Mohammad Mobasheri
SpR General Surgery
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Definition: yellow discolouration of skin and
sclera as a result of hyperbilirubinaemia
Bilirubin >35mmol/L for jaundice to be
visible on examination
Sclera first place to become jaundiced
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Bilirubin is a product of metabolism of haemoglobin (80%) and other haem containing
proteins (e.g. Myoglboin, cytochrome P450: 20%)
Degredation of haemoglobin into bilirubin takes place in macrophages. Bilirubin is
then excreted into plasma and binds with albumin
RBC breakdown
Haemoglobin
Globin
Amino
Acids
Haem (iron + porphyrin)
Biliverdin
Bilirubin
(unconjugated)
Bilirubin binds to albumin in
the plasma
•Uptake of unconjugated bilirubin into hepatocyte
•Unconjugated bilirubin converted to conjugated bilirubin by glucuronyl transferase (this is required before
bilirubin can be excreted into the bile, as this process makes bilirubin water soluble)
•Bilirubin secreted (as component of bile) into the small intestine
•Bacterial enzymes deconjugate bilirubin and convert it into urobilinogen
•90% urobilinogen broken down further into stercobilinogen and stercobilin and excreted in faeces
•10% urobilinogen absorbed (via portal vein)
•Majority of absorbed urobilinogen re-enters hepatocyte and re-excreted in bile (enterohepatic circulation)
•The rest of the absorbed urolbilinogen bypasses liver and is excreted by kidneys
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Disruption of bilirubin metabolism and excretion can cause
hyperbilirubinaemia and subsequent jaundice
Hyperbilirubinaemia maybe unconjugated (indirect) or conjugated
(direct) depending on the cause
Some inherited syndromes of bilirubin handling can result in
hyperbilirubinaemia
◦ Gilbert’s syndrome – reduced activity of glucuronyl transferase
therefore reduced conjugated bilirubin therefore elevated
unconjugated bilirubin
◦ Criggler-Najjar – reduction in amount of glucoronyl transferase
therefore elevated unconjugated bilirubin
◦ Rotor’s/Dubin-Johnson syndrome – defective excretion of
conjugated bilirubin into the biliary cannaliculi therefore elevated
conjugated bilirubin
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Pre-hepatic: pathology occuring prior to the liver
 Any cause of increased haemolysis (e.g. Spherocytosis, thalassaemia, sickle cell
disease, transfusion reaction, auto-immune, malaria etc.) and some drugs
 Causes unconjugated hyperbilirubinaemia
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Intra-Hepatic: pathology occuring within the liver
 All the causes of hepatitis/cirrhosis (e.g. Alcohol, viral, auto-immune, primray
biliary cirrhosis, haemochromatosis, wilsons, alpha-1 antitrypsin deficiency etc.),
inherited condition on previous slide and some drugs
 Can result in hepatocyte destruction and therefore unconjugated
hyperbilirubinaemia or in bile cannaliculi destruction and therefore conjugated
hyperbilirubinaemia or both
 Note/ neonatal jaundice: occurs in most newborns as hepatic machinary for
conjugation and excretion of bilirubin not fully matured until 2 weeks of age
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Post-hepatic: pathology occuring after conjugation of bilirubin
within the liver (aka obstructive jaundice)
 Any cause of biliary obstruction (e.g. Gallstones)
 Causes conjugated hyperbilirubinaemia
Following investigations will help to determine
nature of jaundice:
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Liver function tests
 Bilirubin
 ALT/AST
 ALP/GGT
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Conjugated v Unconjugated bilirubin levels
Urine bilirubin and urobilinogen levels
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Total bilirubin and its conjugated and
unconjugated levels help to determine nature
of jaundice
Test
Pre-hepatic
Hepatic
Post-hepatic
Total bilirubin
+
++
+++
Conjugated
bilirubin
Normal
Increased
Increased
Unconjugated
bilirubin
Increased
Increased
Normal
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Liver Enzymes
 ALT/AST mainly present in hepatocytes
 ALP/GGT mainly present in bile cannaliculi biliary tree
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Derrangement of particular liver enzymes in
association with jaundice can determine nature of
the jaundice
Test
Pre-hepatic
Hepatic
Post-hepatic
ALT/AST
Normal
+++
+
ALP/GGT
Normal
+
+++
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Urine bilirubin
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Normally, tiny amount bilirubin (conjugated) excreted in urine
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Pre-hepatic jaundice: Haemolysis causes rise in unconjugated bilirubin (water insoluble) and
this is not excreted by the kidney therefore there is no rise in urine bilirubin
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Some causes of Hepatic jaundice: result in damage to biliary cannaliculi and therefore result
in poor biliary drainage and therefore elevated conjugated bilirubin levels in blood, excreted
into urine (giving dark urine)
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Post-Hepatic juandice: Obstruction to biliary drainage and so conjugated bilirubin (water
soluble) levels in the blood increase and appear in the urine (giving dark urine)
Urine urobilinogen
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Pre-hepatic jaundice: Haemolysis results in increased bilirubin production and subsequent
increase bilirubin metabolism and urobilinogen in stool and therefore in the urine.
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Some causes of Hepatic jaundice : result in hepatocellular destruction and therefore reduced
re-excretion of re-absorbed urobilinogen (i.e. Reduction in entero-hepatic circulation of
urobilinogen) resulting in elevated levels in urine
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Post-Hepatic jaundice: Less bilirubin reaching intestine therefore reduction in urobilinogen
therefore reduction in urine urobilinogen
Test
Pre-hepatic
Hepatic
Post-hepatic
Urine Bilirubin
negative
Negative (but maybe increased
depending on cause)
Increased
Urine urobilinogen
Increased
Normal (but maybe increased
depending on cause)
Decreased/negative
Urine colour
Normal
Normal (but maybe dark
depending on cause)
Dark
Stool colour
Normal
Normal
Pale
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How long been jaundiced?
Ever been jaundiced before?
Any associated fevers or abdominal pain or weight loss?
Pale stool and dark urine (suggests obstructive/post-hepatic
jaundice)?
Any recent foreign travel (hepatitis, malaria)?
Any risk factors for hepatitis (tattoos, IVDU, high risk
professions, blood transfusions, multiple sexual partners)?
PMH of blood disorders (e.g. SCD, thalassemia)?
DH any new medications that can cause jaundice?
SH excess alcohol intake
FH of jaundice (inherited disorders of bilirubin metabolism)
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If jaundice associated with background of intermittent RUQ
pains think gallstones and choledocholithiasis
If jaundice associated with long history of upper abdominal
pain and weight loss and patient elderly thing pancreatic
cancer
If jaundice associated with recent foreign travel think
hepatitis (A,E) or malaria
If jaundice occuring in patient with risk factors think hepatitis
B,C
If jaundice occuring on a background of alcohol abuse think
alcoholic liver disease
If jaundice is painless and family history of blood disorder
think pre-hepatic jaundice
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Blood tests
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FBC (low HB suggesting haemolysis
LFTs (bilirubin, ALT/AST, ALP/GGT, albumin)
Conjugated and unconjugated bilirubin
Clotting (INR)
U&E (hepatorenal syndrome)
Urine
 Bilirubin
 Urobilinogen
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Above tests used to determine if jaundice
pre/intra/post hepatic which will determine
further investigations
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Pre-hepatic
 Sickle cell test
 Serum electrophoresis
 Blood film
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Hepatic
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Serum iron, ferritin, copper, alpha-1 antitrypsin levels
auto-antibody screen
Hepatitis screen
Liver USS
Post-hepatic
 As surgeons we deal with post-hepatic jaundice
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Causes
 Luminal
 Gallstone
 Intra-mural
 Benign stricture (e.g. As complication of cholecystectomy or
due to pancreatitis)
 Malignant stricture: cholangiocarcinoma
 Extra-mural
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Head of pancreas cancer
Pancreatitis (oedema of head of pancreas)
Pancreatic pseudocyst
Compression by malignant lymph nodes at porta hepatis
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Blood tests
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FBC (elevated WCC in ascending cholangitis)
U&E (monitor renal function in case of hepato-renal syndrome)
LFTs (elevated bilirubin, ALP/GGT)
Conjugated/unconjugated bilirubin
Clotting (INR maybe elevated)
USS
 Look for gallstones, biliary tree dilatation, stone in CBD (though
often not seen due to bowel gas).
 Look at pancreas to look for cancer (often poor views due to
overlying bowel gas)
 Look at liver to exclude parenchymal disease.
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CT
 Used to assess pancreas in cases of suspected pancreatic cancer
 Less sensitive that USS for picking up gallstones
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MRCP
 Used to assess biliary tree anatomy and determine cause of
obstruction (gallstone, stricture)
 Diagnostic only but non-invasive
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ERCP – performed by gastro-enterologist
 Used to assess biliary tree anatomy and determine cause of
obstruction
 Furthermore, obstruction can be relieved (diagnostic and
therepeutic, but invasive)
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Stone extraction with balloon trawel
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Sphincterotomy
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Biliary stent (if stricture: benign or malignant)
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Brushings for cytology (if stricture, to look for cholangiocarcinoma)
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PTC (percutaneous transhepatic
cholangiogram) – performed by interventional
radiologist
 Diagnostic and therepeutic (biliary drain to relieve
obstruction) but invasive
 More invasive and Higher complication rate than ERCP
(particularly haemorrhage) therefore used in situations
where ERCP unavailable (out of hours in patient with
cholangitis) or unsuccesful
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Monitor for acute renal failure (hepato-renal
syndrome)
 Ensure patients well fluid resuscitated and monitor
urine output to reduce the risk of the above
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Monitor INR
 If derranged give vitamin K
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Determine cause of obstructive jaundice
Danger is progression to ascending
cholangitis (Charcot’s triad) – can be life
threatening!
 Must un-obstruct Biliary tree to prevent development
of cholangitis
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ERCP preferred method
 Balloon trawl or dormia basket (for stones)
 Sphincterotomy (to prevent future stones from obstructing)
 Stent (to allow free drainage of bile past a stricture)
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PTC
 Used where ERCP unavailable or unsuccesful (as more invasive
and higher complication rate)
 Drain inserted percuteously, trans-hepatically (through the liver)
and into the biliary tree to allow free drainage of bile
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Surgical
 Most often used in the context of gallstones
 At time of cholecystectomy an intra-operative cholangiogram is
performed to confirm stones in CBD
 If present then consider:
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Laparoscopic Trans-cystic (through cystic duct) removal using fogarty
catheter
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Laparoscopic CBD exploration
 In context of malignancy (head of pancreas Ca or external
compression by enlarged malignant lymph nodes)
 Palliative bypass procedures such as hepaticojejunostomy where
ERCP/PTC + stenting has failed
Questions?