Red Cells, Haemoglobin, and Introduction to Anaemia

Question 1

Describe the shape of the Normal Red Blood cell

Answer 1

• Discoid
• 7 micrometre diameter
• Big pink circles with central pallor (due to thinness)
• No nucleus or RNA: nucleus extruded during processing
• Big Blue Cells: polychromatic as they still have RNA in them

Question 2

What does the shape of the RBC allow and what is the RBC function?

Answer 2

Unique shape and deformability Allows:

• Flexibility + movement (to squeeze through capillaries 3.5 micrometres)
• Increased areas for gas exchange

Function:

• Haemaglobin carriage (Haem repsonsible for most of Gas exchange)
• O₂ transport: from lungs to tissues
• CO₂ tissues to lungs

Question 3

What determines the shape of Red blood cells and what happens if there are abnormalities in this?

Answer 3

RBC shape is determined by

• Membrane (bipolar lipid layer)
• Cytoskeleton proteins (spectrin, actin, ankyrin)

Abnormalities of these:

• Inherited rigid membrane → shortened life span of red cell
• Hereditary spherocytosis: a sphere, no biconcave disc

Question 4

RBCs keep haemaglobin in a _______ state for?

Answer 4

RBCs keep haemaglobin in a reduced state to maintain osmotic equilibrium

• Glycolytic pathways produce ATP; maintains osmotic equilibrium
• HexoseMonoPhosphate Shunt produces NADPH: keeps Hb reduced

Inherited defects in this pathways → haemolysis and Red cell turnover
Lots of people have without realising and it’s not till they have an insult that they’ll have a haemolytic crisis
eg; G6PD deficiency

Question 5

Within the RBC you have aminoacids that drive Haem production (this is because the Iron element receptor is switched on) How does this work

Answer 5

1. Iron Element Receptor grabs Fe³⁺ from Transferrin in the blood into RBC
2. Aminoacid precursors are assembled (know these)
3. AT the stage of Pyrotoporphyrin , iron (Fe³⁺) gets added to create Haem molecule
4. Assembled with Globin chains
5. Makes a four (2 alpha and 2beta) Haemaglobin molecule

Question 6

Haemaglobin and RBC properties

Answer 6

Primarily for gas exchanfe

HbA principle haemaglobin in adults

• 2 alpha + 2 beta + haem group
• Small amounts of HbF (fetal) and HbA2 also included in adult
  
  • excess HbF in sickle cell anaemia
• Thalassaemia: defective production of Globulin chains (usually inherited)*
• Deficiency of Iron: Reduced production of Haem → low Hb*

Question 7

Embryology of Red cells

Answer 7

• Primitive Red Cells forming in the Blood
• Form blood islands in the Embryo in AGM and Liver
• By 3rd trimester babies blood in in the bone marrow

Question 8

HSM are at a ____ frequency but _________

Further down there’s a ____ frequency of specific cells, but these __________

Answer 8

HSM are at a low frequency but can self renew

Further down there’s a high frequency of specific cells, but these can’t self renew

• Not until the more mature/recognisable proeurythroblasts /pronormoblasts that you get the huge number of them seen in the bone marrow
  
  • before pronormoblast all controlled by eurythropoietin with a high rate of E receptors
• Pronormoblast → Mature RBC take ~7 days

Question 9

What are these

Answer 9

Pronormoblasts: Big diffuse cells, fine chromatin

More mature Cells have : dense pignotic (dying) nucleus.

Prochromatic (later) cells: increased Glucoforrin A.

Transferrin Receptor : Increased earlier on in the Pronormoblast stage as this is where iron feeds in

Question 10

What happens to your Red cell production if you are hypoxic

Answer 10

• When your hypoxic and need O₂ you want to drive eurythropoiesis with HIF-1 and HIF-1B and these will upregulate the transferrin receptor to supply iron to the system. More iron
• Also angiogenesis is upregulated for increased blood capillary growth. More capillaries
• Glycolytic Enzymes switched on for ATP/energy to the cell More energy

If too much O₂ this is just down regulated