Bilirubin Metabolism & Types of Jaundice Flashcards Preview

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Flashcards in Bilirubin Metabolism & Types of Jaundice Deck (47)
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Where does bilirubin come from?

  • every haem molecule produces one molecule of bilirubin


  • haem molecules are found in haemoglobin and myoglobin


  • cytochrome enzymes also produce one molecule of bilirubin


Where does production of bilirubin mostly take place?


What is the name of the cells that perform this function?

  • production of bilirubin from haem mostly occurs in the spleen (by macrophages) and in the liver (by Kupfer cells)


  • it also occurs by macrophages all over the body and in renal tubular cells


  • the cells that perform this job are collectively known as the reticuloendothelial system 


What is the purpose of the reticuloendothelial system?


What are the 2 main cellular components?

it is made up of Kuppfer cells in the liver and reticular cells in the bone marrow 


the system defends the body against hazardous substances by phagocytosis



What happens once bilirubin-forming molecules are taken up by reticuloendothelial cells?

  • bilirubin-forming molecules (i.e. haem) are taken up by reticuloendothelial cells 


  • inside these cells, haem oxygenase enzymes break down the haem


  • iron (which is recycled) and carbon monoxide are removed


  • this produces biliverdin


What is the main difference in properties of bilirubin and biliverdin?

biliverdin is very water soluble, whilst bilirubin is not 


What test can determine how much haem is being turned into biliverdin?

the detection of carbon monoxide in breath


this can be used to determine how much haem is being turned into biliverdin


What happens to biliverdin whilst within the reticuloendothelial cells?

whilst still in the reticuloendothelial cell, biliverdin is converted to bilirubin


this is performed by biliverdin reductase 


What is a benefit of not directly secreting biliverdin, but converting it to bilirubin first?

bilirubin is not just a waste product


it takes up free radicals and acts as an antioxidant 


What happens to bilirubin after it is released from reticuloendothelial cells?


What happens if there are very high concentrations of bilirubin?

  • it travels in the blood bound to albumin


  • this ensures that no bilirubin is excreted in the urine


  • at very high concentrations, bilirubin can slowly diffuse into the peripheral tissues where it is toxic 


How is bilirubin removed from circulation?


Is this passive or active?

  • bilirubin is removed from the circulation in the sinusoids by hepatocytes 


  • this is a passive process that occurs down a concentration gradient 


  • the fact that hepatocytes are in direct contact with the sinusoidal fluid helps this process 


What happens to bilirubin as soon as it enters the hepatocyte?

  • it becomes bound to glucuronyl transferase which conjugates bilirubin ready for excretion


  • bilirubin is joined with glucuronic acid in the conjugation process


  • very small amounts of bilirubin evade this process and end up  in bile as unconjugated bilirubin


What is the benefit of conjugating bilirubin when it is secreted?

it requires energy to secrete conjugated bilirubin into the canniculi


the process of conjugation makes the bilirubin water soluble and easier to excrete 


What happens in situations where the liver cannot excrete conjugated bilirubin?

  • in situations where the liver cannot excrete conjugated bilirubin, the kidneys take over this job


  • once plasma concentrations are high enough (above 600 umol/L) then the kidneys cannot conjugate bilirubin and can only excrete it after this process has occurred 





What happens to bilirubin that is deconjugated by bacteria in the gut?


What makes this process more likely to occur?

  • bilirubin that is deconjugated by bacteria in the gut will be reabsorbed in the colon


  • this process is more likely in the presence of increased bile acids (i.e. bile acid malabsorption)






When does bile acid malabsorption occur?


What compensatory mechanism is in place in these patients and what is the associated increased risk?

bile acid malabsorption occurs in cases of intestinal disease and resection 


in these patients, as a compensatory mechanism, the body excretes higher concentrations of bile salts 


this increases the risk of gallstones 


How does fasting affect the amount of bilirubin that is reabsorbed?

more bilirubin is reabsorbed during fasting 


this also increases the risk of gallstones 


What is bilirubin in the colon turned into?

much of the bilirubin in the colon is turned into stercobilogens and urobilogens 


urobilogens are colourless


stercobilogens give faeces its colour 


What happens to urobilogens that enter the circulation?

  • some urobilogens are absorbed and enter the circulation, where they are removed mainly by the liver, but also by the kidney


  • in liver disease and excessive haemolysis, the liver may not be able to remove all excess urobilogens and so more are removed by the kidney


Why is bile green in colour?

bilirubin oxidises back to biliverdin after excretion 


this leads to the green colour of bile 


What are the 4 stages of bilirubin metabolism and the enzymes involved?



converted to biliverdin by haem oxygenase


converted to bilirubin by biliverdin reductase


converted to conjugated bilirubin by glucoronyl transferase 


What is jaundice?


What is normal bilirubin level?

a condition where there is yellowing of the skin, sclera and mucous membranes as a result of increased bilirubin concentration in bodily fluids


normal bilirubin level is 1 - 20 umol / L


What type of disease does jaundice indicate?


What level does bilirubin have to reach before jaundice is visible?

jaundice is the clinical sign of hyperbilirubinaemia that indicates the presence of disease of the liver or biliary tree


it is usually detectable when bilirubin concentrations reach 50 umol/L


Where is jaundice usually first visible?


What becomes darker and what is not affected?

jaundice is first visible in the sclera, and more subtly in the skin 


urine is also likely to be dark


sputum and saliva are not affected 


What can occasionally mimic jaundice and how can these be told apart?

carotenemia may mimic jaundice 


this is usually caused by eating too many carrots or vitamin A


the yellowness is more visible in the palms than the sclera if this is the case 


What is another name for haemolytic jaundice?


What causes it?

pre-hepatic jaundice 


this results from excessive RBC (or their precursors in the bone marrow) breakdown 





Why does it take a long time for pre-hepatic (haemolytic) jaundice to show up?


Why do babies often appear jaundiced shortly after birth?

  • the liver is able to secrete 6x the normal amount of bilirubin before it becomes overwhelmed


  • a very large amount of bilirubin is needed before jaundice will develop


  • newborn babies have a reduced ability to remove bilirubin, so often appear jaundiced shortly after birth