The document provides an overview of bilirubin metabolism and the different types of jaundice, which is characterized by the yellowing of skin and mucous membranes due to elevated bilirubin levels. Jaundice can be classified into pre-hepatic, hepatic, and post-hepatic based on the underlying causes, with specific conditions and symptoms associated with each type. It also explains the roles of various enzymes and pathologies in bilirubin processing and the implications of hyperbilirubinemia on health.

1. Jaundice

2. PA 25.3
Describe Bilirubin Metabolism, Enumerate
etipathogenesis of , jaundice & Distinguish
between Direct and Indirect hyperbilirubinemia

3. Bilirubin Metabolism
• Bilirubin is a toxic end product of heme degradation that is
processed by the liver and excreted in the bile
• The majority of the bilirubin produced daily (0.2 to 0.3 g, 85%) is
derived from breakdown of senescent red cells by macrophages
in the spleen, liver, and bone marrow.
• The remaining bilirubin comes from multiple sources like
myoglobin,cytochromes etc
• The bilirubin produced is then transported to the liver in the
bound form with plasma albumin.

4. BILIRUBIN METABOLISM
• Conjugation of bilirubin takes place in the liver by UDP-
glucronyltransferase and this conjugation is essential for
water solubility and elimination.
• Conjugated bilirubin is excreted into the bile. The bile is
then passed to the duodenum via biliary system.
• Some bilirubin is metabolized by the intestinal flora into
urobilinogens and then reabsorbed.
• urinobilinogens are then removed by the kidney and
excreted via urinary system.

8. Jaundice
• The word Jaundice is actually a derivative of French word
‘Jaune’ which means ‘yellow’.
• Jaundice is defined as a yellowing of skin, mucous
membranes and sclera due to the deposition of yellow
orange bile pigment i.e. bilirubin
• Normal Serum bilirubin levels -0.3 and 1.2 mg/dL. Jaundice
becomes evident when the serum bilirubin levels rise above 2
to 2.5 mg/dL.

9. Hyperbilirubinemia Types
• Depending on the underlying etiology the elevation can
predominantly involve unconjugated (indirect) or
conjugated (direct) bilirubin.
• Excess bilirubin production or defective conjugation leads
to the accumulation of unconjugated bilirubin which is
insoluble and cannot be excreted in the urine.

10. Hyperbilirubinemia Types
• At excessive levels the unbound fraction rises and may
diffuse into tissues, particularly the brain in infants, and
produce neurologic damage (kernicterus).
• Conjugated hyperbilirubinemia most often results from
hepatocellular disease, bile duct injury, and biliary
obstruction. Since this form is water-soluble and loosely
bound to serum albumin, it can be excreted in the urine

11. TYPES of JAUNDICE
• Pre Hepatic/Hemolytic Jaundice
• Intra Hepatic/Hepatocellular Jaundice
• Post Hepatic/Obstructive Jaundice

13. PREHEPATIC JAUNDICE
Mainly caused due to hemolysis.
• Congenital :
Spherocytosis,Elliptocytosis,Thalassemia, Sickle cell
anemia,Pyruvate kinase deficiency,G6PD deficiency,
Erythroblastosis fetalis
Aquired :
Resorption of extensive hematomas,Auto immune hemolysis,
Transfusion reactions, Trauma, Hemolytic uremic syndrome,
Long distance runners,Malaria, Toxins e.g. snake venoms,
Chemicals e.g. nitrites, aniline dyes,etc.Vitamin B12,Folic acid def

14. Clinical presentation
• Anemia,
• Yellowing of sclera
• Dark yellow-brown colored urine
• Yellowish skin and
• High bilirubin levels.

15. HEPATIC JAUNDICE
• Basic defect lies within the liver mainly in the hepatocytes.
• Any pathology of the liver leading to defect in capture,
conjugation and excretion can cause hepatic jaundice
• Main enzyme of conjugation is UDP-Glucronyltransferase
• This enzyme can be defective due to the genetic mutation of the
UTG1A gene on chromosome 2
• The defective conjugating enzyme leads to the hepatic jaundice.

16. HEPATIC JAUNDICE
• Any defect in the hepatic excretory mechanism of bilirubin can
also cause hepatic jaundice.
• The excretory mechanisms involve hepatocytic bile acid-
independent secretion hepatocytic bile acid-dependent secretion
and bile ductular secretion.
• Any defect in the above mentioned excretory mechanisms can
lead to the accumulation of bilirubin in blood causing hepatic
jaundice.

17. HEPATIC JAUNDICE-Congenital Causes
• Wilson’s Disease
• Rotor’s Syndrome
• Haemochromatosis
• CriglerNajar syndrome
• Gilbert’s syndrome
• Dubin-Johnson’s syndrome

18. NEONATAL JAUNDICE
Physiologic Jaundice of the Newborn
• The amount of bilirubin production in neonates is much higher
than adults.
• Levels of UGT1A1 the enzyme that is responsible for bilirubin
glucuronidation are low at birth
• Transient and mild unconjugated hyperbilirubinemia is nearly
universal in the first week
• Breastfeeding may exacerbate unconjugated
hyperbilirubinemia, possibly because of the presence of
bilirubin deconjugating enzymes in breast milk.

19. NEONATAL JAUNDICE
Hereditary Hyperbilirubinemia
• Crigler-Najjar syndrome type 1 -caused by severe UGT1A1
deficiency and is fatal around birth;
• Crigler-Najjar type 2 and Gilbert syndrome, -some UGT1A1
activity is preserved, leading to a milder phenotype.
• Dubin-Johnson syndrome and Rotor syndrome lead to
conjugated hyperbilirubinemia.Both are autosomal recessive
disorders and clinically innocuous

20. Acquired causes of Hepatic Jaundice
Acquired causes of hepatic jaundice
• Viral Hepatitis
• Alcoholic Hepatitis
• Auto immune Hepatitis
• Drug related Hepatitis (e.g. NSAIDs)
• Sepsis
• Systemic Diseases (e.g. celiac disease)

21. Clinical Presentation
• Abdominal pain
• Fever, vomiting and nausea along with
• the complications involving satiety
• Gastrointestinal bleeding
• Diarrhea
• Anemia
• Weight-loss and associated weakness
• If unchecked leading to mental disturbances like
kernicterus, coma or even death.

22. POST HEPATIC JAUNDICE
• Cause lies in the biliary portion of hepatobiliary system
• The major cause of post hepatic jaundice is extra hepatic biliary
obstruction. Therefore it is also known as obstructive jaundice.

23. Congenital obstruction
The congenital obstruction involves
• Biliary Atresia
• • Cystic Fibrosis
• • Idiopathic dilation of common bile duct
• • Pancreatic biliary malfunction
• • Choledochal CyST

24. Acquired Causes of Biliary Obstruction
• Cholecystitis
• • Trauma
• • Pancreatitis
• • Strictures
• • Choledocholithiasis
• • AIDS
• • Intra-Abdominal Tuberculosis
• • Tumors
• • Common bile duct Obstruction

25. Clinical Presentation
• Dark urine
• Pale stools and generalized pruritus
• History of fever
• Biliary colic
• Weight loss
• Abdominal pain and abdominal mass
• Obstructive Jaundice may lead to various complications
including cholangitis, pancreatitis,renal and hepatic
failure.

26. Differentiating types of Jaundice
• Elevated serum levels of unconjugated bilirubin and Urobilinogen & Normal
serum levels on conjugated bilirubin,alkaline phosphatase, Alanine
transferase and Aspartate transferase -pre-hepatic jaundice
• The hepatic jaundice can be differentiated from post hepatic and pre hepatic
jaundice on the basis of five times high bilirubin levels.
• Post Hepatic-Elevated serum bilirubin level along with the
conjugation .Serum gamaglutamyltranspeptidase (Serum GGT), alkaline
phosphatase and transaminases may be elevated