Degradation of heme; bilirubin

Question 1

How is bilirubin synthesized?

Answer 1

• Hemoglobin is cleaved (->) to heme and globin.
• Heme -> iron and bilirubin
• Bilirubin binds with albumin, and is then transported to the liver

Question 2

What is the first step in bilirubin synthesis?

Answer 2

Heme is converted to biliverdin, via NADPH and heme oxygenase

Question 3

What is the second step in bilirubin synthesis?

Answer 3

Biliverdin is reduced to bilirubin; bilirubin is then bound to albumin and then transferred to the liver

Question 4

What is the third (and rate-limiting) step?

Answer 4

Bilirubin and UDP-glucuronate come together IN THE GI TRACT, to form urobilinogen, which then become sterocobilin (pigment of feces) and urobilin (pigment of urine)

Question 5

What causes jaundice?

Answer 5

Caused by the deposition of both unconjugated and conjugated bilirubin

Question 6

Hemolytic jaundice characteristics

Answer 6

Massive levels of RBC lysis (bilirubin produced faster than it can be conjugated) -> increased levels of unconjugated bilirubin

• Unconjugated levels of bilirubin increase in blood causing jaundice (urine is normal colored)

Question 7

Obstructive jaundice characteristics

Answer 7

• Increase in conjugated bilirubin occurs due to bile duct obstruction (therefore, does NOT go to the GI tract, and thus “urobilinogen -> urobilin” does not occur)
• Increased alkaline phosphatase is also seen

Question 8

Hepatocellular jaundice characteristics

Answer 8

• Total bilirubin is increased in liver disease

- Is essentially a combination of hemolytic and obstructive

Question 9

What is ALT?

Answer 9

ALT is a liver fxn test that asses liver damage

A major increase in measured ALT indicates possible liver damage

Late onset of bilirubin increase may also indicate liver damage

Question 10

Neonatal jaundice

Answer 10

UDP-glucuronate levels are low; bilirubin accumulates

Directly measure the levels of bilirubin in the blood of newborns

Crigler-Najjar syndrom occurs (unconjugated bilirubin -x-> conjugated bilirubin)

Question 11

Tx for neonatal jaundice?

Answer 11

Blue fluorescent light; converts bilirubin in the skin to a water soluble substance (lumirubin) that can then be excreted

Question 12

How does starvation lead to mild elevation of bilirubin in the blood?

Answer 12

A increase in heme production leads to negative feedback of heme production; degrading this heme leads to an increase in bilirubin and iron products.

Because of this degradation, bilirubin is increased in the blood

Question 13

How is creatine formed? (Slide 22)

Answer 13

Creatine is synthesized from glycine. Glycine is converted to guanidino acetate, which is then acted on by SAM to produce creatine.

Question 14

How is creatine phosphate degraded? And what is it measured for?

Answer 14

1-2% is spontaneously cyclized to creatinine; it is used to measure muscle mass.

Question 15

Creatinine clearance and its role in renal function

Answer 15

Creatinine clearance = (creatinine in urine) x 24 hr vol / (plasma creatinine clearance) x (24 x 60min)

Decreased values of creatinine indicated renal dysfxn

Thus, increased levels of creatinine levels in the blood indicated impaired renal fxn