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Flashcards in Pathology of the liver Deck (95):
1

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

The lobular concept and the acinar concept

2

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

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

3

Are all liver cells capable of regeneration?

Yes

4

Do liver cells replicate frequently?

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.

5

What is the late stage of all chronic liver diseases?

Cirrhosis

6

What is cirrhosis defined as?
What effects does it have on the liver?

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.

7

What are the possible outcomes of acute liver failure?

complete recovery
chronic liver disease
death from liver failure

8

Are all patients with severe liver disease jaundiced?

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.

9

How is jaundice classified?

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

Conjugated
Unconjugated

10

What causes pre-hepatic jaundice?
What type of bilirubin causes the jaundice?

Haemolysis of any type.
Unconjugated bilirubin

11

What causes hepatic jaundice?

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

12

What causes post hepatic jaundice?

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

13

Is cirrhosis reversible or irreversible?

Irreversible

14

What are features of cirrhosis?

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

15

How is cirrhosis classified?

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

16

What are the major complications of cirrhosis?

Liver failure
Portal hypertension
Infection
Liver cell carcinoma

17

What are common causes of cirrhosis?

Alcohol
Hep B and C
Iron overload

18

Is liver failure a manifestation of compensated or decompensated cirrhosis?

Decompensated

19

What causes hepatic encephalopathy?

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

20

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

Renal failure (hepato-renal syndrome)

21

What does failure to eliminate endogenous steroid hormones result in?

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

22

What are results of portal hypertension?

Oesophageal varices
Caput medusa
Haemorrhoids
Ascites

23

Is cirrhosis the only cause of portal hypertension?

No

24

What is the reason for oedema in chronic liver disease?

Reduced albumin synthesis resulting in hypoalbuminaemia

25

What is the reason for ascites in chronic liver disease?

Hypoalbuminaemia
Secondary hyperaldosteronism
Portal hypertension

26

What is the cause of haematemesis in chronic liver disease?

Ruptured oesophageal varices due to portal hypertension

27

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

Hyperoestrogenism

28

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

Reduced clotting factor synthesis

29

What is the cause of coma in chronic liver disease?

Failure to eliminate toxic gut bacteria metabolites (false neurotransmitters)

30

What is the cause of infection in chronic liver disease?

Reduced Kuppfer cell number and function

31

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

Alcohol liver disease

32

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

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.

33

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

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

34

Outline the pathogenesis of alcoholic liver disease

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.

35

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

It is identical

36

Which patients get non-alcoholic steatohepatitis?

Patients with diabetes, hyperlipidaemia and obesity

37

What can non-alcohol steatohepatitis lead to?

In a proportion of patients it can progress to cirrhosis

38

How does Hep A cause liver damage?

It is directly cytopathic

39

It is possible to have Hep A carriers?

No

40

is it possible to have Hep B carriers?

yes

41

What are the different outcomes of Hep B infection?

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

42

What are the different outcomes of Hep C infection?

Chronic Hepatitis
Cirrhosis

43

Is autoimmune hepatitis more common in males or females?

Females

44

What can autoimmune hepatitis cause?

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

45

How is autoimmune hepatitis characterised histologically?

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

46

Which autoimmune liver disease is associated with antibodies to mitochondria?

Primary biliary cirrhosis

47

What causes primary biliary cirrhosis?

Unknown

48

What is the indication for biopsy in primary biliary cirrhosis?

To stage the disease

49

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

Granulomas
Bile duct loss

50

What are clinical features of primary biliary cirrhosis?

Pruritis
Xanthelasmas

51

What is the pathogenesis of primary biliary cirrhosis if untreated?

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

52

What autoantibodies are present in autoimmune hepatitis?

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

53

What could be a potential trigger for autoimmune hepatitis?

Some drugs

54

What may chronic drug-induced hepatitis trigger?

Autoimmune hepatitis

55

Which drugs can damage the liver?

Innumerable

56

What can cause the damage to the liver by drugs?

It may be dose related, or idiosyncratic (unpredictable)

57

What harmful effects can drugs have on the liver?

Hepatitis
Granulomas
Fibrosis
Necrosis
Failure
Cholestasis
Cirrhosis

58

Which liver diseases can drug induced liver injury mimic?

Any

59

What is primary sclerosing cholangitis?

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.

60

What does primary sclerosing cholangitis lead to?

Periductal fibrosis
Duct destruction
Jaundice
Fibrosis

61

What other inflammatory disease is primary sclerosing cholangitis linked to?

Ulcerative colitis

62

Are males or females more affected by primary sclerosing cholangitis?

Males

63

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

Malignancy in bile ducts and colon

64

Name some storage diseases of the liver

Haemochromatosis
Wilsons disease
Alpha-1-antitrypsin deficiency

65

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

Hepatocytes

66

What can large amounts of iron in the liver cause?

Liver damage

67

What is haemochromatosis?

Excess iron within the liver

68

What is primary haemochromatosis?

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

69

What can cause secondary haemochromatosis?

Iron overload from the diet
Transfusions
Iron therapy

70

How is primary haemochromatosis inherited?

It is an autosomal recessive condition

71

What protects younger women from the effects of primary haemochromatosis?

Menstruation

72

Describe how primary haemochromatosis progresses

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

73

What does primary haemochromatosis predispose to?

Carcinoma

74

What other conditions does haemochromatosis cause?

Diabetes
Cardiac failure
Impotence

75

Which stain on a biopsy confirms iron in hepatocytes?

Perl's stain
this stains iron blue

76

What factors does the outcome of haemochromatosis depend on?

genetics
therapy (venesection)
cofactors such as alcohol

77

What are possible outcomes of haemochromatosis?

Cirrhosis
Hepatocellular carcinoma

78

What is Wilson's disease?

Inherited autosomal recessive disorder of copper metabolism

79

Where does copper accumulate in Wilson's disease?

The liver and the basal ganglia of the brain

80

How does Wilson's disease manifest in the eyes?

Kayser-Fleischer rings (dark rings around the iris)

81

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

Ceruloplasmin

82

What does Wilson's disease cause?

Causes chronic hepatitis and neurological deterioration

83

What is alpha-1 antitrypsin deficiency?

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

84

What does alpha 1 antitrypsin deficiency cause?

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.

85

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

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

86

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

Macronodular

87

What are the tumours of the liver?

Primary- rare
Hepatocellular adenoma
Hepatocellular carcinoma (hepatoma)

Secondary- common
multiple
metastases from colon, pancreas, stomach, breast, lung, others

88

What is a hepatocellular adenoma?

A benign, well-differentiated neoplasm of hepatocytes.

89

Is hepatocellular adenoma more common in males or females?

Females

90

What can hepatocellular adenomas cause?

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

91

Is hepatocellular carcinoma rare or common in Europe?

Rare

92

What is hepatocellular carcinoma associated with?

HBV
HCV
Cirrhosis

93

How does hepatocellular carcinoma usually present?

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

94

What is a diagnostic marker of hepatocellular carcinoma?

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

95

What is cholangiocarcinoma?

Adenocarcinoma arising in bile ducts

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