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Gastrointestinal > Aetiology and Pathophysiology of Chronic Liver Disease > Flashcards

Aetiology and Pathophysiology of Chronic Liver Disease Flashcards

1
Q

what is chronic liver disease

A

duration > 6 months

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2
Q

outcome of chronic liver disease

A

cirrhosis

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3
Q

symptoms and signs of chronic liver disease

A

dependent on underlying disease or features of cirrhosis

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4
Q

pathology of chronic liver disease

A

recurrent inflammation
repair with fibrosis and regeneration = cirrhosis compensated
cirrhosis eventually becomes decompensated

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5
Q

what are kupffer cells

A

specialised macrophages lining the walls of sinusoids

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6
Q

causes of chronic liver disease - cirrhosis causes

A 
alcohol 
NAFLD
HCV
primary biliary cholangitis 
autoimmune hepaititis 
HBC
haemochromatosis 
primary sclerosing cholangitis 
wilson's disease
alpha 1anti-trypsin 
budd-chiari
methotrexate
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7
Q

diseases affecting the liver which are chronic

A

amyloid
rotor syndrome
they are not causes of chronic liver disease as they do not causes cirrhosis

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8
Q

causes of NAFLD

A

metabolic syndromes;
obesity
type II diabets (insulin resistance)
HDL cholesterol

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9
Q

progression of NAFLD

A

steatosis
NASH (fibrosis)
steatohepatitis with fibrosis
cirrhosis

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10
Q

pathogenesis of NAFLD

A

unknown

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11
Q

treatment of NAFLD - steatosis

A

limited options
weight loss
exercise

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12
Q

die causes of NAFLD

A

energy intake
density
fat
fructose

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13
Q

histologic features of NASH

A

inflammation
hepacyte degeneration
fibrosis

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14
Q

inflammation features in NASH

A

mild
lobular
mixed mononuclear and neutrophilic

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15
Q

hepatocyte degeneration features in NASH

A

ballooning

mallory bodies

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16
Q

fibrosis features in NASH

A

initially pericellular

later bridging

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17
Q

risk factors of NAFLD

A

triglycerides

hypertension

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18
Q

tests for NAFLD - steatosis

A

ultrasound

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19
Q

complications of NAFLD - steatosis

A

increased CVD risk

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20
Q

tests for NAFLD - NASH

A

liver biopsy

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21
Q

complications of NAFLD - NASH

A

progression to cirrhosis

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22
Q

treatment for NAFLD - NASH

A

weight loss
exercise
experimental treatments

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23
Q

types of autoimmune liver disease

A 
primary biliary cholangitis (PBC) (cirrhosis)
auto-immune hepatitis 
primary sclerosing cholangitis 
alcohol related liver disease 
drug reactions
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24
Q

PBC aetiology

A

genetic mutation - M2-E2 E3 subunits of PDC-E2 in inner leaflet of mitochondrial membrane
middle aged woman

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25
Q

immunopathology of PBC

A

T cell mediated - CD4+ react to M2 target resulting in loss of tolerance

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26
Q

symptoms of PBC

A

asymptomatic
fatigue
itch without rash
Xanthesalma

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27
Q

tests for PBC

A

anti-mitochondrial antibodies
cholestatic LFTs
liver biopsy

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28
Q

treatment for PBC

A

Urseo deoxycholic acid

Obeticholic acid

29
Q

outcomes of PBC

A

many patients may not develop symptoms or liver failure

many liver failures caused by PBC will be unfit for transplant

30
Q

describe auto-immune hepatitis

A

affects woman more than men
type 1 - adult

poor prognosis if untreated
cirrhosis likely to develop

31
Q

describe type 2 aut-immune hepatitis

A

affects children and young adults

very rare

32
Q

immunology of type 2 auto-immune hepatitis

A

LKM-1

anti-mitochondrial antibodies

33
Q

describe type 1 auto-immune hepatitis

A

affects adults (young and elderly)
more common in females
uncommon

34
Q

immunology of type 1 auto-immune hepatitis

A

anti nuclear antibody
anti-smooth muscle antibodies
soluble liver antigens antibodies severity

35
Q

extra hepatic manifestations of autoimmune hepatitis

A 
Autoimmune thyroiditis
graves disease
chronic UC
Less commonly with;
RA
pernicious anemia
systemic sclerosis
ITP
SLE
36
Q

symptoms of autoimmune hepatitis

A 
acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis;
malaise
fatigue 
lethargy 
nausea
abdominal pain 
anorexia
37
Q

LFTs of autoimmune hepatitis

A

elevated AST and ALT

elevated PT

38
Q

signs of autoimmune hepatitis

A

hepatomegaly
jaundice
stigma of chronic liver disease
splenomegaly

39
Q

tests for autoimmune hepatitis

A

LFTs
elevated IgG
presence of autoimmune antibodies
liver biopsy

40
Q

histology of autoimmune hepatitis

A

chronic hepatitis with marked piecemeal necrosis and lobular involvement
interface hepatitis and plasma cells

41
Q

genetic predisposing factors of autoimmune hepatitis

A

HLA-DR3 - early onset, severe
HLA-DR4 - late onset, extrahepatic manifestations, good response to steroids
IgG
T cell receptors

42
Q

environmental triggers of autoimmune hepatitis

A

certain viruses
drugs
toxins

43
Q

drugs triggering autoimmune hepatitis

A 
Oxyphenisatin
Methyldopa
Nitrofurantoin
Diclofenac
Minocycline
statins
44
Q

treatment for autoimmune hepatitis

A

prednisone - high and taper down

azathioprine

45
Q

complications autoimmune hepatitis

A

oesophageal varies

cirrhosis

46
Q

what is primary sclerosing cholangitis

A

autoimmune destructive disease of large and medium sized bile ducts
recurrent cholangitis

47
Q

epidemiology of primary sclerosing cholangitis

A

men

patients usually have colitis (UC)

48
Q

tests for primary sclerosing cholangitis

A

imaging of biliary tree - MRCP and ERCP

49
Q

treatment for primary sclerosing cholangitis

A

maintain bile flow

monitor for cholangiocarcinoma and colo-rectal cancer

50
Q

what is haemochromatosis

A

genetic iron overload syndrome - mono genetic autosomal recessive

51
Q

mutated gene in haemochromatosis

A

HFE gene

52
Q

pathology of haemochromatosis

A

cirrhosis
cardiomyopathy
pancreatic failure

53
Q

treatment of haemochromatosis

A

venesection

54
Q

what is Wilsons disease

A

lenticular hepatic degeneration - mono genetic autosomal recessive disease

55
Q

mutated gene is Wilsons disease

A

loss of function or loss of protein muationsin caeruloplasmin;
copper binding protein
loss of copper regulation
massive tissue deposition of copper, especially liver and basal ganglia

56
Q

clinical features of Wilsons disease

A

Neurological- chorea-atheitoid movements
Hepatic – cirrhosis or sub-fulminant liver failure
Kaiser Fleisher rings

57
Q

treatment for Wilsons disease

A

copper chelation drugs

58
Q

describe alpha 1 anti-trypsin deficiency

A

genetic mutations in A1AT genes at multiple sites - causing variable phenotype
protein function lost excess tryptic activity

59
Q

clinical features of alpha 1 anti-trypsin deficiency

A

lung emphysema

liver disposition of mutant protein, cell damage

60
Q

treatment for alpha 1 anti-trypsin deficiency

A

supportive management

61
Q

what is Budd-chiari

A

thrombosis of hepatic veins;
congenital webs
thrombotic tendency, protein C or S deficiency

62
Q

clinical features of budd-chiari

A

acute - jaundice, tender hepatomegaly

chronic - ascites

63
Q

tests for Budd-chiari

A

ultrasound of hepatic veins

64
Q

treatment for Budd-chiari

A

recanalization or TIPS

65
Q

what is methotrexate

A

drug used to treat rheumatoid arthritis and psoriasis

66
Q

effect of methotrexate on the liver

A

dose dependent liver toxin - progressive fibrosis

stop drug to prevent fibrosis

67
Q

describe cardiac cirrhosis

A

secondary to high right heart pressures

68
Q

causes of cardiac cirrhosis

A

incompetent tricuspid calve
congenital
rheumatic fever
constrictive pericarditi

69
Q

cardiac cirrhosis effect on the liver

A

congestive heart failure causing;
ascites
liver impairment

Gastrointestinal (71 decks)

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