clinical manifestations

Answer 29

Autosomal recessive Pathogenesis: deficiency of α1-Antitrypsin ➡️ elastase activity increases ➡️: 1. Lung: panacinar emphysema 2. Liver: cirrhosis

Question 30

α1-Antitrypsin deficiency | genetics and microscopy

Answer 30

``` Genetics: 1. PiMM - normal 2. PiMZ - heterozygous 3. PiZZ - α1-Antitrypsin deficiency Microscopy: 1. Steatosis 2. Cytoplasmic globules in periportal area: PAS +ve Diastase resistant ```

Question 31

Hepatitis viruses | types

Answer 31

``` A. Picorna Faeco-oral 2-6 weeks B. Hepadna, the only DNA virus C. Flavi D. Delta E. Hep E virus Faeco-oral 4-5 weeks Maximum mortality in pregnancy 🤰 ```

Question 32

Common features among hepatitis B, C and D viruses

Answer 32

Parenteral, vertical and sexual transmission 2-26 weeks gestation B and C viruses are carcinogenic Hep C is M/C cause of chronic hepatitis among viruses

Question 33

Microscopy of acute hepatitis

Answer 33

1. Ballooning degeneration: swelling of hepatocytes 2. Disruption of lobular architecture 3. Inflammation 4. Spotty necrosis 5. Councilman bodies- apoptotic bodies 6. Absence of portal inflammation 7. Central-portal bridging necrosis 8. Drop out of hepatocytes

Question 34

Chronic hepatitis | microscopy

Answer 34

1. Ground glass hepatocytes: Seen in hep B infection due to deposition of surface antigens 2. Bridging fibrosis: bridged between the central vein and portal tract 3. Mononuclear portal inflammation 4. Interface hepatitis 5. Cirrhosis

Question 35

Microscopy of hep C infection

Answer 35

1. Steatosis 2. Lymphoid aggregates 3. Bile duct damage and proliferation

Question 36

Autoimmune hepatitis

Answer 36

``` Females > males Three types Microscopy: 1. Increased plasma cells infiltration 2. Hepatic rosettes 3. Emperipolesis 4. Interface hepatitis ```

Question 37

Types of autoimmune hepatitis

Answer 37

``` 1. Type 1: • HLA DR3 • Positive for ANCA, SMA and anti-mitochondrial Ag 2. Type 2: • Ab against LKM +ve • Three types 3. Type 3: • No ANCA, LKM • LSA +ve, liver soluble antigen ```

Question 38

Types of type 2 autoimmune hepatitis

Answer 38

Ab against LKM +ve 1. LKM 1: Hep C 2. LKM 2: drugs 3. LKM 3: Hep D