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Path: Liver 2 - Failure (iii) (Extraheptaic duct obstruction (Mirizzi…
Path: Liver 2 - Failure (iii)
Jaundice
aka icterus
yellow discolouration of tissues (skin + sclera)
clinical jaundice: bilirubin > 50 mol/l
if > 18 but < 50 = biochem jaundice (hyperbilirubinaemia without jaundice)
has a variety of causes, 1 = cholestasis (failure of bile flow)
cholestasis has other features apart from jaundice
classification
Mechanism/clinical context
excess bilirubin production
abnormalities in uptake/conjugation/excretion enzymes
heptatocellular disease
infiltrative disease in liver
intraheptatic biliary tract disease
extra hepatic biliary tract obstruction/disease
site
pre-hepatic
hepatic
post-hepatic
biochem
unconjugated (indirect)
conjugated (direct)
causes
isolated hyperbilirubinaemia - consider separately
almost always unconjugated
sometimes jaundice
haemolysis (prehepatic)
FBC, film, reticulocyte count, haptoglobin, LDH
Gilbert's syndrome - typically mild elevation
liver + biliary tract disease
predominantly conjugated
not useful for distinguishing hepatocellular damage from obstruction/cholestasis, or acute from chronic
with other abnormal LFTs
what is context + other LFTs?
acute damage
acute obstruction/cholestasis
ALF (+/- HE)
acute flares of chronic liver disease (alcoholic hepatitis, HBV reactivation, AIH)
end stage chronic liver disease
US easy to perform to exclude extra hepatic duct obstruction (post-hepatic)
Bilirubin metabolism
haem breakdown produces unconjugated bilirubin - high water insoluble, circulates bound to albumin
unconjugated bilirubin actively taken up by hepatocytes, along with gluconorate - both get efficiently conjugated using UDPGT-1 enzyme
conjugated bilirubin is water soluble - can be excreted in bile
conjugated hyperbilirubianaemia (hepatic or post hepatic) causes biliruninuria (dark urine as metabolised by kidneys because it can't get to intestine)
bilirubin oxidised in bowel to urobilinogen (makes faeces dark)
only paeds labs measure unconjugated (indirect) bilirubin vs unconjugated (direct) bilirubin separately
Gilbert's syndrome
genetic defect in bilirubin conjugation enzyme
in 3% of pop
causes isolated mildly raised unconjugated hyperbilirubinaemia
esp with fasting, illness
NB: don't label as chronic liver disease
other LFTs normal
excl haemolysis + drugs
Effects of cholestasis
conjugated hyperbilirubinaemia
jaundice
dark urine (bilirubinaemia - often appears first)
obstruction of bile salt excretion into gut
pale stools
pruritus due to retained bile salts (esp in PBC)
fat malabsorption (steatorrhoea)
fat soluble vit (ADEK) malabsorption
hypercholesterolaemia
elevated ALP + gGT
imaging critical - find dilated ducts + cause
Extraheptaic duct obstruction
stone in CBD
Mirizzi syndrome
rare
common hepatic duct obstruction caused by extrinsic compression from an impacted stone in cystic duct of infundibulum of GB
tumour (within, @ end of, outside compressing)
stricture (PSC or post-intervention)
identify dilated ducts (US)
identify + tx cause (US, MRCP, EUS, ERCP)
if left unrelieved risk of ascending cholangitis + sepsis
surgical jaundice now obsolete
lab reference range
quoted as mean for pop +/- 2 SDs (i.e. incl 95% of pop)
therefore, outside range doesn't necessarily mean clinically abnormal, esp if multiple tests performed
hepatocellular damage pattern of abnormal LFTs
v high (>1000): acute viral infection, drugs, ischaemia, ALF
PT = best guide to severity + prognosis
sometimes acute flares of chronic disease
transaminases predominate
can be less marked in alcohol, NAFLD, drugs, chronic viral disease, AIH, HFE, passive congestion, cirrhosis (suspect of low albumin + platelets)