Liver and Biliary Disease

Question 1

How much does the liver weigh and where does it get it’s blood supply from?

Answer 1

1500g

Portal vein and hepatic artery

Question 2

What issues may arise in gall bladder surgery?

Answer 2

Anatomy is very variable - surgeons may accidentally tie off both sources of blood

Question 3

Name 6 different cell types of the liver and their roles

Answer 3

hepatocytes
bile ducts
blood vessels
endothelial cells - line sinusoids, unique cells
kupffer cells - resident macrophages, clear debris and endotoxin
stellate cells - store vitamin A in healthy individuals. when activated, these become myofibroblasts and produce collagen - involved in liver scarring and diseases involving fibrosis.

Question 4

What is the arrangement of the liver?

Answer 4

Arranged in hexagonal lobules. Hepatic vein at the centre connected to sinusoids.
At each corner lies the portal triad - hepatic artery, portal vein and bile duct.
Blood flows from triads, through sinusoids and into hepatic vein

Question 5

What are the zones of the liver?

Answer 5

1 - periportal - closest to portal triad, rich O2 supply
2 - mid zonal - between 1 and 3
3 - perivenular - surrounding hepatic vein, poor O2 supply
Different diseases occur in different zones

Question 6

How do stellate cells become activated?

Answer 6

Lie between endothelial cells and hepatocytes.
Endothelial cells don’t sit on a BM and are discontinuous.
Blood flows between endothelial cells to get to hepatocytes. When the liver is injured, kupffer cells activated. Endothelium becomes continuous and secretes a BM. Stellate cells become activated to become myofibroblasts and then there is collagen int the space of disse. Microvilli are lost from hepatocytes. - reduced function of the liver.
Reduced contact with blood for homeostasis and own nutrition is impaired.

Question 7

Define cirrhosis

Answer 7

End-stage liver disease, regardless of cause.
Whole liver is involved, there is fibrosis and nodules of regenerating hepatocytes with distortion of liver vascular architecture (intra and extra-vascular shunting of blood).

Question 8

What is seen histologically in liver cirrhosis?

Answer 8

hepatocytes surrounded by fibrous tissue

Question 9

How can cirrhosis be classified?

Answer 9

1) according to nodule size - micro, macro (>3mm) or mixed
2) according to aetiology - alcohol or insulin resistance (secondary to T2DM) - tends to be micronodular
If you drink a weekends, nodules become macronodular as have time to recover
viral hepatitis - tends to be macronodular

Question 10

What are the complications of cirrhosis?

Answer 10

portal hypertension, hepatic encephalopathy, liver cell cancer, splenic congestion

Question 11

What are the causes of acute hepatitis?

What does histology show?

Answer 11

Viruses - Hep A, B, C, D, E
Drus

Spotty necrosis

Question 12

Define chronic hepatitis

What are the causes of chronic hepatitis?

Answer 12

hepatitis for 6 months or more
Viruses - Hep B, C or D - D only occurs in patients with B. Either already present or acquired together.
Drugs
Autoimmune
Idiopathic

Question 13

What does histology show?

Answer 13

Grade: severity of inflammation
Stage: severity of fibrosis - risk of developing acutal cirrhosis
Piecemeal necrosis - line between portal tract and hepatocytes - limiting plate.
Interface hepatitis - along this line
Actually apoptosis and not necrosis
Can also get lobular inflammation

Fibrosis in histology = closer to developing cirrhosis
lymphocytic

Question 14

How do viral hepatitises progress?

Answer 14

All start acutely - chronic - cirrhosis - liver cell cancer

Question 15

What are the three categories of Alcoholic Liver disease?

Answer 15

Fatty liver disease
Alcoholic hepatitis
Cirrhosis

Question 16

Fatty liver disease features

Answer 16

pale, yellow and greasy liver
Histology - fat droplets visible throughout
REVERSIBLE as fatty changes are metabolic

Question 17

Alcoholic hepatitis features

Answer 17

Fatty change, damage and inflammatory cells present (neutrophilic)
Mallory-denk bodies
Alcohol not toxic, acetaldehyde binds to lysine residues and cross-links cytoskeleton leading to clumps
Ballooning of hepatocytes due to loss of cytoskeleton. Get fibrosis around individual cells - pericellular fibrosis

Question 18

Cirrhosis features…

Answer 18

Alcoholic cirrhosis - pale, yellow, greasy and fatty. Usually micronodular.

Question 19

Non-alcoholic fatty liver disease

Answer 19

histologically looks like alcoholic liver disease
due to insulin resistance associated with increased BMI and diabetes
Most important liver disease in western countries.

Question 20

Primary Biliary Cirrhosis

Answer 20

Bile duct loss associated with chronic inflammation (with granulomas)
Anti-mitochondrial antibodies are diagnostic
May develop cirrhosis
Destruction of bile ducts by granulomas

Liver biopsy - bile duct surrounded by granuloma (organised collection of activated macrophages, for secretion, not phagocytosis).
Portal tract looks inflamed with absence of bile duct.

Question 21

Primary Sclerosis Cholangitis

Answer 21

Sclerosing = fibrosis
Damage of ducts due to scarring (not inflammation).
Periductal bile duct fibrosis
Associated with UC
Increased risk of  cholangiocarcinoma
Dx via ERCP

Histology: bile duct surrounded by fibrosis - squeezed until leads to disappearing bile duct syndrome disease

Question 22

Haemochromatosis

Answer 22

Genetically determined increased gut iron absorption
Gene on chromosome 6
Parenchymal damage to organs secondary to iron deposition

iron overload in hepatocyes
catalysis of oxidation reactions
affects many other parts of the body e.g. pancreas and skin (pigmentation).

Present at birth but takes until middle-age to see liver damage

Histology: iron in hepatocytes.
Chocolatey brown liver, accumulates in all organs

Question 23

Haemosiderosis

Answer 23

Accumulation of iron in macrophages
Due to excessive blood transfusion
Most commonly seen in those with SCD and Beta thalassaemia, who are awaiting BM transplantation

Phagocytosis of RBCs - macrophages accumulate iron
Biopsy shows - scattered iron accumulation in liver macrophages

Question 24

Wilson’s disease

Answer 24

Accumulation of copper due to failure to excrete by hepatocytes in bil
Genes on chromosome 13
Accumulates in liver and CNS
Becomes multi-organ disease
Psychiatric patients - abnormal LFT (?Wilson’s disease)

Rhodanine stain - copper accumulation in hepatocytes
KF rings

Question 25

AI hepatitis

Answer 25

interface hepatitis with plasma cells
anti-smooth muscle actin antibodies
responds to sterods
more common in women
Liver biopsy - plasma cells (clock face nuclei, paranuclear hoff)

Question 26

Alpha 1 antitrypsin deficiency

Answer 26

RARE, affecting liver and lungs
Failure to secrete A1a - little or none in blood, excess in liver
Intra-cytoplasmic inclusion (due to excess anti-trypsin leads to emphysema in lungs)
Hepatitis and cirrhosis

Question 27

Name 3 BENIGN liver tumours

Answer 27

Liver cell adenoma (linked to OCP)
Bile duct adenoma
Hemangioma (most common, 1 in 5 have these)

Question 28

Name 4 PRIMARY MALIGNANCIES of the liver

Answer 28

Hepatocellular carcinoma
Hepatoblastoma - rare in children
Cholangiocarcinoma
Haemangiosarcoma

Question 29

How do SECONDARY MALIGNANCIES of the liver differ?

Answer 29

much more common than primary tumours
linked to blood supply
reach liver from aorta, breast and bronchus
or from GI via hepatic portal vein

Usually ADENOMCARCINOMAS (glandular)
- make glands, secrete mucus
Can use liver biopsy to try to determine where primary tumour is from