Heme Degradation

Question 1

Haptoglobin vs hemoopexin

Answer 1

During extracellular degradation, Haptoglobin Picks up the hemoglobin and uses a transporter to bring it into the macrophage Where the Hb is broken down into AAs and the heme is converted. Hemopexin on the other hand will pick up heme alone and bring it into the macrophage via the transporter.

Question 2

What Is the initial precursor of bilirubin?

Answer 2

Heme.

Question 3

What is a byproduct of the conversion of heme to biliverdin? what is the enzyme that does this?

Answer 3

CO and Fe3+, heme oxygenase

Question 4

What carries bilirubin through the blood stream?

Answer 4

Albumin

Question 5

GST-B

Answer 5

The trap that brings bilirubin into the liver

Question 6

UDPGT

Answer 6

Causes conjugation of bilirubin in the liver into bilirubin monoglucuronide (BG) and then bilirubin diglucuronide (BG2)

Question 7

What happens Once the Conjugated bilirubin leaves the liver?

Answer 7

It enters the gall bladder and eventually the colon where it is converted back into bilirubin and then into urobilinogen. 10% of the urobilinogen will be reabsorbed back into the liver. The other 90% will be excreted In the feces, which is where most of the excretion takes place. In the feces, urobilinogen is converted into urobilin, which gives feces its red color. The small part that is excreted in the urine will be converted into stercobilinogen before it is excreted.

Question 8

What is the difference between direct and indirect bilirubin?

Answer 8

Direct is conjugated

Indirect is unconjugated

Question 9

Biliverdin

Answer 9

Precursor to bilirubin and is an antioxidant And is green

Question 10

CO

Answer 10

Released in the process of making biliverdin from heme and is a vasodilator.

Question 11

What happens if the activity of UTP-GT is reduced?

Answer 11

There will be more Bilirubin monoglucuronide than there is bilirubin diglucuronide. This is because the conversion to BG2 is rate limiting.

Question 12

Why is the sclera of the eye yellow with jaundice?

Answer 12

Because the elastin binds and has an affinity for bilirubin.

Question 13

Why do newborns often have jaundice?

Answer 13

They do not have enough UDP-GT so they will have a buildup of unconjugated bilirubin.

Question 14

Kernicterus

Answer 14

When you have too much bilirubin in newborns. Baby will have yellow staining in the deep nuclei of the brain. In the early stage, the baby will be jaundiced, extremely lethargic, will have poor feeding, and have an absent startle reflex. If it progresses, the later stage will be that the child will have neurological defects, seizures, and hearing loss.

Question 15

Why are infants put under a blue light?

Answer 15

Because they have too much bilirubin and we don’t want them to get to toxic levels so they give the kid some light, which converts the bilirubin to a more soluble derivative.

Question 16

Critter-Najjar Syndrome

Answer 16

Absence or mutation of UDPGT gene, which will cause kernicturis in a newborn.

Question 17

Gilbert

Answer 17

Reduction in translation of UDPGT due to mutation in the promoter region. With physiologic stress there is mild jaundice. Occurs during the adolescence.

Question 18

Dublin-Johnson

Answer 18

Mutation in MRP2 so patient will get jaundice. Appears during adolescence or early adulthood. Common in Jews or people from the Middle East.

Question 19

Rotor

Answer 19

Inactivating mutations of OAT1B1 and OAT1B3 leading to mild conjugated and unconjugated hyperbilirubinemia. Will occur shortly after birth Or childhood.

Question 20

Hemolytic. Jaundice

Answer 20

Pre-hepatic. Massive lysis of RBCs causing massive amounts of heme to be released into the blood to the point that the liver can’t process them all into bilirubin. There will be increased bilirubin both as conjugated and unconjugated.

Question 21

Neonatal jaundice

Answer 21

Hepatic. Generally occurs in infants. Low levels of UDPGT or GST-B at birth. Indirect bilirubin levels will be increased Because they can’t be converted into direct.

Question 22

Obstructive jaundice

Answer 22

Post-hepatic. Obstruction of the bile duct prevents the draining of the conjugated bilirubin into the intestines. Feces will be white Because the bilirubin never makes it to the intestines and therefore doesn’t get converted into stercobilin. You will have an increase in both conjugated and unconjugated bilirubin in the plasma Because the conjugated will go back into the hepatocyte and then back into the blood.

Question 23

Hepatocellular jaundice

Answer 23

Damage to liver cells due to Liver diesease, alcoholism etc. so that the cells can’t meet the required loads to take the unconjugated bilirubin and convert it into conjugated bilirubin. Therefore, you will have increased conjugated and unconjugated bilirubin in the blood but. Probably mostly unconjugated. Also, white feces because less conjugated bilirubin, so less stercobilin.

Question 24

Extracellular vs intracellular hemolysis

Answer 24

Extracellular - macrophages in the spleen and liver phagocytize RBCs. Characterized by spherocytes.
Intracellular - RBCs lyse in circulation and release the hemoglobin into the plasma. Happens during mechanical trauma, toxic damage etc. Characterized by fragmented RBCs called schistocytes.

Question 25

Extravascular hemolysis

Answer 25

Responsible for 90% of hemolysis. RBCs are phagocytized in the liver and spleen when they are old. Under a microscope they are characterized by spherocytes (Round, smaller, dense red blobs).

Question 26

Intravascular hemolysis

Answer 26

Responsible for 10% of heme degradation. RBCs lyse in circulation, releasing hemoglobin into circulation. Under a microscope they are seen as schistocytes (squiggly and kind of look like the ghosts from pac-man)

Question 27

Van den Bergh reaction

Answer 27

Tells us how much direct and indirect bilirubin we have. The amount that reacts with a diazonium salt without any type of accelerator like alcohol is the direct bilirubin. Once you add the alcohol you will see the total amount of bilirubin. You can then subtract to figure out the amount of indirect.

Question 28

Normal values for direct and total bilirubin

Answer 28

Direct - 0-.3mg/dL

Total - 0.3-1.9mg/dL

Question 29

WHat is bilirubin Conjugated to in the liver?

Answer 29

Glucoronic acid

Question 30

Where does the conversion of heme into bilirubin take place?

Answer 30

In the macrophage

Question 31

OATP

Answer 31

Responsible for Picking up bilirubin bound to albumin into the Sinusoidal side of the hepatocytes.

Question 32

MRP2

Answer 32

Responsible for secretion of bilirubin into the biliary caniliculus

Question 33

Why do neonates have high bilirubin levels?

Answer 33

Because their UTP-GT isn’t at normal levels yet so they can’t convert bilirubin into the conjugated forms.

Question 34

What transporter is responsible for bringing bilirubin into the hepatocytes of the liver?

Answer 34

OATP