Bilirubin Pathways & Bile Production Flashcards
What is erythropoiesis?
Red blood cell synthesis
Where is erythropoietin made?
In the kidney - amount made depends on how well oxygenated the blood is
What does erythropoietin do?
It goes to the bone marrow to stimulate red blood cell production
What does RBC synthesis require?
iron, globin, vitamin B12, erythropoietin
What is a reticulocyte?
An immature RBC
What is the lifespan of a RBC?
120 days
Where do red blood cells go to die?
The liver, spleen or red bone marrow where they are broken down by macrophages
How does the macrophage know that the RBC is old?
There is low levels of neuraminic acid and higher levels of phosphatidylserine on the RBC
What are RBCs broken down into?
heme and globin
What happens to the globin?
it is broken down into amino acids that are reused for protein synthesis
What happens to the heme?
It is split up into iron and biliverdin
What enzyme converts haem to biliverdin?
haem oxygenase
What is the structure of haem oxygenase?
a dimer with a globin like structure
What happens to the iron?
It is packed with transferrin and goes to the liver or bone marrow
What colour is biliverdin?
green
What happens to the biliverdin?
It is broken down into bilirubin
What enzyme converts biliverdin to bilirubin?
biliverdin reductase
What is the structure of bilirubin?
An open chain of four pyrolle rings
What colour is bilirubin?
yellow
What is haemolysis?
pathological early breakdown of RBCs causing anemia and jaundice
What causes haemolysis?
external attack on cells by bacteria (streptococcus and enterococcus), parasitic haemolysis (malaria), congenital or genetic factors
What is haptoglobin?
A plasma protein that binds haemoglobin released from RBCs that are haemolysed at a site other than the spleen
What is haemopexin?
a protein which carries haem to the liver
What is low haemopexin a sign of?
haemolytic anemia
What are the consequences of haemolysis?
unconjugated hyperbilirubinemia due to conversion of Hb to bilirubin exceeding the liver’s capacity to conjugate and excrete bilirubin, also increased sterobilin in the stool and increased urobilinogen in the urine, also reticulocytosis due to increased production of RBCs, also possible gall stones
What are the symptoms of haemolysis?
pallor, fatigue, dizziness, hypotension, fever, pain in back and abdomen, jaundice, splenomegaly
What causes the bluish purple colour of bruises in the first 1-2 days?
deoxy and met haemoglobin
What causes the greenish yellowish colour of bruises after 5-10 days?
biliverdin
What causes the brownish colour of bruises after 0-14 days?
bilirubin
How is bilirubin transported in blood?
bound to serum albumin
What happens to bilirubin in the liver?
It is conjugated by bilirubin UDP glucoronyltransferase
How is conjugated bilirubin pumped into the bile cannaliculi?
cMOAT
What is Dubin-Johnson syndrome?
a defect in cMOAT
What is the treatment for Dubin-Johnson syndrome?
no treatment (what is Dubin-Johnson syndrome?)
What is Crigler Najjar syndrome?
a lack of UDPGT - can’t conjugate bilirubin
What are the symptoms of Crigler Najjar syndrome?
persistent jaundice, kernicterus (bilirubin encephalopathy and brain damage)
What is the treatment of Crigler Najjar syndrome?
Uv light - flips the ZZ isomer of bilirubin to the E,Z isomer and the E,E isomer which are non toxic
What happens to bilirubin in the bile?
It is broken down by bacteria to urobilinogen and stercobilin
What happens to urobilinogen?
Some goes into the faeces, some (9%) is taken back up into the liver and some (1%) is transported to the kidney and excreted in urine
What makes urine yellow?
urobilin - oxidated urobilinogen
What makes faeces brown?
stercobilin
What causes dark urine in hepatitis?
the 9% of urobilinogen that is normally taken back to the liver isn’t because of the back up and so the entire 10% is transported to the kidney and excreted in the urine
What causes pale faeces in hepatitis?
The liver is backed up so is releasing less conjugated bilirubin so there is less stercobilin so faeces is paler
