Liver diseases Flashcards
What are the histological features in liver diseases?
1-Inflammation (hepatitis):
Acute and chronic inflammation,
granulomas (collection of epithelioid histiocytes and
lymphocytes) abscesses (neutrophils, fibroblasts, cellular debris, capillaries)
2-Degeneration:
Swelling and oedema of hepatocytes, accumulation of fat, Mallory hyalines (intermediate filaments), viral particles, iron and copper
3-Necrosis: due to any significant insult, eg: ischaemia, apoptosis. Can be focal or massive
4-Regeneration: occurs unless fulminant disease
5-Fibrosis: occurs as a result of inflammation followed by regeneration resulting eventually in cirrhosis
What is cirrhosis?
•In top 10 causes of death in Western world.
Defined as:
“Irreversible destruction of the liver architecture associated with fibrosis and nodule formation which may follow necrosis”
Pathogenesis:
Progressive fibrosis with collagen laid down throughout the lobule between portal tracts by the cells of Ito (a perisinusoidal cell which normally stores Vit A is transformed into myofibroblast-like cells)
Can result in :
Hepatic failure
Portal Hypertension
Hepatocellular carcinoma (HCC)
What happens in hepatic failure due to cirrhosis?
80-90% of liver function needs to be lost before
this happens:
•Jaundice and cholestasis •Hypoalbuminemia (oedema, reduced plasma oncotic pressure)
•Hypoglycemia (reduced glucose release) •Coagulopathy,DIC (clotting factor deficiency)
•Raised liver enzymes
•Gynecomastia (man boobs), testicular atrophy, spider naevi (hyperoestrogenism, local vasodilatation)
•Hepatic encephalopathy (“false neurotrasmitters” failure to eliminate toxic from gut bacteria, increase blood ammonia levels, impaired neuronal function)
•Hepatorenal syndrome
Mortality 70-90%
What are the causes of jaundice?
The retention of bilirubin which is deposited in the tissues.
Cholestasis: failure of excretion of bile due to hepatocellular dysfunction or biliary obstruction.
What is portal hypertension seen as clinically?
Ascites (big belly)
What are the main liver diseases in the West?
• Alcoholic liver disease 60-70% • Viral Hepatitis 10% • Biliary disease 5-10% • Haemocromatosis 5% • Wilsondisease - rare • alpha1-AT Deficiency - rare 2 -Drugs & Toxins 3. Neoplasm
What can alcoholic liver disease cause?
Fatty liver
Alcoholic hepatitis
Alcoholic cirrhosis
What are the different forms of hepatitis one could have?
Asymptomatic carrie
Acute hepatitis
Chronic carrier (had disease for more than 6 months)
What are the different types of hepatitis?
Hep A (RNA): •No carrier state •No chronic disease, rarely fatal •Usual faeco-oral transmission.
Hep B: Carrier state, 300 milion people, chronic hepatitis 10% (90% in neonates) due to immunologically mediated hepatocytes necrosis by sensitised CD8+T cells, HCC. Blood and sexual transmission.
Hep C: Carrier state, chronic hepatitis 50% with cirrhosis and HCC. Blood/transfusion transmission.
Hep D (RNA): need HBV to replicate. Coinfection or superinfection with HDV alters the course of HBV infection. Can get fulminant hepatitis.
Hep E (RNA): Infection by enteric route. No carrier state. Bad in pregnancy otherwise self-limiting.
What are biliary diseases?
They can be primary or secondary.
1-Primary:
A-Primary Biliary Cirrhosis: Chronic progressive disease with destruction of intrahepatic bile ducts, granulomatous portal inflammation and scarring. Associated with Sjorgren Syndrome, thyroiditis, scleroderma, coeliac disease.
B. Primary Sclerosing Cholangitis: [middle aged men] Chronic progressive disease with inflammation, obliterative fibrosis and segmental dilatation of the intra and extrahepatic bile ducts (70% have UC)
2. Secondary Biliary Cirrhosis: stones, strictures and tumours.
What is haemochromatosis?
When Iron accumulates as ferritin and haemosiderin in parenchymal tissues eg liver, pancreas, myocardium. Iron weighed in unfixed liver.
Aetiology: •M:F 6:1, autosomal recessive •Defect in the HFE gene (C282Y, H63D mutations) which regulate the amount of iron absorbed from intestine.
What is Wilson’s disease?
[AR, Ch 13, ATP7B gene transmembrane ATPase defective in excreting copper into bile] CLD in childhood, Kayser-Fleischer rings, hepatolenticular degeneration (deposit in the basal ganglia)
What is alpha-1 antitrypsin deficiency?
- Serum protein normally synthesised in the liver.
- Gene mutations lead to accumulation in hepatocytes.
- Decreased serum levels of protease inhibitor.
- Clinically: seen in neonatal hepatitis and cholestatic jaundice. Cirrhosis in adults. 2- 3% develop HCC.
- Treatment: liver transplant
What drugs are toxic to the liver (hepatoxic)?
Carbon tetrachloride, Paracetamol, Alcohol, Tetracycline, Methotrexate
Give examples of benign neoplasms of the liver.
- Cavernous haemangiomas (commonest)
- Nodular regenerative hyperplasia: nodular transformation of the liver without fibrosis
associated with autoimmune disease - Focal nodular hyperplasia: young to middle aged adults with non encapsulated tumour
and central stellate scar - Liver cell adenoma: young women on OCP.
Can rupture if subcapsular
