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Introduction to Haematology > Introduction to Haemopoiesis > Flashcards

Introduction to Haemopoiesis Flashcards

1
Q

what is haemopoiesis

A

blood cell formation. refers to the origin and development of blood cells. All cells of the blood originate from multipotent stem cells in the bone marrow- haematopoietic stem cells.

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2
Q

how many blood cells does a healthy individual make each day?

A

~4.5x10^11 blood cells

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3
Q

what is the daily production of RBCs, WBCs and platelets?

A

~2x10^11 RBCs
~1x10^11 WBCs
~1 x 10^11 platelets

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4
Q

can we increase production of cells rapidly and efficiently when necessary?

A

yes

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5
Q

formation of RBCs

A

erythropoiesis

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6
Q

formation of WBCs

A

myelopoiesis

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7
Q

formation of platelets

A

thrombopoiesis

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8
Q

stem cells are undifferentiated cells that have 2 unique features, what are the 2 unique features?

A

capacity for self-renewal
ability to differentiate into a variety of mature cell types

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9
Q

what is the hierarchy of stem cells?

A

totipotent cells - > pluripotent cells -> blood stem cells and other stem cells

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10
Q

what are totipotent cells?

A

capable of dividing and developing to form a complete, mature organism

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11
Q

what are pluripotent cells?

A

capable of developing into many different cell types

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12
Q

what potency do blood stem cells have?

A

multipotent stem cells

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13
Q

where do all blood cells come from?

A

haematopoietic stem cells (HSCs)

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14
Q

how many HSC are in bone marrow

A

~1 in every 20 million nucleated cell in bone marrow is a HSC

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15
Q

what potency does a HSC have?

A

multipotent stem cell

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16
Q

CD34+, CD38-, LIN-

A

appearance of a small to medium size lymphocyte

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17
Q

what are the sites of haemopoiesis in a foetus?

A

0-2 months yolk sac/(aorta-gonads-mesonephros (AGM))
2-7 months liver and spleen
5-9 months bone marrow

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18
Q

what is the site of haemopoiesis in an infant

A

bone marrow - practically all bones)

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19
Q

what is the site of haemopoiesis in adults?

A

vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal ends of femur

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20
Q

where does the 1st wave of haemopoiesis pccur and what happens?

A

embryo
occurs in yolk sac
produces primitive erythroid cells (EryP) as well as macrophages

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21
Q

where does definitive erythropoiesis begin in the embryo? 2nd wave of haemopoiesis in embryo

A

it begins with the formation of self-renewing haemopoietuc sremm cells in aorta-gonad-mesonephros (AGM)
within the dorsal aorta you can detect CD34+ HSCs
ability to make a wider range of haematopoietic stem cells including lymphocytes
hb variants are Gower 1, Gower 2 and Portland

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22
Q

where does the foetal stage of haemopoiesis take place and what happens?

A

the liver is the primary site of blood cell production
Yolk sac and AGM cease their role
Hb F replaces Hb variants

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23
Q

what happens to haemopoiesis at 6 months gestation?

A

the BM becomes the primary site of gestation

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24
Q

which production of cells moves to BM 1st in foetus?

A

granulocytic and megakaryocytic production shifts to BM 1st, followed by erythoropoiesis

25
Q

what are the major sites of adult haemopoiesis?

A

the sternum, femur and pelvis

26
Q

what are minor sites of adult haemopoiesis?

A

ribs, skull and sacrum

27
Q

haemopoiesis occurring in the BM is called?

A

intramedullary haemopoiesis

28
Q

what is extrinsic control of haemopoiesis?

A

cell to cell interactions, extracellular matrix, environmental regulators such as cytokines

29
Q

what is intrinsic control of haemopoiesis?

A

genetic events, transcription factors, stage-specific cell cycle regulation

30
Q

what plays a pivotal role in the extrinsic regulation of haemopoiesis?

A

the BM microenvironment , <50% of the intertrabecular tissue is haemopoietic tissue

31
Q

what cells are the major source of growth factors in extrinsic regulation of haemopoiesis?

A

stromal cells

32
Q

how do stromal cells work in the extrinsic regulation of haemopoiesis?

A

stromal cells are the major source of growth factors, adipocytes, fibroblasts, endothelial cells and macrophages, secrete extracellular matrix molecules such as collagen and fibronectin and secrete a number of growth factors that are necessary for stem cell survival.

33
Q

what happens to haemopoiesis during disease?

A

the fatty bone marrow is capable of reversion to haemopoiesis and in many cases there is also expansion of haemopoiesis down the long bones. The liver and spleen are also capable of resuming their foetal haemopoietic activity known as extramedullary haemopoiesis.

34
Q

what is erythopoiesis?

A

the production of red blood cells

35
Q

how many erythrocytes do adult humans produce?

A

2.3 million erythrocytes every second, or 138 million every minute. 10^12 new erythrocytes each day.

36
Q

what is the lifespan of an erythrocyte?

A

120 days

37
Q

what does the balance between RBC production and destruction depend on?

A

hormonal controls
adequate supplies of iron, amino acids and B vitamins

38
Q

what is erythropoietin (EPO)

A

the essential erythroid-specific growth factor

39
Q

what is the 1st recognisable precursor?

A

pronormoblast

40
Q

hb increases

A

as RBCs develop

41
Q

what is the order of erythropoiesis?

A

HSC->erythroblast (committed cell)-> developmental pathway: phase 1 ribosome synthesis -> phase 2 hb accumulation -> phase 3 ejection of nucleus -> reticulocyte -> erythrocyte

42
Q

properties of erythocytes?

A

still contain some ribosomal RNA
sit in the BM for 1-2 days
matures for 1-2 days in the peripheral blood when RNA is lost completely
reticulocyte count indicates the rate of RBC formation

43
Q

properties of normoblast, reticulocyte and mature RBC?

A

nuclear DNA - Normoblast Y. Reticulocyte N. Mature RBC N.

RNA in cytoplasm- Normoblast Y. Reticulocyte Y. Mature RBC N.

in marrow - Normoblast Y. Reticulocyte Y. Mature RBC Y.

in blood=- Normoblast N. Reticulocyte Y. Mature RBC Y.

Y=Yes, N=No

44
Q

which cell in development pathway -erythropoiesis has higher hb conc?

A

RBC

45
Q

what stimulates EPO?

A

hypoxia (inadequate o2 delivery) due to decreased RBC count.
Decreased amount of Hb - decreased availability of o2.

46
Q

what is thrombopoiesis?

A

the production of platelets

47
Q

what is the function of platelets?

A

essential to repair the minute vascular damage that occurs with daily life
initiate thrombus formation in the event of overt vascular injury

48
Q

what is a megakaryocyte?

A

a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes) which are necessary for normal clotting

49
Q

how are megakaryocytes formed?

A

CFU-Meg, this is a unique process called endomitotic replication

50
Q

what is endomitotic replication?

A

where DNA replication and cytoplasmic expansion occur but not cell division. therefore cells can be polyploid up to 64N DNA content

51
Q

what is essential for platelet production?

A

thrombopoietin (TPO)

52
Q

what do developing megakaryocytes undergo prior to cytoplasmic development

A

nuclear maturation (plodization)

53
Q

at what ploidy level can megakaryocytes undergo cytoplasmic maturation and platelet production?

A

any ploidy level >8N

54
Q

where are platelets 1st released?

A

between the endothelial cells of the marrow sinuses as proplatelets

55
Q

what happens to proplatelets?

A

they break into mature platelets and are released into the peripheral blood.

56
Q

how many platelets can each megakaryocyte produce?

A

1000-3000

57
Q

what does thrombopoietin (TPO) do?

A

influences all stages of megakaryocyte production
TPO stimulates megakaryocyte survival and proliferation

58
Q
A

Introduction to Haematology (10 decks)

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