Pathology of the liver

Question 1

What are the two concepts of microanatomical units in the liver?

Answer 1

The lobular concept and the acinar concept

Question 2

Which acinar zones are used to describe patterns of liver injury?
Which cells are most vulnerable do injury?

Answer 2

Zone 1: periportal
Zone 2: Mid acinar
Zone 3: Pericentral
Zone 3 cells are most vulnerable to injury

Question 3

Are all liver cells capable of regeneration?

Answer 3

Yes

Question 4

Do liver cells replicate frequently?

Answer 4

No, they are stable and only replicate infrequently.
However if the liver is injured nearly all surviving hepatocytes can enter the cell cycle and rapidly replace destroyed hepatocytes.

Question 5

What is the late stage of all chronic liver diseases?

Answer 5

Cirrhosis

Question 6

What is cirrhosis defined as?

What effects does it have on the liver?

Answer 6

It is defined anatomically by the presence throughout the liver of fibrous septa that subdivide the parenchyma into nodules.
Perfusion of sinusoids is inefficient, liver cell function is impaired, and intraheptic pressure is increased.

Question 7

What are the possible outcomes of acute liver failure?

Answer 7

complete recovery
chronic liver disease
death from liver failure

Question 8

Are all patients with severe liver disease jaundiced?

Answer 8

No, there are many who are not.

The liver has a massive reserve and can handle a build up of bilirubin with just a third of the cells.

Question 9

How is jaundice classified?

Answer 9

By site and type
Pre-hepatic
Intra-hepatic
Post-hepatic

Conjugated
Unconjugated

Question 10

What causes pre-hepatic jaundice?

What type of bilirubin causes the jaundice?

Answer 10

Haemolysis of any type.

Unconjugated bilirubin

Question 11

What causes hepatic jaundice?

Answer 11

Liver cells that are injured or dead.
e.g.
Alcoholic hepatitis
Cirrhosis (decompensated)
Bile duct loss (atresia, PBC, PSC)
Pregnancy

Question 12

What causes post hepatic jaundice?

Answer 12

Bile cannot escape into the bowel
E.g.
Congenital biliary atresia
Gallstones block CBDuct
Strictures of CBDuct
Tumours (Ca head of pancreas)

Question 13

Is cirrhosis reversible or irreversible?

Answer 13

Irreversible

Question 14

What are features of cirrhosis?

Answer 14

There is alteration of hepatic microvasculature and many hepatocytes now have a compromised blood supply
There is loss of hepatic function
The liver is nodular, hard and craggy

Question 15

How is cirrhosis classified?

Answer 15

Morphologically:
classified by the average size of the regenerative nodules
micronodular- nodules up to 3mm in diameter
macronodular- nodules greater than 3mm in diameter

Aetiologically

Question 16

What are the major complications of cirrhosis?

Answer 16

Liver failure
Portal hypertension
Infection
Liver cell carcinoma

Question 17

What are common causes of cirrhosis?

Answer 17

Alcohol
Hep B and C
Iron overload

Question 18

Is liver failure a manifestation of compensated or decompensated cirrhosis?

Answer 18

Decompensated

Question 19

What causes hepatic encephalopathy?

Answer 19

Failure of the liver to eliminate toxic nitrogenous products of gut bacteria

Question 20

What other type of failure may also occur with hepatic failure?

Answer 20

Renal failure (hepato-renal syndrome)

Question 21

What does failure to eliminate endogenous steroid hormones result in?

Answer 21

Secondary hyperaldosteronism, causing sodium and water retention
In the male, it causes loss of secondary sexual characteristics and gynaecomastia due to hyperoestrogenism.

Question 22

What are results of portal hypertension?

Answer 22

Oesophageal varices
Caput medusa
Haemorrhoids
Ascites

Question 23

Is cirrhosis the only cause of portal hypertension?

Answer 23

No

Question 24

What is the reason for oedema in chronic liver disease?

Answer 24

Reduced albumin synthesis resulting in hypoalbuminaemia

Question 25

What is the reason for ascites in chronic liver disease?

Answer 25

Hypoalbuminaemia Secondary hyperaldosteronism Portal hypertension

Question 26

What is the cause of haematemesis in chronic liver disease?

Answer 26

Ruptured oesophageal varices due to portal hypertension

Question 27

What is the cause of spider naevi and gynaecomastia in chronic liver disease?

Answer 27

Hyperoestrogenism

Question 28

What is the cause of purpura and bleeding in chronic liver disease?

Answer 28

Reduced clotting factor synthesis

Question 29

What is the cause of coma in chronic liver disease?

Answer 29

Failure to eliminate toxic gut bacteria metabolites (false neurotransmitters)

Question 30

What is the cause of infection in chronic liver disease?

Answer 30

Reduced Kuppfer cell number and function

Question 31

What is the commonest cause of chronic liver disease in the UK?

Answer 31

Alcohol liver disease

Question 32

What is the spectrum of alcohol liver injury which can be seen in liver biopsies?

Answer 32

Fatty change/steatosis: fat globules in the cytoplasm of liver cells a disturbance of energy metabolism which on its own is reversible when alcohol consumption stops Alcoholic steatohepatitis: A combination of fatty change with cell swelling. This is reversible, but can lead to liver cell death and fibrosis which is not reversible. Progressive architectural damage ranging from pericellular fibrosis to cirrhosis.

Question 33

Outline the stages of fatty liver disease, when they occur in terms of duration of drinking, and whether or not they are reversible.

Answer 33

2-3 days drinking: fatty liver- reversible 4-6 weeks drinking: hepatitis- reversible months-years: fibrosis- irreversible Years: cirrhosis- irreversible

Question 34

Outline the pathogenesis of alcoholic liver disease

Answer 34

Alcohol metabolism disturbs other metabolic pathways, such as carbohydrate and fat metabolism, so fat accumulates in the liver cells Acetaldehyde, the main product of alcohol metabolism, binds to liver cell proteins, resulting in injured hepatocytes and an inflammatory reaction Alcohol stimulates collagen synthesis in the liver, leading to fibrosis and eventually cirrhosis.

Question 35

How does non-alcoholic steatohepatitis compare pathologically to alcohol liver disease?

Answer 35

It is identical

Question 36

Which patients get non-alcoholic steatohepatitis?

Answer 36

Patients with diabetes, hyperlipidaemia and obesity

Question 37

What can non-alcohol steatohepatitis lead to?

Answer 37

In a proportion of patients it can progress to cirrhosis

Question 38

How does Hep A cause liver damage?

Answer 38

It is directly cytopathic

Question 39

It is possible to have Hep A carriers?

Answer 39

No

Question 40

is it possible to have Hep B carriers?

Answer 40

yes

Question 41

What are the different outcomes of Hep B infection?

Answer 41

``` Fulminant acute infection (Death) Chronic hepatitis Cirrhosis Hepatocellular carcinoma Assymptomatic (Carrier) ```

Question 42

What are the different outcomes of Hep C infection?

Answer 42

Chronic Hepatitis | Cirrhosis

Question 43

Is autoimmune hepatitis more common in males or females?

Answer 43

Females

Question 44

What can autoimmune hepatitis cause?

Answer 44

it can cause acute liver failure | Without treatment, it can progress rapidly to cirrhosis

Question 45

How is autoimmune hepatitis characterised histologically?

Answer 45

Extensive interface hepatitis Numerous plasma cells and rosette-like arrangements of swollen liver cells There may be bridging and panacinar necrosis

Question 46

Which autoimmune liver disease is associated with antibodies to mitochondria?

Answer 46

Primary biliary cirrhosis

Question 47

What causes primary biliary cirrhosis?

Answer 47

Unknown

Question 48

What is the indication for biopsy in primary biliary cirrhosis?

Answer 48

To stage the disease

Question 49

What may be seen on biopsy of the liver in primary biliary cirrhosis?

Answer 49

Granulomas | Bile duct loss

Question 50

What are clinical features of primary biliary cirrhosis?

Answer 50

Pruritis | Xanthelasmas

Question 51

What is the pathogenesis of primary biliary cirrhosis if untreated?

Answer 51

Bile duct loss leads to cholestasis, liver injury, inflammation, fibrosis and cirrhosis.

Question 52

What autoantibodies are present in autoimmune hepatitis?

Answer 52

Auto-antibodies to: Smooth muscle antigen (SMA) Nuclear DNA (anti-nuclear antibody, ANA) Liver-kidney microsomal (LKM) antigens

Question 53

What could be a potential trigger for autoimmune hepatitis?

Answer 53

Some drugs

Question 54

What may chronic drug-induced hepatitis trigger?

Answer 54

Autoimmune hepatitis

Question 55

Which drugs can damage the liver?

Answer 55

Innumerable

Question 56

What can cause the damage to the liver by drugs?

Answer 56

It may be dose related, or idiosyncratic (unpredictable)

Question 57

What harmful effects can drugs have on the liver?

Answer 57

``` Hepatitis Granulomas Fibrosis Necrosis Failure Cholestasis Cirrhosis ```

Question 58

Which liver diseases can drug induced liver injury mimic?

Answer 58

Any

Question 59

What is primary sclerosing cholangitis?

Answer 59

An autoimmune disease that results in a chronic inflammatory process, causing damage and destruction of bile ducts It affects intrahepatic and/or extrahepatic bile ducts, often in a patchy way.

Question 60

What does primary sclerosing cholangitis lead to?

Answer 60

Periductal fibrosis Duct destruction Jaundice Fibrosis

Question 61

What other inflammatory disease is primary sclerosing cholangitis linked to?

Answer 61

Ulcerative colitis

Question 62

Are males or females more affected by primary sclerosing cholangitis?

Answer 62

Males

Question 63

What is there an increased risk of in primary sclerosing cholangitis?

Answer 63

Malignancy in bile ducts and colon

Question 64

Name some storage diseases of the liver

Answer 64

Haemochromatosis Wilsons disease Alpha-1-antitrypsin deficiency

Question 65

What is the body's main storage site for iron?

Answer 65

Hepatocytes

Question 66

What can large amounts of iron in the liver cause?

Answer 66

Liver damage

Question 67

What is haemochromatosis?

Answer 67

Excess iron within the liver

Question 68

What is primary haemochromatosis?

Answer 68

A genetic condition | There is iron overload due to a failure to switch off intestinal absorption of iron and abnormal iron metabolism

Question 69

What can cause secondary haemochromatosis?

Answer 69

Iron overload from the diet Transfusions Iron therapy

Question 70

How is primary haemochromatosis inherited?

Answer 70

It is an autosomal recessive condition

Question 71

What protects younger women from the effects of primary haemochromatosis?

Answer 71

Menstruation

Question 72

Describe how primary haemochromatosis progresses

Answer 72

Iron is deposited in the liver- the patient is asymptomatic for years Eventually iron is deposited in the portal connective tissue which stimulates fibrosis If not treated, it can lead to cirrhosis

Question 73

What does primary haemochromatosis predispose to?

Answer 73

Carcinoma

Question 74

What other conditions does haemochromatosis cause?

Answer 74

Diabetes Cardiac failure Impotence

Question 75

Which stain on a biopsy confirms iron in hepatocytes?

Answer 75

Perl's stain | this stains iron blue

Question 76

What factors does the outcome of haemochromatosis depend on?

Answer 76

genetics therapy (venesection) cofactors such as alcohol

Question 77

What are possible outcomes of haemochromatosis?

Answer 77

Cirrhosis | Hepatocellular carcinoma

Question 78

What is Wilson's disease?

Answer 78

Inherited autosomal recessive disorder of copper metabolism

Question 79

Where does copper accumulate in Wilson's disease?

Answer 79

The liver and the basal ganglia of the brain

Question 80

How does Wilson's disease manifest in the eyes?

Answer 80

Kayser-Fleischer rings (dark rings around the iris)

Question 81

What is there a low serum concentration of in Wilson's disease?

Answer 81

Ceruloplasmin

Question 82

What does Wilson's disease cause?

Answer 82

Causes chronic hepatitis and neurological deterioration

Question 83

What is alpha-1 antitrypsin deficiency?

Answer 83

Inherited autosomal recessive disorder of production of an enzyme inhibitor that is produced in the liver

Question 84

What does alpha 1 antitrypsin deficiency cause?

Answer 84

Injury to hepatocytes which results in progressive fibrosis and cirrhosis It also predisposes to pulmonary emphysema due to the unopposed actions of neutrophil enzymes damaging the alveolar walls.

Question 85

What happens to the abnormal protein in alpha 1 antitrypsin deficiency?

Answer 85

The protein is misfolded and it cannot be secreted from the hepatocyte It accumulates in the periportal hepatocytes where it can be visualised as globular inclusions

Question 86

Is the risk of liver cell carcinoma greater in macronodular or micronodular cirrhosis?

Answer 86

Macronodular

Question 87

What are the tumours of the liver?

Answer 87

Primary- rare Hepatocellular adenoma Hepatocellular carcinoma (hepatoma) Secondary- common multiple metastases from colon, pancreas, stomach, breast, lung, others

Question 88

What is a hepatocellular adenoma?

Answer 88

A benign, well-differentiated neoplasm of hepatocytes.

Question 89

Is hepatocellular adenoma more common in males or females?

Answer 89

Females

Question 90

What can hepatocellular adenomas cause?

Answer 90

They can become big They can rupture and bleed However most remain asymptomatic

Question 91

Is hepatocellular carcinoma rare or common in Europe?

Answer 91

Rare

Question 92

What is hepatocellular carcinoma associated with?

Answer 92

HBV HCV Cirrhosis

Question 93

How does hepatocellular carcinoma usually present?

Answer 93

As a mass, pain or obstruction | It can also present as decompensation of cirrhosis due to replacement of liver by the cancer

Question 94

What is a diagnostic marker of hepatocellular carcinoma?

Answer 94

Raised alpha-fetoprotein, although it is not usually detectable in early or well differentiated HCC

Question 95

What is cholangiocarcinoma?

Answer 95

Adenocarcinoma arising in bile ducts