Erythrocytes Flashcards
Blood gas transport
Haemoglobin binds O2 in lungs (where PO2 is high) and unbinds it in tissues (where PO2 is low)
Hb moves CO2 in opposite direction
Cooperativity and chemical allosteric effects more O2 is bound in lungs and is deposited in tissues
Oxygen
Poorly soluble in plasma – normal arterial blood carries 70X more O2 on Haemoglobin (Hb in RBCs) than dissolved directly in plasma
Hb is needed to carry O2
Thus, it is possible for arterial PO2 to be normal but hypoxia to occur (b/c there is no Hb to carry O2)
Why you need O2:
Oxidative Respiration Produces More Energy
Oxygen delivery to tissues by Hb
Hb must bind O2 (to carry it to tissues)
Hb must ALSO RELEASE the O2
Binding of O2 to Hb must be weak enough to be reversible
There need to be mechanisms at the muscles for reducing O2 affinity
Haemoglobin
95% of dry weight of RBC
Each subunit has a small haem group (616 Da) + a large globin peptide (17,000 Da)
Haem is coloured, contains one Iron atom, and is site of O2 binding
picks up oxygen in lungs and releases it in tissues
haemoglobin has allosteric properties:
cooperativity
Haem group
Haem is a porphyrin ring
They are rigid, 2 dimensional, and highly coloured due to sharing of electrons
Hence red and blue colour
Not due to Iron
conjugated to iron ion
Ferrous (Fe2+)
Porphyrins
Naturally occurring heterocyclic compounds similar to this structure.
HbA vs HbF
Healthy Adults (HbA) 2 alpha subunits + 2 beta subunits (4 subunits = tetramer) Also called “maternal Haemoglobin”
Foetal Haemoglobin (HbF)
2 alpha subunits + 2 gamma subunits
Adults have a small percentage of HbF
Binds O2 more strongly than HbA
CO2 & H+ affect O2 binding to Hb
the “Bohr effect” †
Increase blood carbon dioxide level —> affinity of Hb for O2
Decrease blood pH —> affinity of Hb for O2
b/c of carbonic anhydrase rxn
Increase blood carbon dioxide level —> decrease blood pH
CO2 & H+ bind Hb but at a different site from O2
CO2 transport in blood
A) 10% as dissolved, B) 22% as carbamino, C) 68% as HCO3-
Curve shapes: myoglobin and haemoglobin
Myoglobin curve is hyperbolic in shape, whilst haemoglobin curve is sigmoidal (ie “S-shaped”)
Adult Haemoglobin curve (green) is S shaped.
This is b/c of cooperativity
Myoglobin curve (red) is exponential; not S shaped
Regulation of oxygen affinity
CO2 -> rightward shift (R)
H+ -> rightward shift
Cl- -> rightward shift
2,3-DPG -> R
Diphospho-glycerate
Bis-phospho-glycerate
Muscle activity encourages Hb to release O2
R (rightward shift) affinity for O2
2,3-DPG
2,3 diphosphoglycerate
- OR 2,3 bis phosphoglycerate,
Binds to Hb
Lowers affinity of Hb for O2
2,3-DPG found in erythrocytes at 5 mM
Increase 2,3-DPG —> decrease affinity for O2
Breathing Controlled by O2, CO2, H+
Plasma O2 must drop precipitously before respiratory drive increases
Main driver to increase respiratory rate: H+ in CSF
Not H+ in blood
H+ in the blood is slow to get into the CSF, but
CO2 gas can get into the CSF, and
once CO2 is in CSF, it makes carbonic acid & H+
The response to CO2 is > the response to H+
because blood H+ is only based on signal from carotid arch.
Medullary receptors
sample from the interstitial and CSF fluid.
Erythrocytes
Red blood cells (RBCs)
“definitive” = mature
Biconcave disc
Anucleate, lack organelles
7 um diam, 2 um height
Contain haemoglobin
Red when oxygenated
Out of body O2
Survive ~120 days
Very flexible – fold and stack in blood vessels
Erythropoiesis: Locations
Erythropoiesis = development/production of RBCs
After birth: bone marrow only
After age 20: membranous bones only (e.g. vertebrae)
During embryogenesis: Liver Spleen Lymph nodes Yolk sac
Haematopoiesis = Haemopoiesis = devel blood cells
