Haemoglobin

Question 1

Describe the structure of haemoglobin(2)

Answer 1

a globular haemoprotein made up of 1/3 of red blood cell
2. Haemoproteins are a group of specialized proteins that contain haem as a tightly bound prosthetic group. The haeme is not a protein

Question 2

Describe the structure of the haem(2)

Answer 2

 Haem is a complex of protoporphyrin IX and ferrous iron (Fe2+).
 Iron held in the centre of haem molecule by bonds to the 4 nitrogen of a porphyrin ring

Question 3

Describe the rate of synthesis of the haem and the globin

Answer 3

Although haem and globin synthesis occur separately within developing red cell precursors, their rates of synthesis are carefully coordinated to ensure optimal efficiency of Hb assembly

Question 4

Describe the co-ordinations of iron

Answer 4

Iron has 6 co-ordinations;
4 binds to the 4 pyrrole rings,

one binds with histidine (an amino acid from globulin), and

one free (to bind oxygen)

Question 5

Where does haemoglobin synthesis takes place?

Answer 5

 65% of the Hb is synthesized in the erythroblasts (precursor of the red cells), and

 35% at the reticulocyte stage.

Question 6

Compare normal conc. of Hb in blood of males and females

Answer 6

o Adult male: 13.5 – 16.5 g/dl

o Adult female 12,5 – 15.0 g/dl

Question 7

How is haemoglobin synthesis regulated?

Answer 7

 Stimulated by tissue hypoxia

Question 8

How does hypoxia stimulate synthesis?(3)

Answer 8

 Hypoxia causes the kidneys to increase production of EPO, which increases RBC and Hb production.

Kidney senses low oxygen level and produces EPO.

EPO goes to bone marrow to produce red blood cells

Question 9

Where does haem synthesis mainly take place?

Answer 9

mitochondria of RBC precursors

Question 10

Where does synthesis of the protoporphhyrins occur and what is it mediated by?

Answer 10

 occurs in the mitochondria of RBC precursors

 mediated by EPO and vitamin B6

Question 11

Describe the process of synthesis of haem(5)

Answer 11

1. 2 simple molecules: Glycine (an amino acid) and succinyl CoA (an intermediate of citric acid cycle).
2. The reaction of these 2 molecules with B6 as a co-factor, and a key rate-limiting enzyme delta ALA synthase to produce delta-ALA.
3. Enzyme condenses succinyl CoA and glycine
4. Goes into cytoplasm and back into mitochondria to form protopophyrin
5. Protoporphyrin combines with Fe and forms 4 molecules of Haem

Question 12

Where does globin synthesis occur?

Answer 12

• Globin is a protein so synthesis occurs in the polyribosomes (RER).

Question 13

What does proper globin synthesis depend on?

Answer 13

o precise order of amino acids in the globin chain

Question 14

What are the two clusters of the eight functional globin chains and what chromosomes they are found on?

Answer 14

o Β-cluster (β, γ, δ and ε globin genes) short arm of chromosome 11

o Α-cluster (α1, and ζ globin genes) short arm of chromosome 16

Question 15

What globin chains are found on chromosome 16?

Answer 15

zeta, alpha1 and alpha2

Question 16

What globin chains are found on chromosome 11?

Answer 16

epsilon, gamma glutamic, gamma alanine, delta and beta.

Question 17

What are the three types of embryonic and their globin compositions?

Answer 17

1Haemoglobin Gower I Zeta 2 Epsilon 2 (ζ2ε2)

2. Haemoglobin Portland Zeta 2 Gamma 2 (ζ2γ2)
3. Haemoglobin Gower II Apha 2 Epsilon 2 (α2ε2

Question 18

What is foetal haemoglobin made of?

Answer 18

HbF*
Αlpha 2 Gamma 2
(α2γ2)

Question 19

What are the three types of adult haemoglobin and what they are made of?

Answer 19

1. HbA  (96-98 %)
  Alpha 2 Beta 2
      (α2β2)

2. HbA2 (1.5-3.2 %)
  Alpha 2  Delta 2
  (α2δ2)

3.HbF (0.5 – 0.8%)

Question 20

What week of gestation does globin synthesis occur?

Answer 20

3rd wk of gestation

Question 21

What are the functions of haemoglobin?(3)

Answer 21

 Carry oxygen from the lungs to the tissues

 Remove CO2

 Buffering action, maintains blood pH as it changes from oxyhaemoglobin (carrying O2) to deoxyhemoglobin (without O2)

Question 22

Describe oxygen delivery to tissues(2)

Answer 22

 One Hb can bind to four O2 molecules

 Less than .01 sec required for oxygenation.

Question 23

What happens when oxygen is unloaded?

Answer 23

the beta chains are pulled apart, permitting entry of the metabolite 2,3-diphosphoglycerate (2,3-DPG), resulting in lower affinity for O2.

Question 24

What is 2,3 DPG?

Answer 24

 2,3-diphosphoglycerate

a substance made in the red blood

3. It controls the movement of oxygen from red blood cells to body tissues.

Question 25

What determines the amount of oxygen bound to haemoglobin?(3)

Answer 25

 PO2
 PCO2
 affinity of haemoglobin for O2.

Question 26

What is the Bohr effect?(4)

Answer 26

 Alterations in blood pH, shifts oxygen dissociation curve
 In acidic pH, the curve shifts to the right
3.  results in an enhanced capacity to release O2 where it is needed
4. Acidic pH because of increase in carbonate/ CO2

Question 27

What does the Hb-oxygen dissociation curve depend on?

Answer 27

 Concentration of 2,3-DPG
 H+ ion concentration (pH)
 CO2 in red blood cells
 Structure of Hb

Question 28

What is BE?

Answer 28

The base excess (BE) is defined as the amount of H+ ions that would be required to return the pH of the blood to 7.35 if the pCO2 were adjusted to normal.

Question 29

What is the BE value if a patient is acidiotic?

Answer 29

the base excess will be a negative value; this means acid would have to be taken away to bring the pH to normal.

Question 30

What does -6mEq mean?

Answer 30

6 mEq(milliequivalent) per litre of base would have to be added to bring the patient’s blood to normal pH (7.4)

Question 31

What is p50 mean?

Answer 31

• P50 is the partial pressure of oxygen at which the Hb is 50% saturated (middle line – usually 27mm Hg).

Question 32

What are the three mechanisms of CO2 transport?

Answer 32

 Dissolution in the plasma
 Formation of Carbonic acid
3. Binding to form carbaminohaemoglobin

Question 33

Recall 5 haemoglobin derivatives

Answer 33

 Oxyhaemoglobin (oxyHb): Hb with O2.
 Deoxyhaemoglobin (deoxyHb) = Hb without O2
 Methaemoglobin (metHb) - contains Fe3+, normal Hb has Fe 2+. Met cannot carry oxygen
 Carboxyhaemoglobin (HbCO) - CO binds to Fe2+ in haem in cases of CO poisoning. Binds even stronger
 Carbaminohaemoglobin (HbCO2) – CO2 binds non-covalently to globin chain of Hb. HbCO2 transports CO2 in blood (20%)

Question 34

What is the difference between SCD and Thalassaemia?

Answer 34

 Abnormal synthesis of globin chain as in Sickle Cell Diseases.

 Reduced rate of synthesis of normal globin chains as in Thalassaemia.

Question 35

How does SCD arise at mutation level?

Answer 35

sub of valine for glutamic acid; A to T

Question 36

What are the mutations that occur in the three SCD traits?

Answer 36

• Hb C – lysine replaces GA at position 6
• Hb D glutamine replaces GA
• Hb E lysine replaces GA at position 26

Question 37

Describe the different forms of beta thalassaemia(4)

Answer 37

 Loss of 1 beta-chain causes mild microcytic anaemia (thalassaemia trait)
 Loss of both (beta0) causes thalassaemia major
 Excess α-chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis.
 Los of beta chain mean more alpha leading to precipitation in the cells so low survival

Question 38

Describe the different forms of alpha thalassaemia(3)

Answer 38

 Loss of 1 or 2 causes mild microcytic anaemia

 Loss of 3 causes moderate anaemia - Hb H disease

 Loss of 4 causes death in utero (hydrops fetalis)

Question 39

What are target cells?

Answer 39

• Target cells occur in disproportional increase in SA:V; i.e. abnormally high SA (increased SA), or else decreased intracellular Hb conc.
• It is seen in diseases that affect lipid conc in RBC or decrease Hb; e.g. Thal, IDA,

Question 40

Describe the chain of events that leads to haem production.

Answer 40

→ IRON DELIVERY AND SUPPLY:
→Iron is delivered to the reticulocyte by transferrin.

→ SYNTHESIS OF PROTOPORPHYRINS:
→This occurs in the mitochondria of RBC precursors.
→It is mediated by EPO and Vit B6.
→This is done to create Protoporphyrin IX.

→COMBINING TO MAKE HAEM:
→Protoporphyrin IX and iron combine to make a haem molecule.
→The haem can combine with globin to form haemoglobin.

Question 41

what are examples of situations where the oxygen curve is right shifted?

Answer 41

acidosis and anaemia (even though we may have a lowered number of RBCs, they act more efficiently to deliver O2 to the target).

Question 42

describe what happens during the right shift of an oxygen dissociation curve

Answer 42

→increased P50
→ decreased affinity to O2
→ Hb more willing to release O2 to tissue

Question 43

describe what happens during the left shift of an oxygen dissociation curve(3)

Answer 43

→decreased P50
→ increased affinity to O2 -
→Hb less willing to release O2 to tissue

Question 44

what are examples of situations where the oxygen curve is left shifted?

Answer 44

alkalosis and the presence of abnormal haemoglobins.