Erythropoiesis

Question 1

On average, the body produces _________ red cells per day

Answer 1

2.5 billion red cells/kg/day

Question 2

RBCs gave a lifespan of..

Answer 2

120 days/four months

Question 3

Site of Erythropoiesis in very early foetus

Answer 3

In the yolk sac
From 2 – 5 months gestation, in liver and spleen before finally establishing in the bone marrow from 5 months

Question 4

Site of Erythropoiesis in children

Answer 4

In the bone marrow of most bones

Question 5

Site of Erythropoiesis in adults

Answer 5

Vertebrae, ribs, sternum, sacrum, pelvis and proximal femur

Question 6

When erythropoiesis is inadequate in the bone marrow, this can trigger…

Answer 6

Extramedullary haematopoiesis

Question 7

Extramedullary haematopoiesis is commonly seen in..

Answer 7

Haemoglobinopathies such as thalassaemias and myelofibrosis

Question 8

The production of all blood cells begins with the ___________, a multipotent haematopoietic stem cell

Answer 8

Haemocytoblast

Question 9

What do Haemocytoblasts differentiate into?

Answer 9

Common myeloid progenitor cells

Question 10

Outline the several stages by which common myeloid progenitor cells become fully mature red blood cells?

Answer 10

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)

Question 11

Nucleated red blood cells occur in which conditions?

Answer 11

Thalassaemia, severe anaemia or haematological malignancy

Question 12

Erythropoiesis is driven mainly by the hormone ________, which is a __________ cytokine

Answer 12

Erythropoiesis is driven mainly by the hormone erythropoietin (EPO), which is a glycoprotein cytokine

Question 13

EPO is secreted by the _________

Answer 13

Kidney

Question 14

When there is a reduced partial pressure of oxygen (pO2) in the kidney, this is detected by the..

Answer 14

Renal interstitial peritubular cells

Question 15

__________ can be used as a performance-enhancing drug among athletes

Answer 15

Exogenous EPO - improve the oxygen supply to muscles

Question 16

Define anaemia

Answer 16

Low haemoglobin concentration

Question 17

Anaemia can be caused by..

Answer 17

Decreased red cell production, or increased red cell removal.

Question 18

Reduced red cell production may be due to 3 main things..

Answer 18

• 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

Question 19

Overproduction of red blood cells can occur in conditions such as..

Answer 19

Polycythaemia rubra vera

Question 20

What is Polycythaemia rubra vera?

Answer 20

Myeloproliferative disease which results from dysregulation at the level of the haematopoietic stem cell - JAK-2 mutation

Question 21

Red destruction occurs in the..

Answer 21

Spleen and liver

Question 22

Aged red cells taken up by..

Answer 22

Macrophages and recycled

Globin chains: amino acids
Heme: iron & bilirubin

Question 23

Which two structures are NOT present in RBCs?

Answer 23

Nucleus and mitochondria

Question 24

What is a consequence of RBCs not having a nucleus or mitochondria

Answer 24

No nucleus: Can’t divide, can’t replace damaged proteins - limited cell lifespan

No mitochondria: Limited to glycolysis for energy generation (no Krebs’ cycle)

Question 25

What is a consequence of RBCs having a high surface area/volume ratio?

Answer 25

Need to keep water out

Question 26

What is a consequence of RBCs being flexible?

Answer 26

Specialised membrane required that can go wrong

Question 27

Why do RBCs need energy?

Answer 27

To maintain specific ion concentrations gradient and keep water out

Question 28

What is the structure of HG?

Answer 28

A tetrameric globular protein

Question 29

HbA has 2 _______ chains and 2 _______ chains. Heme group is _______ in a flat porphyrin ring. One heme per subgroup

Answer 29

HbA has 2 alpha and 2 beta chains. Heme group is Fe2+ in a flat porphyrin ring. One heme per subgroup

Question 30

One oxygen molecule binds to one..

Answer 30

Fe2+

Question 31

Functions of HBa

Answer 31

Deliver oxygen to the tissues Act as a buffer for H+ CO2 transport

Question 32

Red cell destruction (recap)

Answer 32

Question 33

How does a red cell keep generating ATP and prevent Fe2+ from becoming Fe3+?

Answer 33

Anaerobic glycolysis pathway generates ATP and NADH (reverses Fe3+ (metHb) to Fe2+ (Hb))

Question 34

How does a red cell prevent oxidative damage to cellular enzymes and Hb from free radicals?

Answer 34

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

Question 35

How does a red cell buffer CO2 for transport?

Answer 35

Only 10% is dissolved in solution Around 30% is bound directly to Hb as carbamino-Hb The other 60% gets there as bicarbonate

Question 36

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

Answer 36

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

Question 37

Curve is shifted right by molecules that interact with Hb (_______________). This results in more O2 delivered to tissues

Answer 37

Curve is shifted right by molecules that interact with Hb (H+, CO2, 2,3 DPG). This results in more O2 delivered to tissues.

Question 38

Three Linked Pathways to remember

Answer 38

Embden-Myerhof Pathway Hexose Monophosphate Shunt (or pentose phosphate pathway) Rapapoport-Lubering Shunt

Question 39

Function of Hexose Monophosphate Shunt (or pentose phosphate pathway)

Answer 39

Generates NADPH -protects against oxidative stress, regenerates glutathione a key protective molecule

Question 40

Function of Rapapoport-Lubering Shunt

Answer 40

Generates 2,3 DPG that right shifts oxygen disassociation curve and allows more oxygen to be released

Question 41

Revision card

Answer 41