PBL 7 - Haematopoiesis Flashcards

1
Q

what is the buffy coat?

A
  • between plasma and the red of formed elements when centrifuged
  • essentially WBCs and platelets
  • less than 1%
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2
Q

give the overview of haematopoiesis starting with a multi potent stem cell

A
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3
Q

what is haematopoiesis?

A

the process by which blood cells are formed

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4
Q

what is the lifespan of platelets?

A

9-10 days

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5
Q

what is the lifespan of erythrocytes?

A

120 days

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6
Q

what is the lifespan of leucocytes?

A

a few days to a few years:

  • 175 billion new RBCs per day
  • 175 billion new platelets per day
  • 1.1 million new blood cells formed every second!!
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7
Q

where does haematopoiesis take place in foetus?

A

0-2 months = yolk sac — blood islands
2-7 months = liver, spleen
5-9 months = bone marrow = more representative of a living person

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8
Q

where does haematopoiesis occur in an infant?

A

bone marrow — practically all bones

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9
Q

where does haematopoiesis occur in an adult?

A

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

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10
Q

where does extramedullary haematopoiesis occur? what can this show?

A

= outside of bone marrow

  • liver, thymus, spleen
  • signs of this show there is a pathology
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11
Q

where are stem cells located?

A

bone marrow

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12
Q

at brith, what colour is all bone marrow?

A

red

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13
Q

what is red marrow?

A

haematopoietic tissue

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14
Q

what is yellow marrow?

A

fat cells, micro environment — stromal cells and stromal matrix (vital for the haematopoietic process)

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15
Q

what stromal cells are there in yellow marrow and what do they do?

A
  • fibroblasts
  • fat cells
  • endothelial cells
  • reticulum cells
  • macrophages

— express adhesion molecules
— secrete growth factors

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16
Q

what is the stromal matrix in yellow marrow for?

A

physical support for haematopoietic stem cells

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17
Q

stem cells mostly exist in a state known as quiescence. what does this mean?

A

a state of of reversible growth arrest

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18
Q

what happens when a stem cell leaves a state of quiescence? what does this allow?

A
  • begin actively dividing again
  • this allows the movement between states in order to be able to differentiate and proliferate when necessary to ensure we have a stem cell population that is available for production for our different cells
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19
Q

when our cell moves from quiescence and becomes active, what does it proliferate, multiply and differentiate into for a specific lineage?

A

progenitor cells

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20
Q

haematopoietic stem cells are also self-renewing, why is this important?

A

when they differentiate, at least some of their daughter cells can remain as haematopoietic stem cells — pool of stem cells is not depleted — consistent maintenance of our stem cell pool

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21
Q

where do all blood cells originate?

A

bone marrow

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22
Q

all blood cells originate from 1 type of haematopoietic stem cell (HSC), capable of what?

A
  • self renewal — able to proliferate and divide forming an exact copy of the cell
  • differentiating into other blood cell types — cells start to become more specialised for the task and function they have to do
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23
Q

what do lymphoid stem cells give rise to?

A

lymphocytes

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24
Q

what do myeloid stem cells give rise to?

A

all other blood cells than lymphocytes — neutrophils, eosinophils, basophils, monocytes, erythrocytes and platelets (thrombocytes)

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25
Q

what is an MK cell? what do they differentiate into?

A

megakaryocyte — differentiates into platelets

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26
Q

what does __blast indicate?

A

immature cell — should remain in bone marrow and not be seen in circulation

27
Q

what is CFU-GEMM?

A

= colony-forming unit - GEMM
- generates myeloid cells

G = granulocyte 
E = erythrocyte 
M = monocyte
M = Mk cell
28
Q

describe erythropoiesis

A
  1. myeloid stem cell
  2. proerythroblast — most immature committed precursor to the RBC. large cell with cytoplasm that stains dark blue
  3. early erythroblast
  4. late erythroblast
  5. normoblast — smaller cells, cytoplasm starts to stain lighter blue. late normoblast have extruded nucleus — becoming more like a mature RBC
  6. reticulocyte — contains some ribosomal RNA. circulates in peripheral blood (1-2 days)
  7. erythrocyte — endpoint. RNA lost
29
Q

what is the approx duration of erythropoiesis?

A

7 days

30
Q

when is Hb made?

A
  • before organelles are lost

- majority made from proethryoblast up to normoblast

31
Q

where is the haem part of Hb made?

A

in the mitochondria in the cytoplasm

32
Q

where is the globin part of Hb made?

A

ribosomes in the cytoplasm

33
Q

what is thrombopoiesis?

A

how platelets are made

34
Q

what is endomitosis used to make?

A

megakaryoblasts

35
Q

what is endomitosis?

A
  • replication of chromosomes occurs but cells don’t divide

- cells become larger

36
Q

once fully mature, endomitosis ceases resulting in what?

A

granulated cytoplasm

37
Q

how long does thrombopoiesis last?

A

2-3 days

38
Q

each megakaryocyte “fragment” produces how many platelets?

A

roughly 4000

39
Q

what are the steps of thrombopoiesis?

A
  1. blood stem cell
  2. myeloid stem cell
  3. megakaryoblast
  4. pro megakaryocyte
  5. MK
  6. platelets
40
Q

what is monopoiesis?

A

production of monocytes

41
Q

describe the steps of monopoiesis

A
  1. blood stem cell
  2. myeloid stem cell
  3. monoblast
  4. promonocyte
    5.monocyte
    ( 6. macrophage )
42
Q

how long do monocytes stay in circulation for?

A

20-40 days

43
Q

what is the shape of the nucleus of monocytes?

A

kidney shape

44
Q

what is the size of monocytes like?

A

very large — up to 20um

much larger than RBCs and lymphocyte

45
Q

what is granulopoieis?

A

the production of neutrophils, basophils and eosinophils

46
Q

describe a myeloblast

A

varying size, large nucleus, no cytoplasmic granules

47
Q

describe granulopoiesis

A
  1. myeloid stem cell
  2. myeloblast
  3. promyelocytes
  4. (eosinophilic/basophilic/neutrophilic) myelocyte
  5. (eosinophilic/basophilic/neutrophilic) mega-myelocyte
  6. (neutrophil band cell)
  7. eosinophil, neutrophil, basophil
48
Q

describe promyelocytes

A

primary cytoplasmic granules

49
Q

describe myelocytes

A

smaller cells with specific cytoplasmic granules, no noticeable nucleoli

50
Q

describe metamyelocytes

A

indented or horse-shoe nucleus, lots of cytoplasmic granules

51
Q

B lymphocytes differentiation in foetus vs adult

A

foetus - in liver

adult - in bone marrow

52
Q

where are plasma cells formed?

A

lymph nodes

53
Q

describe NK cells

A

large cells with cytoplasmic granules

54
Q

what is the lifespan of NK cells?

A

weeks to years

55
Q

what initiates haematopoiesis?

A

stem cell division

56
Q

what is differentiation of cells regulated by? examples?

A

transcription factors eg/

  • PU.1 — cells are differentiated along the myeloid lineage
  • GATA.1 — differentiates cells along the erythropoietic and megakaryocytic cell lineages
57
Q

what are some growth factors that play a role in haematopoiesis?

A
58
Q

describe erythropoietin (EPO)

A
  • growth factor
  • regulates erythropoiesis
  • reduction in red cell number results in decreased O2 to tissues
  • development of hypoxia in kidneys and liver
  • leads to increased production of RBCs

released when host is:

  • anaemic
  • has declining blood perfusion to the kidneys
  • has low O2 saturation
  • has damaged respiratory surfaces of the lungs
  • this corrects hypoxia and EPO synthesis is turned off

—> stimulates increased cell division rates in erythroblast and stem cells
—> speeds up the maturation of RBCs by accelerating the rate of Hb

59
Q

describe thrombopoietin (TPO)

A
  • mainly produced in liver

- stimulates megakaryocytes and platelet production (THROMBOPOIESIS)

60
Q

describe stem cell factor (SCF)

A

synergies with cytokines such as IL-3 and GM-CSF to increase proliferation of stem cells

61
Q

describe IL-3

A

works in conjunction with GM-CSF to proliferate most haemopoietic progenitor cells

62
Q

describe IL-5

A
  • produced by T cells

- plays a role in growth and differentiation of eosinophils

63
Q

describe 3 wider ranging GFs

A

1) Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
- necessary for growth and development of granulocyte and macrophage progenitor cells
- stimulates myeloblasts and monoblasts

2) Macrophage Colony Stimulating Factor (M-CSF)
- plays a role in proliferation and differentiationof haemopoietic stem cells to produce monocytes and macrophages

3) Granulocyte Colony Stimulating Factor (G-CSF)
- is similar to M-CSF but acts on precursor cells which give rise to granulocytes