L25- Heme Catabolism and Jaundice (#7)

Question 1

Roughly ___% of heme destined for degradation by resident macrophages comes from SENESCENT RBCs , and ____% from the turnover of IMMATURE blast cells (in the bone marrow). Where do the rest come from?

Answer 1

70%
15%

Cytochromes (liver and many other cells)

Question 2

What is free heme degraded by (although toxic and not recyclable)?

Answer 2

Heme oxygenase

Question 3

What does heme oxygenase produce?

Answer 3

Biliverdin and releasing iron

Question 4

What converts biliverdin into bilirubin?

Answer 4

Biliverdin reductase

Question 5

What type of enzyme is heme oxygenase?

Answer 5

Cytochrome P450 enzyme, phase 1 drug metab

Question 6

What is the unconjugated bilirubine (UCB) made from? (reaction) What do these two reactions require?

Answer 6

Heme oxygenase produces biliverdin
Biliverdin reductase converts biliverdin into bilirubin which is called UCB

NADPH

Question 7

Why is UCB very hydrophobic? What binding does it form to serum albumin for its transport?

Answer 7

Due to internal H-bonding

UCB forms non-covalent binding to serum albumin for its transport

Question 8

How is conjugated bilirubin formed during the step of uptake of UCB by the liver? What is this reaction catalyzed by?

Answer 8

Attachment of 2 glucornic acid residues

Catalyzed by liver UDP-glucuronyl transferase

Question 9

UCB is taken up itno the liver via what carrier?

Answer 9

OATP

Question 10

The addition of glucuronic acids to the bilirubin which forms CB during the uptake of UCB by liver does what?

Answer 10

Adding it makes CB hydrophilic so now it is amphipathic with both hydrophilic and hydrophobic characteristics

Question 11

Clinical Note: Birds lack biliverdin reductase so in avian sepcies, biliverdin is the major pigment of ___

Answer 11

Bile

Question 12

How is CB actively excreted into the bile?

Answer 12

Via an ATP-dependent carrier, MRP2

Question 13

What happens to CB in healthy animals in relation to the blood? *

Answer 13

CB does NOT leak back into blood because presence of TIGHT JUNCTIONS*

Question 14

Clinical Note: Dubin- Johnson Syndrome is caused by a deficiency in _____ resulting in ______________

Answer 14

caused by MRP2 resulting in conjugated hyperbilirubinemia

Question 15

Clinical Note: Dubin-Johnson Syndrome is significant because there is no _______

Answer 15

Liver damage

Question 16

During the step of formation of urobilinogen, the CB is metabolized by what?

Answer 16

Colonic bacteria

Question 17

Urobilinogen during its formation goes through what type of oxidation? What does it produce?

Answer 17

Non-enzymatic Auto-oxidation

producing sterocobilin

Question 18

The vast majority (>90%) of urobilinogen in the portal blood is ________________

Answer 18

Reabsorped by the liver and re-excreted into bile

Question 19

The process of reabsorbing urobiliongen in blood and re-excreting it into the bile without and chemical alteration is termed what?

Answer 19

Enterohepatic (re)circulation

Question 20

What happens to the small percentage of urobilinogen that is NOT taken up by the liver from the portal blood?

Answer 20

Enters systemic circulation and is filtered by the kidney

Question 21

To produce urine, urobilinogen goes through the non-enzymatic auto-oxiation, yielding what?

Answer 21

Urobilin

Question 22

Where is stercobilin found? Urobilin?

Answer 22

Stercobilin (found in the intestine)

Urobilin (found in the urine)

Question 23

Unconjugated bilirubin is ____ and ______ filtered at the kidney

Answer 23

Hydrophobic and IS NOT filtered at the kidney

Question 24

Conjugated bilirubin (if present) is _______ and ______ filtered at the kidney

Answer 24

Amphipathic and IS FILTERED at the kidney

Question 25

What type of bilirubin would be present in a healthy organism? Unhealthy?

Answer 25

Healthy: Unconj bilirubin Unhealthy: Conj bilirubin

Question 26

Clinical note: Jaundice is not a disease but a ____?

Answer 26

Sign of a disease

Question 27

Clinical note: It is detectable when serum bilirubin exceeds______ mg/dL

Answer 27

2.0-3.0 mg/dL (hyperbilirubineamia)

Question 28

In pre-hepatic jaundice due to hemolysis, what would serum tests say about IBIL (indirect bilirubin) [UCB] and why?

Answer 28

Increased | RBC lysis --> UCB --> Exceed the transport and conjugation capacity

Question 29

In pre-hepatic jaundice due to hemolysis, what would serum tests say about DBIL(direct bilirubin) [CB]?

Answer 29

Normal | Although more bilirubin is being conjugated, the CB is being secreted to bile rather than blood

Question 30

In pre-hepatic jaundice due to hemolysis, what would serum tests say about urinary urobilinogen?

Answer 30

Increase | This increase is due to an increase of prod of CB which is the precursor for urobilinogen

Question 31

In pre-hepatic jaundice due to hemolysis, what would serum tests say about urinary bilirubin?

Answer 31

Normal | This test measures CB- since level of CB in the serum is normal, it is not present in the urine.

Question 32

When UCB accumulates and is highly elevated, it does not get filtered out in the urine because of what?

Answer 32

Too hydrophobic

Question 33

In pre-hepatic jaundice due to hemolysis, what would serum tests say about fecal urobilinogen?

Answer 33

Increased | The increase in urobilinogen is due to an increase in prod of CB which is coverted into urobilinogen

Question 34

In hepatic jaundice due to hemolysis, what would serum tests say about IBIL (indirect bilirubin) [UCB] and why?

Answer 34

Normal to increased The increase is proportional to the extent of the liver cell dysfunction (Note: not a reliable predicator of jaundice)

Question 35

In hepatic jaundice due to hemolysis, what would serum tests say about DBIL?

Answer 35

Increased A decrease transport of CB into the bile: depending on liver dysf severity, the transport of CB from hepatocyte may be reduced. The liver dmg results in leakage of CB in blood (Note: DBIL increase is sign of liver dmg)

Question 36

In hepatic jaundice due to hemolysis, what would serum tests say about urinary urobilinogen?

Answer 36

Increased Liver is unable to reabsorb as much as urobilinogen as normal from the portal vein and more urobilinogen gets into the blood - Serum urobilinogen is amphipathic and is filtered at kidney into urine

Question 37

In hepatic jaundice due to hemolysis, what would serum tests say about fecal urobilinogen?

Answer 37

Normal to decreased | Liver damage results in a decrease in rpod of conjugated bilirubin

Question 38

In hepatic jaundice due to hemolysis, what would serum tests say about urinary bilirubin?

Answer 38

Increased Urinary bilirubin is increased, bc levels of the CB in blood is increased. CB is amphipathic and is readily filtered at the kidney

Question 39

In post-hepatic jaundice due to hemolysis, what would serum tests say about IBIL (indirect bilirubin) [UCB] and why?

Answer 39

Normal to increased | If CB is increased, it is due to 2ndary liver damage- not a good indicator!

Question 40

In oost-hepatic jaundice due to hemolysis, what would serum tests say about DBIL?

Answer 40

Increase | The increase in CB is ude to the backup of CB into the blood secondary to the bile blockage

Question 41

In post-hepatic jaundice due to hemolysis, what would serum tests say about urinary urobilinogen?

Answer 41

Decreased The decrease in urobilinogen is due to a decrease in synthesis because of the blockage of bile duct- thus, CB is not able to enter intestine and to be catabolized into urobilinogen

Question 42

In post-hepatic jaundice due to hemolysis, what would serum tests say about urinary bilirubin?

Answer 42

Increased | Bc levle of CB in blood in increased- CB is amphipathic and ready to be filtered at kidney

Question 43

In post-hepatic jaundice due to hemolysis, what would serum tests say about fecalurobilinogen?

Answer 43

Decreased | The decrease in urobilinogen is due to blockage of the bile duct which prevents CB from entering intestine