10.2 Erythropoiesis Flashcards
What are the functions of blood?
- pH and electrolyte homeostasis
- Has exchange
- Temperature regulation
- Hormone and cytokine distribution
- Distribution of immune effectors
In which areas of bone marrow does haematopoeisis occur in adults vs infants?
- Infants: all bone marrow is haematopoietic
- Adults: axial skeleton; pelvis, ribs, sternum, skull
What % of adult bone marrow is fat?
30-70%
What does normal bone marrow contain?
- Dissolved bubbles of fat
- Haematopoietically active cells
How are mature cells released from bone marrow into peripheral circulation?
Through sinusoids (like in the spleen)
Why do our stem cells divide so slowly?
Because every time they do, there is a risk of mutation
List some normal stressors that can cause an increase in erythropoiesis
- Vigorous exercise
- Pregnancy
Do blood loss and infection increase or decrease haematopoiesis?
Increase
Wht are hematopoietic growth factors? How do they regulate haematopoiesis?
- They are small glycoproteins
- They can act in a paracrine/autocrine fashion locally, or an endocrine fashion throught the circulation
What is the purpose for the bi-concave structure of RBCs?
To wishstand shear forces and enable them to pass through small gaps
What is the main function of red blood cells?
To carry oxygen and deliver it throughout tissues in the body
As Hb binds to oxygen, does its affinity for more O2 increase or decrease?
It increases, until the Hb is saturated
Describe the structure of haemoglobin
- 2 alpha-like chains
- 2 beta-like chains
- Complexed with haem molecule containing Fe, which is what oxygen binds to
Describe the structuure of a heme haem
Small molecule containing iron
What is the earliest precursor to an RBC?
Proerythroblast
What changes occur to a proerythroblast as it becomes an RBC?
- Changes from blue, to purple, to red
- Cell size decreases
- Nucleus shrinks and disappears
How does proerythroblast cytoplasm change colour during RBC development?
- Starts out quite basophilic
- Begins to accumulate haemoglobin
- Takes on pale pink colour
Which two vitamins are most important for DNA synthesis?
- Folic acid
- Vit B12
Where does haem synthesis occur at different points in the process?
- Starts in mitochondria
- Then, occurs in cytoplasm
- Finally, finishes up in mitochondria again
Describe the different types of haemoglobin present before and after birth. How does this influence disease processes?
- 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
Does a small/large amount of haemoglobins molecular weight consist of glycosilation? How does this influence its biological activity?
- High amount is glycosylation
- This means it has high biological activity
Where is EPO released from within the kidneys?
Juxtaglomerular apparatus: specialised interstitial fibroblasts
Describe the different cells produced in the production of erythrocytes
- Proerythoblast
- Early/intermediate/late erythroblast
- Nuclear extrusion
- Reticulocyte (network cell)
- RBC
Describe the feedback loop of the kidneys in response to low O2 sats
- 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
Do RBCs have regenerative capacity?
- No
- They are bags of haemoglobin, there’s nothing they can do to fix themselves
Describe RBC death
- Loss of lipid membrane
- Surface signs of oxidative stress
- Detected by macrophages (e.g. in spleen)
- Phagocytosed; iron recycled
Does it make sense to produce lower or higher weight EPO when produced recombinant EPO for therapeutic purposes?
Higher -> more glycosylated -> more biologically active
RBC lifespan is…
120 days
