Mohammad Mobasheri

SpR General Surgery

 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

 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 Haem (iron + porphyrin)

Amino
Acids 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 (entero-
hepatic circulation)
The rest of the absorbed urolbilinogen bypasses liver and is excreted by kidneys
 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
Gilberts 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
Rotors/Dubin-Johnson syndrome defective excretion of conjugated
bilirubin into the biliary cannaliculi therefore elevated conjugated
bilirubin
 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

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

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:

Liver function tests

Bilirubin
ALT/AST
ALP/GGT
Conjugated v Unconjugated bilirubin levels
Urine bilirubin and urobilinogen levels
 Total bilirubin and its conjugated and
unconjugated levels help to determine
nature of jaundice
Test Pre-hepatic Hepatic Post-hepatic
Total bilirubin + ++ +++
Conjugated Normal Increased Increased
bilirubin
Unconjugated Increased Increased Normal
bilirubin
 Liver Enzymes
ALT/AST mainly present in hepatocytes
ALP/GGT mainly present in bile cannaliculi biliary tree
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 + +++
 Urine bilirubin
Normally, tiny amount bilirubin (conjugated) excreted in urine
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
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)
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
Pre-hepatic jaundice: Haemolysis results in increased bilirubin production and
subsequent increase bilirubin metabolism and urobilinogen in stool and therefore in the
urine.
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
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 Increased

depending on cause)
Urine urobilinogen Increased Normal (but maybe increased Decreased/negative
depending on cause)
Urine colour Normal Normal (but maybe dark Dark
depending on cause)
Stool colour Normal Normal Pale
 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)
 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
 Blood tests
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
Above tests used to determine if jaundice
pre/intra/post hepatic which will determine
further investigations
 Pre-hepatic
Sickle cell test
Serum electrophoresis
Blood film
Hepatic
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
 Causes
Luminal
Gallstone
Intra-mural
Benign stricture (e.g. As complication of cholecystectomy
or due to pancreatitis)
Malignant stricture: cholangiocarcinoma
Extra-mural
Head of pancreas cancer
Pancreatitis (oedema of head of pancreas)
Pancreatic pseudocyst
Compression by malignant lymph nodes at porta hepatis
 Blood tests
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.
 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
 Monitor for acute renal failure (hepato-renal
syndrome)
Ensure patients well fluid resuscitated and monitor urine
output to reduce the risk of the above
Monitor INR
If derranged give vitamin K
Determine cause of obstructive jaundice
Danger is progression to ascending cholangitis
(Charcots triad) can be life threatening!
Must un-obstruct Biliary tree to prevent development of
cholangitis
 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)

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
Questions?