Erythropoiesis Flashcards
On average, the body produces _________ red cells per day
2.5 billion red cells/kg/day
RBCs gave a lifespan of..
120 days/four months
Site of Erythropoiesis in very early foetus
In the yolk sac
From 2 – 5 months gestation, in liver and spleen before finally establishing in the bone marrow from 5 months
Site of Erythropoiesis in children
In the bone marrow of most bones
Site of Erythropoiesis in adults
Vertebrae, ribs, sternum, sacrum, pelvis and proximal femur
When erythropoiesis is inadequate in the bone marrow, this can trigger…
Extramedullary haematopoiesis
Extramedullary haematopoiesis is commonly seen in..
Haemoglobinopathies such as thalassaemias and myelofibrosis
The production of all blood cells begins with the ___________, a multipotent haematopoietic stem cell
Haemocytoblast
What do Haemocytoblasts differentiate into?
Common myeloid progenitor cells
Outline the several stages by which common myeloid progenitor cells become fully mature red blood cells?
1) Become normoblasts (erythroblasts). Present in the bone marrow only
2) Lose their nucleus as they mature into reticulocytes. Some are released into peripheral circulation
3) Lose their remaining organelles as they mature into erythrocytes (via nuclear extrusion)
Nucleated red blood cells occur in which conditions?
Thalassaemia, severe anaemia or haematological malignancy
Erythropoiesis is driven mainly by the hormone ________, which is a __________ cytokine
Erythropoiesis is driven mainly by the hormone erythropoietin (EPO), which is a glycoprotein cytokine
EPO is secreted by the _________
Kidney
When there is a reduced partial pressure of oxygen (pO2) in the kidney, this is detected by the..
Renal interstitial peritubular cells
__________ can be used as a performance-enhancing drug among athletes
Exogenous EPO - improve the oxygen supply to muscles
Define anaemia
Low haemoglobin concentration
Anaemia can be caused by..
Decreased red cell production, or increased red cell removal.
Reduced red cell production may be due to 3 main things..
- Lack of ‘building blocks’ for production, e.g. iron, folate or B12 deficiency
- Failure of the stimulus – i.e. EPO deficiency secondary to chronic kidney disease
- Bone marrow failure, such as aplastic anaemia
Overproduction of red blood cells can occur in conditions such as..
Polycythaemia rubra vera
What is Polycythaemia rubra vera?
Myeloproliferative disease which results from dysregulation at the level of the haematopoietic stem cell - JAK-2 mutation
Red destruction occurs in the..
Spleen and liver
Aged red cells taken up by..
Macrophages and recycled
Globin chains: amino acids
Heme: iron & bilirubin
Which two structures are NOT present in RBCs?
Nucleus and mitochondria
What is a consequence of RBCs not having a nucleus or mitochondria
No nucleus: Can’t divide, can’t replace damaged proteins - limited cell lifespan
No mitochondria: Limited to glycolysis for energy generation (no Krebs’ cycle)
What is a consequence of RBCs having a high surface area/volume ratio?
Need to
keep water out
What is a consequence of RBCs being flexible?
Specialised membrane required
that can go wrong
Why do RBCs need energy?
To maintain specific ion
concentrations gradient and keep water out
What is the structure of HG?
A tetrameric globular protein
HbA has 2 _______ chains and 2 _______ chains. Heme group is _______ in a flat porphyrin ring. One heme per subgroup
HbA 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+
Functions of HBa
Deliver oxygen to the tissues
Act as a buffer for H+ CO2 transport
Red cell destruction (recap)
How does a red cell keep generating ATP and prevent Fe2+ from becoming Fe3+?
Anaerobic glycolysis pathway generates ATP and NADH
(reverses Fe3+ (metHb) to Fe2+ (Hb))
How does a red cell prevent oxidative damage to cellular enzymes and Hb from free radicals?
Glutathione protects us from hydrogen peroxide by reacting with it to form water and an oxidised glutathione product (GSSG). This maintains the redox balance
This can be replenished by NADPH which in turn is generated by the hexose monophosphate shunt
How does a red cell buffer CO2 for transport?
Only 10% is dissolved in solution
Around 30% is bound directly to Hb as carbamino-Hb
The other 60% gets there as bicarbonate
At the same pO2, HbF and myoglobin bind more/less O2. Critical part of the curve clinically is ____ (venous) to ____ (arterial) partial pressures. This explains how O2 is transferred to fetus in utero and to muscles
At the same pO2, HbF and myoglobin bind more O2. Critical part of the curve clinically is 5.3 (venous) to 13.3 (arterial) partial pressures. This explains how O2 is transferred to fetus in utero and to muscles
Curve is shifted right by molecules that interact with Hb (_______________). This results in more O2 delivered to tissues
Curve is shifted right by molecules that interact with
Hb (H+, CO2, 2,3 DPG). This results in more O2 delivered to tissues.
Three Linked Pathways to remember
Embden-Myerhof Pathway
Hexose Monophosphate Shunt (or pentose phosphate
pathway)
Rapapoport-Lubering Shunt
Function of Hexose Monophosphate Shunt (or pentose phosphate
pathway)
Generates NADPH -protects against oxidative stress, regenerates glutathione a key protective molecule
Function of Rapapoport-Lubering Shunt
Generates 2,3 DPG that right shifts oxygen disassociation curve and
allows more oxygen to be released
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