Histopathology - Liver and Biliary disease Flashcards
blood supply of liver
dual
- hepatic portal vein (carries some oxygenated blood)
- hepatic artery
what is the advantage of the dual blood supply?
liver does not tend to get affected by ischaemic diseases
what are the cells of the liver?
hepatocytes bile ducts blood vessels endothelial cells (endothelium is discontinuous in liver) kupffer cells (resident macrophages) stellate cells
what do stellate cells do?
- most people = store Vit A
- when activated, they become myofibroblasts and lay down collagen
- responsible for scarring in liver disease
in what direction does blood flow in the liver?
from portal tract to central vein
what do the cells in zone 3 contain?
more metabolically active enzymes
what is the limiting plate?
ring of collagen around portal triad
describe the endothelium in the liver?
endothelial cells in liver have no basement membrane
have spaces between them = fenestrated sinusoidal endothelium
kupffer cells found within sinusoids
where do stellate cells sit in the endothelium?
in space of Disse
space between endothelial cells and hepatocytes
what are the changes that happen to liver histology in liver injury?
- kupffer cells activated
- endothelial cells stick together (blood finds it hard to make it through)
- collagens are secreted into space of Disse
- hepatocytes lose microvilli
= blood can’t diffuse into hepatocytes
what is the definition of cirrhosis?
- whole liver is involved
- fibrosis
- nodules of regenerating hepatocytes
- distortion of liver vascular architecture (intra and extra hepatic shunting of blood)
what is the normal blood flow through the liver?
normally blood comes from intestines
it is then filtered through liver
comes out via hepatic vein
what happens in extrahepatic shunting of blood?
- blood can’t go through liver as fibrosed
- blood never reaches liver
- backlogs into sites of porto-systemic anastomosis
what happens in intrahepatic shunting of blood?
- blood comes through liver but does not come into contact with hepatocytes
- straight from intestines to portal vein
- blood is unfiltered and toxic
what are the 2 ways cirrhosis can be classified?
- according to nodule size (micronodular, macronodular)
2. according to aetiology (alochol/insulin resistance, viral hepatitis)
what is micronodular associated with?
alcoholism
what is macronodular associated with?
viral infections
what are the complications of cirrhosis?
- portal HTN = varices, splenomegaly
- hepatic encephalopathy
- liver cell cancer
what is the aetiology of acute hepatitis?
- viruses (A+E Mostly)
- drugs
what is the histology in acute hepatitis?
- spotty necrosis
- lots of apoptosis
- lymphocyte and macrophage damage hepatocytes
what is the aetiology of chronic hepatitis?
- viral hepatitis
- drugs
- AI
what is the histology in chronic hepatitis?
- severity of inflammation = GRADE (how bad does it look)
- severity of fibrosis = STAGE (how far has it spread)
what are the different patterns of injury in hepatitis?
- portal inflammation (inflammation limited to portal tracts)
- interface hepatitis (T cell mediated destruction of hepatocytes, inflammation crosses limiting plate)
- lobular inflammation
how does fibrosis lead to intrahepatic shunting?
instead of going through hepatocytes, blood goes straight from portal tract to central vein
doesn’t get filtered
what are the 3 histological patterns in ALD?
- fatty liver
- alcoholic hepatitis
- cirrhosis
what are the features of alcoholic hepatitis?
- ballooning
- mallory denk bodies (collapased cytoskeleton of hepatocytes)
- apoptosis
- pericellular fibrosis
what is NAFLD caused by?
caused by insulin resistance associated with raised BMI and diabetes
what does NAFLD look like histologically?
- a lot like alcoholic liver disease
- distinguished based on history
what is PBC characterised by?
bile duct loss associated with chronic inflammation (with granulomas)
CAUSED BY INFLAMMATION
more common in females
what is the diagnostic test for PBC?
Anti-mitochondrial antibodies
what is the histology in PBC?
- bile duct surrounded by epithelioid macrophages
- suggests granulomatous destruction of bile ducts
what is PSC characterised by?
- periductal bile loss
- CAUSED BY FIBROSIS
- associated with UC and inc risk of cholangiocarcinoma
- more common in men
what is the diagnostic test in PSC?
bile duct imaging
ERCP shows beading of bile ducts
what is haemochromatosis?
genetic (gene on chromosome 6)
increased in gut iron absorption
women present later (lower Fe levels)
where does haemochromatosis cause damage?
- iron deposits in hepatocytes = liver damage
- iron deposits in heart = cardiomyopathy
- iron deposits in testes = infertility
- iron deposits in skin = bronzed skin
- iron deposits in pancreas = diabetes
how is haemosiderosis different?
- iron overload
- doesn’t cause cirrhosis
- iron accumulates in macrophages which are capable of dealing with it
- occurs due to lots of blood transfusions
what is wilson’s disease?
- accumulation of copper
- due to failure of excretion of copper by hepatocytes into bile
- defective genes from Chr 13
where does copper accumulate and cause symptoms?
- in liver and CNS (hepato-lenticular degeneration)
- iris (Kayser-Fleischer rings)
- lentiform nucleus of basal ganglia (movement disorders)
how do you stain for copper?
Rhodanine stain
how do you treat Wilson’s?
penicillamine (copper chelating agent)
what is AI hepatitis?
- more common in females
- active form of chronic hepatitis
- lots of plasma cells
- more inflammation than in viral hepatitis
antibodies and tx in AI hepatitis
Anti-smooth muscle actin antibodies
responds to steroids
what us A1AT characterised by?
failure to secrete A1AT
where is the deficiency of A1AT?
is in the blood
actually an excess in hepatocytes
why is there an excess of A1AT in hepatocytes?
protein sequence is wrong
CANNOT fold properly and cannot exist in hepatocytes
A1AT forms globules with hepatocytes and damages them
= chronic hepatitis
what stain can be used to stain for these globules?
periodic acid-schiff stain
what else can a deficiency of A1AT lead to?
inc risk of emphysema
what are the specific (to the liver) and general causes of granulomas
specific: PBC, drugs
general: TB, sarcoidosis
what are the benign liver tumours?
- liver cell adenoma
- bile duct adenoma
- haemangioma (most common tumour of liver overall)
what are hepatic adenomas associated with?
COCP
what is the most common cause of liver malignancy?
secondary tumours
what are the different primary malignant tumours of the liver?
- hepatocellular carcinoma
- hepatoblastoma (primitive cell tumour, mostly children)
- cholangiocarcinoma (ass w/ PSC, worm infections, cirrhosis)
- haemangiosarcoma
why is the liver such a common site for secondary tumours?
- liver supplied by hepatic artery
- this is branch of aorta
- tumour cells in systemic circulation likely to get to liver
- all blood from portal circulation goes to liver (tumours from stomach, bowel, pancreas)
