W10 Hg structure/function

Question 1

Haem and globin synthesis

Answer 1

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 2

Haemoglobin synthesis

Answer 2

65% of the Hb is synthesized in the erythroblasts, and
35% at the reticulocyte stage.

Normal conc. of Hb in blood:

Adult male: 13.5 – 16.5 g/dl

Adult female 12,5 – 15.0 g/dl

Question 3

Hg synthesis regulation

Answer 3

Stimulated by tissue hypoxia

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

Question 4

Haem synthesis

Answer 4

Haem synthesis occurs largely in the mitochondria.

Chain of Events

Iron delivery & supply
Iron is delivered to the reticulocyte by transferrin

Synthesis of protoporphyrins
Occurs in the mitochondria of RBC precursors
Mediated by EPO and vitamin B6

Protoporphyrin + iron = haem

Question 5

Globin synthesis

Answer 5

Globin synthesis occurs in the polyribosomes

Rates of haem and globin synthesis carefully coordinated to ensure optimal efficiency of Hb assembly

Proper globin synthesis depends on genes

precise order of amino acids in the globin chains is critical to the structure and function of haemoglobin

Question 6

Eight functional globin chains

Answer 6

Eight functional globin chains, arranged in two cluster;

Β-cluster (β, γ, δ and ε globin genes) short arm of chromosome 11
Α-cluster (α and ζ globin genes) short arm of chromosome 16

Question 7

Beta globin

Answer 7

Beta globin expressed at low level in early life; main switch of adult Hb occurs about 3-6mths after birth, when gamma is largely replaced by beta

Question 8

Mutations or deletions may lead to

Answer 8

abnormal synthesis of globin chain as in Sickle Cell Diseases.
Reduced rate of synthesis of normal α- or beta-globin chains as in Thalassaemias

Question 9

Embryonic Haemoglobin

Answer 9

Haemoglobin Gower I Zeta 2 Epsilon 2 (ζ2ε2)

Haemoglobin Portland Zeta 2 Gamma 2 (ζ2γ2)

Haemoglobin Gower II Apha 2 Epsilon 2 (α2ε2)

Question 10

Fetal Haemoglobin

Answer 10

HbF
Αlpha 2 Gamma 2
(α2γ2)

Question 11

Adult Haemoglobin

Answer 11

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

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

HbF (0.5 – 0.8%)

Question 12

Functions of Haemoglobin

Answer 12

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 13

Oxygen delivery to the tissues

Answer 13

One Hb can bind to four O2 molecules

Less than .01 sec required for oxygenation.

When oxygenated 2,3-DPG is pushed out; the ß-chains move closer.

ß-chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2

Question 14

Hb molecule loading/unloading

Answer 14

As Hb molecule loads and unloads O2, the individual globin chains move on each other

The Beta chains slide on the a1b2 and a2b1 contacts during oxygenation and deoxygenation

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

Question 15

2,3-diphosphoglycerate (2,3-DPG)

Answer 15

Substance made in the red blood cells. It controls the movement of oxygen from red blood cells to body tissues

Question 16

2,3-DPG concentrations in cell

Answer 16

The more 2,3-DPG in the cell, the more oxygen is delivered to body tissues

The less 2,3-DPG in the cell, the less oxygen is delivered

Increasing the amount of 2,3-DPG is the body’s primary way of responding to a lack of oxygen

Question 17

The amount of O2 bound to haemoglobin and released to tissues depends on

Answer 17

PO2 and
PCO2, but also the
affinity of haemoglobin for O2

Question 18

Oxygen affinity

Answer 18

The ease with which haemoglobin binds and releases oxygen

Question 19

Increase in Oxygen Affinity

Answer 19

Increases in oxygen affinity means haemoglobin has an increased affinity for O2, so it binds more & strongly.

Question 20

Decrease in Oxygen affinity

Answer 20

Decreases in oxygen affinity, cause O2 to be released

Question 21

What does oxygen affinity determine

Answer 21

Determines the proportion of O2 released to the tissues or loaded onto the cell at a given oxygen pressure

Question 22

P50

Answer 22

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

Decrease oxygen affinity when p50 increases (right shift - ) occurs as CO2 increases or pH decreases (Bohr effect) or when 2,3-DPG level rises

Increased oxygen affinity in the opposite circumstances

Question 23

Hb-O2 dissociation curve

Answer 23

Changes in blood pH shift the oxyhaemoglobin dissociation curve

Increase in CO2 production by tissue + release into blood = generation of hydrogen ions (H+) and a decrease in pH

Shifts the dissociation curve to the right, which has a beneficial effect by aiding in the release of O2 from Hb for diffusion into tissues

The shift to the right in the dissociation curve is due to the decrease in pH and to a direct effect of CO2 on Hgb

Question 24

Bohr Effect

Answer 24

Alterations in blood pH, shifts oxygen dissociation curve

In acidic pH, the curve shifts to the right

results in an enhanced capacity to release O2 where it is needed

Question 25

Right-Shift

Answer 25

Right-Shift

Increased P50

Decreased affinity O2

Hb willing to release O2 to tissue

Examples: anemia, acidosis

Even though there may be less RBC’s, they act more efficiently to deliver O2 to target

Question 26

The normal position of curve depends on

Answer 26

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

Question 27

Standard conditions:

Answer 27

Temp = 37OC
pH = 7.40
BE = 0

Question 28

Carbon Dioxide Transport

Answer 28

Three mechanisms of transport:

Dissolution in the plasma

Formation of Carbonic acid

Binding to carbaminohaemoglobin