Structure and Function of Normal RBCs

Question 1

Why do RBCs have no nucleus?

Answer 1

makes it more deformable

=> more room for Hb molecules

Question 2

RBCs have no mitochondria to make energy. TRUE/FALSE?

Answer 2

TRUE

- can only use glycolysis for energy

Question 3

Why do RBCs have a high surface area to volume ratio?

Answer 3

To allow for gas exchange

Question 4

Why must RBCs be flexible?

Answer 4

To squeeze through capillaries

Question 5

What problems can occur due to the RBC structure?

Answer 5

Full of haemoglobin => High oncotic pressure (pulls water in) also free radicals can form from oxygen rich environment

No nucleus => Can’t divide => limited cell lifespan

No mitochondria => glycolysis for energy generation

Flexible => Specialised membrane required can go wrong

Question 6

Describe the structure of the specialised RBC membrane

Answer 6

Not just a lipid bilayer

- Protein ‘spars’ anchored to membrane by proteins (ankyrin etc)

Question 7

What ion pump is responsible for keeping water OUT of RBCs?

Answer 7

Na/K Pump

• 3 Na out and 2 K in
• sets up membrane potential
• doesn’t allow water in

Question 8

Describe the structure of haemoglobin

Answer 8

• tetramer protein
• in Adult = 2 alpha and 2 beta chains
• Heme group in centre composed of Fe2+ in a flat porphyrin ring

Question 9

What are the main functions of haemoglobin?

Answer 9

• Deliver oxygen to the tissues
• Act as a buffer for H+
• CO2 transport

Question 10

What is produced by the kidney which regulates RBC production?

Answer 10

Erythropoietin

- this increases RBC production if it senses relative or absolute hypoxia

Question 11

Where are red cells destructed and how long do they usually live for?

Answer 11

Normally occurs in spleen (and liver) - average red cell lifespan 120 days

Question 12

HOw are RBCs removed from the circulation?

Answer 12

• Aged red cells engulfed by macrophages
• contents are recycled
  => Globin chains recycled to amino acids
  => Heme group broken down to iron and bilirubin
• Bilirubin taken to liver, conjugated and excreted in bile

Question 13

Why are free radicals dangerous for RBCs?

Answer 13

• Can oxidise Fe2+ to Fe3+ which doesn’t transport oxygen

- Can damage proteins (these cant repair/replace once damaged)

Question 14

What molecule created during glycolysis acts as a “sacrifice” to stop Fe2+ from oxidising to Fe3+?

Answer 14

NADH

- it gets oxidised instead

Question 15

How does the RBC use glycolysis to stop damage from free radicals?

Answer 15

• superoxides are turned into hydrogen peroxide (still damaging)
• glutathione is sacrificed to hydrogen peroxide
• NADPH is sacrificed to replenish glutathione stores

=> Hexose Monophosphate shunt

Question 16

WHat is the rate limiting step in the hexose monophosphate shunt and why is this clinically relevant?

Answer 16

Rate limiting enzyme = glucose-6-phosphate dehydrogenase (G6PD)

• this enzyme is coded on the X chromosome, therefore if patients have a genetic deficiency of this enzyme they will have early blood breakdown

Question 17

How is CO2 transported in the blood?

Answer 17

10% is dissolved in solution

30% is bound directly to Hb (carbamino-Hb)

60% = bicarbonate

Question 18

How many Oxygen molecules are found in one haemoglobin molecule, and how many of these are bound to the Fe2+ of the heme group?

Answer 18

4 O2 molecules per Hb

BUT only 1 bound to Fe2+

Question 19

Hb in patients who are not adults (e.g. in a foetus) have different subunits of Hb for different oxygen carrying capacities. What subunits are found in foetal Hb (HbF)?

Answer 19

HbF

• two alpha, two gamma
• picks up less O2 as baby does not yet need to use lungs to breath in utero

Question 20

Why is the oxygen dissociation curve sigmoidal?

Answer 20

Want high O2 carrying in high partial pressures O2 e.g. lungs
And low O2 carrying capacity in tissues where O2 needs to be released

=> As O2 binds to subunit, Hb shape changes
=> makes it easier for next O2 to bind
=> Cooperative binding

Question 21

Why does foetal Hb (a2g2) saturate more at the same pO2 as in an adult?

Answer 21

Takes O2 from the maternal circulation

Question 22

How can the introduction of other small molecules influence the dissociation curve?

Answer 22

Small molecules burrow into Hb and change the shape
=> make it harder for Hb to pickup oxygen
=> more free in tissues

shifts curve to the right

Question 23

What small molecules can shift the dissociation curve to the right?

Answer 23

2,3-BPG (increases in chronic anaemia)
H+ ions
CO2