biochem of RBCs Flashcards
(28 cards)
sites of hamatopoiesis
Embryo
o Yolk sac then liver then marrow
o 3rd – 7th month -> spleen
At birth - Mostly bone marrow, liver + spleen when needed
Birth to maturity
o Number of actives sites in bone marrow decreases but retain ability for haematopoiesis
Adult
o Not all bones contain bone marrow
o Haematopoiesis restricted to skull, ribs, sternum, pelvis, proximal ends of femur (axial skeleton)
neutrophils
- Most numerous
Structure
- Segmented nucleus (polymorph)
- Neutral staining granules
Function
- Short life in circulation – transit to tissues
- Phagocytose invaders
- Kill with granule contented and die in the process
- Attract other cells using small molecules released
- Increased by body stress – infection, trauma, infarction
eosinophils
Structure
- Usually bi-lobed
- Bright orange/red granules
Function
- Fight parasitic infections
- Involved in hypersensitivity – allergic reactions
- Often elevated in patients with allergic conditions – asthma, atopic rhinitis
- Other functions – immune regulatory
basophils
Structure
- Quite infrequent in circulation
- Large deep purple granules often obscuring nucleus
Function
- Circulating version of tissue mast cell
- Role remains unclear
- Mediates hypersensitivity reactions
- FcReceptors binds IgE
- Granules contain histamine
do monocytes + granulocytes share a common precursor?
yes
monocytes
Structure
- Large single nucleus
- Faintly staining granules, often vacuolated
Function
- Circulate for a week + enter tissues to become macrophages
- Phagocytose invaders
o Kill them
o Present antigen to lymphocytes
- Attract other cells
- Much longer lived than neutrophils
o Means they can access their code/DNA -> cells that can do this have big nuclei
structure + function of red cells
Full of haemoglobin to carry oxygen - High oncotic oxygen rich environment (oxidation risk)
No nucleus makes it more deformable, and more room for Hb molecules - Can’t divide, can’t replace damaged protein – limited cell lifespan
No mitochondria either - Limited to glycolysis for energy generation (no Krebs cycle)
High surface area/volume ratio to allow for gas exchange - Need to keep water out
Flexible to squeeze through capillaries - Specialised membrane require than can go wrong
how do red cells maintain specific ion conc / keep water out?
sodium-potassium pump
- requires ATP
structure of haemoglobin
A tetrameric globular protein
HbA(Adult) has 2 alpha + 2 beta chains
Heme group is Fe2+ in a flat porphyrin ring
- One heme per subgroup
- One oxygen molecule binds to one Fe2+ - oxygen does NOT BIND TO Fe3+
function of haemoglobin
deliver oxygen to tissues
act as a buffer for H+
CO2 transport
red cell production
occurs in bone marrow as a result of proliferation + differentiation of haematopoietic stem cells (HSCs) regulated by erythropoietin
- hypoxia sensed by kidneys which then produces erythropoietin
- this stimulates red cell production
- EPO levels drop
red cell destruction
occurs in spleen (+liver)
aged red cells taken up by macrophages - (taken out of circulation)
red cell contents are recycled
- globin chains recycled to amino acids
- heme group broken down to iron + bilirubin
– bilirubin taken to liver conjugated then excreted in bile
why are red cells so at risk of free radicals + why is this bad
lots of oxygen about - free radicals easily generated
bad
- can oxidise Fe2+ to Fe3+ which doesnt transport oxygen
- free radicals damage proteins - RBCs can’t repair/replce protein (no nucleus)
relevance of embden-myerhof pathway
Anaerobic glycolysis pathway generates ATP + NADH (reverses Fe3+(metHb) to Fe2+(Hb))
NADH acts as electron donor preventing oxidation of Fe2+ to Fe3+ (generates NAD+ in process)
relevance of hexose monophosphate shunt
generates NADPH
- protects against oxidative stress
- regenerates glutathione - a key protective molecule
relevance of rapapoport-lubering shunt
generates 2,3, DPB that right shifts oxygen disassociation curve + allows more oxygen to be released
what is metHb
Hb with Fe3+
-> doesnt carry oxygen
glutathione (GSH)
protects us from free radicals with unpaired electrons (hydrogen peroxide) by reacting with it to form water + an oxidised glutathione product (GSSG)
–> this maintains the redox balance
-> this can be replenished by NADPH which in turn is generated by the hexose monophosphate shunt
what is the rate limiting enzyme in the regeneration of glutathione?
glutathione is regenerated by NADPH which in turn is generated by the hexose monophophate shunt
–> the rate limiting enzyme in this process = G6PD
why is oxygen dissociation curve for Hb graph sigmoidal?
as 1st o2 binds to haem in one subunit the Hb shape changes
- increasing affinity for next o2 to bind to haem in next subunit
cooperative binding -> allosteric effect
how do foetal haemoglobin + myoglobin dissociation curves differ to normal?
FHb - 2alpha2gamma, saturates more at the same pO2 so effectively takes O2 from maternal circulation (1 up form normal)
myoglobin - monomeric myoglobin takes O2 from red cells + has different kinetics (2 up from normal)
why do certain small molecules affect oxygen dissociation curve?
can interact with Hb subunits whihc can alter structure of globin subunit
- can alterposition of haem unit in globin unit + so the ability of oxygen to bind to it
- this in turn can affect the shape of the dissociation curve + so how much o2 is delivered to the tissues at a certain pO2
(2,3 DPG can “get in” between chains + change O2 affinity – so less is bound (ie more is released) at the same pO2)
what shifts the dissociation curve to the left?
- Higher Hb-O2 affinity
- Lower CO2
- Higher pH / decreased H+
- Lower temp
- Decreased 2-3 BPG/DPG
what shifts the dissociation curve to the right?
- By molecules that interact with Hb – H+, CO2, 2,3 BPG
- Result in more O2 being delivered to tissues
- Reduced Hb-O2 affinity
- Higher CO2
- Lower pH / increased H+
- Higher temp
- Increased 2,3 BPG/DPG – (increased also in chronic anaemia)
