Bilirubin Metabolism

Question 1

A metabolite of heme

Answer 1

Bilirubin

Question 2

Very recently, bilirubin has been shown to possess important functions as an

Answer 2

Antioxidant

Question 3

Also serves as a means to excrete unwanted, derived from various heme containing proteins such as hemoglobin, myoglobin, and various P450 enzymes

Answer 3

Bilirubin

Question 4

Bilirubin and its metabolites are also notable for the fact that they provide color to the

Answer 4

Bile and stool (and to a lesser degree, urine)

Question 5

Certain disease states that involve excessive levels of bilirubin in the bloodstream can lead to accumulation of bilirubin in the

Answer 5

Brain

Question 6

Bilirubin can cross the

Answer 6

Blood-brain barrier

Question 7

Certain disease states that involve excessive levels of bilirubin in the bloodstream can lead to accumulation of bilirubin in the brain due to its ability to cross the blood–brain barrier, a condition known as

Answer 7

Kernicterus (yellow stained nucleus)

Question 8

Notable for its yellow coloration

Answer 8

Bilirubin

Question 9

Accumulation of Bilirubin in the blood is the basis of

Answer 9

Jaundice

Question 10

In a healthy individual, red blood cells, and their contents, are turned over after about

Answer 10

120 days

Question 11

Broken down to its constituent amino acids, and the heme ring is released, degraded, and secreted

Answer 11

Hemoglobin

Question 12

Take up aged RBCs and begin to degrade them into a heme iron-porphyrin complex and globin

Answer 12

Cells of the reticuloendothelial system (RES)

Question 13

Heme is further degraded by macrophages using

Answer 13

Heme oxygenase

Question 14

Heme is further degraded by macrophage using heme oxygenase. releasing green pigmented

Answer 14

Biliverdin, as well as Fe and CO

Question 15

This reaction is the only endogenous source of

Answer 15

CO

Question 16

Acts as an antioxidant

Answer 16

Biliverdin

Question 17

Structurally resembles nitric oxide and acts as a signaling molecule and a vasodilator

Answer 17

CO

Question 18

For example, CO has been shown to be beneficial in

Answer 18

Stroke Victims

Question 19

Biliverdin is substrate for biliverdin reductase, producing the red-orange colored

Answer 19

Bilirubin

Question 20

Bilirubin and its derivatives are known as

Answer 20

Bile pigments

Question 21

The changing colors of a bruise mirror the evolution of different

Answer 21

Intermediates of heme degredation

Question 22

Bilirubin is poorly soluble in the aqueous medium of the plasma, so it is transported to the liver bound to

Answer 22

Albumin

Question 23

After entering the hepatocyte, unconjugated bilirubin is bound to the cytosolic protein

-prevents bilirubin from reentering plasma

Answer 23

Glutathione S transferase B

Question 24

Concentrations are low at birth, but appear to reach adult values by 2 weeks of age

Answer 24

Glutathione S-transferase (GST-beta)

Question 25

In the endoplasmic reticulum, bilirubin is solubilized by conjugation to glucuronic acid, which yields

Answer 25

Bilirubin monoglucuronide and diglucuronide

Question 26

The conjugation of glucuronic acid to bilirubin is catalyzed by

Answer 26

Bilirubin uridine diphosphateglucuronosyl transferase (UDPGT)

Question 27

The activity of this enzyme increases 100 fold after birth so that the % of conjugated bilirubin in the bile rises from

Answer 27

20% to 50% in adults

Question 28

Bilirubin monoglucuronide and diglucuronide undergo unidirectional transport by

Answer 28

MRP2

Question 29

The vast majority of bilirubin monoglucuronide and diglucuronide is eliminated in bile, but small amounts are transported at the sinusoidal membrane back into plasma, possibly via

Answer 29

MRP3

Question 30

Intracellular bilirubin monoglucuronide and diglucuronide secreted by MRP3 to the blood can be taken up again into downstream hepatocytes via

Answer 30

OATP1B1 and OATP1B3

Question 31

This secretion-and reuptake loop may prevent the saturation of biliary excretion in the upstream hepatocytes, thereby ensuring efficient

Answer 31

Biliary elimination

Question 32

The conjugated bilirubin excreted into bile drains into the duodenum and passes unchanged through the

Answer 32

Proximal small bowel

Question 33

Conjugated bilirubin is not taken up by the

Answer 33

Intestinal mucosa

Question 34

When the conjugated bilirubin reaches the distal ileum and colon, it is hydrolyzed to unconjugated bilirubin by

Answer 34

Bacterial glucuronidases

Question 35

The unconjugated bilirubin is reduced by normal gut bacteria to form a group of colorless tetrapyrroles called

Answer 35

Urobilinogens

Question 36

About 80–90% of these products are excreted in feces, either unchanged or oxidized to orange derivatives called

Answer 36

Urobilins or stercobilins

Question 37

The remaining 10% of the urobilinogens are passively absorbed, enter the portal venous blood, and are re-excreted by the

Answer 37

Liver

Question 38

A small fraction (usually <3 mg/dL) escapes hepatic uptake, filters across the renal glomerulus, and is excreted in

Answer 38

Urine

Question 39

Results from the rupture or lysis of red blood cells within the circulation

Answer 39

Intravascular hemolysis

Question 40

When the membrane of erythrocytes ruptures, they release their hemoglobin into the

Answer 40

Plasma

Question 41

The hemoglobin breaks down into

Answer 41

Hemoglobin dimers

Question 42

Binds the liberated free hemoglobin dimers -an α-2 globulin produced in the liver

Answer 42

Haptoglobin

Question 43

However, haptoglobin is readily

Answer 43

Saturated

Question 44

If intravascular hemolysis continues, the hemoglobin dimers are in excess in plasma and are filtered readily through the glomerulus. This will cause

Answer 44

Hemoglobinuria

Question 45

Hemoglobinuria is typically visible as

Answer 45

Pink to Red urine

Question 46

The hemoglobin dimers that remain in circulation are oxidized to

Answer 46

Methemoglobin

Question 47

The hemoglobin dimers that remain in circulation are oxidized to methemoglobin, which disassociates into a

Answer 47

Free heme and globin chains

Question 48

The oxidized free heme (met-heme) binds to

Answer 48

Hemopexin (a β-globulin, Hpx)

Question 49

Taken up by a receptor on hepatocytes and macrophages within the spleen, liver and bone marrow

Answer 49

The met-heme-hemopexin complex

Question 50

Similarly, the hemoglobin/haptoglobin complex is taken up by

Answer 50

Hepatocytes and macrophages

Question 51

The function of Hpx thus appears to be to prevent loss of free hemoglobin into the

Answer 51

Kidney

Question 52

This is important because it conserves the valuable

Answer 52

Iron

Question 53

Low levels of haptoglobin are found in patients with hemolytic anemias seen in

Answer 53

Sickle cell anemia, thalassemia, G6PDH and pyruvate kinase deficiency

Question 54

The terms direct- and indirect-reacting bilirubin are based on the original

Answer 54

Van den Bergh reaction

Question 55

This assay, or a variation of it, is still used in most clinical chemistry laboratories to determine the serum level of

Answer 55

Bilirubin

Question 56

The direct fraction is that which reacts in the absence of an accelerator substance such as alcohol with

Answer 56

Diazotized sulfanilic acid

Question 57

The direct fraction provides an approximate determination of the serum levels of

Answer 57

Conjugated Bilirubin

Question 58

The total serum bilirubin is the amount that reacts after the addition of

Answer 58

Alcohol

Question 59

The difference between the total and the direct bilirubin and provides an estimate of the unconjugated bilirubin in serum

Answer 59

Indirect fraction

Question 60

What are the normal values of 1. ) Direct bilirubin 2. ) Total bilirubin

Answer 60

1. ) 0-0.3 mg/dL | 2. ) 0.3-1.9 mg/dL

Question 61

Massive lysis of RBCs, precipitated by some other preexisting condition, releases heme in quantities that exceed the liver’s capacity to process it to bilirubin diglucuronide in the case of

Answer 61

Hemolytic jaundice

Question 62

Bilirubin itself builds up in the blood and hence in peripheral tissue with

Answer 62

Hemolytic Jaundice

Question 63

Stems from a mechanical obstruction of the bile duct, preventing the ‘draining’ of conjugated bilirubin into the intestines

Answer 63

Obstructive Jaundice

Question 64

What is an indicator of obstructive jaundice?

Answer 64

Feces have pale clay color

Question 65

In obstructive jaundice, feces have a characteristic pale clay color, due to the relative absence of the brown colored

Answer 65

Stercobilin

Question 66

Occurs when damage to liver cells results in a decrement in normal biochemical functions of these cells for heme metabolism

Answer 66

Hepatocellular Jaundice

Question 67

Hepatocytes cannot meet the loads presented even under otherwise normal circumstances with

Answer 67

Hepatocellular jaundice

Question 68

Both liver uptake of bilirubin and the conjugation of bilirubin can be affected in

Answer 68

Hepatocellular jaundice

Question 69

Results, particularly in premature infants, due to low levels of the hepatic enzyme UDP-glucuronyl transferase (UDP-GT) at birth

Answer 69

Neonatal Jaundice

Question 70

Neonatal Jaundice results, particularly in premature infants, due to low levels of the hepatic enzyme

Answer 70

UDP-glucuronyl transferase (UDP-GT)

Question 71

Adult levels of UDP-GT is achieved in about a

Answer 71

Month

Question 72

To avoid the adverse neurologic outcomes of elevated circulating bilirubin levels, newborns receive phototherapy to

Answer 72

Convert bilirubin to a soluble derivative