Physiology Flashcards
what is haemopoiesis?
the production of blood cells
- Derived from a relatively small pool of pluripotent stem cells capable of making all the different types of blood cells
where does haemopoiesis happen?
In adults mostly the bone marrow of axial skeleton
- Embryo – Yolk sac then liver then marrow, 3rd to 7th month – spleen
- At Birth – Mostly bone marrow, liver and spleen when needed
- Birth to maturity – number of actives sites in bone marrow decreases but retain ability for haematopoiesis
- Adult – not all bones contain bone marrow, haematopoiesis restricted to skull, ribs sternum, pelvis, proximal ends of femur (the axial skeleton)
what happens the more cells divide in haemopoiesis?
the more divisions the smaller the cells especially red cells
what is a megakaryocyte
Platelets make one megakaryocyte – a huge soup of many platelet nuclei and cytoplasms
properties of red cells
- Full of haemoglobin
- No nucleus
- Can’t divide or repair
- Limited lifespan
- No mitochondria
- High Surface area/volume ratio to allow for gas exchange – need to keep water out
- Flexible to squeeze through capillaries
- Specialized membrane required that can go wrong
how red cells keep water out
through maintaining specific ion concentration gradients with the sodium potassium pump
This pump allows the ion concentrations to be kept right and the systems in the cell to keep working
Keeps water out
Needs ATP (energy)
haemoglobin structure
deliver oxygen to the tissues, act as a buffer or H+, CO2 transport
o Tetrameric globular protein
o HbA(adults) – 2 alpha and 2 beta chains
o Haem group is Fe2+ in a flat porphyrin ring
o 1 haem per subgroup
o 1 O2 molecule binds to 1 Fe2+ (oxygen doesn’t bind to Fe3+)
end of a red cell lifespan
average lifespan 120 days occurs in spleen (& liver) aged RBC taken up by macrophages (out of circulation) RBC contents recycled globin chains - amino acids haem group - iron and bilirubin bilirubin taken to liver and conjugated bilirubin then excreted in bile (colours faeces and urine)
what regulates RBC production?
red cell production is regulated by erythropoietin
• Hypoxia sensed by kidney – erythropoietin produced – erythropoietin stimulates red cell production in bone marrow, erythropoietin levels drop – hypoxia sensed by kidney and so on
what is the metabolic pathway within RBC
glycolysis because no mitochondria
- this makes free radicals which inhibit oxygen transport
- GSH (glutathione) maintains redox balance
- The rate limiting enzyme in this process is glucose-6-phosphate dehydrogenase (G6PD)
- the hexose monophosphate shunt Generates NADPH that maintains GSH levels preventing oxidative damage limited by G6PD activity
carbon dioxide transport
o 10% dissolved in solution
o 30% is bound directly to Hb as carbamino-Hb
o Other 60% gets there as bicarbonate and red cell has an important role in generating that bicarbonate
what allosteric effectors affect O2 binding?
dissociation curve for haemoglobin is sigmoidal
1st O2 binds to haem in one subunit the Hb shape changes so it is easier for further O2 to bind
• A lot of oxygen is released in hypoxic environments so the haemoglobin system works
• Fetal Hb (a2g2) saturates more at the same pO2 so effectively takes O2 from the maternal circulation.
• In muscles the monomeric myoglobin (which otherwise is a similar structure to Hb) takes O2 from red cells and has different kinetics
things which affect O2 dissociation
o Curve is shifted right by molecules that interact with Hb (H+, CO2, 2,3 BPG).
o This results in more O2 delivered to tissues.
o When CO2 and H+ may be increased - good to have more O2 released in these conditions.
o 2,3 BPG (or sometimes called DPG) is increased in chronic anaemia
what is a reticulocyte
red cells which have just left the bone marrow
larger than average red cells
still have RNA remnants
stain purple/deeper red because of RNA
blood film appears ‘polychromatic’
up regulation of reticulocyte production by the bone marrow in response to anaemia takes a few days
iron metabolism
‘closed’ system - only able to absorb a small amount of iron
Tiny amount in circulation moving to/from storage site - principally marrow
Iron turnover in plasma pool is fast (4mg in pool and move 20mg/day)
Circulating iron is bound to transferrin.
It is transferred to the bone marrow macrophages that ‘feed it’ to red cell precursors
Iron is stored in ferritin mainly in the liver
transferrin structure and purpose
- Protein with two binding sites for iron atoms
- Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
-% saturation of transferrin with iron measures iron supply
o reduced in iron deficiency
o reduced in anaemia of chronic disease
o increased in genetic haemachromatosis
life span of neutrophils
7-8 hours
lifespan of platelets
7-10 days
what cell is the most abundant in the blood
red cells
what is a blast
a nucleated precursor cell
what are the 2 types of blasts
erythroblast
myeloblast
megakaryocyte
platelet precursor, polyploid
myelocyte
nucleated precursor between neutrophils and blasts
haemopoietic progenitor cell
precursor of the precursors