PHYSIOLOGY BLOOD UNIT 5

Blood Unit 5 Jaundice

Jaundice

• Definition: yellow discolouration of skin and sclera as a result of hyperbilirubin in the plasma and tissue fluids.
• Normal value- 0.2 - 0.8 mg/dl
• Serum Bilirubin more than 2mg/dl for jaundice to be visible on examination
• Sclera first place to become jaundiced

Source of Bilirubin

• 85% from old RBC
• Hb is degraded to haem and globin
• Iron is extracted from haem and rest converted to bilirubin

Haemoglobin Metabolsim

• Bilirubin is a product of metabolism of haemoglobin (80%) and other haem
containing proteins (e.g. Myoglobin, cytochrome P450: 20%)
• Degradation of haemoglobin into bilirubin takes place by macrophages. Bilirubin is then excreted into plasma and binds with albumin which prevents its excretion by kidney in urine.

•Uptake of unconjugated bilirubin into hepatocyte
•Unconjugated bilirubin converted to conjugated bilirubin by glucuronyl transferase (this is required before bilirubin can be excreted into the bile, as this process makes bilirubin water soluble)
•Bilirubin secreted (as component of bile) into the small intestine
•Bacterial enzymes deconjugate bilirubin and convert it into urobilinogen
       -90% urobilinogen broken down further into stercobilinogen and stercobilin and excreted in faeces
       -10% urobilinogen absorbed (via portal vein)
             --Majority of absorbed urobilinogen re-enters hepatocyte and re-excreted in bile (entero-hepatic circulation)
             --The rest of the absorbed urolbilinogen bypasses liver and is excreted by kidneys

Hyperbilirubinaemia

• Excessive level bilirubin in the blood. Disruption of bilirubin metabolism and excretion can cause hyperbilirubinaemia and subsequent jaundice
• Hyperbilirubinaemia may be unconjugated (indirect) or conjugated (direct) depending on the cause
• Some inherited syndromes of bilirubin handling can result in hyperbilirubinaemia
     - Gilbert's syndrome - reduced activity of glucuronyl transferase therefore reduced conjugated bilirubin therefore elevated unconjugated bilirubin
     - Criggler-Najjar - reduction in amount of glucoronyl transferase therefore elevated unconjugated bilirubin
     - Rotor's/Dubin-Johnson syndrome - defective excretion of conjugated bilirubin into the biliary cannaliculi therefore elevated conjugated bilirubin

Classification of Jaundice

• Physiologic Jaundice
• Patholgical Jaundice
1. Pre Hepatic Jaundice
2. Intra Hepatic Jaundice
3. Post Hepatic / Obstructive Jaundice

 Pre-hepatic (Hemolytic Jaundice): pathology occurring prior to the liver

• Any cause of increased haemolysis (e.g. Spherocytosis, thalassaemia, sickle cell disease, transfusion reaction, auto-immune, malaria etc.) and some drugs
• Causes unconjugated hyperbilirubinaemia
• Increase in Urobilinogen, Faecal stercobilinogen

• Intra-Hepatic: pathology occuring within the liver

• All the causes of hepatitis/cirrhosis (e.g. Alcohol, viral, auto-immune, primray biliary cirrhosis, haemochromatosis, wilsons, alpha-1 antitrypsin
deficiency etc.), inherited condition on previous slide and some drugs
• Can result in hepatocyte destruction and therefore unconjugated hyperbilirubinaemia or in bile cannaliculi destruction and therefore conjugated hyperbilirubinaemia or both

• Post-hepatic: pathology occuring after conjugation of bilirubin within the liver (aka obstructive jaundice)

• Any cause of biliary obstruction (e.g. Gallstones)
• Causes conjugated hyperbilirubinaemia

Physiological Jaundice

• Note- neonatal jaundice: occurs in most newborns as hepatic machinary for conjugation and excretion of bilirubin not fully matured until 2 weeks of age

Phototherapy

• Exposure of skin to white light converts bilirubin to lumirubin which has shorter life than bilirubin.
• Can be easily excreted.

Determining aetiology of Jaundice 

History

• If jaundice associated with background of intermittent RUQ pains think gallstones and choledocholithiasis
• If jaundice associated with long history of upper abdominal pain and weight loss and patient elderly thing pancreatic cancer
• If jaundice associated with recent foreign travel think hepatitis (A,E) or malaria
• If jaundice occuring on a background of alcohol abuse think alcoholic liver disease
• If jaundice is painless and family history of blood disorder think prehepatic jaundice

Obstructive Jaundice: Causes

• Causes
  - Luminal
      " Gallstone
  - Intra-mural
      " Benign structure (e.g. As complication of cholecystectomy or due to pancreatitis)
      " Malignant stricture: cholangiocarcinoma
   -Extra-mural
     " Head of pancreas cancer
     " Pancreatitis (oedema of head of pancreas)
     " Pancreatic pseudocyst
     " Compression by malignant lymph nodes at porta hepatis

Treatment

• During Pregnancy (If severe)
  1. Intrauterine Blood Transfusion
  2. Early delivery
• After Pregnancy
  1. Increase feeds
  2. Phototherapy
  3. Transfusion

Phototherapy