1. M.D. / lecturer of internal medicine
JAUNDICE
DR : RAMY A. SAMY
M.D. / lecturer of internal medicine

2. Jaundice Definition Causes History Investigation-Imaging
Clinical Cases

3. Definition
Jaundice is a yellowing of the skin, conjunctiva and mucous membranes caused by hyperbilirubinaemia.

5. 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

6. Pathophysiology
Jaundice = bilirubin staining of 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

7. What causes jaundice? Category Definition Pre-hepatic Pathology occurs
prior to the liver
Hepatic
Pathology located
within the liver
Post-
hepatic
Pathology located after
the conjugation of bilirubin in the liver

9. 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.

10. 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.

11. 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.

12. KEY POINTS Prehepatic jaundice is most commonly
Caused by haemolytic disease
Bilirubin (unconjugated) is not excreted in urine
Urinary urobilinogen concentration is increased

13. 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).

14. Hepatic Jaundice
The pathogenesis of jaundice in these conditions is complex,
- reduced hepatic uptake,
- decreased conjugation and,
- impaired intracellular transport
of bilirubin, all contributing.

15. 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.

16. 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.

17. 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

18. 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.

19. 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.

20. 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.

21. 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.

22. KEY POINTS Cholestasis may be caused by lesions
within or outside the liver
Jaundice is due to conjugated bilirubin
Bilirubin is found in urine

23. Obstructive Jaundice Common Infrequent Rare 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

24. Broad Differential Diagnosis
↑production
↓transport or ↓conjugation
Impaired excretion
Biliary obstruction
↑ Unconjugate
↑ Conjugated
Hemolysis
Gilbert’s
Rotor’s
CH/CBD stone
Transfusions
Crigler-Najarr
DubinJohnson
Stricture
Sepsis
Cirrhosis
Chronic pancreatitis
Burns
Hepatitis
PSC
Hgb-opathies
Drug inhibition
Amyloidosis
Pregnancy

25. 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

26. 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

27. 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

28. 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

30. Diagnosis History Physical examination Blood tests - laboratory
Ultrasonography CT
MRI
Liver biopsy
ERCP
Endoscopic ultrasound
Diagnosis

31. Laboratory Tests Bilirubin level in serum (total and direct)
Complete blood count
Prothrombin time
Other laboratory tests pertinent to history
Coombs test
Electrophoresis of hemoglobin
Viral hepatitis panel
Bilirubin level in serum (total and direct)
Aminotransferase
Alkaline phosphatase
U/A for bilirubin and urobilogen

32. Treatment
Treatment requires a precise diagnosis of the specific cause and should be directed to the specific problem

33. Summary in liver function tests in the differential diagnosis of jaundice
Test Prehepatic Hepatic Cholestatic
Serum bilirubin Uncojugated Mixed Conjugated
Urine bilirubin Absent//Present Present Present
Urine Urobilinogen Increased Increased Decreased
ALT & AST Normal Marked Slight
increase increase
ALP Normal Slight Marked increase increase

34. 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

35. Emergency admission What investigations would you do ?
What results would you expect?

36. Abdominal Ultrasound showing multiple gallstones in gallbladder

37. US shows stone in Common Bile Duct

38. MRCP showing stone in Common Bile Duct

39. ERCP showing stone in Common Bile Duct

41. 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

42. THANK YOU