Haemoglobin and red cells (3)

Question 1

The erythrocyte:

Answer 1

a very specialised RB cell and has perfect function

Question 2

Oxygen flow:

Answer 2

• Oxygen is absorbed in the high pO2 in lung and transported to tissues bound to haemoglobin
• Needs for oxygen are not the same everywhere, some areas need more than others
• In the middle is the lungs, where the red cells pick up oxygen
• Circulation may require different oxygen levels
• Most of the power in the gut as it does require lots of oxygen Must get there safely, to the places and give oxygen depending on needs

Question 3

Shape of RBC:

Answer 3

Biconcave shape optimises O2 uptake and delivery

Question 4

Cytoskeleton function:

Answer 4

The structure supports circulation and safety

Question 5

Structure/function of haemoglobin:

Answer 5

• Delivers O2 where it is needed
• Oxygen must be released according to need in this case little to arms and brain, lots to the legs. How does haemoglobin do this?
• Haemoglobin has to bind oxygen in the lungs and then has to release it progressively

Question 6

What do we mean by simplicity?

Answer 6

The red cell has given up:

1. Nucleus – more room in the cell for haemoglobin and doesn’t get in the way of the biconcave shape
2. Mitochondria – the red cell gets its oxygen from simple sugars and absorption, it is relatively inefficient (uses glycolysis)
3. Ribosomes – pointless as it cannot transcribe any mRNA as there is no nucleus, cannot commit to apoptosis, lack of protect as proteins cannot repair any damage

Question 7

Why would a RBC give its organelles up?

Answer 7

1. Efficient and stable – nothing unnecessary
2. Room for haemoglobin – no proteins, cannot replicate
3. Unattractive to infecting organisms – pointless to invade as there’s nothing to attack

Question 8

Is RBC giving up its organelles a problem?

Answer 8

1. No nucleus: No capacity for to making mRNA
2. No Mitochondria no TCA cycle – limits the capacity to generate ATP or reducing power - vulnerable
3. No Ribosomes no translation of mRNA no protein synthesis

• highly efficient and adaptable
• but very vulnerable

Question 9

Two parts to cytoskeleton (PM):

Answer 9

1. The membrane links that are the vertical proteins – membrane anchors
2. Linked by the horizontal proteins on the membrane cytoskeleton

Question 10

Bi-concave disc is the optimal shape:

Answer 10

• High surface area to volume ratio
• Allows oxygen to diffuse in and co2 to diffuse out with a short diffusion rate/ pathway
• When in the capillary we want a relaxed biconcave shape
• Want them closely packed together
• In arteries you want to move very fast so do not want the relaxed state

Question 11

Optimal flow:

Answer 11

The structure can adopt an alternative “torpedo” shape in high flow conditions
Basically becomes compressed and more oval

Question 12

Optimal flexibility:

Answer 12

The structure can flex to allow cells to pass through small branched vessels in tissues
Basically becomes like a peanut shape

Question 13

The membrane and damage repair:

Answer 13

The lack of ability to make new proteins limits repair capacity for the cells cannot undergo apoptosis so temporary fixing is needed to prevent toxicity – the membrane structure is self-repairing to limit immediate damage.

This must not happen – haemoglobin released into circulation is highly toxic, the cytoskeleton structure allows a fix to prevent Hb “leakage”.

Question 14

Damage by fibrin strands in the circulation caused by local clotting activation:

Answer 14

1. slicing damage
2. repair and vacuole formation
3. vacuole pops but RBC is sealed
4. further sealed fragments may be formed

Question 15

Inherited abnormal cytoskeleton or antibody may cause diffuse membrane loss:

Answer 15

1. Membrane is damaged diffusely
2. small sealed blebs of membrane are lost
3. the cell shrinks gradually becoming a rigid sphere
4. the rigid damaged ‘sphereocyte’ is lost in the spleen
5. biconcave shape is replaced by a sphere

Question 16

Sigmoid dissociation curve:

Answer 16

An s-shaped curve that has no oxygen to begin with so no saturation, then gradually becomes a straight line which is optimal, then curves off which means all Hb is saturated and can no longer carry oxygen

Question 17

Function of Hb:

Answer 17

1. the oxygen-binding chemical elements: the haem
2. the surrounding protein elements: globin
3. (protein sheath to keep the iron safe and in place)

Question 18

Haem:

Answer 18

Porphyrin structure holds iron in a flat two dimensional structure:

Two interaction sites remain above and below the plane:

1. One fixes the molecule to the globin protein
2. One is available to bind oxygen
3. Iron binds 6 electrons
4. Porphyrin only binds 4 electrons – one binds to the globin molecule and the other is able to bind to oxygen
5. Each haem has 4 binding domains

Question 19

The function of globin:

Answer 19

• Binding to protein keeps haem contained (not free) & therefore safe
• Iron is a free radical producer that must be kept tight in the proteins to ensure no damage occurs
• To produce the sigmoid Oxygen-binding curve

Question 20

Leaving the lung:

Answer 20

4 oxygen molecules bound: “relaxed form”: holds on to oxygen tightly until the oxygen in tissues begins to drop then the first oxygen is released

• Cooperation between chains means that each influences the other. After release of the first oxygen the structure becomes increasingly “tight” and each subsequent release becomes easier.
• One oxygen molecule bound: “tight form”: gives up oxygen easily
• Relaxed form binds very tightly to oxygen
• As you get to a tissue the first oxygen is dropped off
• As soon as this happens the chains get tighter and closer together, holding oxygen less closely, this makes releasing the oxygen a lot easier

Question 21

The tight and relaxed form are influenced by:

Answer 21

1. pH
2. CO2
3. Metabolic products

Present mainly in active tissues and promote the tight form more

Question 22

Physiological Hb variation during development:

Answer 22

1. Foetal development, embryonic and foetal haemoglobin’s
2. During development the embryo, then foetus make a succession of alternative haemoglobin’s
3. The best studied is foetal haemoglobin – this form does not bind 2,3 DPG and therefore has higher affinity for haemoglobin
4. This allows the foetal haemoglobin (HbF) to compete with the mothers haemoglobin for Oxygen – transferring the oxygen from the mother to the developing foetus

Question 23

RBC and Self-defence:

Answer 23

• the iron-rich haemoglobin is inhospitable to bacteria
• exploited by malaria
• immune system does not recognise a damaged cell, only the haemaglobin proteins that are released which can be very toxic

Question 24

MALARIA:

Answer 24

• The malaria parasite introduced by mosqitoes is able to live inside red cells, protected from the immune system and metabolising their haemoglobin for energy, replicating then affecting other red cells.
• Parasite of flies and fish
• Red blood cell becomes pale and gets bigger

Question 25

Summary of RBC diseases:

Answer 25

1. Haemoglobin S [Sickle cells (up to 15% gene frequency)]
2. Beta thalassaemia (gene up to 17%)
3. Deficiency of glucose 6 phosphate dehydrogenase (G6PD) (gene up to 5-25%)
4. Haemoglobin C [gene frequency up to 24%] – protects you against malaria but also makes you very ill

Question 26

G6PD deficiency:

Answer 26

1. G6PD is a red cell enzyme that generates reducing power (NADPH) that protects the haemoglobin from oxidative damage. The simple metabolism of the red cell means it depends on this enzyme.
2. Deficiency of the G6PD means that when oxidative stress is high the haemoglobin is damaged and the red cell destroyed
3. It is believed that during malarial infection oxidative stress in red cells is high and so malarial infected red cells are destroyed providing some protection

Question 27

G6PD deficiency prevalence:

Answer 27

The gene is prevalent in Africa, some Arab states and in some Mediterranean areas and can cause death after some foodstuffs or medications increase oxidation