PBL 7 - Haematopoiesis

Question 1

what is the buffy coat?

Answer 1

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

Question 2

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

Answer 2

Question 3

what is haematopoiesis?

Answer 3

the process by which blood cells are formed

Question 4

what is the lifespan of platelets?

Answer 4

9-10 days

Question 5

what is the lifespan of erythrocytes?

Answer 5

120 days

Question 6

what is the lifespan of leucocytes?

Answer 6

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!!

Question 7

where does haematopoiesis take place in foetus?

Answer 7

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

Question 8

where does haematopoiesis occur in an infant?

Answer 8

bone marrow — practically all bones

Question 9

where does haematopoiesis occur in an adult?

Answer 9

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

Question 10

where does extramedullary haematopoiesis occur? what can this show?

Answer 10

= outside of bone marrow

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

Question 11

where are stem cells located?

Answer 11

bone marrow

Question 12

at brith, what colour is all bone marrow?

Answer 12

red

Question 13

what is red marrow?

Answer 13

haematopoietic tissue

Question 14

what is yellow marrow?

Answer 14

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

Question 15

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

Answer 15

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

— express adhesion molecules
— secrete growth factors

Question 16

what is the stromal matrix in yellow marrow for?

Answer 16

physical support for haematopoietic stem cells

Question 17

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

Answer 17

a state of of reversible growth arrest

Question 18

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

Answer 18

• 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

Question 19

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

Answer 19

progenitor cells

Question 20

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

Answer 20

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

Question 21

where do all blood cells originate?

Answer 21

bone marrow

Question 22

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

Answer 22

• 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

Question 23

what do lymphoid stem cells give rise to?

Answer 23

lymphocytes

Question 24

what do myeloid stem cells give rise to?

Answer 24

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

Question 25

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

Answer 25

megakaryocyte — differentiates into platelets

Question 26

what does __blast indicate?

Answer 26

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

Question 27

what is CFU-GEMM?

Answer 27

= colony-forming unit - GEMM - generates myeloid cells ``` G = granulocyte E = erythrocyte M = monocyte M = Mk cell ```

Question 28

describe erythropoiesis

Answer 28

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

Question 29

what is the approx duration of erythropoiesis?

Answer 29

7 days

Question 30

when is Hb made?

Answer 30

- before organelles are lost | - majority made from proethryoblast up to normoblast

Question 31

where is the haem part of Hb made?

Answer 31

in the mitochondria in the cytoplasm

Question 32

where is the globin part of Hb made?

Answer 32

ribosomes in the cytoplasm

Question 33

what is thrombopoiesis?

Answer 33

how platelets are made

Question 34

what is endomitosis used to make?

Answer 34

megakaryoblasts

Question 35

what is endomitosis?

Answer 35

- replication of chromosomes occurs but cells don’t divide | - cells become larger

Question 36

once fully mature, endomitosis ceases resulting in what?

Answer 36

granulated cytoplasm

Question 37

how long does thrombopoiesis last?

Answer 37

2-3 days

Question 38

each megakaryocyte “fragment” produces how many platelets?

Answer 38

roughly 4000

Question 39

what are the steps of thrombopoiesis?

Answer 39

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

Question 40

what is monopoiesis?

Answer 40

production of monocytes

Question 41

describe the steps of monopoiesis

Answer 41

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

Question 42

how long do monocytes stay in circulation for?

Answer 42

20-40 days

Question 43

what is the shape of the nucleus of monocytes?

Answer 43

kidney shape

Question 44

what is the size of monocytes like?

Answer 44

very large — up to 20um | much larger than RBCs and lymphocyte

Question 45

what is granulopoieis?

Answer 45

the production of neutrophils, basophils and eosinophils

Question 46

describe a myeloblast

Answer 46

varying size, large nucleus, no cytoplasmic granules

Question 47

describe granulopoiesis

Answer 47

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

Question 48

describe promyelocytes

Answer 48

primary cytoplasmic granules

Question 49

describe myelocytes

Answer 49

smaller cells with specific cytoplasmic granules, no noticeable nucleoli

Question 50

describe metamyelocytes

Answer 50

indented or horse-shoe nucleus, lots of cytoplasmic granules

Question 51

B lymphocytes differentiation in foetus vs adult

Answer 51

foetus - in liver | adult - in bone marrow

Question 52

where are plasma cells formed?

Answer 52

lymph nodes

Question 53

describe NK cells

Answer 53

large cells with cytoplasmic granules

Question 54

what is the lifespan of NK cells?

Answer 54

weeks to years

Question 55

what initiates haematopoiesis?

Answer 55

stem cell division

Question 56

what is differentiation of cells regulated by? examples?

Answer 56

transcription factors eg/ - PU.1 — cells are differentiated along the myeloid lineage - GATA.1 — differentiates cells along the erythropoietic and megakaryocytic cell lineages

Question 57

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

Answer 57

Question 58

describe erythropoietin (EPO)

Answer 58

- 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

Question 59

describe thrombopoietin (TPO)

Answer 59

- mainly produced in liver | - stimulates megakaryocytes and platelet production (THROMBOPOIESIS)

Question 60

describe stem cell factor (SCF)

Answer 60

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

Question 61

describe IL-3

Answer 61

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

Question 62

describe IL-5

Answer 62

- produced by T cells | - plays a role in growth and differentiation of eosinophils

Question 63

describe 3 wider ranging GFs

Answer 63

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