Normal Erythropoiesis

Question 1

Function red blood cells​

Answer 1

Full of haemoglobin to carry oxygen
-High oncotic pressure, oxygen rich environment (oxidation risk)​

Question 2

Structure red blood cells​- no nucleus

Answer 2

No nucleus makes it more deformable, and more room for Hb molecules​- Can’t divide, can’t replace damaged proteins - limited cell lifespan

Question 3

Structure red blood cells​- No mitochondria

Answer 3

No mitochondria either​- Limited to glycolysis for energy generation (no Krebs’ cycle)​

Question 4

Structure red blood cells​ - High Surface area/volume ratio

Answer 4

High Surface area/volume ratio to allow for gas exchange​- Need to keep water out ​

Question 5

Structure red blood cells​ - flexible

Answer 5

Flexible to squeeze through capillaries​- Specialised membrane required that can go wrong​

Question 6

Red cell membrane structure (6)

Answer 6

-Complex structure​

-Not just a lipid bilayer
​
-Protein ‘spars’​

-Protein anchors​

-Makes it flexible​

-If a protein is mutated then ​this can have consequences for deformability and shorted red cell survival​

Question 7

Red cells need energy to maintain specific ion concentrations gradient and keep water out (4)

Answer 7

-This pump keeps ion concentrations right​

-Keeps the systems working in the cell​

-Keeps water out​

-But it needs ATP (energy)

Question 8

Haemoglobin structure (5)

Answer 8

-A tetrameric globular protein​

-HbA(Adult) has 2 alpha and 2 beta chains​

-Heme group is Fe2+ in a flat porphyrin ring​

-One heme per subgroup​

-One oxygen molecule binds to one Fe2+ (Oxygen does NOT bind to Fe3+)

Question 9

Haemoglobin function (3)

Answer 9

-Deliver oxygen to the tissues
​
-Act as a buffer for H+​

-CO2 transport​

Question 10

Where does red cell production occurs

Answer 10

in the bone marrow as a result​
of proliferation and differentiation of HSCs​

Question 11

What is red cell production regulated by (5)

Answer 11

erythropoietin​=
-erythropoietin produced
-erythropoietin stimulates red cell production​
-epo levels drop​
-hypoxia sensed by kidney

Question 12

Red cell destruction- where + lifespan

Answer 12

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

Question 13

Red cell destruction- how are aged red cells taken up ?

Answer 13

Aged red cells taken up by macrophages i.e. taken out of the circulation​

Question 14

Red cell destruction- what happens to the contents

Answer 14

Red cell contents are recycled​

Question 15

Red cell destruction -globin chains?

Answer 15

Globin chains recycled to amino acids​

Question 16

Red cell destruction - heme group?

Answer 16

Heme group broken down to iron (Fe2+) and bilirubin​

Question 17

Red cell destruction -billirubin?

Answer 17

Bilirubin taken to liver and conjugated ​

Question 18

Red cell destruction - where does it go?

Answer 18

Then excreted in bile (colours faeces and urine)​

Question 19

Red cells challenges (4)

Answer 19

-no mitochondria- so relies on glycolysis for energy as no Krebs cycle

-glycolysis is a low energy yielding process

-lots of oxygen about and O2 free radicals are easily generated

-free radicals are dangerous- damage proteins

Question 20

What does a red cell need (6)

Answer 20

-a way to make energy

-a way to stop iron oxidising ( Fe 2+ becoming Fe 3+)

-a way to prevent oxidative damage to cellular enzymes and Hb from free radicals

-a way of buffering CO2 for transport​

-a way of holding onto oxygen in transport and dumping it in hypoxic environments
​
-a way of improving tissue oxygen delivery when it needs it most - anemic, metabolic acidosis, high CO2 concentrations

Question 21

Reactive oxygen Species​ (2)

Answer 21

e.g. superoxide and hydrogen peroxide are free radicals and have unpaired free electrons​

capable of interacting with other molecules (proteins, DNA) and damaging their structure​

Question 22

Glutathione (GSH) (3)

Answer 22

-protects us from hydrogen peroxide by reacting with it to form water and an oxidised glutathione product (GSSG)- this maintains the redox balance.​

-can be replenished by NADPH which in turn is generated by the hexose monophosphate shunt​

-rate limiting enzyme in this process is glucose-6-phosphate dehydrogenase (G6PD)​

Question 23

Carbon dioxide transport- how CO2 gets from the tissues to the lungs?​ (3)

Answer 23

-Only 10% is dissolved in solution​

-Around 30% is bound directly to Hb as carbamino-Hb​

-The other 60% gets there as bicarbonate and the red cell has an important role in generating that bicarbonate​

Question 24

Haemoglobin structure (4)

Answer 24

-One oxygen is bound to the Fe2+ in the heme group ​

-4 O2 molecules per Hb​

-Fully saturated 1g Hb will bind 1.34ml O2​

-Other forms of Hb have different subunits eg HbF (two alpha, two gamma)

Question 25

System requirements for oxygen transport by Haemoglobin (4)

Answer 25

Hb needs able to bind oxygen easily when lots around (ie lungs where pO2 is high)​ Needs to hold on to it as pO2 drops a little (ie in transport in blood vessels)​ Needs to then release 02 in the tissues where the pO2 is low ​ Cope with extra demand when stressed and have spare capacity in system to cope when anaemic​ ​

Question 26

Oxygen binding to Hb has unusual kinetics - the allosteric effect (3)

Answer 26

The dissociation curve for haemoglobin is sigmoidal As first oxygen binds to a haem in one subunit the Hb shape changes​ This alters how easy it is for the next O2 to bind to the haem in the next subunit​ and this changes the shape again

Question 27

Oxygen dissociation curve in practice (3)

Answer 27

-Vertical dotted lines are typical values for venous and arterial pO2.​ -Little drop off in transport​ Notice the venous pO2 is at the shoulder of the steep part of the curve​ -All occurs at relatively high saturation so a large reserve of spare capacity

Question 28

Different Hb molecules have different dissociation curves​ (2)

Answer 28

Foetal Hb (alpha2gamma2) saturates more at the same pO2 so effectively takes O2 from the maternal circulation. In muscles the monomeric myoglobin (which otherwise is a similar structure to Hb) takes O2 from red cells and has different kinetics​

Question 29

Small molecules that can effect the oxygen dissociation curve (3)

Answer 29

-CO2 -H -2,3 BPG

Question 30

How small molecules can effect the oxygen dissociation curve (4)

Answer 30

can interact with Hb subunits​ these interactions can alter the structure of the globin subunit​ can alter the position of the haem unit in the globin unit and so the ability of oxygen to bind to it​ can affect the shape of the oxygen dissassociation curve and so how much oxygen is delivered to the tissues at a certain pO2​ ​