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
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

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
bilirubin

Normal

Increased

Increased

Unconjugated
bilirubin

Increased

Increased

Normal

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

Test

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
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

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?