Jaundice Flashcards
What is jaundice and what is the main compound that causes it?
- Jaundice refers to the yellowing of skin, sclera and mucosa
- Occurs due to high levels of bilirubin ≥ 60 umol/L
How is jaundice classified?
=> Site of problem
- Pre hepatic
- Hepatocellular
- Post hepatic (also known as obstructive or cholestatic)
=> Type of circulating bilirubin
- Conjugated hyperbilirubinaemia
- Unconjugated hyperbilirubinaemia
- Both
What are the clinical features of jaundice?
- Yellowing of eyes (first sign)
- Yellowing of skin
- Pale stools and Dark urine (only in obstruction)
- Pruritis
- Abdominal pain
- Fatigue
- Weight loss
- Vomiting
What is the differential diagnosis of jaundice?
=> Causes of hepatocellular jaundice:
- Hepatitis
- Alcohol related liver disease
- Liver metastasis
- Drug induced liver injury
- NASH
=> Causes of obstructive jaundice:
- Ascending cholangitis
- Cholangiocarcinoma
- Pancreatic carcinoma
How is bilirubin produced from RBCs?
- After the end of their lifespan of 120 days, RBCs are engulfed and broken down by macrophages
- The haemoglobin is broken down to form haem and globin
- Haem consists of iron and protoporphyrin. Protoporphyrin is converted into unconjugated bilirubin
- Unconjugated bilirubin is not water soluble, and becomes bound to albumin
- Albumin transports the unconjugated bilirubin to the liver, where the enzyme UGT coverts unconjugated bilirubin to conjugated bilirubin
- Conjugated bilirubin is released into the bile duct as part of bile and stored in the gall bladder
- Gall bladder releases bile into the small intestine as required, where is it eventually converted into urobilogen
- Urobilogen is oxidised to urobilin,
- 20% of urobilin is recycled and transported to the liver and kidneys
=> Urobilin is responsible for the brown colour of faeces and yellow colour of urine
How can the speed of onset of the jaundice be used to confirm the site of the problem?
=> Acute (within days)
- Acute hepatitis
- Alcohol
- Drugs
=> Within few weeks
- Cholestatic
=> Fluctuating
- Gallstones (associated with RUQ pain)
- Carcinoma
Hepatocellular jaundice is typically not associated with pain
What are the causes of jaundice associated with unconjugated hyperbilirubinaemia?
=> Extravascular Haemolytic Anaemia
- Excessive breakdown of RBCs
- Hepatocytes cannot keep up so there is an increase in levels of unconjugated bilirubin
- This also results in a dark urine colour as more conjugated bilirubin is also produced and hence more urobilin
=> Physiological Jaundice of the New Born
- Defect in enzyme responsible for the conversion of unconjugated bilirubin to conjugated bilirubin
=> Gilbert’s syndrome
- Decreased activity of the UGT enzyme which causes the conversion of unconjugated bilirubin to conjugated bilirubin
=> Crigler Najjar syndrome
- No UGT enzyme
What are the causes of jaundice associated with conjugated hyperbilirubinaemia?
=> Dublin Johnson Syndrome
- Autosomal recessive disorder
- Transporter protein deficiency meaning conjugated bilirubin cannot be moved from the hepatocytes to the bile duct
- Up-regulation of transporter that moves this conjugated bilirubin from the hepatocytes to the interstitial space, from where it moves into the blood
=> Obstructive jaundice
- Increased pressure in the bile duct
- Bile pushed out from the duct into the interstital space and blood
- Can cause pruritis and steatorrhoea
What condition results in high levels of both unconjugated and conjugated bilirubin in the blood?
Hepatitis
What are the investigations in suspected jaundice?
=> Urinanlysis
- Bilirubin absent in pre hepatic cause
- Urobilogen absent in obstructive cause
=> Ultrasound
- Looking for any dilation of bile ducts
=> ERCP or MRCP
- Gallstones
=> CT or MRI
Any malignancy
What results of LFTs suggest an obstructive cause of jaundice?
ALP and AND GGT raised higher than ALT
