Normal Erythropoiesis Flashcards

1
Q

What do RBCs contain to carry oxygen?

A

Haemoglobin - high oncotic pressure, oxygen rich environment (oxidation risk)

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2
Q

Do RBCs contain mitochondria?

A

No - limited to glycolysis for energy generation (no Kreb’s cycle)

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3
Q

RBCs do not have a nucleus, what does this allow for?

A

Makes it more deformable, and more room for Hb molecules

Can’t divide, can’t replace damaged proteins - limited cell lifespan

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4
Q

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

A

Allow for gas exchange
Need to keep water out

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5
Q

Why is it important that RBCs are flexible?

A

To squeeze through capillaries - specialised membrane required that can go wrong

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6
Q

Describe the membrane of RBCs

A
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7
Q

Why do RBCs need energy?

A

To maintain specific ion concentrations gradient and keep water out

The sodium potassium pump keeps ion concentrations right
Keeps system working in cell
Keeps water out
But it needs ATP (Energy)

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8
Q

Describe the structure of haemoglobin

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+)

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9
Q

What is the function of haemoglobin?

A

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

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10
Q

Where does red blood cell production occur?

A

In the bone marrow as a result of proliferation and differentiation of HSCs

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11
Q

Describe the pathway by which erythropoietin stimulates RBC production

A
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12
Q

Where does red cell destruction occur?

A

In spleen (and liver)

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13
Q

What is the average red cell lifespan?

A

120 days

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14
Q

Aged red cells are taken up by?

A

Macrophages - taken out of circulation

Red cell contents are recycled

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15
Q

Globin chains are recycled to what?

A

Amino acids

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16
Q

Heme group is broken down to?

A

Iron and bilirubin

17
Q

Bilirubin is taken to?

A

Liver and conjugated - then excreted in bile (colours faeces and urine)

18
Q

Describe the pathway of breaking down heme to bilirubin

A
19
Q

Oxygen free radicals are easily made as there is a lot of oxygen in blood. Why are free radicals dangerous for RBCs?

A

Free radicals are dangerous
Can oxidise Fe2+ to Fe3+ which doesn’t transport oxygen
Free radicals damage proteins ~(remember we can’t repair/replace proteins as no machinery to do so -so once they’re damaged that’s it)

20
Q

What does a red blood cell need?

A
21
Q

Describe this diagram

A
22
Q

What are examples of reactive oxygen species?

A

Superoxide
Hydrogen peroxide

These are free radicals and have unpaired free electrons

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

23
Q

What is glutathione?

A

Protects us from hydrogen peroxide by reacting with it to form water and an oxidised glutathione product (GSSG) -> maintains redox balance

24
Q

How can glutathione be replenished?

A

By NADPH which in turn is generated by the hexose monophosphate shunt

25
Q

What is the rate limiting enzyme in the process of replenishing glutathione?

A
26
Q

What does the hexose monophosphate shunt produce?

A

Generates NADPH that maintains GSH levels preventing oxidative damage

27
Q

How does CO2 get from tissues to lungs?

A

10% dissolved in solution
30% bound directly to Hb as carbamino-Hb
60% gets there are bicarbonate and the RBC has an important role in generating bicarbonate

28
Q

How many oxygen molecules per Hb?

A

4 O2 molecules

29
Q

What are system requirements for oxygen transport by haemoglobin?

A
30
Q

Describe the oxygen binding curve for Hb

A
31
Q

Describe the oxygen dissociation curve in practice

A
32
Q

HbF has what subunits?

A

2 alpha
2 gamma

33
Q

Why does foetal Hb saturate more PO2?

A
34
Q

Why can small molecules like CO2, H, 2,3 BPG affect oxygen dissociation curve?

A
35
Q

Describe how modulation of saturation at critical low PO2 pressures improve O2 delivery

A
36
Q

What pathway makes 2,3-BPG?

A

Rapapport-Lubering Shunt

37
Q

What can shift the oxygen saturation curve to the right?

A

Molecules that interact with Hb

H+, CO2, 2,3-BPG, Increased temp, Decreased pH

Results in more oxygen delivered to tissues

38
Q

What can shift the oxygen saturation curve to the left?

A

Increased pH (less H+), Decreased DPG, Decreased temp

39
Q

What molecule is increased in chronic anaemia?

A

2,3-BPG (sometimes called DPG)