JAUNDICE

DR : RAMY A. SAMY
M.D. / lecturer of internal medicine
[email protected]
 Jaundice

• Definition
• Causes
• History
• Investigation-Imaging
• Clinical Cases
 Definition

• Jaundice is a yellowing of the skin,

conjunctiva and mucous membranes caused
by hyperbilirubinaemia.
 Jaundice

Normal Physiology
• Bilirubin is from breakdown of hemoglobin
• Unconjugated bilirubin transported to liver
– Bound to albumin because insoluble in water
• Transported into hepatocyte & conjugated
– With glucuronic acid → now water soluble
• Secreted into bile
• In ileum & colon, converted to urobilinogen
– 10-20% reabsorbed into portal circulation and
re-excreted into bile or into urine by kidneys
 Jaundice

Pathophysiology
• Jaundice = bilirubin staining of tissue @ lvl
greater than ~2
• Mechanisms:
– ↑ production of bilirubin
– ↓ hepatocyte transport or conjugation
– Impaired excretion of bilirubin
– Impaired delivery of bilirubin into intestine
• “surgically relevant jaundice” or obstructive
jaundice
– “Cholestasis” refers to the latter two, impaired
excretion and obstructive jaundice
 What causes jaundice?

Category Definition

Pathology occurs
Pre-hepatic
prior to the liver

Hepatic Pathology located

within the liver

Post- Pathology located after

hepatic the conjugation of bilirubin in the liver
 Prehepatic Jaundice
• Prehepatic jaundice is caused by increased destruction
of erythrocytes either:

- mature cells or
- precursors (ineffective erythropoiesis).

• The breakdown of mature cells can be caused by:

- haemolysis, or
- as a result of the metabolism of blood
following internal haemorrhage, e.g. into
a soft tissue injury or fracture.

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 Prehepatic Jaundice
• Ineffective erythropoiesis occurs in conditions such as:

- pernicious anaemia, where the

maturation of red cells is impaired, or

- thalassaemia, where the structure

of haemoglobin is abnormal.

• Hyperbilirubinaemia in prehepatic jaundice results from

the accumulation of unconjugated bilirubin; this is not
excreted by the kidney.

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 Prehepatic Jaundice
• Jaundice occurs because the conjugating capacity of the
liver is saturated,

- the capacity of the liver for conjugation is

greater than the normal rate of bilirubin production.

• Increased fluxes of bilirubin through the liver into the gut

• Greater amounts of urobilinogen are produced, with

- increased urobilinogen excretion in urine.

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 KEY POINTS
Prehepatic jaundice is most commonly
Caused by haemolytic disease

Bilirubin (unconjugated) is not excreted in urine

Urinary urobilinogen concentration is increased

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 Hepatic Jaundice
• Congenital disorders of bilirubin transport lead to
jaundice because of:
- defective uptake, reduced conjugation
or impaired excretion of bilirubin.

• Generalized hepatocellular dysfunction may

occur in hepatitis and hepatic cirrhosis.

• Drugs may cause hepatocellular damage, either

due to dose-dependent hepatoxicity (e.g.
paracetamol).
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 Hepatic Jaundice

• The pathogenesis of jaundice in these

conditions is complex,

- reduced hepatic uptake,

- decreased conjugation and,
- impaired intracellular transport
of bilirubin, all contributing.

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 Hepatic Jaundice
• When hyperbilirubinaemia is caused by impaired
conjugation of bilirubin;

- unconjugated bilirubin, and no

increased fluxes of bilirubin through the liver,

- bilirubinuria does not occur and

- urinary urobilinogen is not increased.

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 Hepatic Jaundice
• Serum bilirubin may be unconjugated or conjugated, as
glucuronyl transferase and intracellular transport may be
defective.

• If the rate of conjugation exceeds excretory capacity;

- conjugated hyperbilirubinaemia will

occur and bilirubin may be excreted,in urine,

- this is sometimes seen in recovery from acute

viral hepatitis.

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 KEY POINTS
Jaundice due to hepatocyte dysfunction may be
caused by selective transport defects
of generalized cell dysfunction

Both conjugated and unconjugated hyperbilrubinaemia

may occur in hepatocellular jaundice

Bilirubin and excess urobilinogen may be

found in urine

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 Cholestatic Jaundice
• Cholestatic jaundice results from interference to biliary
flow between the sites of secretion by the hepatocyte
and drainage into the duodenum.

• It may be caused by lesions;

- within the liver (intrahepatic cholestasis),

or in the biliary tree or head of the
pancreas (extrahepatic cholestasis);

- the term cholestatic is preferable to post-hepatic

to describe this pattern of jaundice.

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 Cholestatic Jaundice
• Intra- and extra-hepatic cholestasis can be differentiated by;

- ultrasound examination or

- liver biopsy, but not by liver function tests.

• Intrahepatic cholestasis may result from generalized hepatocellular

dysfunction, such as occurs in;

- Hepatitis,

- Hepatic cirrhosis

• Hepatic malignancies may block branches of the biliary tree.

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 Cholestatic Jaundice
• Some drugs may cause intrahepatic cholestasis such as:

- anabolic steroids, and

- phenothiazines

• Extrahepatic obstruction may be due to tumours in:

- major branches of the biliary tract,

- head of pancreas.

• Gallstones may obstruct biliary flow.

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 Cholestatic Jaundice
• Jaundice is due to impaired excretion and
accumulation of conjugated bilirubin which can
be filtered by the kidney and appear in urine.

• If obstruction is complete bilirubin does not

reach the gut, therefore urobilinogen:
- is not produced, and
- is absent in urine.

• Under such circumstances the stools are pale.

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 KEY POINTS
Cholestasis may be caused by lesions
within or outside the liver

Jaundice is due to conjugated bilirubin

Bilirubin is found in urine

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 Obstructive Jaundice
• Common
– Common bile duct stones
– Carcinoma of the head of pancreas
– Malignant lymph nodes at the porta hepatis
• Infrequent
– Ampullary carcinoma
– Pancreatitis
– Liver secondaries
• Rare
– Benign strictures - iatrogenic, trauma
– Recurrent cholangitis
– Mirrizi's syndrome
– Sclerosing cholangitis
– Cholangiocarcinoma
– Bilary atresia
– Choledochal cysts
 Jaundice

Broad Differential Diagnosis

↑production ↓transport or Impaired Biliary
↓conjugation excretion obstruction
↑ Unconjugate ↑ Unconjugate ↑ Conjugated ↑ Conjugated

Hemolysis Gilbert’s Rotor’s CH/CBD stone

Transfusions Crigler-Najarr DubinJohnson Stricture

Sepsis Cirrhosis Cirrhosis Chronic

pancreatitis
Burns Hepatitis Hepatitis PSC

Hgb-opathies Drug inhibition Amyloidosis

Pregnancy
 Jaundice

DDx: Unconjugated bilirubinemia

• ↑production
– Extravascular hemolysis
– Extravasation of blood into tissues
– Intravascular hemolysis
– Errors in production of red blood cells
• Impaired hepatic bilirubin uptake(trnsport)
– CHF
– Portosystemic shunts
– Drug inhibition: rifampin, probenecid
 Jaundice

DDx: Unconjugated bilirubinemia

• Impaired bilirubin conjugation
– Gilbert’s disease
– Crigler-Najarr syndrome
– Neonatal jaundice (this is physiologic)
– Hyperthyroidism
– Estrogens
– Liver diseases
• chronic hepatitis, cirrhosis, Wilson’s disease
 Jaundice

DDx: Conjugated Bilirubinemia

• Intrahepatic cholestasis/impaired excretion
– Hepatitis (viral, alcoholic, and non-alcoholic)
• Any cause of hepatocellular injury
– Primary biliary cirrhosis or end-stage liver dz
– Sepsis and hypoperfusion states
– TPN
– Pregnancy
– Infiltrative dz: TB, amyloid, sarcoid, lymphoma
– Drugs/toxins i.e. chlorpromazine, arsenic
– Post-op patient or post-organ transplantation
– Hepatic crisis in sickle cell disease
 Jaundice

DDx: Obstructive Jaundice

• Obstructive Jaundice– extrahepatic
cholestasis
– Choledocholithiasis (CBD or CHD stone)
– Cancer (peri-ampullary or cholangioCA)
– Strictures after invasive procedures
– Acute and chronic pancreatitis
– Primary sclerosing cholangitis (PSC)
– Parasitic infections
• Ascaris lumbricoides, liver flukes
Jaundice
 Diagnosis
 History
 Physical examination
 Blood tests - laboratory
 Ultrasonography
 CT
 MRI
 Liver biopsy
 ERCP
 Endoscopic ultrasound
Laboratory Tests
 Bilirubin level in  Complete blood
serum (total and count
direct)  Prothrombin time
 Aminotransferase  Other laboratory
tests pertinent to
 Alkaline
history
phosphatase
 Coombs test
 U/A for bilirubin and  Electrophoresis of
urobilogen
hemoglobin
 Viral hepatitis panel
Treatment
 Treatment requires a precise diagnosis
of the specific cause and should be
directed to the specific problem
 Summary in liver function tests in the
differential diagnosis of jaundice

Test Prehepatic Hepatic Cholestatic

Serum bilirubin Uncojugated Mixed Conjugated

Urine bilirubin Absent//PresentPresent Present

Urine Urobilinogen Increased Increased Decreased

ALT & AST Normal Marked Slight

increase increase

ALP Normal Slight Marked

increase increase

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 • Clinical Case 1
• 50 year old female
• Acute, severe pain in RUQ
• Nausea and vomiting
• Calls GP – pethidine pain relief
• Next few days notices dark urine and pale stools
• Her husband comments she has a pale yellow tinge
 Emergency admission

• What investigations would you do ?

• What results would you expect?

Abdominal Ultrasound showing
multiple gallstones in gallbladder
US shows stone in Common Bile
Duct
MRCP showing stone in
Common Bile Duct
ERCP showing stone in Common
Bile Duct
 Case 1
• Obstructive jaundice due to gallstone in
common bile duct
• Blood tests show high bilirubin and high
alkaline phosphatase
• Urine contains bilirubin
• Treatment includes ERCP to remove stone
and then plan Cholecystectomy