Liver pathology Flashcards
Zones of liver and diseases affecting each zone
- Periportal: viral hepatitis
- Midzonal: yellow fever
- Centrilobular:
• alcohol
• acetaminophen toxicity
• CVC
• ischemia
• Budd Chiari syndrome
Zones of liver most susceptible to toxin induced & ischemic damage respectively
To toxin induced damage: zone 1 Periportal area (like viral hepatitis)
To ischemic damage: zone 3
(Centrilobular area)
Space of Disse
Space between hepatocytes and lining of sinusoids
- Vitamin A storage
- Ito cells/ Stellate cells- fibrosis in cirrhosis
- Amyloid is first seen here
Canals of Herring
Kupffer cells
Present between hepatocytes
Contain oval cells/stem cells of liver
Kupffer cells (macrophages) are located in the sinusoids
Cirrhosis
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
Micronodular cirrhosis
<3 mm
- Early ALD
- Hemochromatosis
- 1° biliary cirrhosis
- Indian childhood cirrhosis
Macronodular cirrhosis
> 3 mm
- Late ALD
- Wilson’s disease
- α-1 antitrypsin deficiency
- Viral hepatitis
- Drugs and toxins
Causes of cirrhosis
- Alcoholic liver disease
- Non-alcoholic steatohepatitis NASH
- Metabolic disorders:
• α-1 antitrypsin deficiency
• Wilson’s disease
• Hemochromatosis - Viral hepatitis
- Autoimmune hepatitis
- Drugs and chemicals
- Biliary diseases
Pathogenesis of cirrhosis
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
Minimum amount of alcohol that can cause alcoholic liver disease
60-80 ml/day for 10 years
Alcoholic liver disease gross features
Soft, yellow, greasy
Manifestations of alcoholic liver disease
1. Steatosis • Fatty liver • Reversible • starts in centrilobular area (zone-3) • micro or macrovesicular 2. Hepatitis 3. Cirrhosis: • Irreversible • Fibrosis seen
Features of hepatitis of alcoholic liver disease
- Hepatocyte swelling ➡️
- Ballooning degeneration
- Neutrophilic infiltrate
- Mallory hyaline bodies
- Some fibrosis
Laennac cirrhosis
End stage of alcoholic liver disease
Liver is reduced to a fibrotic scar
Mallory hyaline bodies
Mallory deny bodies
composed of
Composed of intermediate filaments like CK8, CK18
Mallory denk bodies or
Mallory hyaline bodies
are seen in
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
Microvesicular steatosis is seen in
D. Drugs and toxins
A. Acute fatty liver of pregnancy 🤰
R. Reye’s syndrome
E. Early alcoholic liver disease
Macrovesicular steatosis is seen in
C. Chronic hepatitis C L. Late alcoholic liver disease O. Obesity N. NASH E. PEM
NASH
Non Alcoholic Steatohepatitis
Features similar to ASH, except no history of alcohol Seen in: 1. Obesity 2. Metabolic syndrome 3. Insulin resistance
Differences between alcoholic steatohepatitis and NASH
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
Reye’s syndrome
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
Haemochromatosis
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)
Causes of hemochromatosis
Hereditary: 1. HFE gene mutation on chr 6p 2. HAMP gene 3. HJV juvenile hemochromatosis Secondary: 1. Repeated blood transfusions 2. Bantu siderosis (iron 🍽)
Hemochromatosis
clinical features
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
Lab diagnosis of hemochromatosis
- Serum iron increases
- Serum ferritin increases
- Serum transferrin saturation increases
- Serum TIBC decreases
Liver biopsy: - Brownish pigmentation-hemosiderin
- Micronodular cirrhosis
- On Prussian blue, bluish iron deposits can be seen
Wilson’s disease
pathogenesis
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
Wilson’s disease
clinical manifestations
- Liver - cirrhosis
- Eye 👁: Kayser Fleisher ring
Brownish discolouration of Descemet’s membrane of cornea - Brain 🧠:
putamen and basal ganglia are affected ➡️ neuropsychiatric manifestations
Wilson’s disease
diagnosis and treatment
- Increased copper levels
- Decreased ceruloplasmin
Liver biopsy:
• Stain for Cu: Rhodamine, Rubeanic acid
• Stain for ceruloplasmin: orcein
Most sensitive: increased urinary Cu excretion
Treatment: copper chelators
α1-Antitrypsin deficiency
basics and clinical manifestations
Autosomal recessive
Pathogenesis: deficiency of α1-Antitrypsin ➡️ elastase activity increases ➡️:
1. Lung: panacinar emphysema
2. Liver: cirrhosis
α1-Antitrypsin deficiency
genetics and microscopy
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
Hepatitis viruses
types
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 🤰
Common features among hepatitis B, C and D viruses
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
Microscopy of acute hepatitis
- Ballooning degeneration: swelling of hepatocytes
- Disruption of lobular architecture
- Inflammation
- Spotty necrosis
- Councilman bodies- apoptotic bodies
- Absence of portal inflammation
- Central-portal bridging necrosis
- Drop out of hepatocytes
Chronic hepatitis
microscopy
- Ground glass hepatocytes:
Seen in hep B infection due to deposition of surface antigens - Bridging fibrosis: bridged between the central vein and portal tract
- Mononuclear portal inflammation
- Interface hepatitis
- Cirrhosis
Microscopy of hep C infection
- Steatosis
- Lymphoid aggregates
- Bile duct damage and proliferation
Autoimmune hepatitis
Females > males Three types Microscopy: 1. Increased plasma cells infiltration 2. Hepatic rosettes 3. Emperipolesis 4. Interface hepatitis
Types of autoimmune hepatitis
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
Types of type 2 autoimmune hepatitis
Ab against LKM +ve
- LKM 1: Hep C
- LKM 2: drugs
- LKM 3: Hep D
