2. Haematopoiesis

Question 1

definition of haematopoiesis

Answer 1

the highly controlled production of all mature blood cells in the circulation
to safely supply the appropriate number of mature cells, to adapt to change physiological requirements and to respond rapidly to the changing needs of the body

Question 2

draw the diagram of development of blood cells

Answer 2

multipotent haematopoietic stem cell
common precursor
committed precursors
megakaryocyte (to platelets) , erythrocyte monocyte neutrophil basophil and eosinophil

Question 3

features of haematopoietic stem cell

Answer 3

multipotent: can produce any of the the different mature cell types
can self renew and have lineage choice

Question 4

lineage choice

Answer 4

making mature cells of the right type, the stem cell system ensures we can produce the type of cells we need

Question 5

self renewal

Answer 5

making an identical copy of itself , this stem cell system ensures we have always got cells able to make blood
maintains stem cell pool, increases or decreases stem cell number

Question 6

a stem cell has what two choices

Answer 6

self renewal or differentiation
self renew ie form an identical copy or daughter cell can differentiate and form a mature blood cell so daughter cell can no longer self renew

Question 7

importance of choice in stem cell system

Answer 7

decides the cell fate and we need to control the system
self renewal ensures we don’t run out of stem cells with age but cant form too many or too little
differentiation important for mature cell production but if all cells entered differentiation we would have no stem cells left. lineage committed cells that cant self renew

Question 8

self renewal choice

Answer 8

high rates of self renewal the population increases
if each division produces one identical daughter cell the number is maintained
low rates of self reneal, population reduces
-self renewal rates control stem cell number

Question 9

differentiation choice

Answer 9

to rbcs wbcs and platelets
important for flexibility so stem cells can become committed to different lineages
controlling which lineage allows for selective expansion of one or more mature cell types

Question 10

two ways in which stem cells can lead to cancer

Answer 10

if stem cell mutates and loses control of self renewal this can lead to cancer
or if cells cant mature then primitive forms accumulate (acute leukaemia)

Question 11

what would we neeed to avoid cancer of the stem cells

Answer 11

keep stem cell numbers low so lower risk of mutation and less vulnerability to damage
keep fewer numbers of divisions as damage is more likely during proliferation

Question 12

what is the solution to avoiding cancer

Answer 12

once haematopoietic stem cell is committed to development its committed daughter cells must then make up to 19 cycles of division before a mature blood cell is made
stem cell itself only needs to divide once so relatively few stem cells and stem cell divisions
gives up to 500k mature cells from each stem cell

Question 13

how can you tightly control stem cells

Answer 13

stem cell niche - the cells and proteins surrounding the stem cells
stem cells cant survive out the niche so if stem cell dies lose control of self replication it overcrowds the niche but cant expand as wont survive

Question 14

red blood cell

Answer 14

120 day lifespan
carries o2 from lungs to tissues
large amounts produced which vary according to need

Question 15

when do we get increased production of red blood cells

Answer 15

in bleeding after injury, body must also maintain wbc numbers and replace platelets
high altitudes where less oxygen is available
with disease eg sickle cell disease rbc production can increase for life

Question 16

inherited red cell disorder

Answer 16

defects in Hb production mean rbc don’t survive long enough / don’t contin enough Hb
increased red blood cell production means bone marrow expands to support red blood cell production so we get very large cheeks full of bone marrow

Question 17

what is an issue of too many red blood cells

Answer 17

blood too thick = stroke and thrombosis

Question 18

white blood cells

Answer 18

5-10 day lifespan
fight infection in body, 10 billion made per day
during infection the neutrophil detects and ingests bacteria and is then removd from the circulation. in this case would need to be removed after hours or minutes as bacteria rapidly divide

Question 19

problem with too many and too few white blood cells

Answer 19

too many wbc would lead to damage as wbc behave abnormally and too many neutrophils are present so they attack normal skin
too few leads to infection as body cant protect itseld against bacteria eg those present on skin

Question 20

platelets

Answer 20

small cell fragments that provide a plug which controls initial bleeding after a cut or damage
promotes clotting
survives minutes to days
400b produced daily, rapidly used upin massive injury but if not needed removed from body after two weeks

Question 21

problem with too many and too few platelets

Answer 21

too many means blood is too sticky and platelets then block blood vessels causing death of tissues . affects small capillaries
too few platelets results in severe bleeding after trauma and visible small haemorrhagic spots called petichae where small capillaries leak and aren’t sealed by platelets

Question 22

committed precursor cells

Answer 22

link stem cells to mature cells

a single stem cell entering the committed precursor pool can make up to 20 generations of division and maturation

Question 23

blood cells in bone marrow

Answer 23

initial cells highly proliferative but as process develops to later cells which acquire more functional characteristics to resemble functional cells
cells begin to act like mature cells with fewer numbers of division until fully mature where they can no longer proliferate

Question 24

how are proliferating cells protected from cancers

Answer 24

they cant self renew

Question 25

rates of cell death on proliferative pool and importance

Answer 25

40% ie any single cell has 40% chance of death rather than continuing to divide or mature
controls cell number

Question 26

which has bigger impact, death of early or late cells and why

Answer 26

death of early cells as less cells will then go on to divide, takes longer to affect eventual cell number

Question 27

reducing cell death will

Answer 27

expand mature cell numbers
reducing red cell precursor death ie enhancing survival of progenitors in erythroid lineage increases the probability of erythroid lineage differentiation and this increases rbc output

Question 28

cytokines

Answer 28

small locally active peptide hormones that alter cell death in proliferating cells but also alter mature clel function
eg EPO TPO and G-CSF

Question 29

erythropoietin

Answer 29

EPO enhances the survival of red cell erythroid precursors in the proliferating cell pool
increases maturation rate to expand number of rbc
can also increase the total numbers of divisions made (one more division doubles no of cells formed)

Question 30

how is erythropoietin controlled

Answer 30

oxygen level is sensed in the kidney
if O2 levels drop due to blood loss altitude or disease EPO secretion is increased to make more rbc
when o2 level sufficient epo secretion decreased

Question 31

granulocyte colony stimulating factor G-CSF

Answer 31

ensures baseline number of wbc to protect the body but also respond rapidly to infection with no upper limit
acts mainly on late granulocyte precursors by increasing their survival and the maturation rate & granule formation to massively increase output and function

Question 32

how does GCSF alter the function of neutrophils

Answer 32

by making them better able to fight infection by increasing their mobility, the number of granules they contain and their ability to stick to bacteria

Question 33

how is G-CSF controlled

Answer 33

body senses infection/ inflammation, amount of gcsf produced greatly increased and body releases G-CSF. neutrophils immediately mass produced until infection ends
a baseline production of G-CSF keeps a low level of neutrophil production to provide first line of defence against bacteria

Question 34

thrombopoietin TPO

Answer 34

control platelet production by sensing platelet number
ensures always enough platelets to prevent haemorrhage
acts mainly on megakaryocyte precursors within the proliferating pool to increase number and rate of maturation

Question 35

how is TPO controlled

Answer 35

TPO is produced in fairly constant amounts, but can be produced in response to inflammation like GCSF
control is achieved because mature platelets bind to TPO and destroy it, so if platelet levels too high the level of TPO is reduced
if platelet numbers are reduced then TPO level rises to stimulate production

Question 36

long term control

Answer 36

haematopoietic stem cell provide a self renewing supply of blood cell precursors
varying stem ell number can change the supply of blood cells, but takes a long time to result in mature cells

Question 37

short term control

Answer 37

the proliferating pool allows each stem cell to form many daughter cells
built in high death rates of cells in proliferating pool means that by altering survival of these cells the number of mature cells of different types can be rapidly increased or reduced