Bile Pigment

Bile Pigment

Q. 1

A 25 year old man developed symptoms of gallstones which is being investigated. 

 
Assertion: Brown pigment stones are rare in the gallbladder.
 
Reason: Stone formation is related to the deconjugation of bilirubin diglucuronide by bacterial beta glucuronidase.
 
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Q. 1

A 25 year old man developed symptoms of gallstones which is being investigated. 

 
Assertion: Brown pigment stones are rare in the gallbladder.
 
Reason: Stone formation is related to the deconjugation of bilirubin diglucuronide by bacterial beta glucuronidase.
 
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Ans. B

Explanation:

Brown pigment stones contain calcium bilirubinate, calcium palmitate, calcium stearate, as well as cholesterol.

Brown stones are rare in the gallbladder.

They form in the bile duct and are related to bile stasis and infected bile.

Ref: Bailey & Love’s Short Practice of Surgery, 24th Edition, Pages 1103-1104.

Q. 2

All are true about bilirubin , EXCEPT:

 A

Hydrophobic and toxic compound

 B

It is a tetrapyrrole

 C

Daily production is 4 mg/kg

 D

Most hemoglobin is derived from ineffective erythropoiesis

Q. 2

All are true about bilirubin , EXCEPT:

 A

Hydrophobic and toxic compound

 B

It is a tetrapyrrole

 C

Daily production is 4 mg/kg

 D

Most hemoglobin is derived from ineffective erythropoiesis

Ans. D

Explanation:

Bilirubin

Hydrophobic and potentially toxic compound
It is tetrapyrrole and an end product of heme degradation. 
Daily production is 4 mg/kg of bilirubin . 
Most bilirubin (70% to 80%) is derived from degradation of hemoglobin 
Minor component arises from ineffective erythropoiesis
Ref:Sleisenger and Fordtran’s,E-9,P-323

Q. 3

False statement about bilirubin is

 A

Bilirubin circulating in plasma by covalently binding with albumin

 B

Bilirubin is taken up across the sinusoidal (basolateral) membrane of hepatocytes by a carrier-mediated mechanism

 C

Conjugated bilirubin in plasma undergoes stool elimination

 D

Conjugated bilirubin is then directed primarily toward the canalicular (apical) membrane

Q. 3

False statement about bilirubin is

 A

Bilirubin circulating in plasma by covalently binding with albumin

 B

Bilirubin is taken up across the sinusoidal (basolateral) membrane of hepatocytes by a carrier-mediated mechanism

 C

Conjugated bilirubin in plasma undergoes stool elimination

 D

Conjugated bilirubin is then directed primarily toward the canalicular (apical) membrane

Ans. C

Explanation:

Bilirubin transport:

  • Bilirubin circulates in plasma noncovalently, bound to albumin. 
  • It is taken up across the sinusoidal membrane of hepatocytes by a carrier-mediated mechanism. 
  • Bilirubin uptake is mediated by a liver-specific sinusoidal organic anion transport protein, (OATP1B1, SLC21A6)
  • Then bilirubin is directed by cytosolic binding proteins (e.g., glutathione S-transferase B, fatty acid binding protein) to the ER.
  • It is conjugated with uridine diphosphate (UDP)–glucuronic acid by the enzyme bilirubin UDP–glucuronyl transferase (B-UGT).
  • Conjugated bilirubin is directed toward the canalicular membrane, and it is transported into the bile canaliculus by an adenosine triphosphate (ATP)-dependent pump. 
  • The responsible protein is multidrug resistance–associated protein-2 (MRP2, ABCC2)
  • Small amounts of bilirubin glucuronides are secreted across the sinusoidal membrane via MRP3 (ABCC3)
  • Conjugated bilirubin in plasma undergoes renal elimination 
Ref: Sleisenger and Fordtran’s, E-9, P-324

Q. 4

Heme is converted to bilirubin mainly in:

 A

Kidney

 B

Liver

 C

Spleen

 D

Bone marrow

Q. 4

Heme is converted to bilirubin mainly in:

 A

Kidney

 B

Liver

 C

Spleen

 D

Bone marrow

Ans. C

Explanation:

Heme is converted to bilirubin by the macrophages of reticuloendothelial system (mostly spleen, also liver and bone marrow).

Ref: Schiff’s Diseases of the Liver By Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, 2007, Page 215

Q. 5

The conjugation of bilirubin to glucuronic acid in the liver;

 A

Converts a hydrophilic compound to a hydrophobic one

 B

Converts a hydrophobic compound to a hydrophilic one

 C

Enables the bilirubin molecule to cross the cell membrane

 D

Is increased during neonatal jaundice

Q. 5

The conjugation of bilirubin to glucuronic acid in the liver;

 A

Converts a hydrophilic compound to a hydrophobic one

 B

Converts a hydrophobic compound to a hydrophilic one

 C

Enables the bilirubin molecule to cross the cell membrane

 D

Is increased during neonatal jaundice

Ans. B

Explanation:

. B i.e. Converts a hydrophobic compound to a hydrophilic one


Q. 6

Bilirubin is absent in urine because it is :

 A

Distributed in the body fat

 B

Conjugated with glucoronide

 C

Not filterable

 D

Lipophilic.

Q. 6

Bilirubin is absent in urine because it is :

 A

Distributed in the body fat

 B

Conjugated with glucoronide

 C

Not filterable

 D

Lipophilic.

Ans. D

Explanation:

Q. 7

Pigment providing colour to stool is:

 A

Stercobilinogen

 B

Urobilinogen

 C

Mevobilirubin

 D

Bilirubin

Q. 7

Pigment providing colour to stool is:

 A

Stercobilinogen

 B

Urobilinogen

 C

Mevobilirubin

 D

Bilirubin

Ans. A

Explanation:

Q. 8

The conjugation of bilirubin to glucuronic acid in the liver;

 A

Converts a hydrophilic compound to a hydrophobic one

 B

Converts a hydrophobic compound to a hydrophilic one

 C

Enables the bilirubin molecule to cross the cell membrane

 D

Is increased during neonatal jaundice        

Q. 8

The conjugation of bilirubin to glucuronic acid in the liver;

 A

Converts a hydrophilic compound to a hydrophobic one

 B

Converts a hydrophobic compound to a hydrophilic one

 C

Enables the bilirubin molecule to cross the cell membrane

 D

Is increased during neonatal jaundice        

Ans. B

Explanation:

Q. 9

Bilirubin in conjugation with glucoronic acid conjugation has properties:         

 A

Able to cross cell membrane

 B

Hydrophillic to hydrophobic

 C

Hydrophobic to hydrophilic

 D

A & C

Q. 9

Bilirubin in conjugation with glucoronic acid conjugation has properties:         

 A

Able to cross cell membrane

 B

Hydrophillic to hydrophobic

 C

Hydrophobic to hydrophilic

 D

A & C

Ans. D

Explanation:

 

only sparingly (slightly) soluble in water, but its solubility in plasma is increased by non covalent binding to albumin. Each albumin molecule has one high & one low affinity site for bilirubin. Only 25 mg of bilirubin can be tightly boud to albumin at its high affinity site in 100 ml plasma. The excess amount bound loosely & can be easily detached.

– Bilirubin enters hepatocytes via facilitated transport system and binds to cytosolic proteins (ligandin, protein Y), which to keep it solubilized & prevent its efflux back into blood stream before conjugation.

– Bilirubin is nonpolar & would persist in cells if not rendered water solubleQ. Solubility of bilirubin is increased in hepatocytes by addition of 2 molecules of glucuronic acid to convent it to a polar form. This process k/a conjugation is catalyzed by microsomal bilirubin glucuronyl transferase and use uridine diphosphate – (UDP) – glucuronic acid as glucuronate donor.

So conjugation of bilirubin makes them polar, water soluble, hydrophilic and able to cross cell membrane


Q. 10

Bilirubin is secreted by:

 A

Bile Salts

 B

Bile pigments

 C

Secretin

 D

CCK.

Q. 10

Bilirubin is secreted by:

 A

Bile Salts

 B

Bile pigments

 C

Secretin

 D

CCK.

Ans. A

Explanation:

A i.e. Bile salts

Substances that increase the secretion of bile are called as cholerecticsQ. Bile salts are amongst the most important physiological cholerectionQ


Q. 11

Bilirubin is derived from:

 A

Myoglobin

 B

Hemoglobin

 C

Muscle

 D

A & B

Q. 11

Bilirubin is derived from:

 A

Myoglobin

 B

Hemoglobin

 C

Muscle

 D

A & B

Ans. D

Explanation:

A i.e. Myoglobin; B i.e. Hemoglobin

The daily bilirubin formation in human is approx. 250- 350mg, deriving mainly (70-80%) from hemoglobinQ but also from ineffective erythropoiesis and from various other heme proteins such as cytochrome P450 and myoglobinQ.

I gm of Hemoglobin yields 35mg of bilirubinQ.


Q. 12

Bilirubin is the degradation product of –

 A

Albumin

 B

Globulin

 C

Heme

 D

Transferrin

Q. 12

Bilirubin is the degradation product of –

 A

Albumin

 B

Globulin

 C

Heme

 D

Transferrin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Heme

Bilirubin metabolism

o Bilirubin is the end product of heme degradation.

o The heme is derived from –

(i)       Senescent erythrocytes by mononuclear phagocytic system in the spleen, liver and bone marrow (major source).

(ii)     Turnover of hemoproteins (e.g. cytochrome p.450).

o Heme is oxidized to biliverdin by heme oxygenase.

o Biliverdin is then reduced to bilirubin by biliverdin reductase.

o Bilirubin is transported to liver in bound form with albumin.

o There is carrier mediated uptake of bilirubin in the liver.

o This bilirubin is conjugated with glucuronic acid by UDP glucuronyl transferase (UGT1A1) to from conjugated bilirubin (bilirubin glucronides).

o Conjugated bilirubin is excreted into bile.

o Most of the conjugated bilirubin is deconjugated and degraded to urobilinogen.

o The most of the urobilinogen is excreted in the feces.

o Approximately 20% of the urobilinogen is reabsorbed in the ileum and colon and is returned to the liver, and promptly rexcreted into bile —> Enterohepatic circulation.

o The small amount that escapes this enterohepatic circulation is excreted in urine.


Q. 13

What is/are true about bilirubin?

 A

Conjugation is rate limiting step

 B

Bilirubin has affinity for elastin

 C

Conjugated bilirubin is maximum in blood

 D

All

Q. 13

What is/are true about bilirubin?

 A

Conjugation is rate limiting step

 B

Bilirubin has affinity for elastin

 C

Conjugated bilirubin is maximum in blood

 D

All

Ans. B

Explanation:

Ans. is ‘b’ i.e., Bilirubin has affinity for elastin

o Excretion of conjugated bilirubin into biliary canaliculi is the rate limiting step in bilirubin metabolism o Bilirubin has affinity for elastin, therefore jaundice is most easily seen in the sclera.

o Normally unconjugated bilirubin is more than conjugated bilirubin, in blood

Total bilirubin                                 0.3 — 1.9 mg/dl

Conjugated bilirubin                         —> 0 to 0.3 mg/dl

Unconjugated bilirubin                    —> Total – conjugated (0.3 — 1.6 mg/dl)

o Normally hemoglobin content of blood is between 120-160 gm/L (Harrison 17th/e p. A-2), and a normal adult usually have 5 litre of blood. So total hemoglobin is 600-800 gm.


Q. 14

Which substance is/are not deposited in hepatocyte?

 A

Lipofuschin

 B

Melanin like pigment

 C

Bile pigment

 D

Melanin

Q. 14

Which substance is/are not deposited in hepatocyte?

 A

Lipofuschin

 B

Melanin like pigment

 C

Bile pigment

 D

Melanin

Ans. D

Explanation:

Ans. is `d’ i.e., Melanin

o Pseudomelanin or melanin like pigment is deposited in liver ( not melanin).

o Lipofuscin, iron (hemosiderosis) and bile pigments are deposited in liver.


Q. 15

One gm of Hb liberates mg of bilirubin ‑

 A

40

 B

34

 C

15

 D

55

Q. 15

One gm of Hb liberates mg of bilirubin ‑

 A

40

 B

34

 C

15

 D

55

Ans. B

Explanation:

Ans. is ‘b’ i.e., 34

o Bilirubin is the end product of catabolism of hemoglobin.

o 1 gm of hemoglobin yields 35mg of bilirubin.


Q. 16

Meconium contains all except –

 A

Lanugo

 B

Bacterial flora

 C

Epithelial debris

 D

Bilirubin

Q. 16

Meconium contains all except –

 A

Lanugo

 B

Bacterial flora

 C

Epithelial debris

 D

Bilirubin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Bacterial flora

Meconium contains –

i)           Intestinal epithelial cells           iii) Mucus                           v) Bile

ii)          Lanugo                                   iv) Amniotic fluid                 vi) Water


Q. 17

Which of the following subtance is toxic to neurons‑

 A

Unconjugated bilirubin

 B

Bile salt

 C

Haemoglobin

 D

Melanin

Q. 17

Which of the following subtance is toxic to neurons‑

 A

Unconjugated bilirubin

 B

Bile salt

 C

Haemoglobin

 D

Melanin

Ans. A

Explanation:

Ans. is ‘a’ i.e., Unconjugated bilirubin


Q. 18

Bilirubin is absent in urine because it is‑

 A

Distributed in the body fat

 B

Conjugated with glucoron

 C

Not filtered

 D

None

Q. 18

Bilirubin is absent in urine because it is‑

 A

Distributed in the body fat

 B

Conjugated with glucoron

 C

Not filtered

 D

None

Ans. C

Explanation:

Answer is C (Not filtered)

Normal urine does not contain bilirubin because normal blood contains bilirubin in the uncongugated form. Unconjugated bilirubin is lipid soluble or lipophilic (water insoluble) because it is transported in the blood as a complex with albumin (albumin-bilirubin complex) which is not allowed to filter through the glomerulus.

Although conjugated bilirubin is water soluble and filterable at the glomurulus, conjugated bilirubin is not present in the blood normally and hence does not filter to appear in the urine.

Unconjugated bilirubin present in blood is complexed with albumin to make it soluble in blood and transport it to the liver. However, the glomerulus does not allow the albumin bilirubin complex to filter and hence bilirubin does not appear in urine.

Conjugated bilirubin is formed in the liver and directly excreted into the GIT through bile where it is reduced to urobilinogen and stercobilinogen. Conjugated bilirubin does not normally circulate in the blood at all and hence despite being filterable and water soluble it does not appear in urine.


Q. 19

Cholesterol is not a precursor of:

 A

Bile acid

 B

Bile pigment

 C

Vitamin D

 D

Sex hormones

Q. 19

Cholesterol is not a precursor of:

 A

Bile acid

 B

Bile pigment

 C

Vitamin D

 D

Sex hormones

Ans. B

Explanation:

 

Cholesterol is the precursor of bile acids [Bile contains bile salts (conjugated bile acids), which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K].

 


Q. 20

End product of porphyrin metabolism ‑

 A

Albumin

 B

CO2 & NH2

 C

Bilirubin

 D

None

Q. 20

End product of porphyrin metabolism ‑

 A

Albumin

 B

CO2 & NH2

 C

Bilirubin

 D

None

Ans. C

Explanation:

Ans. is ‘c’ i.e., Bilirubin

  • Heme is the most important porphyrin.
  • It is degraded into bilirubin.

Q. 21

Bilirubin bound inside hepatocyte to ‑

 A

Albumin

 B

Ubiquinone

 C

Ligandin

 D

Globulin

Q. 21

Bilirubin bound inside hepatocyte to ‑

 A

Albumin

 B

Ubiquinone

 C

Ligandin

 D

Globulin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Ligandin

Bilirubin metabolism

Bilirubin is the end product of heme degradation.

The heme is derived from –

i) Senescent erythrocytes by mononuclear phagocytic system in the spleen, liver and bone marrow (major source).

ii) Turnover of hemoproteins (e.g. cytochrome p.450).

Heme is oxidized to biliverdin by heme oxygenase.

Biliverdin is then reduced to bilirubin by biliverdin reductase.

Bilirubin is transported to liver in bound form with albumin.

Bilirubin is transferred to hepatocytes where it is bound to ligandin.

There is carrier mediated uptake of bilirubin in the liver.

This bilirubin is conjugated with glucuronic acid by UDP glucuronyl transferase (UGT1A1) to from conjugated bilirubin (bilirubin glucronides).

Conjugated bilirubin is excreted into bile.

Most of the conjugated bilirubin is deconjugated and degraded to urobilinogen.

The most of the urobilinogen is excreted in the feces.


Q. 22

Uronic acid pathway is important for the formation of‑

 A

GAG (glycosamine glycans)

 B

Glycoproteins

 C

Conjugation of bilirubin

 D

All of the above

Q. 22

Uronic acid pathway is important for the formation of‑

 A

GAG (glycosamine glycans)

 B

Glycoproteins

 C

Conjugation of bilirubin

 D

All of the above

Ans. D

Explanation:

 

UDP-glucuronate (a product of uronic acid pathway) is a donar of glucuronate residue for various conjugation and synthetic processes.


Q. 23

All are involved in bilirubin metabolism except‑

 A

ALA synthase

 B

Heme oxygenase

 C

Biliverdine reductase

 D

Glucuronyl transferase

Q. 23

All are involved in bilirubin metabolism except‑

 A

ALA synthase

 B

Heme oxygenase

 C

Biliverdine reductase

 D

Glucuronyl transferase

Ans. A

Explanation:

Ans. is ‘a’ i.e., ALA synthase 



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