Lecture 2: Red cells, haemoglobin and anaemia Flashcards
Describe the appearance of RBC:
Discoid
No nucleus or RNA
Describe the function of RBC shape:
Shape permits
- Flexibility (deformability) (movement thru small caps)
- Increased area for gas exchange
(therefore changes in membrane/SA/flexibility are v problematic)
Function:
- Haemoglobin carriage
- Oxygen transport
What determines RBC shape/flexibility?
Determined by membrane and cytoskeleton proteins
Whats a clinical example of abnormal RBC membrane and what are the consequences?
Abnormalities of the membrane can result in shortened lifespan of the red cell
i.e hereditary sherocytosis
More easily damaged…
Describe how the membrane properties of RBC are linked to osmotic equilibrium:
Keeps heamoglobin in reduced state and maintains osmotic equilibrium
- Glycolytic pathways produce ATP - maintains osmotic equilibrium
- HMP shunt produces NADPH - Keeps Hb reduced.
How do defects in enzyme pathways influence RBC clinically?
G6PD enzyme deficiency can lead to heamolysis (reduced lifespan)
Checked/screened before any heamolytic drugs given
Fava beans can produced oxidative stress and in presence of G6DP deficiency leads to heamolysis and anaemia
Whats the binding ratio of Hb?
Hb
- Gas exchange
- HbA is principle Hb
2 alpha and 2 beta globin chains and heam group.
What is beta thalassemia?
Decreased production of beta chains, leads to reduced RBC production and anaemia (can happen to alpha chain too, thalassemia)
What does a deficiency of iron lead to?
Deficiency of iron - reduced production of haem resulting in low Hb (Anaemia)
What happens as the common myeloid progenitor turns into a RBC? What are some important landmarks?
As it progresses through the generations of differentiation: There is progressive increase in haemoglobin chromatin clumping, extruding of nucleus and loss of RNA.
i.e early RBC precursor still has RNA but no nucleus. These cells are indicative of bone marrow function. (Reticulocytes) i.e if heamolysis you would expect increased reticulocytes as the bone marrow attempts to produce more RBC
Describe the kinetics of erythropoiesis:
4 cell cycles / divisions
1 pronormoblast ledas to 16 RBCs
Process is 7-10 days
Reticulocytes 2 days but lifespan of around 20 days
Write some notes on erythropoetin:
Major regulator of heamatopoesis
- Glycoprotein
- Produced in kidneys
- responds to low oxygen tensions - increased EPO production
Describe the regulation of EPO:
Anything that reduces oxygen delivery to the kidney increase EPO production i.e
- Reduced atmospheric O2
- O2 dissociation curve
- Cardiopulmonary function
- Hb concentration
- Renal circulation
i.e Surgery, lung disease COPD, renal stenosis
EPO acts on Pronormoblasts to commit them to reticulocytes and thus RBC
What are the effects of EPO?
Binds to EPO receptor to increase red cell production:
- Stimulation fo BFU-E and CFU-E (early erythroid precursor stimulation)
- Increased Hb synthesis
- Reduced RBC maturation time
- Increased reticulocyte release
= Increased RBC and thus oxygen delivery
What often causes polycythemia?
Acquired JAK2 mutations in bone marrow cause constitutive activation of the signalling pathway absent of EPO - resulting in overproduction of RBC and high Hb.
(myoproliferative neoplasms)
