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3MB Haematology > Erythropoiesis > Flashcards

Erythropoiesis Flashcards

1
Q

On average, the body produces _________ red cells per day

A

2.5 billion red cells/kg/day

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2
Q

RBCs gave a lifespan of..

A

120 days/four months

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3
Q

Site of Erythropoiesis in very early foetus

A

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

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4
Q

Site of Erythropoiesis in children

A

In the bone marrow of most bones

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5
Q

Site of Erythropoiesis in adults

A

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

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6
Q

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

A

Extramedullary haematopoiesis

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7
Q

Extramedullary haematopoiesis is commonly seen in..

A

Haemoglobinopathies such as thalassaemias and myelofibrosis

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8
Q

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

A

Haemocytoblast

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9
Q

What do Haemocytoblasts differentiate into?

A

Common myeloid progenitor cells

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10
Q

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

A

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)

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11
Q

Nucleated red blood cells occur in which conditions?

A

Thalassaemia, severe anaemia or haematological malignancy

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12
Q

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

A

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

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13
Q

EPO is secreted by the _________

A

Kidney

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14
Q

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

A

Renal interstitial peritubular cells

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15
Q

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

A

Exogenous EPO - improve the oxygen supply to muscles

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16
Q

Define anaemia

A

Low haemoglobin concentration

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17
Q

Anaemia can be caused by..

A

Decreased red cell production, or increased red cell removal.

18
Q

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

A
  • 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
19
Q

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

A

Polycythaemia rubra vera

20
Q

What is Polycythaemia rubra vera?

A

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

21
Q

Red destruction occurs in the..

A

Spleen and liver

22
Q

Aged red cells taken up by..

A

Macrophages and recycled

Globin chains: amino acids
Heme: iron & bilirubin

23
Q

Which two structures are NOT present in RBCs?

A

Nucleus and mitochondria

24
Q

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

A

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

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

25
Q

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

A

Need to
keep water out

26
Q

What is a consequence of RBCs being flexible?

A

Specialised membrane required
that can go wrong

27
Q

Why do RBCs need energy?

A

To maintain specific ion
concentrations gradient and keep water out

28
Q

What is the structure of HG?

A

A tetrameric globular protein

29
Q

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

A

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

30
Q

One oxygen molecule binds to one..

A

Fe2+

31
Q

Functions of HBa

A

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

32
Q

Red cell destruction (recap)

A
33
Q

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

A

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

34
Q

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

A

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

35
Q

How does a red cell buffer CO2 for transport?

A

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

36
Q

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

A

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

37
Q

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

A

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

38
Q

Three Linked Pathways to remember

A

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

39
Q

Function of Hexose Monophosphate Shunt (or pentose phosphate
pathway)

A

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

40
Q

Function of Rapapoport-Lubering Shunt

A

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

41
Q

Revision card

A

3MB Haematology (23 decks)

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