Lecture 1 - Haemopoeisis Flashcards
Haematopoiesis
Ensures the appropriate cell types in the appropriate numbers when needed
RBCs: vertical and horizontal interactions
Vertical interactions - anchoring proteins
Horizontal interactions - proteins located just under the membrane, interacting with and cross-linking anchoring proteins
What shape do RBCs take when travelling through vessels?
Torpedo shape, more efficient for vessel travel, no round shape bouncing around
Strengths for the RBC adaptations
Efficient and stable - maximises oxygen transport
Lots of space - more haemoglobin
Unattractive to infecting organisms (no DNA, mitochondria, ribosomes etc.)
Weaknesses of the RBC adaptations
No protein synthesis
No ATP/reducing power can be produced
RBC slicing damage repair: why is it required, what may cause it, and what is the process behind it?
If a RBC gets damaged, haemoglobin (an extremely toxic and oxidative substance) pours into the bloodstream
Cuts from fibrin … smtn sepsis (rewatch leccy)
The cytoskeleton will repair by sealing the cell, using the vacuole when necessary
RBC membrane damage repair: why is it required, what may cause it, and what is the process behind it?
The membrane loses parts as damage occurs, increasing the risk of internal contents leaking
Heat, antibody, pH, etc…
The cell shrinks as membrane parts diffuse
RBCs: how many, what lifespan, and how many are produced per day?
20-30 trillion in the body
Lifespan up to 120 days
Produce 4000 million per day on average – can vary greatly
WBCs
Fight infection in the body
Survive around 5-10 days on average, but may be much less during infection
Make 10,000 million per day
Platelets: what are they, how long do they survive, and how many are produced per day?
Small cell fragments that promote clotting
Survive minutes to days
Produce 400,000 million/day
petechiae
Caused by low platelet quantity - capillaries not sealed by platelets, blood leaks
Cytokines
Small peptide hormones that affect haemoptysis
Acute leukaemia
a stem cell mutation leads to cells failing to mature and increasing their number through uncontrolled self-renewal
Stem cell niche
Environment of cytokines, adhesive proteins, and stromal cells
Stem cells struggle to survive outside of this niche - acts as a way to prevent cancer
With around 19-20 generations of division one stem cell produces up to half a million mature cells
Proliferating cells summary
Proliferating cells have many cycles of replication before they mature – this allows a huge number to be formed from a single stem cell
Proliferating cells cannot self-renew so the system is protected from forming cancers
Many proliferating cells die – this allows number to be controlled by reducing death rate
The cell types formed may be directed by reducing death selectively.
Erythropoietin
Ensures red cell number is sufficient for oxygen delivery to tissues
Secretion controlled by blood oxygen in the kidney - too low, +EPO, high enough, -EPO
Granulocyte colony stimulation factor
Ensures that the neutrophil number and function are sufficient to fight infection without overproduction
Acting mainly on late granulocyte precursors it enhances the survival of the precursors and increases maturation rate and granule formation to increase output and function massively
It is produced when the body detects infection or inflammation: G-CSF is released by endothelial cells causing increased neutrophil formation release and infection
Thrombopoietin
Increases platelet production
To ensure that there are always enough platelets to prevent haemorrhage
Acting mainly on megakaryocytes it enhances the survival of megakaryocyte precursors within the proliferating pool to increase number and rate of maturation
Like G-CSF it can be produced in response to inflammation, but mainly the Tpo is produced in fairly constant amounts by the liver – control is achieved because mature platelets are able bind the Tpo and destroy it. This means if platelet numbers are high the level of Tpo is reduced, but if platelet numbers are reduced e.g. after bleeding, the Tpo level rises to stimulate production!
Importance of cell death
the ability to respond rapidly to increase cell production depends on cell death
Under normal circumstances, up to 40% of cells produced in bone marrow spontaneously die
This may seem really wasteful, but it is in fact crucial to the whole system of blood cell production - Cell death provides us with the flexibility to adapt to sudden change in need
