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GI > Bilirubin Metabolism > Flashcards

Bilirubin Metabolism Flashcards

1
Q

A metabolite of heme

A

Bilirubin

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2
Q

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

A

Antioxidant

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3
Q

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

A

Bilirubin

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4
Q

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

A

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

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5
Q

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

A

Brain

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6
Q

Bilirubin can cross the

A

Blood-brain barrier

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7
Q

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

A

Kernicterus (yellow stained nucleus)

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8
Q

Notable for its yellow coloration

A

Bilirubin

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9
Q

Accumulation of Bilirubin in the blood is the basis of

A

Jaundice

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10
Q

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

A

120 days

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11
Q

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

A

Hemoglobin

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12
Q

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

A

Cells of the reticuloendothelial system (RES)

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13
Q

Heme is further degraded by macrophages using

A

Heme oxygenase

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14
Q

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

A

Biliverdin, as well as Fe and CO

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15
Q

This reaction is the only endogenous source of

A

CO

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16
Q

Acts as an antioxidant

A

Biliverdin

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17
Q

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

A

CO

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18
Q

For example, CO has been shown to be beneficial in

A

Stroke Victims

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19
Q

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

A

Bilirubin

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20
Q

Bilirubin and its derivatives are known as

A

Bile pigments

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21
Q

The changing colors of a bruise mirror the evolution of different

A

Intermediates of heme degredation

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22
Q

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

A

Albumin

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23
Q

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

-prevents bilirubin from reentering plasma

A

Glutathione S transferase B

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24
Q

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

A

Glutathione S-transferase (GST-beta)

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25
Q

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

A

Bilirubin monoglucuronide and diglucuronide

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26
Q

The conjugation of glucuronic acid to bilirubin is catalyzed by

A

Bilirubin uridine diphosphateglucuronosyl transferase (UDPGT)

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27
Q

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

A

20% to 50% in adults

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28
Q

Bilirubin monoglucuronide and diglucuronide undergo unidirectional transport by

A

MRP2

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29
Q

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

A

MRP3

30
Q

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

A

OATP1B1 and OATP1B3

31
Q

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

A

Biliary elimination

32
Q

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

A

Proximal small bowel

33
Q

Conjugated bilirubin is not taken up by the

A

Intestinal mucosa

34
Q

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

A

Bacterial glucuronidases

35
Q

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

A

Urobilinogens

36
Q

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

A

Urobilins or stercobilins

37
Q

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

A

Liver

38
Q

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

A

Urine

39
Q

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

A

Intravascular hemolysis

40
Q

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

A

Plasma

41
Q

The hemoglobin breaks down into

A

Hemoglobin dimers

42
Q

Binds the liberated free hemoglobin dimers

-an α-2 globulin produced in the liver

A

Haptoglobin

43
Q

However, haptoglobin is readily

A

Saturated

44
Q

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

A

Hemoglobinuria

45
Q

Hemoglobinuria is typically visible as

A

Pink to Red urine

46
Q

The hemoglobin dimers that remain in circulation are oxidized to

A

Methemoglobin

47
Q

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

A

Free heme and globin chains

48
Q

The oxidized free heme (met-heme) binds to

A

Hemopexin (a β-globulin, Hpx)

49
Q

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

A

The met-heme-hemopexin complex

50
Q

Similarly, the hemoglobin/haptoglobin complex is taken up by

A

Hepatocytes and macrophages

51
Q

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

A

Kidney

52
Q

This is important because it conserves the valuable

A

Iron

53
Q

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

A

Sickle cell anemia, thalassemia, G6PDH and pyruvate kinase deficiency

54
Q

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

A

Van den Bergh reaction

55
Q

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

A

Bilirubin

56
Q

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

A

Diazotized sulfanilic acid

57
Q

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

A

Conjugated Bilirubin

58
Q

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

A

Alcohol

59
Q

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

A

Indirect fraction

60
Q

What are the normal values of

  1. ) Direct bilirubin
  2. ) Total bilirubin
A
  1. ) 0-0.3 mg/dL

2. ) 0.3-1.9 mg/dL

61
Q

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

A

Hemolytic jaundice

62
Q

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

A

Hemolytic Jaundice

63
Q

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

A

Obstructive Jaundice

64
Q

What is an indicator of obstructive jaundice?

A

Feces have pale clay color

65
Q

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

A

Stercobilin

66
Q

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

A

Hepatocellular Jaundice

67
Q

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

A

Hepatocellular jaundice

68
Q

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

A

Hepatocellular jaundice

69
Q

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

A

Neonatal Jaundice

70
Q

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

A

UDP-glucuronyl transferase (UDP-GT)

71
Q

Adult levels of UDP-GT is achieved in about a

A

Month

72
Q

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

A

Convert bilirubin to a soluble derivative

GI (59 decks)

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