2. Haematopoiesis Flashcards
definition of haematopoiesis
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
draw the diagram of development of blood cells
multipotent haematopoietic stem cell
common precursor
committed precursors
megakaryocyte (to platelets) , erythrocyte monocyte neutrophil basophil and eosinophil
features of haematopoietic stem cell
multipotent: can produce any of the the different mature cell types
can self renew and have lineage choice
lineage choice
making mature cells of the right type, the stem cell system ensures we can produce the type of cells we need
self renewal
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
a stem cell has what two choices
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
importance of choice in stem cell system
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
self renewal choice
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
differentiation choice
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
two ways in which stem cells can lead to cancer
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)
what would we neeed to avoid cancer of the stem cells
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
what is the solution to avoiding cancer
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
how can you tightly control stem cells
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
red blood cell
120 day lifespan
carries o2 from lungs to tissues
large amounts produced which vary according to need
when do we get increased production of red blood cells
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
inherited red cell disorder
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
what is an issue of too many red blood cells
blood too thick = stroke and thrombosis
white blood cells
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
problem with too many and too few white blood cells
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
platelets
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
problem with too many and too few platelets
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
committed precursor cells
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
blood cells in bone marrow
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
how are proliferating cells protected from cancers
they cant self renew
rates of cell death on proliferative pool and importance
40% ie any single cell has 40% chance of death rather than continuing to divide or mature
controls cell number
which has bigger impact, death of early or late cells and why
death of early cells as less cells will then go on to divide, takes longer to affect eventual cell number
reducing cell death will
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
cytokines
small locally active peptide hormones that alter cell death in proliferating cells but also alter mature clel function
eg EPO TPO and G-CSF
erythropoietin
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)
how is erythropoietin controlled
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
granulocyte colony stimulating factor G-CSF
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
how does GCSF alter the function of neutrophils
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
how is G-CSF controlled
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
thrombopoietin TPO
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
how is TPO controlled
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
long term control
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
short term control
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
