6. Jaundice Flashcards
Obstructive jaundice is commonly caused by gall stones within what structure?
common bile duct
What is the structure in the middle of the hepatic lobule?
central vein
What is the cause of physiological jaundice of the newborn?
excess breakdown of foetal haemoglobin
Bacterial enzyme hydrolysis in the gut produces this compound which is excreted in faeces.
Stercobilinogen
Microsomal enzyme uridine diphosphoglucoronosyl transferase (glucuronyl transferase) catalyses the formation of what?
Conjugated bilirubin
What structure is situated within the duodenal loop?
Pancreas
What is jaundice?
- Jaundice refers to a yellow discolouration of the sclera and skin
- Results from high bilirubin levels (hyperbilirubinemia). Jaundice occurs at bilirubin levels roughly greater than 50 µmol/L.
- Bilirubin is a breakdown product of the catabolism of haem and therefore is formed when red blood cells are destroyed
- In healthy individuals bilirubin undergoes conjugation in the liver making it water soluble and then it is excreted via the bile into the GI tract.
- Disruption in this pathway leads to jaundice and there are 3 different types of jaundice that are each based on where the pathway is altered.
Pre-hepatic jaundice
there is excessive red blood cell breakdown which produces an excess of bilirubin and hence overwhelms the livers ability to conjugate bilirubin. This leads to unconjugated hyperbilirubinemia (although some bilirubin is still conjugated by the liver it can’t conjugate it all).
HEPATOCELLULAR Jaundice
there is a disfunction of the hepatic cells. The liver loses its ability to conjugate bilirubin. However in some cases the liver may become cirrhotic (the liver may scar) and this scar tissue may compress the intra-hepatic portions of the biliary tree leading to a degree of obstruction. This can lead to an excess of both conjugated and unconjugated bilirubin in the blood (‘a mixed picture’)
post-hepatic jaundice
In post-hepatic jaundice the biliary drainage is obstructed. Therefore the bilirubin that is not excreted will have been conjugated by the liver hence this leads to conjugated hyperbilirubinemia
Causes of pre-hepatic jaundice
sickle cell disease Hereditary Spherocytosis Hereditary Elliptocytosis G6PD deficiency Pyruvate Kinase deficiency
causes of hepatocellular jaundice
Alcoholic liver disease viral hepatitis autoimmune hepatitis primary biliary cirrhosis Hepatocellular carcinoma
Causes of post-hepatic jaundice
Gallstones
Cholangiocarcinoma
pancreatic cancer
why does urine turn dark in some jaundice patients
- People with Jaundice have conjugated bilirubin
- Conjugated bilirubin is unable to get into the gallbladder, so it is backed up in the blood which results in increased renal excretion of conjugated bilirubin
- when a blockage or other problem prevents bilirubin from being eliminated in stool it causes more bilirubin to be eliminated in urine
- Bilirubin is pigmented, bili-rubin (rubin for red, which is why you get dark urine).
Why do stools turn pale in some jaundice patients
- Stercobilin is a bile pigment and is one end-product of haeme catabolism. It is the chemical responsible for the brown colour of human faeces
- In obstructive jaundice, you don’t have secretion of conjugated bilirubin (bile) into the GI tract due to a blockage or other problem
- So the bacteria in the large intestine does not have any bilirubin to breakdown into stercobilin which is why you get pale stool
What is bilirubin?
- Yellow bile pigment
- Produced through breakdown of RBCs in haemolysis
- Metabolised before excretion in faeces and urine
Bilirubin + Haemoglobin creation - hepatic uptake
- RBCs are produced in the bone marrow by erythropoiesis
- After 120 days – Reticuloendothelial cells (macrophages) in spleen + bone marrow engulf & degrade RBCs (release haemoglobin)
- Haemoglobin is broken down → haem + globin
- Globin broken down into amino acids (which are then recycled → erythropoiesis)
- Kupffer cells in the liver (resident macrophages) also break down RBCs
- Haem → biliverdin + iron - catalysed by haem oxygenase, iron recycled, biliverdin used to create unconjugated bilirubin
- Unconjugated bilirubin is toxic so must be removed
- Unconjugated bilirubin binds to albumin in the bloodstream - Albumin facilitates transport of bilirubin to the liver because bilirubin is lipid-soluble
conjugation
• Conjugation occurs in the liver:
• Glucuronic acid added to unconjugated bilirubin via glucuronyl transferase enzyme to form conjugated bilirubin
Bilirubin + glucuronic acid (+ glucuronyl transferase) → conjugated bilirubin
• Conjugated bilirubin is water-soluble – can be excreted by the liver in bile
• Bile + bile salts secreted into small intestine via common bile duct
• Conjugated bilirubin in small intestine travels to colon (large intestine)
excretion
- Bacteria in the colon deconjugate bilirubin by converting bilirubin 🡪 urobilinogen (hydrolysis reduction reaction - glucuronic acid removed)
- Urobilinogen is lipid soluble.
- 80% of urobilinogen 🡪 stercobilin by intestinal bacteria
- Oxidation reaction
- Stercobilin is a brown pigment – excreted by body (gives faeces its colour)
- 20% urobilinogen reabsorbed into bloodstream via enterohepatic circulation
- 5% urobilinogen carried to liver via portal system – taken up by liver and re-secreted into bile
- 5% urobilinogen transported to kidneys
- urobilinogen 🡪 urobilin (oxidation) and excreted in urine
- Urobilin = yellow pigment (gives urine its colour)
