Author: Neelam Maurya

Iron Deficiency

Iron Deficiency

Q. 1

Best test to detect iron deficiency in community is –

 A

Transferrin

 B

Serum ferritin 

 C

Serum iron

 D

Hemoglobin

Q. 1

Best test to detect iron deficiency in community is –

 A

Transferrin

 B

Serum ferritin 

 C

Serum iron

 D

Hemoglobin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Serum ferritin

“The single most sensitive tool for evaluating the iron status is by measurement of serum jerritin” – Park

“It is the most usefill indicator of iron status in a population where the Prevalence” of iron deficiency is not high.


Q. 2

Anemia of Chronic disease can be differentiated from Iron deficiency anemia by:

 A

↑ TIBC

 B

↓ TIBC

 C

↑ S.ferritn

 D

b and c

Q. 2

Anemia of Chronic disease can be differentiated from Iron deficiency anemia by:

 A

↑ TIBC

 B

↓ TIBC

 C

↑ S.ferritn

 D

b and c

Ans. D

Explanation:

Answer is B &  C  (↓TIBC;↑Ferritin)

Anemia of chronic disease is associated with decreased TIBC and increased serum Ferritin while Iron deficiency anemia is associated with Increased TIBC and reduced serum Ferritin

Differential diagnosis of Microcytic Hypochromic Anemia

 

Parameters

Iron deficiency

Chronic Inflammatory

Smear

Microcytic hypochromic + target cell

Normocytic Normochromic

> Microcytic Hypochromic

Se Fe

< 30 (4)

4(<50) 50)

TIBC

> 360 (i)

i (< 300)

Saturation

< 10 (4)

4- ( l 0-20)

Ferritin

< 15 (1-)

T (30-200)

Free Erythrocyte

Protporphrin

ted

ted


Q. 3

Iron deficiency anemia is seen with all of the following except:

September 2008

 A

Chronic blood loss

 B

Achlorhydria

 C

Extensive surgical removal of the proximal small bowel

 D

Excess of meat in the diet

Q. 3

Iron deficiency anemia is seen with all of the following except:

September 2008

 A

Chronic blood loss

 B

Achlorhydria

 C

Extensive surgical removal of the proximal small bowel

 D

Excess of meat in the diet

Ans. D

Explanation:

Ans. D: Excess of meat in the diet

Causes of iron deficiency anemia:

  • Diet

– The prevalence of iron deficiency anemia is low in geographic areas where meat is an important constituent of the diet.

Substances that diminish the absorption of ferrous and ferric iron are phytates, oxalates, phosphates, carbonates, and tannates. Ascorbic acid increases the absorption of ferric and ferrous iron.

  • Hemorrhage

–  Bleeding for any reason produces iron depletion. If sufficient blood loss occurs chronically, iron deficiency anemia ensues.

  • Malabsorption of iron

– Prolonged achlorhydria may produce iron deficiency because acidic conditions are required to release ferric iron from food.

– Extensive surgical removal of the proximal small bowel or chronic diseases, such as untreated sprue or celiac syndrome, can diminish iron absorption.

  • Increased demand: pregnancy, lactation and growth periods.

Quiz In Between


Q. 4

Which of the following is the first symptom of iron deficiency anemia?   

September 2010

 A

Low iron concentration in blood

 B

Reduced hemoglobin

 C

Reduced PCV

 D

Reduced ferritin

Q. 4

Which of the following is the first symptom of iron deficiency anemia?   

September 2010

 A

Low iron concentration in blood

 B

Reduced hemoglobin

 C

Reduced PCV

 D

Reduced ferritin

Ans. D

Explanation:

Ans. D: Reduced ferritin


Q. 5

Iron Deficiency anemia is commonly caused by:

September 2005, March 2009

 A

Enterobius vermicularis

 B

Taenia solium

 C

Ancylostoma duodenale

 D

All of the above

Q. 5

Iron Deficiency anemia is commonly caused by:

September 2005, March 2009

 A

Enterobius vermicularis

 B

Taenia solium

 C

Ancylostoma duodenale

 D

All of the above

Ans. C

Explanation:

Ans. C: Ancylostoma duodenale

An adult Ancylostome (hookworm) can suck about 0.2 ml blood a day, while the smaller necator sucks in about 0.03 ml per day. These worms frequently leave one site and attach themselves to other site. As the secretions of the worm contain anticoagulant activity, bleeding from the site may continue for several days adding to the blood loss.

This chronic blood loss over a period of time leads to a microcytic hypochromic anemia. Pinworm (Enterobius vermicularis) causes irritation and pruritis in the perianal and perineal area. It may cause symptoms of chronic salpingitis and appendicitis.

Taenia solium causes cysticercus cellulosae commonly in the subcutaneous tissues and muscles. It may also affect eye, brain, heart, lung or liver.


Q. 6

Pattern in peripheral smear in iron deficiency anemia ‑

 A

Normocytic normochromic

 B

Hypochromic normocytic

 C

Hypochromic microcytic

 D

Normochromic microcytic

Q. 6

Pattern in peripheral smear in iron deficiency anemia ‑

 A

Normocytic normochromic

 B

Hypochromic normocytic

 C

Hypochromic microcytic

 D

Normochromic microcytic

Ans. C

Explanation:

Ans. is ‘c’ i.e., Hypochromic microcytic

Quiz In Between


Q. 7

Following is true about iron dextran except ‑

 A

It is parenteral iron preparation

 B

It can be given either iv or im

 C

It binds to transferrin

 D

It is not excreted

Q. 7

Following is true about iron dextran except ‑

 A

It is parenteral iron preparation

 B

It can be given either iv or im

 C

It binds to transferrin

 D

It is not excreted

Ans. C

Explanation:

Ans. is ‘c’ i.e., It binds to trnasferrin


Q. 8

The iron preparation that can be given intravenously is ‑

 A

Ferrous sulphate

 B

Iron dextran

 C

Iron sorbitol citric acid complex

 D

Colloidal ferric hydroxide

Q. 8

The iron preparation that can be given intravenously is ‑

 A

Ferrous sulphate

 B

Iron dextran

 C

Iron sorbitol citric acid complex

 D

Colloidal ferric hydroxide

Ans. B

Explanation:

Ans. is ‘b’ i.e., Iron dextran


Q. 9

Which of the following statements about iron deficiency anemia is correct

 A

Decreased TIBC

 B

Increased ferritin levels

 C

Bone marrow iron is decreased after serum iron is decreased

 D

Bone marrow iron is decreased earlier than serum iron

Q. 9

Which of the following statements about iron deficiency anemia is correct

 A

Decreased TIBC

 B

Increased ferritin levels

 C

Bone marrow iron is decreased after serum iron is decreased

 D

Bone marrow iron is decreased earlier than serum iron

Ans. D

Explanation:

Ans. is ‘D’ i.e., Bone marrow iron is decreased earlier than serum iron

In iron deficiency anemia the first change is decrease in iron stores “

The decrease in iron stores is demonstrated by decreased serum ferritin level.

Remember,

Serum ferritin reflects the amount of storage iron in the body.

As the total body iron level begins to fall a characteristic, sequence of events ensue :

  • First Stage or Prelatent Stage of Iron Depletion
  • When iron loss exceeds absorption, a negative iron balance exists.
  • Stored iron begins to be, mobilized from stores. The iron present in the macrophages of liver, spleen and bone marrow are depleted
  • Decrease in stored iron is reflected by decrease in serum ferritin.
  • At this stage all other parameters of iron status are normal.

Second Stage or Stage of Latent Iron Deficiency :

  • Iron stores are exhausted but the blood hemoglobin level remains higher than the lower limit of normal. o After the exhaustion of iron stores :
  • The plasma iron concentration fallsQ.
  • Plasma iron binding capacity increases2.
  • Percentage saturation falls below 15%Q.
  • The percentage of sideroblast decreases in the bone marrowQ.

Third Stage or Stage of Apparent Iron Deficiency Anemia

  • Supply of iron to marrow becomes inadequate for normal hemoglobin production,
  • So the blood hemoglobin concentration fallsQ below the lower limit of normal and iron deficiency anemia is apparent.

Q. 10

Iron deficiency causes ‑

 A

Megaloblastic anemia

 B

Microcytic hypochromic anemia

 C

Macrocytic hypochromic anemia

 D

Microcytic hypochromic anemia

Q. 10

Iron deficiency causes ‑

 A

Megaloblastic anemia

 B

Microcytic hypochromic anemia

 C

Macrocytic hypochromic anemia

 D

Microcytic hypochromic anemia

Ans. B

Explanation:

Ans. is ‘b’ i.e., Microcytic hypochromic anemia 

Quiz In Between



Iron Deficiency

Iron Deficiency


IRON DEFICIENCY ANEMIA

  • Iron deficiency can be divided into 3 stages-
  1. Negative iron balance
  2. Iron deficient erythropoiesis
  3. Iron deficiency anemia- microcytic hypochromic anemia

Causes of Iron Deficiency Anemia-

  • Increased demand for iron- pregnancy, erythropoietin therapy, growth period.
  • Increased Iron loss- acute & chronic blood loss, phlebotomy
  • Decreased iron absorption- diet, malabsorption of iron, surgery or gastrectomy.

 Lab diagnosis-

  • Decreased serum ferritin
  • Total iron binding capacity increased.
  • Iron deficiency can be indicated by MCHC.
  • Test to detect iron deficiency is serum ferritin.
  • Mentzer index more than 13 suggests a diagnosis of iron deficiency anemia.

Clinical features-

  • Fatigue, pallor
  • Chielosis
  • Koilonychias

Treatment

  • Red cell transfusion
  • Oral iron therapy- 200mg per day (100- 150 mg per day)
  • Parenteral iron therapy– iv iron,
    • Total parenteral iron requirement can be calculated by : 4.3 x Body weight (kg) x Hb deficit (g/dl)
    • Ferumoxytol delivers 510 mg of iron per injection, ferric gluconate 125mg per injection, ferric carboxymaltose 750 mg per injection, and iron sucrose 200 mg per injection.
  • Iron dextran (highest risk of anaphylaxis).

Exam Important

  1. Iron deficiency anemia- microcytic hypochromic anemia
  2. Causes- Decreased iron absorption- diet, malabsorption of iron, surgery or gastrectomy.
  3. Lab diagnosis-
  • Decreased serum ferritin
  • Total iron binding capacity increased.
  • Iron deficiency can be indicated by MCHC.
  • Test to detect iron deficiency is serum ferritin.
  • Mentzer index more than 13 suggests a diagnosis of iron deficiency anemia.

Treatment

  • Red cell transfusion
  • Oral iron therapy- 200mg per day (100- 150 mg per day)
  • Parenteral iron therapy– iv iron,
    • Total parenteral iron requirement can be calculated by : 4.3 x Body weight (kg) x Hb deficit (g/dl)
    • Ferumoxytol delivers 510 mg of iron per injection, ferric gluconate 125 mg per injection, ferric carboxymaltose 750 mg per injection, and iron sucrose 200 mg per injection.
  • Iron dextran (highest risk of anaphylaxis).
Don’t Forget to Solve all the previous Year Question asked on Iron Deficiency

Module Below Start Quiz

Regulation & Factors of Heme Synthesis

Regulators & Factors of Heme Synthesis

Q. 1

Lead inhibits which enzymes in the heme synthesis pathway:           

CMC (Vellore) 07

 A

Aminolevulinate synthase

 B

Ferrochelatase and 6-ALA dehydratase

 C

Porphobilinogen deaminase

 D

Uroporphyrinogen decarboxylase

Q. 1

Lead inhibits which enzymes in the heme synthesis pathway:           

CMC (Vellore) 07

 A

Aminolevulinate synthase

 B

Ferrochelatase and 6-ALA dehydratase

 C

Porphobilinogen deaminase

 D

Uroporphyrinogen decarboxylase

Ans. B

Explanation:

Ans. Ferrochelatase and 6-ALA dehydratase


Q. 2

Rate limiting step in heme synthesis is catalyzed by ‑

 A

ALA dehydratase

 B

ALA synthase

 C

UPG decarboxylase

 D

Ferrochelatase

Q. 2

Rate limiting step in heme synthesis is catalyzed by ‑

 A

ALA dehydratase

 B

ALA synthase

 C

UPG decarboxylase

 D

Ferrochelatase

Ans. B

Explanation:

Ans. is ‘b’ i.e., ALA synthase

Quiz In Between



Regulation & Factors of Heme Synthesis

Regulation & Factors of Heme Synthesis


REGULATION & FACTORS OF HEME SYNTHESIS

  • ALA synthase is the key regulatory enzyme in hepatic biosynthesis of Heme.
  • ALA synthase occurs in hepatic and erythrocytes.

Factors That Heme Synthesis-

  • Drugs- Barbiturates, Griseofulvin.
  • Lead– inhibits catalyzed by ALA dehydratase and ferrochelatase.
  • INH– decreases PLP.
  • Intracellular buffer due to histidine residue.The NH2 group on intermediate histidine residues.

Exam Important

  • ALA synthase is the key regulatory enzyme in hepatic biosynthesis of Heme.
  • ALA synthase occurs in hepatic and erythrocytes.

Factors That Heme Synthesis-

  • Drugs- Barbiturates, Griseofulvin.
  • Lead– inhibits catalyzed by ALA dehydratase and ferrochelatase.
  • INH– decreases PLP.
  • Intracellular buffer due to histidine residue.The NH2 group on intermediate histidine residues.
Don’t Forget to Solve all the previous Year Question asked on Regulation & Factors of Heme Synthesis

Module Below Start Quiz

Hyperbilirubenimia

Hyperbilirubinemia

Q. 1

Unconjugate hyperbilirubinemia is seen in

 A

Physiological jaundice

 B

Breast milk jaundice

 C

Gilbert syndrome

 D

All

Q. 1

Unconjugate hyperbilirubinemia is seen in

 A

Physiological jaundice

 B

Breast milk jaundice

 C

Gilbert syndrome

 D

All

Ans. D

Explanation:

Ans. is ‘a’ i.e., Physiological jaundice; ‘b’ i.e., Breast milk jaundice; ‘c’ i.e., Gilbert syndrome


Q. 2

Unconjugated hyperbilirubinemia is seen in

 A

Rotor syndrome

 B

Dubin-Johnson syndrome

 C

Biliary atresia

 D

Crigler-Najjar syndrome

Q. 2

Unconjugated hyperbilirubinemia is seen in

 A

Rotor syndrome

 B

Dubin-Johnson syndrome

 C

Biliary atresia

 D

Crigler-Najjar syndrome

Ans. D

Explanation:

Ans. is ‘d’ i.e., Crigler-Najjar syndrome

Predominantly Unconjugated fliperbilirubinenrict

Excess production of bilirubin Hemolytic anemias

Resorption of blood from internal hemorrhage (e.g. alimentary

tract bleeding, hematomas)

Ineffective erythropoiesis syndromes (e.g. pernicious anemia, thalassemia)

Reduced hepatic uptake

Drug interference with membrance carrier systems

Some cases of Gilbert syndrome Impaired bilirubin conjugation

Physiologic jaundice of the newborn (decreased UGT I A I activity,

decreased excretion)

Breast milk jaundice (b-glucrurondases in milk)

Genetic deficiency of UGT 1 AI activity (Crigler-Najjar syndrome types I and II)

Gilbert syndrome (mixed etiologies)

Diffuse hepatocellular disease (e.g. viral or drug-induced hepatitis, cirrhosis)

Predominantly conjugated hyperbilirubinemia

Deficiency of canalicular membrane transporters (Dubin-Johnson syndrome, Rotor syndrome) Impaired bile flow.


Q. 3

Causes of conjugated hyperbilirubinemia is ‑

 A

Rotor syndrome

 B

Breast milk jaundice

 C

Crigler najjar

 D

Gilbert syndrome

Q. 3

Causes of conjugated hyperbilirubinemia is ‑

 A

Rotor syndrome

 B

Breast milk jaundice

 C

Crigler najjar

 D

Gilbert syndrome

Ans. A

Explanation:

Ans. is ‘a’ i.e., Rotor syndrome

Quiz In Between


Q. 4

Indirect hyperbilirubinemia are seen in

 A

Dubin-Johnson syndrome

 B

Rotor syndrome

 C

Gilbert syndrome

 D

Gallstone

Q. 4

Indirect hyperbilirubinemia are seen in

 A

Dubin-Johnson syndrome

 B

Rotor syndrome

 C

Gilbert syndrome

 D

Gallstone

Ans. C

Explanation:

Ans is ‘c’ i.e., Gilbert syndrome


Q. 5

Unconjugated hyperbilirubinemia in neonate is seen in all of the following except –

 A

Physiological jaundice

 B

Dubin johnson syndrome

 C

Hypothyroidism

 D

Hemolytic anemia

Q. 5

Unconjugated hyperbilirubinemia in neonate is seen in all of the following except –

 A

Physiological jaundice

 B

Dubin johnson syndrome

 C

Hypothyroidism

 D

Hemolytic anemia

Ans. B

Explanation:

Ans. is ‘b’ i.e., Dubin Johnson Syndrome


Q. 6

Autosomal dominant familial nonhemolytic hyperbilirubinemia occurs in all except –

 A

Crigler-Najjar syndrome

 B

Dubin – Johnson syndrome

 C

Gilbert syndrome

 D

Cryoglobulinemia

Q. 6

Autosomal dominant familial nonhemolytic hyperbilirubinemia occurs in all except –

 A

Crigler-Najjar syndrome

 B

Dubin – Johnson syndrome

 C

Gilbert syndrome

 D

Cryoglobulinemia

Ans. B

Explanation:

Ans. is ‘b’ i.e., Dubin-Johnson syndrome

Dubin-Johnson syndrome is an autosomal recessive disorder.

o Note sure about option d.

Quiz In Between


Q. 7

Hyperbilirubinemia in a child can be due to

 A

Breast milk jaundice

 B

Cystic fibrosis

 C

Fanconi’s syndrome

 D

All

Q. 7

Hyperbilirubinemia in a child can be due to

 A

Breast milk jaundice

 B

Cystic fibrosis

 C

Fanconi’s syndrome

 D

All

Ans. A

Explanation:

Ans. is ‘a’ i.e., Breast milk jaundice


Q. 8

Following are causes of unconjugated hyperbilirubinemia, except:

 A

Hemolytic anemia

 B

Large hematoma

 C

Rotor syndrome

 D

Megaloblastic anemia

Q. 8

Following are causes of unconjugated hyperbilirubinemia, except:

 A

Hemolytic anemia

 B

Large hematoma

 C

Rotor syndrome

 D

Megaloblastic anemia

Ans. C

Explanation:

Answer is C (Rotor syndrome)

Rotor’s syndrome is an Autosomal recessive inherited disorder characterized by a deject in biliary excretion leading to conjugated hyperbilirubinemia:

Indirect hyperbilirubinemia                                                              

Direct hyperbilirubinemia

A.   Hemolytic disorders

A.   Inherited conditions

1.    Inherited

1.     Dubin-Johnson syndrome

a.   Sperocyteosis, elliptocytosis

2.     Rotor’s syndrome

Glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies

b. Sickle cell anemia

 

2.    Acquired                         _

a. Microangiopathic hemolytic anemias

b. Paraoxysmal nocturnal hemoglobinuria

c. Immune hemolysis

 

B.    Ineffective erythropoesis

 

1.    Cobalamin, folate, thalassemia, and severe iron deficiencies

 

C. Drugs

 

1.    Rifampicin, probenbecid, ribavirin

 

D.   Inherited conditions

 

1.    Crigler-Najjar types I and II

 

2.    Glibert’s syndrome

 


Q. 9

A patient presents with unconjugated hyperbilirubinemia and presence of urobilinogen in urine. Which amongst the following is the least likely diagnosis:

 A

Hemolytic jaundice

 B

Crigler Najjar syndrome

 C

Gilbert’s syndrome

 D

Dubin Johnson syndrome

Q. 9

A patient presents with unconjugated hyperbilirubinemia and presence of urobilinogen in urine. Which amongst the following is the least likely diagnosis:

 A

Hemolytic jaundice

 B

Crigler Najjar syndrome

 C

Gilbert’s syndrome

 D

Dubin Johnson syndrome

Ans. D

Explanation:

Answer is D (Dubin Johnson Syndrome)

Dubin Johnson syndrome is associated with conjugated hyperbilirubinemia & not unconjugated hjperbilirubinemia. Dubin Johnson Syndrome results from a hereditary defect in excretion of conjugated bilirubin across the canalicular membrane and leads to conjugated hyperbilirubinemia.

Dubin Johnson syndrome is an inherited disorder charachterized by defective excretion of conjugated bilirubin from hepatocytes into biliary canaliculi. It thus presents with a clinical picture similar to obstructive jaundice with conjugated hyperbilirubinemia and absence of urobilinogen in urine.

Hemolytic Anemia typically presents with unconjugated hyperbilirubinemia and elevated urinary urobilinogens. Gilberts syndrome and Cri2ler Najjar syndrome also present with unconjugated hyperbilirubinemia. Urinary Urobilinogens are however not elevated in these conditions. Urobilinogen may never the less be present in urine (N or in these conditions

Quiz In Between


Q. 10

Conjugated hyperbilirubinemia is seen in all EX­CEPT:

March 2013

 A

Dubin Johnson syndrome

 B

Rotor syndrome

 C

Gilbert syndrome

 D

None of the above

Q. 10

Conjugated hyperbilirubinemia is seen in all EX­CEPT:

March 2013

 A

Dubin Johnson syndrome

 B

Rotor syndrome

 C

Gilbert syndrome

 D

None of the above

Ans. C

Explanation:

Ans. C i.e. Gilbert syndrome

Gilbert syndrome presents with unconjugated hyperbilirubinemia


Q. 11

Unconjugated hyperbilirubinemia is seen in all of the following except:   

March 2010

 A

Crigler Najjar Syndrome

 B

Physiological jaundice

 C

Dubin-Johnson syndrome

 D

Gilbert syndrome

Q. 11

Unconjugated hyperbilirubinemia is seen in all of the following except:   

March 2010

 A

Crigler Najjar Syndrome

 B

Physiological jaundice

 C

Dubin-Johnson syndrome

 D

Gilbert syndrome

Ans. C

Explanation:

Ans. C: Dubin-Johnson Syndrome

Dubin-Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin without elevation of liver enzymes (ALT, AST).

This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile.

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.

Pigment deposition in lysosomes causes the liver to turn black.

Other causes of conjugated/direct hyperbilirubinemia:

  • Hepatocellular diseases:

– Hepatitis:

  • Neonatal idiopathic hepatitis
  • Viral (Hepatitis B, C, TORCH infections)
  • Bacterial (E. colt, urinary tract infections)

–        Total parenteral nutrition

–        Hepatic ischemia (post-ischemic damage)

–        Erythroblastosis fetalis (late, “Inspissated Bile Syndrome”)

Metabolic disorders:

  • Alpha-1 antitrypsin deficiency
  • Galactosemia, tyrosinemia, fructosemia
  • Glycogen storage disorders
  • Cystic fibrosis

Biliary tree abnormalities:

–         Extrahepatic biliary atresia: In first 2 weeks, unconjugated bilirubin predominates; elevated conjugated bilirubin is late.

–        Paucity of bile ducts

–        Choledochal cyst

–        Bile plug syndrome

Causes of unconjugated/indirect hyperbilirubinemia:

  • Increased lysis of RBCs (i.e., increased hemoglobin release)

–        Isoimmunization (blood group incompatibility: Rh, ABO and minor blood groups)

–        RBC enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency)

–        RBC structural abnormalities (hereditary spherocytosis, elliptocytosis)

–        Infection (sepsis, urinary tract infections)

–        Sequestered blood (e.g., cephalohematoma, bruising, intracranial hemorrhage)

–        Neonatal Jaundice

–        Polycythemia

–        Shortened life span of fetal RBCs

Decreased hepatic uptake and conjugation of bilirubin

–        Immature glucuronyl transferase activity in all newborns: term infants have 1% of adult activity, preterm infants have 0.1%.

–        Gilbert Syndrome

–        Crigler Najjar Syndrome (Non-hemolytic Unconjugated Hyperbilirubinemia): inherited conjugation defect (very rare)

–        Breastmilk Jaundice (pregnanediol inhibits glucuronyl transferase activity)

Increased enterohepatic reabsorption

–        Breastfeeding jaundice (due to dehydration from inadequate milk supply)


Q. 12

Conjugated hyperbilirubinemia

 A

Dubin johnson syndrome

 B

Criggler naj jar syndrome

 C

Breast milk jandice

 D

Gilbert syndrome

Q. 12

Conjugated hyperbilirubinemia

 A

Dubin johnson syndrome

 B

Criggler naj jar syndrome

 C

Breast milk jandice

 D

Gilbert syndrome

Ans. A

Explanation:

Ans. is ‘a’ i.e., Dubin johnson syndrome

Breast milk jaundice –

  • Decrease bilirubin uptake across hepathocyte membrane.
  • Entero-hepatic recirculation.
  • Leads to indirect hyperbilirubinemia.

Crigler naj jar & Gilbert syndrome (deficiency of glucuronyl transferase)

  • Decrease conjugation leads to Indirect hyperbilirubinemia.
  • Defect in hepatocyte secretion of conjugated bilirubin.
  • Leads to direct hyperbilirubinemia

Quiz In Between



Hyperbilirubenimia

Hyperbilirubenimia


HYPERBILIRUBINEMIAS

JAUNDICE

  • Sclera icterus indicates bilirubin >3mg/dL.
  • Sclera icterus in fetus bilirubin >15mg/dL

 Congenital Hyperbilirubinemia

  • Unconjugated hyperbilirubinemias
  1. Glibert’s disease
  2. Crigler- Najjar syndrome
  3. Physiological Jaundice
  4. Breast Milk Jaundice
  5. Lucey Driscoll Syndrome

Conjugated Hyperbilirubinemias

  • Dubin Johnson’s syndrome- caused due to mutation of gene encoding MRP2.
  • Rotor syndrome- defective bile excretion
  • Benign recurrent intrahepatic cholestatsis
  • Progressive Familial intrahepatic cholestatsis

ACQUIRED HYERBILIRUBINEMIA

  • Hemolytic jaundice
  • Hepatic jaundice
  • Obstructive jaundice 

Exam Important

  • Sclera icterus in fetus bilirubin >15mg/dL

Congenital Hyperbilirubinemia

  • Unconjugated hyperbilirubinemias
  1. Glibert’s disease
  2. Crigler- Najjar syndrome
  • Physiological Jaundice
  • Breast Milk Jaundice
  • Lucey Driscoll Syndrome

Conjugated Hyperbilirubinemias

  • Dubin Johnson’s syndrome- caused due to mutation of gene encoding MRP2.
  • Rotor syndrome- defective bile excretion
  • Benign recurrent intrahepatic cholestatsis
  • Progressive Familial intrahepatic cholestatsis
Don’t Forget to Solve all the previous Year Question asked on Hyperbilirubenimia

Module Below Start Quiz

Heme Catabolism

Heme Catabolism

Q. 1

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. 1

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. 2

Heme is converted to bilirubin mainly in:

 A

Kidney.

 B

Liver.

 C

Spleen

 D

Bone marrow.

Q. 2

Heme is converted to bilirubin mainly in:

 A

Kidney.

 B

Liver.

 C

Spleen

 D

Bone marrow.

Ans. C

Explanation:

C i.e. Spleen

Breakdown of heme to bilirubin occurs in macrophages of the reticuloendothelial system mainly in the spleenQ also in the liver and bone marrow.


Q. 3

Bilirubin is secreted by:

 A

Bile Salts

 B

Bile pigments

 C

Secretin

 D

CCK.

Q. 3

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

Quiz In Between


Q. 4

Bilirubin is the degradation product of –

 A

Albumin

 B

Globulin

 C

Heme

 D

Transferrin

Q. 4

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. 5

One gm of Hb liberates mg of bilirubin

 A

40

 B

34

 C

15

 D

55

Q. 5

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. 6

Bilirubin bound inside hepatocyte to ‑

 A

Albumin

 B

Ubiquinone

 C

Ligandin

 D

Globulin

Q. 6

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.

Quiz In Between



Heme Catabolism

Heme Catabolism


HEME CATABOLISM

  • Daily bilirubin formation in humans is approx 250-350mg.
  • 1gm of haemoglobin yields 35mg of bilirubin.
 
  • Site- reticuloendothelial cells of liver, spleen and bone marrow.
  • Hemo oxygenase is green pigment, biliverdin is produced.
  • Hemo oxygenase is the only source of endogenous CO in the body.
  • Biliverdin Reductase (yellow) takes place in the cytosol.

TRANSPORT OF BILIRUBIN

  • Bilirubin is transported to liver bound to serum albumin.
  • Bilirubin is transferred to hepatocytes where it is bound to ligandin.

Exam Important

  • Daily bilirubin formation in humans is approx 250-350mg.
  • 1gm of haemoglobin yields 35mg of bilirubin.
  • Site- reticuloendothelial cells of liver, spleen and bone marrow.
  • Hemo oxygenase is green pigment, biliverdin is produced.
  • Hemo oxygenase is the only source of endogenous CO in the body.
  • Biliverdin Reductase (yellow) takes place in the cytosol.
  • Bilirubin is transported to liver bound to serum albumin.
  • Bilirubin is transferred to hepatocytes where it is bound to ligandin.
Don’t Forget to Solve all the previous Year Question asked on Heme Catabolism

Module Below Start Quiz

Myoglobin

MYOGLOBIN


MYOGLOBIN

  • Myoglobin is seen in muscle.
  • It is rich in alpha helix.
  • Myoglobin has similar structure like haemoglobin.
  • It is a heme binding hydrophobic pocket.
  • Myoglobin can bind only one molecule of oxygen.
  • Myoglobin cannot show the phenomenon of cooperative binding.
  • Oxygen- myoglobin dissociation curve is hyperbola.

Exam Important

  • Myoglobin is seen in muscle.
  • It is rich in alpha helix.
  • Myoglobin has similar structure like haemoglobin.
  • It is a heme binding hydrophobic pocket.
  • Myoglobin can bind only one molecule of oxygen.
  • Myoglobin cannot show the phenomenon of cooperative binding.
  • Oxygen- myoglobin dissociation curve is hyperbola.
Don’t Forget to Solve all the previous Year Question asked on MYOGLOBIN

Module Below Start Quiz

Myoglobin

Myoglobin

Q. 1

Binding of oxygen to myoglobin:

 A

Is characterized by the sigmoidal saturation curve

 B

Occurs at multiple sites

 C

Is characterized by the sigmoid and multiple hyperbolic saturation curve

 D

Is characterized by the hyperbolic saturation curve

Q. 1

Binding of oxygen to myoglobin:

 A

Is characterized by the sigmoidal saturation curve

 B

Occurs at multiple sites

 C

Is characterized by the sigmoid and multiple hyperbolic saturation curve

 D

Is characterized by the hyperbolic saturation curve

Ans. D

Explanation:

Myoglobin molecule contains a single O2 binding site and thus the saturation process is characterized by a simple hyperbolic curve, in contrast to hemoglobin, sigmoid saturation curve of which shows positive cooperativity of multiple oxygen binding sites.

Ref: Lippincott’s Biochemistry, 5th Ed  page 26


Q. 2

Hemoglobin unlike myoglobin shows:

 A

Sigmoid curve of oxygen dissociation

 B

Positive cooperativity

 C

Hills coefficient of one

 D

A & B

Q. 2

Hemoglobin unlike myoglobin shows:

 A

Sigmoid curve of oxygen dissociation

 B

Positive cooperativity

 C

Hills coefficient of one

 D

A & B

Ans. D

Explanation:

A i.e. Sigmoid curve of oxygen dissociation & B i.e. Positive co-operativity

Unlike Myoglobin, hemoglobin shows:

–  Tetrameric structure

–  Can bind four 02 moleculeQ

–  Sigmoid saturation kineticsQ

–  Co-operativity or co-operative binding kinetics: property that permits it to bind a maximal quantity of 02 at respiratory organs & to deliver a maximal quantity of 02 at

peripheral tissue. Here binding of Hb with 02 facilitates binding of other 02 molecules thus positive co-operativity.


Q. 3

The oxygen dissociation curve of myoglobin & hemoglobin is different due to‑

 A

Hb can bind to 2 oxygen molecules

 B

Cooperative binding in Hb

 C

Myogloobin has little oxygen affinity

 D

Hemoglobin follows a hyperbolic curve

Q. 3

The oxygen dissociation curve of myoglobin & hemoglobin is different due to‑

 A

Hb can bind to 2 oxygen molecules

 B

Cooperative binding in Hb

 C

Myogloobin has little oxygen affinity

 D

Hemoglobin follows a hyperbolic curve

Ans. B

Explanation:

Ans. is `b’ i.e., Cooperative binding in Hb

  • Cooperative binding is responsible for sigmoid shape of the oxygen-hemoglobin dissociation curve.
  • As myoglobin is monomeric (consists of one polypeptide chain only), it can bind only one molecule of oxygen and for the same reason myoglobin cannot show the phenomenon of cooperative binding. Hence, the oxygen‑myoglobin dissociation curve is hyperbola as compared to sigmoid shape of Hb-O2 curve.

Hemoglobin – O2  binding

  • Each molecule of hemoglobin can combine with upto four molecules of oxygen. Combination with the first molecule alters the conformation of the hemoglobin molecule in such a way as to facilitate combination with the next oxygen molecule. In light of this, if we look at the curve, as the PO2 starts rising from 0 mm Hg upwards, initially all hemoglobin molecules in blood starts combining with their first oxygen molecule. This is the most difficult molecule to combine with. Hence saturation rises only slowly with initial rise in PO2. As PO2 rises further, hemoglobin molecules combine with their second, third and fourth molecules, which are progressively easier to combine with. Hence saturation rises steeply between PO2 of 15 mm Hg and 40 mm Hg. When PO2 rises still further, oxygen finds most of the hemoglobin molecules carrying four molecules of oxygen each. Since no molecules of hemoglobin can carry more than four molecules of oxygen, there is not much scope for more O2 combining with hemoglobin. Hence the curve becomes almost flat again beyond the PO2 of 60 mm Hg.
  • Thus, the primary reason for the sigmoid shape of the oxygen-hemoglobin dissociation curve is that out of the four molecules of oxygen that can combine with a hemoglobin molecules, the first combines with the greatest difficulty and binding of an oxygen molecules increases affinity to next O2 molecule. This phenomenon is termed as cooperative binding or cooperativity, i.e., a molecule of O2 binds to a hemoglobin tetramer more readily if other O2 molecules are already bound.

Myoglobin O2  binding

  • Myoglobin is present in higher concentration in red (slow) muscle fibers. Myoglobin has greater affinity for oxygen than hemoglobin and its P50 is only 5 mm Hg (as compared to PO2 of hemoglobin which is about 26 mm Hg). Therefore, myoglobin-oxygen dissociation curve is shifted far to the left than Hb-O2 dissociation curve. It has shape of hyperbola as compared to sigmoid shape of Hb-O2 curve because it binds 1 molecule of O2 per mole (in comparison to Hb which binds 4 molecules of O2 per mole). The role of myoglobin is to bind O2 at very low PO2 and release them at even lower PO2, for example in exercising muscles where PO2 close to zero.

Q. 4

True about O2 binding to myoglobin

 A

Sigmoid shaped curve

 B

More affinity than hemoglobin

 C

Binds 4 molecule of O2 to myoglobin

 D

P50 is 26 mmHg

Q. 4

True about O2 binding to myoglobin

 A

Sigmoid shaped curve

 B

More affinity than hemoglobin

 C

Binds 4 molecule of O2 to myoglobin

 D

P50 is 26 mmHg

Ans. B

Explanation:

Ans. is ‘b’ i.e., More affinity than hemoglobin

Myoglobin is present in higher concentration in red (slow) muscle fibers.

Myoglobin has greater affinity for oxygen than hemoglobin and its P50 is only 5 mm Hg (as compared to P50 of hemoglobin which is about 26 mm Hg).

Therefore, myoglobin-oxygen dissociation curve is shifted far to the left than Hb-O2 dissociation curve.

It has shape of hyperbola as compared to sigmoid shape of Hb-O2 curve because it binds 1 molecule of 02 per mole (in comparison to Hb which binds 4 molecules of O2 per mole).

The role of myoglobin is to bind O2 at very low PO2 and release them at even lower PO2, for example in exercising muscles where PO2 close to zero.

Quiz In Between



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