approach to jaundice

1. APPROACH TO JAUNDICE

2. JAUNDICE
● Yellowish discoloration of body tissues resulting from the deposition of
bilirubin
○ Sclera -High elastin -3mg/dL
○ 2nd Site - Under the tongue
○ Skin → Yellow → Long standing - Green ( Biliverdin)

3. JAundcie - scleral
Under tongue
biliverdin

4. Differential Diagnosis for yellowing
● Carotenoderma
○ Most commonly due to - Ingestion of excessive amount of vegetables - Carrots , leafy
vegetables
○ Commonly associated with
■ Diabetes
■ Hypothyroidism
■ Anorexia Nervosa
● Drug induced
○ Quinacrine
○ Sunitinib
○ Sorafenib
○ Phenol exposure

5. Carotenoderma
● Pigment concentrated on
○ Palms
○ Soles
○ Forehead
○ Nasolabial folds
● Sclerae Spared

6. Bilirubin
● Prematurely destroyed erythroid
cells
● Myogolobin
● Cytochromes
80-85 %
Breakdown of Senescent RBC
Reticuloendothelial Cells
Biliverdin
CO
Iron

7. Biliverdin
Bilirubin
Biliverdin Reductase
● Insoluble in Water
● Bind to Albumin for transport
Carrier Mediated Membrane transport to
Hepatocytes

8. Unconjugated Bilirubin
Glutathione -S - Transferase Superfamily
Reduce Efflux back
Endoplasmic Reticulum
Conjugation to Glucouronic acid
Uridine Diphosphate glucouronosyl transferase
Bilirubin Monoglucouronide
Bilirubin Diglucouronide
Bile Canaliculi Sinusoid
MRP 2
MRP 3
OATP1B1 / OATP1B3

10. Conjugated Bilirubin
Small Intestine
Distal Ileum /Colon
Unconjugated bilirubin
Urobilinogen /
Urobilins
80-90 %
Excreted in Fecus
10-20 %
Enterohepatic cycling
Not absorbed due to
● Hydrophilicity
● Large molecular size
Bacterial Beta-Glucuronidase
Normal Gut Bacteria

11. Serum Bilirubin
Direct = Conjugated
Indirect = Unconjugated
● Diazotized sulfanilic acid → Stable
compound absorbs maximally @
540nm
● Accelerator - Alcohol

12. New Techniques
● 1) In Normal Persons /Gilbert Syndrome = almost 100% of Serum Bilirubin is Unconjugated :
<3 % is Monoconjugated
● 2)Hepatobiliary disease = Monoconjugated predominance
● 3)Direct fraction also includes Delta Fraction
○ Delta fraction = delta Bilirubin = Biliprotein
○ Conjugated Bilirubin which covalently Bound to albumin
○ Important fraction in people with Hepatobiliary disorders / Cholestasis
○ This explains - Absence of Bilirubinuria and Serum bilirubin falls slowly

13. Urine Bilirubin
● Unconjugated = Bound to albumin = Not excreted in Urine
● Delta Bilirubin = Bound to albumin = Not excreted in Urine →
● Conjugated → Filtered in Glomerulus → Majority absorbed at PCT
● Presence of Bilirubinuria = Elevated Conjugated fraction = Hepatobiliary
disease
False Negative

15. Kumar and clark 34.8
49-1 table harrison

16. Unconjugated Hyperbilirubinemia
Hemolytic disorders
Inherited
● Spherocytes
● Sickle cell anemia
● Thalasemia
● Pyruvate Kinase Deficiency
● G-6-PD deficiency
Aquired
● Microangiopathic Hemolytic anaemia
● Paroxysmal nocturnal hemoglobinuria
● Spur cell anaemia
● Immune Hemolysis
● Parasitic Infections

19. Crigler Najjar
Type 1
Exceptionally rare
Bilirubin > 20 mg/dL
Neurological deficit
Death at infancy / Childhood
Absence of UDPGT Activity
Type 2
Live into adulthood
Bilirubin ~ 6-25 mg/dL
<10% of Enzyme is active due to
mutation
UDPGT activity can induced by
Phenobarbital
Susceptible under illness

20. Gilbert Syndrome
● Impaired conjugation due to reduced Bilirubin UDPGT activity (10~35 %)
● Bilirubin ~ 6 mg/dL
● Intermittent Jaundice
● Incidence is 3-7 %
● Male : Female = 1.5-7

21. Conjugated Hyperbilirubinemia
Patient presents with asymptomatic jaundice
Rotor Syndrome
Dubin johnson Syndrome

22. History
● Exposure to chemicals/ medications/Alternative medicines
● Any transfusions/ IV drug intake/ ABuse
● Alcohol COnsumption
● Arthralgia / Myalgia preceding the jaundice →Drug induced / Viral Hepatitis
● Sudden onset of Right upper quadrant pain with Chills → CHoledocolithiasis ?
Ascending cholangitis

23. Physical Examination
● Proximal muscle wasting → Long standing disease
● Look for stigmata of Chronic Liver disease

26. Abdominal Examination
● Any dilated Veins
● Visible Organomegaly
● Abdominal distension
● Liver - Size and consistency → Look below xiphoid for enlarged Left lobe
● Ascites +/-
● Splenomegaly
● Murphy's sign

27. Laboratory Tests
● Total and DIrect bilirubin Fraction
● SGOT,SGPT,ALP (49-1)
● Albumin levels → if low = Chronic Disease
● Prothrombin time → Vit K deficiency due to prolonged jaundice /
Malabsorption
○ If the PT not corrected with Vitamin K supplementation → Hepatocellular Injury

28. ● Wilson - Young Patients
● Alcoholic -> Pattern of AST:ALT >2:1
● Viral / Toxin → Enzyme > 500 u/L
○ ALT > AST
● Acute hepatocellular disease
○ 25 x Normal Value may be seen
● Hepatocellular / Cholestatic disease
○ < 8 x Normal Value

29. ACUTE VIRAL
HEPATITIS
Hepatitis A
IgM Antibody Assay
Hepatitis B
Surface Antigen (HbSAg)
Anti- HbC IgM Assay
Hepatitis C
Viral RNA test
Hepatitis E
IgM Antibody Assay Done depending on the circumstances
Not Use full in Acute Hep C
Takes 6 weeks to Positive
EBV
CMV
Hep D
WILSONS
Ceruloplasmin Level
Autoimmune Hepatitis
ANA
Anti - SMooth muscle Antibody

30. Drug Induced
Predictable
Acetaminophen
Unpredictable
Idiosyncratic
reaction
Environmental toxins
Vinyl Chloride
Kava
Amanita phalloides
Jamaica bush tea

31. Cholestatic Conditions
Intrahepatic Extra -hepatic
USG
Absence of
biliary dilatation
Presence of
biliary dilatation
● CT
● MRCP -INITIAL DIAGNOSTIC TEST
● ERCP -GOLD STD -CHOLEDOCOLITHIASIS
● PTC
● EUS-Has comparable sensitivity to MRCP and can
take Biopsy

33. Intrahepatic
Hepatitis B
Hepatitis C
Hepatitis A & E
Alcoholic Hepatitis
EBV
CMV
Anabolic
Contraceptives
Chlorpromazine
Tolbutamide
Primary biliary cholangitis
● Progressive destruction of interlobular bile
ducts
● Anti-mitochondrial Ab
Primary sclerosing cholangitis
● Fibrosis of larger bile duct
● Segmental sclerosis
● MRCP
● 75 % have inflammatory bowel disease
TPN
Malignancy
Paraneoplastic
stauffer syndrome - RCC
Hodgkin,Medullary Carcinoma Thyroid
Infection
Sepsis
Plasmodium falciparum
Weil's disease - Jaundice + Renal failure + fever
Other
Ischemic hepatitis
Heart failure - Congestion

35. Intrahepatic
Familial forms
Progressive familial intrahepatic cholestasis type 1-3
Benign recurrent cholestasis type 1&2
Benign recurrent cholestasis type 1&2
Episodic attacks of pruritus
Cholestasis
Jaundice - debilitating
Serum bile acids = elevated
GGT =Normal
Doesn’t lead to chronic Liver disease
Progressive familial intrahepatic
cholestasis type 1-3
Begin at childhood
Lead to CLD
Progressive cholestasis
Serum bile acids = Elevated
Type 3 —> GGT = elevated

36. Extrahepatic
Choledocolithiasis
Mild right upper quadrant discomfort
Cholangitis with jaundice
Sepsis
Circulatory collapse
IgG4 associated cholangitis
Responds to corticosteroids
Chronic pancreatitis
AIDS cholangiopathy
Infection of epithelium with CMV / Cryptosporidium
No jaundice
Elevated ALP

38. Thank you