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Non-Viral Liver Disease Flashcards

1
Q

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

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

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

A
  1. production of acetaldehyde

2. reduced nicotinamide adenine

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3
Q

What is steatosis?

A

fatty change to the liver

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4
Q

What is steatohepatitis?

A

fatty change and acute inflammation

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5
Q

What are the causes of macrovesicular steatosis? (5)

A
  1. obesity
  2. diabetes melitus
  3. malnutrition
  4. drugs/toxins
  5. chronic illness
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6
Q

What are the causes of microvesicular steatosis? (4)

A
  1. acute fatty liver of pregnancy
  2. reye’s syndrome
  3. tetracycline toxicity
  4. hepatitis C
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7
Q

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

A
  1. asymptomatic
  2. malaise
  3. abdominal discomfort
  4. nausea
  5. anorexia
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8
Q

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

A
  1. no signs

2. hepatomegaly - tender

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9
Q

What lab values increase in fatty liver disease?

A
  1. serum bilirubin

2. alkaline phosphatase

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10
Q

What are characteristics of alcoholic hepatitis? (4)

A
  1. mallory hyaline inclusions in hepatocytes
  2. necrosis of hepatocytes
  3. neutrophil inflammatory infiltrate
  4. fibrosis
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11
Q

What is the pathogenesis of alcoholic hepatitis? (5)

A
  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
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12
Q

What are the symptoms of alcoholic hepatitis? (6)

A
  1. acute onset
  2. malaise
  3. abdominal discomfort
  4. nausea
  5. anorexia
  6. +/- fulminant liver failure
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13
Q

What are the signs of alcoholic hepatitis? (3)

A
  1. none
  2. hepatomegaly - tender
  3. Jaundice
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14
Q

What values increase in alcoholic hepatitis? (3)

A
  1. aminotransferases
  2. bilirubin
  3. neutrophils
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15
Q

What is the pathogenesis of live fibrosis? (4)

A
  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
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16
Q

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

A
  1. obesity
  2. hypertension
  3. type II diabetes
  4. hyperlipidaemia
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17
Q

Why are infarcts of the liver uncommon?

A

there is dual supply

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18
Q

What causes extrahepatic obstruction of the portal vein?

A
  1. peritoneal sepsis
  2. hilar lymph node enlargement
  3. splenic vein thrombosis secondary to pancreatitis
  4. post surgical
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19
Q

What is budd chiari syndrome?

A

thrombosis of the portal vein

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20
Q

what is primary biliary cholangitis?

A

chronic non-suppurative, destructive cholangitis

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21
Q

What is Charcot’s triad in ascending cholangitis?

A
  1. fever
  2. jaundice
  3. Biliary colic/RUQ pain
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22
Q

What happens in primary biliary cholangitis?

A

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

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23
Q

Who is affected by primary biliary cholangitis?

A

women mid 50s

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24
Q

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

A
  1. fatigue
  2. jaundice
  3. pruritus
  4. hepatomegaly
  5. xanthelasma
  6. xanthomas
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25
What lab values are different in primary biliary cholangitis? (4)
1. increased alkaline phosphatase 2. increased bilirubin 3. increased cholesterol 4. aminotransferases are normal or slightly elevated
26
What are the disease associations of primary biliary cholangitis? (7)
1. sjogren's syndrome 2. scleroderma 3. rheumatoid arthritis 4. autoimmune thyroiditis 5. coeliac disease 6. SLE 7. pulmonary fibrosis
27
What is the macroscopic pathology of primary biliary cholangitis? (2)
1. early - no abnormality | 2. advanced - cirrhotic, heavily bile-stained liver
28
What are the four stages of primary biliary cholangitis? (4)
1. florid duct lesion 2. ductular proliferation 3. fibrosis 4. cirrhosis
29
What is the florid duct lesion in primary biliary cholangitis? (2)
1. random focal destruction of bile ducts associated with heavy chronic inflammation 2. granulomas are often present
30
What is ductular proliferation in primary biliary cholangitis?
more extensive involvement of ducts with reduction in the number of bile ducts and proliferation of ductules
31
What is fibrosis in primary biliary cholangitis? (3)
1. expansion of portal tracts by fibrous tissue 2. may bridge 3. ducts diminished
32
What is cirrhosis in primary biliary cholangitis?
micronodular cirrhosis with focal scant inflammation
33
What happens immunologically in primary biliary cholangitis? (3)
1. increased IgM 2. autoantibodies especially anti-mitochondrial antibody 3. circulating immune complexes
34
What anti-mitochondrial antibodies are present in primary biliary cholangitis? (2)
1. anti-M2 is always present and specific to PBC | 2. anti-M4 and anti-M8 indicate aggressive disease
35
What is the aetiology of primary biliary cholangitis? (3)
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
36
What is primary sclerosing cholangitis?
chronic inflammatory and scarring condition of intra and extrahepatic ducts
37
Who is affected by primary sclerosing cholangitis?
men more than women
38
What is the appearance of primary sclerosing cholangitis on cholangiography?
beading, chain of lakes
39
What is primary sclerosing cholangitis associated with?
chronic inflammatory bowel disease - ulcerative colitis
40
What is the pathology of primary sclerosing cholangitis?
aberrant homing of T cells activated by colonic mucosal inflammation
41
What are the symptoms of primary sclerosing cholangitis?
1. fatigue 2. pruritus 3. jaundice 4. ascending cholangitis 5. cirrhosis
42
What does primary sclerosing cholangitis put people at risk of?
cholangiocarcinoma
43
What is the pathogenic mechanism of autoimmune hepatitis? (3)
1. cytotoxic t cell mediated 2. high titres of non-organ specific autoantibodies 3. high levels of organ specific antibodies
44
What is the histopathology of autoimmune hepatitis? (4)
1. interface hepatitis? 2. regenerative hepatocyte rosettes? 3. lymphocytes 4. plasma cells
45
What are hepatocytotoxic metabolic diseases? (3)
1. haemochromatosis 2. Wilson's disease 3. alpha1-antitrypsin deficiency
46
What are hyperbilirubinaemic metabolic diseases? (3)
1. Gilbert's disease 2. Dublin Johnson Syndrome 3. Rotor Syndrome
47
What is haemochromatosis?
excessive accumulation of body iron
48
What is primary haemochromatosis?
Hepatocytes then kupffer cells
49
What is secondary haemochromatosis?
Kupffer cells then hepatocytes
50
What causes secondary haemochromatosis? (4)
1. parenteral iron overload 2. increased oral intake and absorption 3. ineffective erythropoiesis 4. chronic liver disease
51
What is the cause of hereditary haemochromatosis?
mutation of haemochromatosis gene which encodes a HLA class I like molecule that regulates intestinal absorption of dietary iron
52
What are the most common mutations in haemochromatosis? (2)
1. C282Y | 2. H63D
53
What is the classic triad in haemochromatosis? (3)
1. pigmented micronodular cirrhosis 2. skin pigmentation 3. diabetes melitis
54
How does haemochromatosis? (5)
1. hepatomegaly 2. abdominal pain 3. cardiac dysfunction 4. atypical arthritis 5. hypogonadism
55
How is haemochromatosis treated?
phlebotomy
56
What is Wilson's disease?
insufficient copper excretion
57
What is the inheritance pattern of Wilson's disease? (2)
1. autosomal recessive | 2. ATPB7 gene - copper transporting ATPase
58
What is the pathogenesis of Wilson's disease? (5)
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
59
What causes alpha 1 anti-trypsin deficiency?
autosomal recessive mutations cause abnormal protein folding and impaired release cause liver disease and cirrhosis
60
What is the commonest mutant in alpha 1 anti-trypsin disease?
PiZ
61
What is the histological characteristics of alpha 1 anti-trypsin deficiency? (2)
1. round to oval cytoplasmic globular inclusions in hepatocytes 2. indistinct on H and E stains 3. Strong PAS-positivity 4. Diastase resistant
62
What is Gilbert's syndrome? (2)
1. impaired glucuronidation therefore mildly increased un-conjugated serum bilirubin 2. heritable un-conjugated hyperbilirubinaemia
63
What is the cause of Gilbert's syndrome? (2)
1. autosomal recessive | 2. abnormal HUG-Br1 promoter
64
What are the heritable conjugated hyperbilirubinaemia? (2)
1. Dubin Johnson syndrome | 2. rotor syndrome
65
What is dubin johnson syndrome? (2)
1. can't get bilirubin into hepatocytes and conjugated | 2. can't get it out of hepatocytes to bile
66
What is rotor syndrome?
abnormal organic anion transporters into hepatocytes and impaired biliary excretions

GI/GU Illness (15 decks)

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