Jaundice

Jaundice
• 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
 Haemoglobin Metabolism
• 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
 Hyperbilirubinaemia
• 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
 Classification of Jaundice
• 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
Pre-hepatic/hepatic/post-hepatic?
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
 Determining aetiology of Jaundice
 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
 Determining aetiology of jaundice
• 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 + +++
 •
Determining aetiology of Jaundice
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 depending on Dark
cause)
Stool colour Normal Normal Pale
 Determining aetiology of Jaundice:
History
• 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
 Investigations
• 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
 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
 Obstructive Jaundice: Causes
• 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
 Obstructive Jaundice: Investigations
• 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.
 Obstructive Jaundice: Investigations
• CT
• Used to assess pancreas in cases of suspected pancreatic cancer
• Less sensitive that USS for picking up gallstones

• MRCP
• Used to assess biliary tree anatomy and determine cause of obstruction
(gallstone, stricture)
• Diagnostic only but non-invasive

• 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)
• Stone extraction with balloon trawel
• Sphincterotomy
• Biliary stent (if stricture: benign or malignant)
• Brushings for cytology (if stricture, to look for cholangiocarcinoma)
 Obstructive Jaundice: Investigations
• 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
 Obstructive Jaundice: Management
• 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
(Charcot’s triad) – can be life threatening!
• Must un-obstruct Biliary tree to prevent development
of cholangitis
 Obstructive Jaundice: biliary
decompression
• 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
 Obstructive Jaundice: biliary
decompression
• 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:
• Laparoscopic Trans-cystic (through cystic duct) removal using fogarty
catheter
• 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