Jaundice

1
Jaundice

• Definition
• Accumulation of yellow pigment in the skin and
  other tissues (Bilirubin)

2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6

• Bilirubin Metabolism
• Bilirubin formation
• Transport of bilirubin in plasma
• Hepatic bilirubin transport
• Hepatic uptake
• Conjugation
• Biliary excretion
• Enterohepatic circulation

7
Bilirubin formation
120ds
8
Transport of Bilirubin in Plasma
Albumin UB UB Albumin Complex
H affinity binding sites
21
Bilirubin
Plasma protein Albumin
Molar Ratio
L affinity binding sites
gt21
Bilirubin
Other organic anions PH?
can be replaced by
UB?
9
Hepatic Bilirubin Transport
(lipid soluble)
3.Biliary Excretion of Bilirubin
(water soluble)
Transfer across Microvillar membrane
CB
Bile canaliculus
10

• UDPGT Uridine Diphosphate Glucuronyl Transferase
• UCB because of its tight albumin binding and
  lipid solubility, it is not excreted in urine.
• CB is less tightly bound to albumin and is water
  soluble, so it is filtered at the glomerulus and
  appears in the urine.

11
Entero-hepatic circulation
T
be degraded Bacterial Enzymes
CB
B and I
Urobilinogens (coloress)
feces (feceal urobilinogens)
50-200 mg/d
mostly
20
Reabsorbed
plasma
trace
circulation
kidneys
urine urobilinogen
4 mg/d

• The serum of normal adults contains ?1 mg of
  bilirubin per 100 ml.
• In healthy adults

The direct fraction is usually lt0.2 mg/100 ml The
indirect fraction is usually lt0.8 mg/100 ml
12
Pathophysiologic classification of Jaundice

• Hemolytic Jaundice
• Hepatic Jaundice
• Obstructive Jaundice(Cholestasis)
• Congenital Jaundice

13
Jaundice classification

• predominantly unconjugated hyperbilirubinaemia
• predominantly conjugated hyperbilirubinaemia

14
Hemolytic Jaundice

• Pathogenesis
• Overproduction
• Hemolysis (intra and extra vascular)
• inherited or genetic disorders
• acquired immune hemolytic anemia
• (Autoimmune hemolytic anemia)
• nonimmune hemolytic anemia
• (paroxysmal nocturna Hemoglobinruia)
• Ineffective erythropoiesis
• Overproduction may overload the liver with UB

15

• Hemolytic Jaundice
• Symptoms
• weakness, Dark urine, anemia,
• Icterus, splenomegaly
• Lab
• UB? without bilirubinuria
• fecal and urine urobilinogen?
• hemolytic anemia
• hemoglobinuria (in acute intravascular hemolysis)
• Reticulocyte counts?

16
Hemolytic Jaundice (pre-hepatic)

• Serum / blood
• bilirubin (micormoles/l) 50-150 normal range
  3-17
• AST I.U. lt 35 normal range lt35
• ALP I.U. lt250 normal range lt250
• gamma GT I.U. 15-40 normal range 15-40
• albumin g/l 40-50 normal range 40-50
• reticulocytes() 10-30 normal range lt1
• prothrombin time (seconds) 13-15 normal range
  13-15

17
Hemolytic Jaundice (pre-hepatic)

• urinary changes
• bilirubin absent
• urobilinogen increased or normal
• faecal changes stercobilinogen normal

18
Obstructive Jaundice

• Pathogenesis
• it is due to intra- and extra hepatic obstruction
  of bile ducts
• intrahepatic Jaundice Hepatitis, PBC, Drugs
• Extra Hepatic Biliary Obstruction Stones,
  Stricture, Inflammation, Tumors, (Ampulla of
  Vater)

19
Etiology of Obstructive Jaundice

• Intrahepatic-Liver cell Damage/Blockage of Bile
  Canaliculi
• Drugs or chemical toxins
• Dubin-Johnson syndrome
• Estrogens or Pregnancy
• Hepatitis-viral,chemical
• Infiltrative tumors
• Intrahepatic biliary hypoplasia or atresia
• Primary biliary cirrhosis

20
Etiology of Obstructive Jaundice

• Extrahepatic-Obstructive of bile Ducts
• Compression obstruction from tumors
• Congenital choledochal cyst
• Extrahepatic biliary atresia
• Intraluminal gallstones
• Stenosis-postoperative or inflammary

21
cholestasisclinical features

• pain, due to gallbladder disease, malignancy, or
  stretching of the liver capsule
• fever, due to ascending cholangitis
• palpable and / or tender gallbladder
• enlarged liver, usually smooth

22
General signs of cholestasis

• xanthomas palmar creases, below the breast, on
  the neck. They indicate raised serum cholesterol
  of several months. Xanthomas on the tendon
  sheaths are uncommonly associated with
  cholestasis.
• xanthelasma on the eyelids
• scratch marks excoriation
• finger clubbing
• loose, pale, bulky, offensive stools
• dark orange urine

23

• Obstructive Jaundice
• Lab Findings
• Serum Bilirubin?
• Feceal urobilinogen? (incomplete obstruction)
• Feceal urobilinogen absence (complete
  obstruction)
• urobilinogenuria is absent in complete
  obstructive jaundice
• bilirubinuria ?
• ALP ?
• cholesterol ?

24
Obstructive Jaundiceextrahepatic

• serum / blood
• bilirubin (micromoles/l) 100-500 normal range
  3-17
• AST I.U. 35-400 normal range lt35
• ALP I.U. gt500 normal range lt250
• gamma GT I.U. 30-50 normal range 15-40
• albumin g/l 30-50 normal range 40-50
• reticulocytes() lt1 normal range lt1
• prothrombin time (secs) 15-45 normal range 13-15
  
• ( " parenteral vitamin K) falls

25
Obstructive Jaundiceextrahepatic

• urinary changes
• bilirubin increased
• urobilinogen reduced or absent
• faecal changes
• stercobilinogen reduced or absent

26
Hepatic Jaundice

• Due to a disease affective hepatic tissue
  either congenital or acquired diffuse
  hepatocellular injury

27

• Hepatic Jaundice
• Pathogenesis
• Impaired or absent hepatic conjugation of
  bilirubin
• decreased GT activity (Gilberts syndrome)
• hereditary absence or deficiency of UDPGT
  (Grigler-Najjar Syndrome)
• Familiar or hereditary disorders
• Dubin-Johnson Syndrome
• Rotor syndrome
• Acquired disorders
• hepatocellular necrosis
• intrahepatic cholestasis
• (Hepatitis, Cirrhosis, Drug-related)

28
(No Transcript)
29
Gross specimen of cirrhosis of the liver
30

• Hepatic Jaundice
• Symptoms
• weakness, loss appetite, hepatomegaly, palmar
  erythema, spider
• Lab Findings
• liver function tests are abnormal
• both CB and UCB?
• Bilirubinuria ?

31
(No Transcript)
32
(No Transcript)
33
Hepatic Jaundice

• serum / blood
• bilirubin (micromoles/l) 50-250 normal range
  3-17
• AST I.U. 300-3000 normal range lt35
• ALP I.U. lt250-700 normal range lt250
• gamma GT I.U. 15-200 normal range 15-40
• albumin g/l 20-50 normal range 40-50
• reticulocytes() lt1 normal range lt1
• prothrombin time (secs) 15-45 normal range 13-15
  
• ( " parenteral vit. K) 15-45

34
Hepatic Jaundice

• urinary changes
• bilirubin normal or increased
• urobilinogen normal or reduced
• faecal changes
• stercobilinogen normal or reduced

35
Jaundicediagnosis(1)

• history and examination
• urine, stools
• serum biochemistry
• bilirubin
• transaminases - AST, ALT
• albumin
• alkaline phosphatase

36
Jaundicediagnosis(2)

• haematology
• haemoglobin
• WCC
• platelets
• prothrombin time /- parenteral vitamin K
• abdominal ultrasound and chest X-ray
• further investigations - determined by the basis
  of the jaundice, e.g. pre-hepatic, hepatic,
  extra-hepatic

37
conjugated hyperbilirubinaemia

• the liver is able to conjugate bilirubin, but the
  excretion is impaired.
• failure of bilirubin excretion by hepatocytes
• Dubin-Johnson syndrome
• Rotor's syndrome
• obstruction to biliary flow i.e. cholestasis,
  both intra-hepatic and extra-hepatic

38
The proportion of conjugated bilirubin to the
total raised bilirubin

• 20-40 of total more suggestive of hepatic than
  posthepatic jaundice
• 40-60 of total occurs in either hepatic or
  posthepatic causes
• gt 50 of total more suggestive of posthepatic
  than hepatic jaundice
• less than 20 secondary to haemolysis or
  constitutional e.g. Gilbert's disease,
  Crigler-Najjar syndrome

39
unconjugated hyperbilirubinaemia

• increased bilirubin formation
• failure of bilirubin uptake(Gilbert's disease)
• failure of bilirubin conjugation

40
unconjugated hyperbilirubinaemia increased
bilirubin formation

• haemolysis
• ineffective erythropoiesis
• megaloblastic anaemia
• iron deficiency
• haemoglobinopathies

41
unconjugated hyperbilirubinaemia failure of
bilirubin conjugation

• neonatal jaundice
• Crigler Najjar syndrome
• drug inhibition e.g. chloramphenicol
• extensive hepatocellular disease e.g. hepatitis,
  cirrhosis

42
Cholestasisdiagnosis

• elevated serum bilirubin - in proportion to
  duration of cholestasis returns to normal once
  cholestasis is relieved
• raised serum alkaline phosphatase - to more than
  3X upper limit of normal
• LFTs - aminotransferases mildly raised raised
  gamma GT
• increased urinary bilirubin
• urinary urinobilinogen is excreted in proportion
  to amount of bile reaching the duodenum i.e.
  absence of urinobilinogen indicates complete
  biliary obstruction

43
Identification of cause

• dilated ducts on ultrasound - percutaneous
  transhepatic cholangiograpy
• undilated ducts on ultrasound - endoscopic
  retrograde cholangio-pancreatography
• needle biopsy of the liver

44
(No Transcript)
45
(No Transcript)
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49
(No Transcript)
50
Hepatocellular carcinoma
51
Primary sclerosing cholangitis in childhood
52
(No Transcript)
53
Accompanied Symptoms

• Fever
• Pain,Charcot syndrome
• Hepatomegaly
• Spleenmegaly
• Ascites
• GI bleeding
• itch

54
Jaundice- Differential diagnosis

• 1. Once Jaundice is recognized, it is important
  to determine whether hyperbilirubinemia is
  predominantly CB or UCB?
• 2. Differentiation of hemolitic from other type
  of Jaundice is usually not difficult.
• 3. The laboratory findings are in constant in
  partial biliary obstruction and differentiation
  from intrahepatic cholestesis is particularly
  difficult.

55

• Jaundice- Differential diagnosis
• Differential Diagnosis
• UCB or CB
• Exclude UCB (e.g. hemolysis or Gilbert Synd.)
• Distinguish hepatocellular from obstructive
• Distinguish intrahepatic from extra hepatic
  cholestasis

56
Case Study1

• History 68-year-old,jaundice,stomach pain,
• dark urine,itching of the
• skin,rapid weight loss of 21lb
• Lab data
• CBC within narmal limits
• Total bilirubin238µmol/l
• GGT300U/l
• ALP360U/l
• AST80u/l
• ALT75u/l
• Urinalysispositive bilirubin,normal urobilinogen
• Serum amylaseelevated

57
Case Study1

• Question
• What is the most probable diagnosis for this
  patient?
• Which labtory tests provided the most
  information,and which provided the least?

58
Case Study2

• History38-year-old white
• female,jaundice,right upper
• quadrant abdominal
• pain,nausea,vomiting,itching
• skin.She has a history of
  
• intravenous drug use and
  alcohol
• abuse.

59
Case Study2

• Lab data
• elevated total bilirubin(136 µmol/l)
• elevated conjugated bilirubin(102µmol/l)
• Urineorange-brown,3bilirubin,normal
  urobilinogen
• elevated ALP(1.5ULT),GGT(3ULT),ALT,AST(5ULT)
• Modest increaseSerum cholesterol and
  triglyceride

60
Case Study2

• Question
• What is the probable diagnosis for this
  patient?Why?
• What other laboratory test would recommend to
  confirm this diagnosis?
• Which laboratory tests ordered provided the most
  information?Why?

61
SUMMARY

• Have the patient had an isolated elevation of
  serum bilirubin?

62
SUMMARY

• Is the bilirubin elevation due to an increased
  unconjucated or conjucated fraction?

63
SUMMARY

• Is the hyperbilirubinemia hepatocellular or
  cholestatic?

64
SUMMARY

• If cholestatic,is it intra-or extrahepatic?

65
(No Transcript)