Bilirubin Pathways & Bile Production

Question 1

What is erythropoiesis?

Answer 1

Red blood cell synthesis

Question 2

Where is erythropoietin made?

Answer 2

In the kidney - amount made depends on how well oxygenated the blood is

Question 3

What does erythropoietin do?

Answer 3

It goes to the bone marrow to stimulate red blood cell production

Question 4

What does RBC synthesis require?

Answer 4

iron, globin, vitamin B12, erythropoietin

Question 5

What is a reticulocyte?

Answer 5

An immature RBC

Question 6

What is the lifespan of a RBC?

Answer 6

120 days

Question 7

Where do red blood cells go to die?

Answer 7

The liver, spleen or red bone marrow where they are broken down by macrophages

Question 8

How does the macrophage know that the RBC is old?

Answer 8

There is low levels of neuraminic acid and higher levels of phosphatidylserine on the RBC

Question 9

What are RBCs broken down into?

Answer 9

heme and globin

Question 10

What happens to the globin?

Answer 10

it is broken down into amino acids that are reused for protein synthesis

Question 11

What happens to the heme?

Answer 11

It is split up into iron and biliverdin

Question 12

What enzyme converts haem to biliverdin?

Answer 12

haem oxygenase

Question 13

What is the structure of haem oxygenase?

Answer 13

a dimer with a globin like structure

Question 14

What happens to the iron?

Answer 14

It is packed with transferrin and goes to the liver or bone marrow

Question 15

What colour is biliverdin?

Answer 15

green

Question 16

What happens to the biliverdin?

Answer 16

It is broken down into bilirubin

Question 17

What enzyme converts biliverdin to bilirubin?

Answer 17

biliverdin reductase

Question 18

What is the structure of bilirubin?

Answer 18

An open chain of four pyrolle rings

Question 19

What colour is bilirubin?

Answer 19

yellow

Question 20

What is haemolysis?

Answer 20

pathological early breakdown of RBCs causing anemia and jaundice

Question 21

What causes haemolysis?

Answer 21

external attack on cells by bacteria (streptococcus and enterococcus), parasitic haemolysis (malaria), congenital or genetic factors

Question 22

What is haptoglobin?

Answer 22

A plasma protein that binds haemoglobin released from RBCs that are haemolysed at a site other than the spleen

Question 23

What is haemopexin?

Answer 23

a protein which carries haem to the liver

Question 24

What is low haemopexin a sign of?

Answer 24

haemolytic anemia

Question 25

What are the consequences of haemolysis?

Answer 25

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

Question 26

What are the symptoms of haemolysis?

Answer 26

pallor, fatigue, dizziness, hypotension, fever, pain in back and abdomen, jaundice, splenomegaly

Question 27

What causes the bluish purple colour of bruises in the first 1-2 days?

Answer 27

deoxy and met haemoglobin

Question 28

What causes the greenish yellowish colour of bruises after 5-10 days?

Answer 28

biliverdin

Question 29

What causes the brownish colour of bruises after 0-14 days?

Answer 29

bilirubin

Question 30

How is bilirubin transported in blood?

Answer 30

bound to serum albumin

Question 31

What happens to bilirubin in the liver?

Answer 31

It is conjugated by bilirubin UDP glucoronyltransferase

Question 32

How is conjugated bilirubin pumped into the bile cannaliculi?

Answer 32

cMOAT

Question 33

What is Dubin-Johnson syndrome?

Answer 33

a defect in cMOAT

Question 34

What is the treatment for Dubin-Johnson syndrome?

Answer 34

no treatment (what is Dubin-Johnson syndrome?)

Question 35

What is Crigler Najjar syndrome?

Answer 35

a lack of UDPGT - can’t conjugate bilirubin

Question 36

What are the symptoms of Crigler Najjar syndrome?

Answer 36

persistent jaundice, kernicterus (bilirubin encephalopathy and brain damage)

Question 37

What is the treatment of Crigler Najjar syndrome?

Answer 37

Uv light - flips the ZZ isomer of bilirubin to the E,Z isomer and the E,E isomer which are non toxic

Question 38

What happens to bilirubin in the bile?

Answer 38

It is broken down by bacteria to urobilinogen and stercobilin

Question 39

What happens to urobilinogen?

Answer 39

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

Question 40

What makes urine yellow?

Answer 40

urobilin - oxidated urobilinogen

Question 41

What makes faeces brown?

Answer 41

stercobilin

Question 42

What causes dark urine in hepatitis?

Answer 42

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

Question 43

What causes pale faeces in hepatitis?

Answer 43

The liver is backed up so is releasing less conjugated bilirubin so there is less stercobilin so faeces is paler