GI Flashcards
what disease causes gene defect of UDP enzyme deficiency
crigler najjar - severe form from birth
gilbert syndrome - mild hyperbilirubinaemia
UGT1AT gene defect, causes UDP deficiency
so less bilirubin metabolism causing high UNconjugated bilirubin
what gene defect causes Dublin-johnson syndrome
MRP2 gene defect
what does INR measure
extrinsic coagulation
3+7 -> 10 -> 2 (thrombin) -> 1 (fibrin)
bilirubin/INR measure prognosis
what are time scales for acute, subacute, chronic liver diseases
acute <6wk, subacute 6-25wk, chronic 25+wk
what are the stages of progressive liver disease
normal -> steatohepatitis -> fibrosis ->
(IRREVERSIBLE) cirrhosis -> hepatocellular carcinoma
fibrosis is reversible, cirrhosis is not
cirrhosis is when liver architecture replaced by fibrotic nodules
how does cirrhosis appear on liver US
heterogenous irregular liver
splenomegaly, ascites
how is hepatic fibrosis assessed invasively + non
non:
ALT/AST levels
fibroscan for liver stiffness
FIB-4 scan
ELF test
invasive: biopsy (gold standard)
what are features of decompensated liver disease
jaundice
ascites
vatical bleed/haemorrhage
hepatic encephalopathy
coagulopathy INR >2
what is acute liver failure
jaundice -> encephalopathy within 4wk
no pre-existing liver disease
if pre-existing disease, acute on chronic liver failure instead
what is Budd chiari syndrome
portal vein thrombosis = main vessel to liver
triad - ascites, abdo pain, hepatomegaly
what is screened for in:
hepatitis serology
autoimmune hepatitis
ASH/NASH
PBC
alpha-1 antitrypsin deficiency
wilson disease
hereditary haemochromoatosis
hepatitis: hepA IgM, hepB sAg, hepC Ab, hepE IgM
autoimmune: ANA, anti-smooth muscle, LKM antibodies
ASH/NASH depends on ALT/AST ratio, if ALT high = fatty, if AST high = alcohol
PBC: anti-M2 (mitochondrial)
alpha-1: serum alpha-1 AT, phenotype
wilson: low serum Cu, low serum caeruloplasmin
HH: high serum ferritin
what is autoimmune hepatitis (what is it associated with) and how is it treated
usually affects women
associated with HLA DRB1/3
ANA, anti-smooth muscle, LMK Ab
treat with immunosuppression
what is PBC and how is it treated
usually affects women 40-50yr
causes granulomatous hepatitis affecting interlobular bile ducts
anti-M2
causes jaundice, pruritus/itch
treat with ursodeoxycholic acid (2nd line obtecholic acid)
what is PSC and how is it treated
associated with UC
triggered by bacteria and PAMP entering portal circulation via inflamed intestine
affects intra + extra hepatic bile ducts
biopsy shows concentric fibrosis of intra+extra-hepatic ducts
no effective treatment
increased risk of cholangiocarcinoma
what are congenital cholestatic syndromes
PFIC/PBIC
PFIC1 - ATP8 18q gene = reduced cholesterol secretion into bile
PFC2 - ATP11 2q gene = reduced bile acid secretion into bile, so hepatic BA accumulation and slowed hepatic BA flow
PFC3 - ACB4 7 q gene = less PL secretion, so bile more toxic
how do acute + chronic hepatitis differ
acute 1-3months = more florid
chronic 6month+ = abnormal LFT, positive serology
how many stages of hepatic fibrosis
6
s1-s3 = fibrosis of more portal areas
s4 = fibrosis bridging portal areas
s5 = probable cirrhosis
s6 = confirmed cirrhosis
summarise the different hepatitis viruses
A = acute infection, RNA picornavirus transmitted via faecal/oral route
investigate by checking HepA IgM
B (VACCINE) = acute->chronic, DNA virus transmitted via blood
most common cause globally
investigate with serology
if HepB sAg +ve, then treat (1st line: peginterferon a2, 2nd live: tenofovir/ectovir)
C = chronic, RNA virus transmitted via blood (body fluids - needles, sex OR vertical transmission)
usually IVDU
if HCV RNA +ve, then treat (sofosbuvir)
D = chronic, RNA virus that only infects if HepB also present, so spread via blood
treat with pegylated interferon-a (low success rate)
E = acute, ssRNA spread via faecal-oral route
if pregnant, risk of fulminant hepatitis
how does HBV replicate
DNA virus
via reverse transcription of RNA intermediate
how does immune system down regulate HBV viral replication and protein synthesis
TLR3 recognises HBV’s PAMP with RIG-I signalling
IFN NF-kB activates interferon stimulating genes
these form IFN a/B that reduce viral replication + protein synthesis
also promote adaptive immunity via MHC-class1 expression on APC
causing cell death via perforins
what antibody provides lifelong immunity against HBV
HepB sAb - neutralising Ab against HBsAg that prevents uptake by uninfected hepatocytes
early priming of CD4+ and CD8+ intrehepatically
how does HBV persist to cause chronic infection
HBX protein protects cccDNA, preventing antigen presentation/processing
T-reg express more FoxP3, suppressing CD4/CD8
CD28 upregulated causes apoptosis of HBV specific T cell
IFN-a/y inhibited
what does HBV DNA correlate to
risk of fibrosis + HCC
why does HDV rely on HBV
HDV is an incomplete RNA virus, enclosed in shell of HBsAg
HDV is a satellite virus, so can not make its own viral proteins or replicate independently
how is chronic HBV + HCV treated
HBV - pegylated interferon-a2, tenofovir, ectovir (if HBsAg +ve)
HBV vaccine available
HCV - sofosbuvir (if HCV RNA +ve)
no vaccine for HepC
how does HCV cause chronic infection
RNA virus with rapid replication rate, so high viral load
many mutants (quasi-species that escape immune system) form as high error rate of RNA-polymerase
HCV non-structural viral proteins disrupt RIG-I signalling, inhibiting innate immunity
neutralising Ab develop too slowly and don’t last long
