Heme Degradation and Jaundice

Question 1

characteristics of jaundice

Answer 1

hyperbilirubinemia, bilirubin bound to connective tissue, yellowish discoloration of skin, mucous membrane, sclera, and nail beds

Question 2

organs involved in formation and excretion of bilirubin

Answer 2

spleen, liver, and kidney

Question 3

where does bilirubin arise

Answer 3

from heme containing proteins like myoglobin, cytochromes, and most importantly hemoglobin

Question 4

enzymes from heme –> biliverdin (green)

Answer 4

heme oxygenase (also convert Fe2+ to Fe3+ and lose CO)

Question 5

enzyme from biliverdin to biliribun

Answer 5

biliverdin reductase

Question 6

where does heme –> bilirubin take place

Answer 6

spleen

Question 7

what binds unconjugated (indirect) bilirubin in the blood

Answer 7

albumin

Question 8

what drugs can displace bilirubin from albumin

Answer 8

salicylates and sulfonamides

Question 9

what happens when bilirubin is displaced from albumin the blood

Answer 9

you will have free unconjugated bilirubin which can cross blood brain barrier to cause kernicterus

Question 10

when bilirubin enters the liver, what is it bound to

Answer 10

ligandin

Question 11

what happens to unconjugated bilirubin in the liver

Answer 11

it is converted to conjugated bilirubin using microsomal UDP glucuronyl transferase

Question 12

what donates the glucuronic acid used in conversion of bilirubin to its conjugated form

Answer 12

UDP glucuronic acid

Question 13

fate of bilirubin after being conjugated in the liver

Answer 13

actively transported to bile caniculus by ABC transporter where it is released into the second part of the duodenum

Question 14

disease associated with defective ABC transporter in bilirubin transportation

Answer 14

Dubin-Johnson syndrome

Question 15

diseases associated with defect with UDP glucuronyl transferase

Answer 15

Crigler Najjar syndrome Type I and II

and Gilbert

Question 16

what happens to bilirubin in the large intestine

Answer 16

it is acted upon by bacterial flora and deconjugated and converted to urobilinogen (colorless)

Question 17

fate of urobilinogen

Answer 17

most excreted in urine as urobilin (yellow), absorbed into the portal blood, excreted into bile caniculus, or acted upon by bacteria to form stercobilin

Question 18

fate of stercobilin

Answer 18

excreted in feces

Question 19

lab test done to detect type of bilirubin

Answer 19

van den bergh reaction

Question 20

how does van den bergh reaction work

Answer 20

conjugated bilirubin readily react with diazo reagent to prove it is water soluble

unconjugated would react in presence of methanol

Question 21

how to calculate total bilirubin

Answer 21

unconjugated bilirubin + conjugated bilirubin

Question 22

how do we classify jaundice

Answer 22

prehepatic (hemolytic), hepatic, and posthepatic (obstructive)

Question 23

what type of bilirubin in elevated in prehepatic jaundice

Answer 23

unconjugated bilirubin

Question 24

characteristics of prehepatic jaundice

Answer 24

elevated serum total bilirubin, normal serum conjugated bilirubin, elevated unconjugated bilirubin, absent urine bilirubin, and increased urine urobilinogen

Question 25

why is bilirubin not found in urine in prehepatic jaundice

Answer 25

unconjugated bilirubin is bound to albumin

Question 26

type of bilirubin elevated in hepatic jaundice

Answer 26

both unconjugated and conjugated

Question 27

type of bilirubin found in urine in hepatic jaundice

Answer 27

conjugated

Question 28

characteristic of hepatic jaundice

Answer 28

serum total bilirubin is increased, both conjugated and unconjugated bilirubin increased, urine bilirubin in present, and urine urobilinogen can either be normal, decreased, or increased

Question 29

cause of prehepatic jaundice

Answer 29

increased breakdown of RBC

Question 30

cause of hepatic jaundice

Answer 30

decreased conjugation capacity of liver and decreased excretion of bilirubin

Question 31

cause of posthepatic jaundice

Answer 31

decreased excretion of bilirubin via bile

Question 32

type of bilirubin elevated in post hepatic jaundice

Answer 32

conjugated bilirubin

Question 33

characteristic of posthepatic jaundice

Answer 33

serum tot bilirubin elevated, serum conjugated bilirubin elevated, unconjugated bilirubin is normal, urine bilirubin present, and urine urobilinogen is either decreased or absent depending on if it is completer or partial obstruction

Question 34

why is there jaundice in the newborn period

Answer 34

low activity of hepatic UDP glucuronyl transferase hence increased unconjugated bilirubin

fixes itself at about 7th day of life

Question 35

what can increased the amount of unbound unconjugated bilirubin

Answer 35

hypoalbuminemia, low pH (weaken albumin-bilirubin bond), sulfonamides, salicylates

Question 36

symptoms of kernicterus

Answer 36

neurological symptoms like choreoathetosis, spasticity, muscular rigidity, ataxia, mental retardation

Question 37

use of phototherapy in neonatal jaundice

Answer 37

light converts bilirubin to more polar, water soluble isomers that can be excreted in bile without conjugation (bili-lights)

Question 38

most severe unconjugated hyperbilirubinemia

Answer 38

crigler najjer syndrome I (arias syndrome)

Question 39

percentage of UDP glucuronyl transferase activity and treatment of Crigler Najjar syndrome type I

Answer 39

10-20%

phenobarbitol

Question 40

percentage of UDP glucuronyl transferase activity in Gilbert

Answer 40

50%