10.2 Erythropoiesis

Question 1

What are the functions of blood?

Answer 1

• pH and electrolyte homeostasis
• Has exchange
• Temperature regulation
• Hormone and cytokine distribution
• Distribution of immune effectors

Question 2

In which areas of bone marrow does haematopoeisis occur in adults vs infants?

Answer 2

• Infants: all bone marrow is haematopoietic
• Adults: axial skeleton; pelvis, ribs, sternum, skull

Question 3

What % of adult bone marrow is fat?

Answer 3

30-70%

Question 4

What does normal bone marrow contain?

Answer 4

• Dissolved bubbles of fat
• Haematopoietically active cells

Question 5

How are mature cells released from bone marrow into peripheral circulation?

Answer 5

Through sinusoids (like in the spleen)

Question 6

Why do our stem cells divide so slowly?

Answer 6

Because every time they do, there is a risk of mutation

Question 7

List some normal stressors that can cause an increase in erythropoiesis

Answer 7

• Vigorous exercise
• Pregnancy

Question 8

Do blood loss and infection increase or decrease haematopoiesis?

Answer 8

Increase

Question 9

Wht are hematopoietic growth factors? How do they regulate haematopoiesis?

Answer 9

• They are small glycoproteins
• They can act in a paracrine/autocrine fashion locally, or an endocrine fashion throught the circulation

Question 10

What is the purpose for the bi-concave structure of RBCs?

Answer 10

To wishstand shear forces and enable them to pass through small gaps

Question 11

What is the main function of red blood cells?

Answer 11

To carry oxygen and deliver it throughout tissues in the body

Question 12

As Hb binds to oxygen, does its affinity for more O2 increase or decrease?

Answer 12

It increases, until the Hb is saturated

Question 13

Describe the structure of haemoglobin

Answer 13

• 2 alpha-like chains
• 2 beta-like chains
• Complexed with haem molecule containing Fe, which is what oxygen binds to

Question 14

Describe the structuure of a heme haem

Answer 14

Small molecule containing iron

Question 15

What is the earliest precursor to an RBC?

Answer 15

Proerythroblast

Question 16

What changes occur to a proerythroblast as it becomes an RBC?

Answer 16

• Changes from blue, to purple, to red
• Cell size decreases
• Nucleus shrinks and disappears

Question 17

How does proerythroblast cytoplasm change colour during RBC development?

Answer 17

• Starts out quite basophilic
• Begins to accumulate haemoglobin
• Takes on pale pink colour

Question 18

Which two vitamins are most important for DNA synthesis?

Answer 18

• Folic acid
• Vit B12

Question 19

Where does haem synthesis occur at different points in the process?

Answer 19

• Starts in mitochondria
• Then, occurs in cytoplasm
• Finally, finishes up in mitochondria again

Question 20

Describe the different types of haemoglobin present before and after birth. How does this influence disease processes?

Answer 20

• Until birth: Hb F [foetus] (alpha 2 gamma 2)
• During first 6 months: replaced with Hb A [adult] (alpha 2 beta 2), and a little of Hb A2 (alpha 2 delta 2)
• This means that, if there is some defect in the beta chain, it may not be seen until 6 months of age

Question 21

Does a small/large amount of haemoglobins molecular weight consist of glycosilation? How does this influence its biological activity?

Answer 21

• High amount is glycosylation
• This means it has high biological activity

Question 22

Where is EPO released from within the kidneys?

Answer 22

Juxtaglomerular apparatus: specialised interstitial fibroblasts

Question 23

Describe the different cells produced in the production of erythrocytes

Answer 23

• Proerythoblast
• Early/intermediate/late erythroblast
• Nuclear extrusion
• Reticulocyte (network cell)
• RBC

Question 24

Describe the feedback loop of the kidneys in response to low O2 sats

Answer 24

• Detected by kidneys
• Kidneys release EPO into blood
• Travels to bone marrow, and stimulates erythropoiesis
• O2 carrying capacity increases
• More blood returns to kidneys
• EPO release is shut down

Question 25

Do RBCs have regenerative capacity?

Answer 25

- No - They are bags of haemoglobin, there's nothing they can do to fix themselves

Question 26

Describe RBC death

Answer 26

- Loss of lipid membrane - Surface signs of oxidative stress - Detected by macrophages (e.g. in spleen) - Phagocytosed; iron recycled

Question 27

Does it make sense to produce lower or higher weight EPO when produced recombinant EPO for therapeutic purposes?

Answer 27

Higher -> more glycosylated -> more biologically active

Question 28

RBC lifespan is...

Answer 28

120 days