Liver pathology Flashcards
Liver anatomy
Cells of the liver
Hepatocytes - metabolic function
bile ducts
blood vessels
endothelial cells - discontinuois, not on a well formed basement membrane - allow blood right up to mirovillous boundary of liver
kupffer cells - macrophages
stellate cells - store vit A. become myofibroblasts - can contract and secrete collagen
Normal structure of the liver
Portal tract containing portal triad - bring blood into liver and bile out of the live r- look up vessels in here
Sinusoid - pale lines containing red cells
Blood goes to central vein -> hepatic vein etc
Hepatocytes born in zone 1 - grow up in 2 - die in 3
where is alcohol metabolised in the liver
In zone 3 - most metabolically active cells in the liver - alcohol metabolised here to acetylaldehyde
requires a huge amount of metabolism - pO2 falls critically low in zone 3
histopathology of portal tract
Every portal tract contains a bile duct
Limiting tract - interphase between portal tract and hepatocytes
structure of liver at cell level
Macrophages in sinusoid themselves
Endothelial cells - gap between them
Space of Disse - in here is the stellate cells - quiescent cell with Vit A
Microvilli increase SA for transfer
effect of liver injury on liver structure
- Kupffer cells activated
- Gaps between the endothelium are closed
- Collagen deposited in space of Disse - synthesised by activated stellate cells
- Impact on blood to the microvillus border
definition of cirrhosis
- whole liver involved
- fibrosis
- nodules of regenerating hepatocytes
- distrotion of liver vascular architecture - intra- and extra- hepatic (eg gastro-oesophageal) shunting of blood
effect of cirrhosis of liver function
Even in advanced liver disease the nodules are trying to regenerate
Functionally the most important change is distortion of vasculature - blood from portal circ finds it difficult to find its way into liver - has to go another way - portosystemic anaestomosis
Get shunting inside and outside the liver - oesophageal varices
If blood not into liver - don’t get the metabolic homeostasis, and hepatocytes wont get the blood that they need.
Cirrhotic liver - around each nodule is fibrous tissue
Histology of cirrhotic liver
nodules of regenerating hepatocytes and fibrous tissue around it
Classification of liver cirrhosis
according to size - micronodular, macronodular
according to aetiology - alcohol/insulin resistance, viral hepatitis
alcohol usually micronodular, viral usually macro
complications of liver cirrhosis
portal hypertension
hepatic encephalopathy - because toxic substances reach the brain
liver cell cancer
oesophageal varices
Hepatocellular cancer
Is cirrhosis reversible
can be
Aetiology of acute hepatitis
viruses
* A-E all cause acute
* A and E mainly - fecal-oral route, small RNA virus
drugs
* Because main site of drug metabolism - toxic metabolites released
* Therefore any liver disease can be caused by drugs
Histology of acute hepatitis
spotty necrosis
damage to hepatocytes - inflammation is in lobule - zones 1 2 or 3
histology fo chronic hepatitis
severity of inflammation = grade
severity of fibrosis = stage
histology of interface hepatitis
histology of lobular inflammation
In chronic most is in or around portal tract. In acute more commonly in lobular
histology of fibrosis in the liver
Intrahepatic shunting of blood - straight bridge from portal tract to central vein
instead of going around hepatocytes
Fatty liver
Normal liver is a red colour
This is pale because it is really fatty
microscopy of fatty liver
histology of alcoholic hepatitis
ballooning +- mallory denk bodies
apoptosis
pericellular fibrosis
mainly seen in zone 3
Cells swell up - acetaldehyde in zone 3 - binds to lysine residue = cross linking of intermediate filament of liver = cant maintatain their shape
liver
cirrhosis
Pale
Nodules are small and regular - micronodular
Summarise primary biliary cholangitis
> female
bile duct loss associated with chronic inflammation (with granulomas)
diagnostic test - detection of anti-mitochondrial antibodies
only 50% have cirrhosis
summarise primary sclerosing cholangitis
> male
periductal bile duct fibrosis due to intra and extrahepatic inflammation -> loss of bile duct
associated with UC
increased risk of cholangiocarcinoma
dx test - MRCP (bile duct imaging)
Summarise haemochromatosis
genetic
increased gut iron absorption
gene on chr 6 (HFe) - dominant
parenchymal damage to organs secondary iron deposition (bronzed diabetes)
systemic disease: fibrosis -> cirrhosis
skin pigmentation and chronic pancreatitis - damage to islets -> dm
macroscopic liver in haemochromatosis
summarise haemosiderosis
accumulation of iron in macrophages
RF - multiple blood transfusion
Summarise wilson’s disease
accumulation of copper due to failure of excretion by hepatocytes into bile
ix - biopsy/biochem
genes - Chr 13
accumulates in liver and CNS - hepatolentigular degeneration including keyser-fleisher rings, psychiatric disturbance
summarise autoimmune hepatitis
> female
active chronic hepatitis with plasma cells
anti-smooth muscle actin antibodies in the serum
responds to steroids
very actively leads to cirrhosis
summarise alpha one antitrypsin
failure to secrete alpha-one antitrypsin - so too much in hepatocytes endoplasmic reticulum and a deficiency in the blood
intra-cytoplasmic inclusions due to misfolded protein
hepatitis and cirrhosis
also associated with emphysema - because dont get the dampening of inflammation from alpha-1 antitrypsin
summarise paracetamol toxicity in liver
causes and histology of hepatic granulomas
PBC
drugs
TB
sarcoid
benign liver tumours
liver cell adenoma
bile duct adenoma
haemangioma
malignnat liver tumours
secondary tumours - commonest - because blood from everywhere is going to the liver (adenocarcinomas are the most common liver biopsy in UK)
primary
* hepatocellular carcinoma
* hepatoblastoma
* cholangiocarcinoma
* haemangiosarcoma
summarise hepatocellular carcinoma
usually associated with cirrhosis
can be via Hep B which is onchogenic
summarise cholangiocarcinoma
associated with
* PSC
* worm infections
* cirrhosis
can arise from
* intrahepatic ducts
* extrahepatic ducts - including gall bladder
