Liver pathology

Question 1

Liver anatomy

Answer 1

Question 2

Cells of the liver

Answer 2

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

Question 3

Normal structure of the liver

Answer 3

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

Question 4

where is alcohol metabolised in the liver

Answer 4

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

Question 5

histopathology of portal tract

Answer 5

Every portal tract contains a bile duct
Limiting tract - interphase between portal tract and hepatocytes

Question 6

structure of liver at cell level

Answer 6

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

Question 7

effect of liver injury on liver structure

Answer 7

• 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

Question 8

definition of cirrhosis

Answer 8

1. whole liver involved
2. fibrosis
3. nodules of regenerating hepatocytes
4. distrotion of liver vascular architecture - intra- and extra- hepatic (eg gastro-oesophageal) shunting of blood

Question 9

effect of cirrhosis of liver function

Answer 9

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.

Question 10

Answer 10

Cirrhotic liver - around each nodule is fibrous tissue

Question 11

Histology of cirrhotic liver

Answer 11

nodules of regenerating hepatocytes and fibrous tissue around it

Question 12

Classification of liver cirrhosis

Answer 12

according to size - micronodular, macronodular

according to aetiology - alcohol/insulin resistance, viral hepatitis

alcohol usually micronodular, viral usually macro

Question 13

complications of liver cirrhosis

Answer 13

portal hypertension
hepatic encephalopathy - because toxic substances reach the brain
liver cell cancer

Question 14

Answer 14

oesophageal varices

Question 15

Answer 15

Hepatocellular cancer

Question 16

Is cirrhosis reversible

Answer 16

can be

Question 17

Aetiology of acute hepatitis

Answer 17

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

Question 18

Histology of acute hepatitis

Answer 18

spotty necrosis
damage to hepatocytes - inflammation is in lobule - zones 1 2 or 3

Question 19

causes of chronic hepatitis

Answer 19

viral
* B C D - D incomplete DNA virus can only infect if already have B.
* B and D together = co-infection.
* D on top of B = superinfection

drugs

autoimmune
* more in women
* certain HLA associated
* will have other autoimmune diseases
* will respond to steroids

Question 20

histology fo chronic hepatitis

Answer 20

severity of inflammation = grade
severity of fibrosis = stage

Limiting plate - inflammation only in portal tract = portal inflammation

Question 21

histology of interface hepatitis

Answer 21

Inflammation crossed limiting plate = interface hepatitis - hepatocytes destroyed

Question 22

histology of lobular inflammation

Answer 22

In chronic most is in or around portal tract. In acute more commonly in lobular

Question 23

histology of fibrosis in the liver

Answer 23

Intrahepatic shunting of blood - straight bridge from portal tract to central vein
instead of going around hepatocytes

Question 24

stages of alcholic liver disease

Answer 24

fatty liver - reversible and metabolic
alcoholic hepatitis
cirrhosis

Question 25

Answer 25

Fatty liver Normal liver is a red colour This is pale because it is really fatty

Question 26

microscopy of fatty liver

Answer 26

Question 27

histology of alcoholic hepatitis

Answer 27

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

Question 28

liver

Answer 28

cirrhosis Pale Nodules are small and regular - micronodular

Question 29

summarise non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH)

Answer 29

histologically looks like alcoholic liver disease due to insulin resistance - associated with raised BMI and dm one of commonest causes of liver disease world-wide

Question 30

Summarise primary biliary cholangitis

Answer 30

>female bile duct loss associated with chronic inflammation (with granulomas) diagnostic test - detection of anti-mitochondrial antibodies only 50% have cirrhosis

Question 31

summarise primary sclerosing cholangitis

Answer 31

>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)

Question 32

Summarise haemochromatosis

Answer 32

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

Question 33

macroscopic liver in haemochromatosis

Answer 33

Question 34

summarise haemosiderosis

Answer 34

accumulation of iron in macrophages RF - multiple blood transfusion

Question 35

Summarise wilson's disease

Answer 35

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

Question 36

summarise autoimmune hepatitis

Answer 36

>female active chronic hepatitis with plasma cells anti-smooth muscle actin antibodies in the serum responds to steroids very actively leads to cirrhosis

Question 37

summarise alpha one antitrypsin

Answer 37

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

Question 38

summarise paracetamol toxicity in liver

Answer 38

Question 39

causes and histology of hepatic granulomas

Answer 39

PBC drugs TB sarcoid

Question 40

benign liver tumours

Answer 40

liver cell adenoma bile duct adenoma haemangioma

Question 41

malignnat liver tumours

Answer 41

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

Question 42

summarise hepatocellular carcinoma

Answer 42

usually associated with cirrhosis can be via Hep B which is onchogenic

Question 43

summarise cholangiocarcinoma

Answer 43

associated with * PSC * worm infections * cirrhosis can arise from * intrahepatic ducts * extrahepatic ducts - including gall bladder