Bile and jaundice Flashcards
What is bile?
- A brownish-yellow or green fluid that is secreted by liver and stored in gallbladder.
What are the functions of bile?
- Excretory
- Digestive
Discuss the excretory function of bile.
- Exogenous and endogenous products can accumulate in bile and be excreted.
What are the names of the macrophages of the liver?
- Kupffer cells: maintain liver function.
Discuss the digestive function of bile.
- Associated mainly with fats.
- Increases pH to neutralise acidity of gastric content. Alkaline secretion.
- Bile salts and phospholipids emulsify fats into smaller droplets.
- Bile salts activate pancreatic hydrolyse precursors.
Where do we get bile acids and salts from?
- Come from breakdown of cholesterol.
Name 2 primary bile acids (Liver).
- Cholic acid
- Chenodeoxycholic acid.
Name 2 secondary bile acids (Gut).
- Deoxycholic acid
- Lithocholic acid
What is bilirubin?
- A natural degradation product of haem in erythrocytes.
What processes need to happen for production of bilirubin?
- Phagocytosis and/or lysis of RBCs.
Describe extra-vascular formation of bilirubin.
- RBC undergoes phagocytosis and/or lysis.
- Haemoglobin is released and broken into Haem and Globin.
- Globin is further degraded into AAs.
- Haem is broken into Fe2+ and a product of its breakdown is bilirubin.
Discuss haem degradation and processing.
- Haem is degraded into bilirubin.
- Bilirubin binds to albumin and is transported in bloodstream.
- Then taken up by liver.
- It is then conjugated with glucuronic acid to make it water soluble.
- It is then excreted into bile.
- Urobilinogens then form in intestinal tract.
- Can either be re-absorbed and excreted from kidney as urinary urobilin, or excreted as faecal stercobilin
How exactly is haem degraded into bilirubin?
- Via 2 enzymes:
1. Haem oxygenate
2. Biliverdin reductase - Haem–biliverdin—unconjugated bilirubin
Discuss the metabolism of bilirubin.
- Haem is degraded and produces bilirubin.
- Bilirubin binds to albumin, transported into bloodstream then is taken up by liver.
- In the liver, binds to cytoplasmic proteins: ligand + protein Y.
- Then conjugated with glucoronic acid is catalysed by UDP-glucuronyl transferase to make it water soluble.
- Conjugated bilirubin is secreted into biliary tree.
- Bile excreted from liver to gut and de-conjugated.
What pigment gives faeces brown colour?
- Stercobilin.
What gives urine yellow colour?
- Urinobilin.
What is jaundice?
- Hyperbilirubinemia.
Discuss the classifications of jaundice.
- Pre-hepatic: haemolytic.
- Intra-hepatic: viral, drugs
- Post-hepatic: obstruction
What is pre-hepatic jaundice?
- Haemolytic jaundice.
- Bilirubin production is exceeding liver uptake capacity.
- Commonly due to autoimmune dx: Rh- incompatibility, sickle cell dx, haemolytic disease of newborn.
- Unconjugated
What is intrahepatic jaundice?
- Hepatocellular jaundice.
- Problem within hepatocytes function.
- Impaired uptake, conjugation or secretion.
- Unconjugated or conjugated.
What is post-hepatic jaundice?
- Obstructive/ choleostatic jaundice.
- Obstruction in biliary tract.
- Conjugated bilirubin regurgitated back into systemic circulation.
- Pale stools + dark urine.
What is Kernicterus (bilirubin encephalopathy)?
- Results from untreated hyperbilirubinemia w/bilirubin levels 25 or higher.
- Signs: lethargy, tonic motions such as backward arching of the neck and trunk, hypotonia.
What is Gilbert’s syndrome?
- Benign congenital unconjugated hyperbilirubinemia.
- Defect in UDP glucuronyl transferase.
- Treatment: phenobarbitone.
What is Crigler-Najjar syndrome?
- Congenital unconjugated hyperbilirubinemia.
- Defect in UDP glucuronyl transferase.
- Type 1&2.
What is Dubin- Johnson syndrome and Rotor Syndrome?
- Benign autosomal recessive disorders presenting with conjugated hyperbilirubinemia.
- Characterised by impaired biliary secretion of conjugated bilirubin.
- Grossly black liver. Benign.
- Mutation in MRP2 (DJS).
