Non-Viral Liver Disease

Question 1

How does ethanol consumption lead to alcoholic liver disease? (3)

Answer 1

1. promotion of lipid accumulation within the liver
2. liver cell injury due to increased oxidative stress
3. decreased intake of vitamins

Question 2

How does ethanol metabolism lead to alcoholic liver disease? (2)

Answer 2

1. production of acetaldehyde

2. reduced nicotinamide adenine

Question 3

What is steatosis?

Answer 3

fatty change to the liver

Question 4

What is steatohepatitis?

Answer 4

fatty change and acute inflammation

Question 5

What are the causes of macrovesicular steatosis? (5)

Answer 5

1. obesity
2. diabetes melitus
3. malnutrition
4. drugs/toxins
5. chronic illness

Question 6

What are the causes of microvesicular steatosis? (4)

Answer 6

1. acute fatty liver of pregnancy
2. reye’s syndrome
3. tetracycline toxicity
4. hepatitis C

Question 7

What are the symptoms of fatty liver disease? (5)

Answer 7

1. asymptomatic
2. malaise
3. abdominal discomfort
4. nausea
5. anorexia

Question 8

What are the signs of fatty liver disease? (2)

Answer 8

1. no signs

2. hepatomegaly - tender

Question 9

What lab values increase in fatty liver disease?

Answer 9

1. serum bilirubin

2. alkaline phosphatase

Question 10

What are characteristics of alcoholic hepatitis? (4)

Answer 10

1. mallory hyaline inclusions in hepatocytes
2. necrosis of hepatocytes
3. neutrophil inflammatory infiltrate
4. fibrosis

Question 11

What is the pathogenesis of alcoholic hepatitis? (5)

Answer 11

1. increased GI ppermeability to endotoxin
2. fee radicals generated by the microsomal ethanol oxidising system react with cellular membranes and proteins
3. alcohol affects microtubule and mitochondrial function and membrane fluidity
4. acetaldehyde increases lipid peroxidation and is a cell toxin
5. induction of cyto P450 increases transformation of rugs to toxic metabolites

Question 12

What are the symptoms of alcoholic hepatitis? (6)

Answer 12

1. acute onset
2. malaise
3. abdominal discomfort
4. nausea
5. anorexia
6. +/- fulminant liver failure

Question 13

What are the signs of alcoholic hepatitis? (3)

Answer 13

1. none
2. hepatomegaly - tender
3. Jaundice

Question 14

What values increase in alcoholic hepatitis? (3)

Answer 14

1. aminotransferases
2. bilirubin
3. neutrophils

Question 15

What is the pathogenesis of live fibrosis? (4)

Answer 15

1. Kupffer cell activation leads to proinflammatory cytokines
2. amplification of cytokine stimuli by platelet activating factor released by endothelial and kupffer cells
3. neutrophil infiltration, activation, release
4. stellate cells produce collagen type I and III in the space of Disse

Question 16

Wha are the risk factors for non-alcoholic fatty liver disease? (4)

Answer 16

1. obesity
2. hypertension
3. type II diabetes
4. hyperlipidaemia

Question 17

Why are infarcts of the liver uncommon?

Answer 17

there is dual supply

Question 18

What causes extrahepatic obstruction of the portal vein?

Answer 18

1. peritoneal sepsis
2. hilar lymph node enlargement
3. splenic vein thrombosis secondary to pancreatitis
4. post surgical

Question 19

What is budd chiari syndrome?

Answer 19

thrombosis of the portal vein

Question 20

what is primary biliary cholangitis?

Answer 20

chronic non-suppurative, destructive cholangitis

Question 21

What is Charcot’s triad in ascending cholangitis?

Answer 21

1. fever
2. jaundice
3. Biliary colic/RUQ pain

Question 22

What happens in primary biliary cholangitis?

Answer 22

progressive cholestatic condition of unknown aetiology characterised by chronic inflammation of small to medium sized intrahepatic bild ducts leading to their destruction and eventually cirrhosis

Question 23

Who is affected by primary biliary cholangitis?

Answer 23

women mid 50s

Question 24

What are the symptoms of primary biliary cholangitis? (6)

Answer 24

1. fatigue
2. jaundice
3. pruritus
4. hepatomegaly
5. xanthelasma
6. xanthomas

Question 25

What lab values are different in primary biliary cholangitis? (4)

Answer 25

1. increased alkaline phosphatase 2. increased bilirubin 3. increased cholesterol 4. aminotransferases are normal or slightly elevated

Question 26

What are the disease associations of primary biliary cholangitis? (7)

Answer 26

1. sjogren's syndrome 2. scleroderma 3. rheumatoid arthritis 4. autoimmune thyroiditis 5. coeliac disease 6. SLE 7. pulmonary fibrosis

Question 27

What is the macroscopic pathology of primary biliary cholangitis? (2)

Answer 27

1. early - no abnormality | 2. advanced - cirrhotic, heavily bile-stained liver

Question 28

What are the four stages of primary biliary cholangitis? (4)

Answer 28

1. florid duct lesion 2. ductular proliferation 3. fibrosis 4. cirrhosis

Question 29

What is the florid duct lesion in primary biliary cholangitis? (2)

Answer 29

1. random focal destruction of bile ducts associated with heavy chronic inflammation 2. granulomas are often present

Question 30

What is ductular proliferation in primary biliary cholangitis?

Answer 30

more extensive involvement of ducts with reduction in the number of bile ducts and proliferation of ductules

Question 31

What is fibrosis in primary biliary cholangitis? (3)

Answer 31

1. expansion of portal tracts by fibrous tissue 2. may bridge 3. ducts diminished

Question 32

What is cirrhosis in primary biliary cholangitis?

Answer 32

micronodular cirrhosis with focal scant inflammation

Question 33

What happens immunologically in primary biliary cholangitis? (3)

Answer 33

1. increased IgM 2. autoantibodies especially anti-mitochondrial antibody 3. circulating immune complexes

Question 34

What anti-mitochondrial antibodies are present in primary biliary cholangitis? (2)

Answer 34

1. anti-M2 is always present and specific to PBC | 2. anti-M4 and anti-M8 indicate aggressive disease

Question 35

What is the aetiology of primary biliary cholangitis? (3)

Answer 35

1. epithelial transcytosis of circulating IgA bound PDC-E2 2. chronic infection with a pathogen carrying an antigen cross-reacting with M antigen may activate T cell clones which recognise the cross reacting determinants on bile duct epithelium 3. antibodies and circulating t-cells to the pyruvate dehydrogenase

Question 36

What is primary sclerosing cholangitis?

Answer 36

chronic inflammatory and scarring condition of intra and extrahepatic ducts

Question 37

Who is affected by primary sclerosing cholangitis?

Answer 37

men more than women

Question 38

What is the appearance of primary sclerosing cholangitis on cholangiography?

Answer 38

beading, chain of lakes

Question 39

What is primary sclerosing cholangitis associated with?

Answer 39

chronic inflammatory bowel disease - ulcerative colitis

Question 40

What is the pathology of primary sclerosing cholangitis?

Answer 40

aberrant homing of T cells activated by colonic mucosal inflammation

Question 41

What are the symptoms of primary sclerosing cholangitis?

Answer 41

1. fatigue 2. pruritus 3. jaundice 4. ascending cholangitis 5. cirrhosis

Question 42

What does primary sclerosing cholangitis put people at risk of?

Answer 42

cholangiocarcinoma

Question 43

What is the pathogenic mechanism of autoimmune hepatitis? (3)

Answer 43

1. cytotoxic t cell mediated 2. high titres of non-organ specific autoantibodies 3. high levels of organ specific antibodies

Question 44

What is the histopathology of autoimmune hepatitis? (4)

Answer 44

1. interface hepatitis? 2. regenerative hepatocyte rosettes? 3. lymphocytes 4. plasma cells

Question 45

What are hepatocytotoxic metabolic diseases? (3)

Answer 45

1. haemochromatosis 2. Wilson's disease 3. alpha1-antitrypsin deficiency

Question 46

What are hyperbilirubinaemic metabolic diseases? (3)

Answer 46

1. Gilbert's disease 2. Dublin Johnson Syndrome 3. Rotor Syndrome

Question 47

What is haemochromatosis?

Answer 47

excessive accumulation of body iron

Question 48

What is primary haemochromatosis?

Answer 48

Hepatocytes then kupffer cells

Question 49

What is secondary haemochromatosis?

Answer 49

Kupffer cells then hepatocytes

Question 50

What causes secondary haemochromatosis? (4)

Answer 50

1. parenteral iron overload 2. increased oral intake and absorption 3. ineffective erythropoiesis 4. chronic liver disease

Question 51

What is the cause of hereditary haemochromatosis?

Answer 51

mutation of haemochromatosis gene which encodes a HLA class I like molecule that regulates intestinal absorption of dietary iron

Question 52

What are the most common mutations in haemochromatosis? (2)

Answer 52

1. C282Y | 2. H63D

Question 53

What is the classic triad in haemochromatosis? (3)

Answer 53

1. pigmented micronodular cirrhosis 2. skin pigmentation 3. diabetes melitis

Question 54

How does haemochromatosis? (5)

Answer 54

1. hepatomegaly 2. abdominal pain 3. cardiac dysfunction 4. atypical arthritis 5. hypogonadism

Question 55

How is haemochromatosis treated?

Answer 55

phlebotomy

Question 56

What is Wilson's disease?

Answer 56

insufficient copper excretion

Question 57

What is the inheritance pattern of Wilson's disease? (2)

Answer 57

1. autosomal recessive | 2. ATPB7 gene - copper transporting ATPase

Question 58

What is the pathogenesis of Wilson's disease? (5)

Answer 58

1. impaired copper excretion and impaired binding to caeruloplasmin 2. decreased biliary copper excretion 3. decreased movement of caeruloplasmin into the blood 4. builds up in liver 5. liver saturation, non-caeruloplasmin bound copper spills out into circulation and into other organs

Question 59

What causes alpha 1 anti-trypsin deficiency?

Answer 59

autosomal recessive mutations cause abnormal protein folding and impaired release cause liver disease and cirrhosis

Question 60

What is the commonest mutant in alpha 1 anti-trypsin disease?

Answer 60

PiZ

Question 61

What is the histological characteristics of alpha 1 anti-trypsin deficiency? (2)

Answer 61

1. round to oval cytoplasmic globular inclusions in hepatocytes 2. indistinct on H and E stains 3. Strong PAS-positivity 4. Diastase resistant

Question 62

What is Gilbert's syndrome? (2)

Answer 62

1. impaired glucuronidation therefore mildly increased un-conjugated serum bilirubin 2. heritable un-conjugated hyperbilirubinaemia

Question 63

What is the cause of Gilbert's syndrome? (2)

Answer 63

1. autosomal recessive | 2. abnormal HUG-Br1 promoter

Question 64

What are the heritable conjugated hyperbilirubinaemia? (2)

Answer 64

1. Dubin Johnson syndrome | 2. rotor syndrome

Question 65

What is dubin johnson syndrome? (2)

Answer 65

1. can't get bilirubin into hepatocytes and conjugated | 2. can't get it out of hepatocytes to bile

Question 66

What is rotor syndrome?

Answer 66

abnormal organic anion transporters into hepatocytes and impaired biliary excretions