Seminar on jaundice for medical students . Post graduation students . DNB medicine students

1. JAUNDICE

2. Introduction
• Jaundice/ icterus, is a condition characterized by yellow discoloration of skin,
conjunctivae, and mucus membranes as a result of widespread tissue deposition of the
pigmented metabolite bilirubin.
• Normal total bilirubin level <1-1.5mg/dl
• Jaundice seen if Value exceeds 3mg/dl
• Bilirubin have high affinity for elastin rich tissues eg sclera, frenulum of tongue,so jaundice
appear first here .

3. Bilirubin metabolism
bilirubin is the end product of heme Degradation

4. • Bilirubin uptake to be mediated by liver specific bilirubin transporter (BT) by facilitating
diffusion process and by simple diffusion process
• Intracelluar binding to S-glutathion transferase to keep bilirubin in solution
• Conjugation with uridine diphosphate (UDP)-glucuronic acid done by the enzyme
bilirubin UDP-glucuronosyl transferase(B-UGT1A1) into monoglucuronide,diglucuronide
• Conjugated bilirubin transported into the bile canaliculus by an ATP-dependant export
pump eg.MRP-2,ABCC2

5. • Conjugated bilirubin in intestine converted to Urobilinogen by bacterial action which undergo
hepatic reuptake and partly renal elimination.
• Small amount secreted across sinusoidal membrane by MRP-3,that undergo renal elimination and
reuptake to hepatocyte by OAP1B1,OATP1B3

6. Differential diagnosis of jaundice
1. Isolated disorders of bilirubin metabolism-
Unconjugated hyperbilirubinemia-
• Increased bilirubin production-
• Haemolysis
• Ineffective erythropoiesis
• Blood transfusion
• Resorption of hematomas
•Decreased hepatocellular uptake-
• Drugs such as rifampicin
• Various cholecystography contrast agents

7. •Decreased conjugation –
• Gilbert’s syndrome, Crigler-Nazzer syndrome type1 and type2
• Physiological jaundice of newborn
• Drugs such as indinavir, atazanavir
Conjugated or mixed Hyperbilirubinemia-
Dubin johnson syndrome, Rotor’s syndrome

8. 2.Liver diseases-
a. Hepatocellular dysfunction –
Acute or subacute hepatocellular injury –
• Viral hepatitis
• Hepatotoxins such as ethanol, acetaminophen ,isoniazid , phenytoin
• Ischaemia such as in hypotension , vascular outflow obstruction
• Metabolic disorders such as Wilson’s ds, Reye’s syndrome

9. Chronic hepatocellular disease -
• Viral hepatitis
• Alcoholic liver disease
• Hepatotoxins such as ethanol , vinyl chloride , vitamin A
• Autoimmune hepatitis
• Metabolic disorders such as Hemochromatosis , Wilson's ds, NAFLD, a1-antitrypsin deficiency

10. b. Cholangiocytic injury-
• Primary biliary cirrhosis
• Graft-versus-host disease
• Drugs such as erythromycin, trimetholrim-sulfamethxazole,
• Cystic fibrosis

11. 3. Obstruction of the bile ducts
• Choledocholithiasis
• Primary sclerosing cholangitis
• Post surgical strictures
• Cholangiocarcinoma
• Pancreatic cancer
• Metastatic lymphadenopathy
• Ampullary carcinoma
• Pancreatitis

12. Diagnostic approach to jaundice
When clues are evaluated in the context of the physical findings and routine
laboratory tests , jaundice can be characterized correctly as obstructive or
nonobstructive.

14. History
• H/O biliary surgery , fever, abdominal pain in right upper quadrant= Biliary obstruction with
cholangitis
• C/O anorexia, malaise, myalgia With H/O a known infectious exposure, injection drug use
,prior transfusions of blood products= suggestive of viral hepatitis
• Family H/O jaundice or liver disease= suggest hereditary hyperbilirubinaemia or genetic
liver disease

15. Physical Examination
• High fever and abdominal tenderness in RUQ=suggests cholangitis
• Palpable abdominal mass= Neoplastic cause of obstructive jaundice
• Silver coloured stool=Suggests ampullary neoplasms
• Ascites , splenomegaly and prominent abdominal veins= Suggests cirrhosis
• Abdominal scar in midline or RUQ=Prior biliary surgery

16. Essential laboratory studies in patient with jaundice
1. Serum total bilirubin, Direct bilirubin
2. Alkaline phosphatase (ALP)
3. AST/SGOT
4. ALT/SGPT
5. Complete blood count
6. Prothrombin time

17. Serum bilirubin
• Bilirubin is found in two fractions-
Unconjugated or indirect- Insoluble in water, bound to albumin
Conjugated bilirubin – water soluble ,excreted by kidney
• Normal value of total serum bilirubin -1-1.5 mg/dl
• If the direct acting fraction is <15% of total ,the bilirubin can be
considered to all be indirect.

18. Alkaline phosphatase (ALP)
• Increases in biliary obstruction and intrahepatic cholestasis
• Not a specific marker
• Elevation more than 4 times of normal is significant
• More specific markers for cholestasis are gamma glutamyl transpeptidase[GGT], 5’
Nucleotidase

19. Aminotransferase (ALT,AST)
• ALT, Cytosolic enzyme found predominantly in hepatocytes
• AST, Found in cytosol and mitochondria of parenchymal cells of liver
• Normal serum concentrations –10-40 IU/L
• Levels of upto 300 IU/L are nonspecific and may be found in any liver disorder
• Level >1000 IU/L occur almost exclusively in disorders associated with extensive hepatocellular
injury such as in viral hepatitis, ischaemic liver injury, toxins or drug induced liver injury.

20. • Predominantly elevation of serum aminotransferase activity in comparison with
alkaline phosphatase activity suggests that jaundice is the result of intrinsic
hepatocellular disease
• Pattern of the aminotransferase elevation can be helpful diagnostically
AST:ALT Ratio <1 is suggestive of chronic viral hepatitis and NAFLD
AST:ALT Ratio >2 is highly suggestive of alcoholic liver disease

21. Complete blood count
• Leucocytosis= Suggests Biliary tract obstruction or other inflammatory disorders
• Anaemia = Suggests haemolysis is the cause of bilirubin overload
• Thrombocytopenia=. Characteristic finding in cirrhosis results from reduced platelet production
from decrease hepatocyte synthesis of thrombopoietin or from increase of platelet consumption
from splenic sequestration

22. Prothrombin time
• Measure the plasma activities of coagulation factor 1,2,5,7,10 each of which is synthesized by
hepatocytes
• Prolongation of PT(and an associated increase in INR) can result from impaired hepatic synthesis
of these proteins and from deficiency of vitamin K which is required as a cofactor for essential
posttranslational modification of factor 2,7,9,10.

23. Efficient absorption of vitamin K by the small intestine requires an intact enterohepatic circulation
of bile salts(hence ,an unobstructed biliary tree).
Exogenous administration of vitamin K will generally normalize a prolonged PT in patients with
Obstructive jaundice and intrahepatic cholestasis but not in patients with liver disease caused by
hepatocellular injury.

24. Algorithm for evaluation and management

25. References
1.Harrison’s principles of internal medicine
2.Sleisenger and fordtran’s gastrointestinal and liver disease

26. Thank you