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Red blood cells

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Red blood cells

Claudia Cheng

Updated in August 2006


1. Oxygen carriage – RBC help uptake, transport oxygen from the lungs and release oxygen to the tissues. This is made possible by the following mechanisms:-

  • Haemoglobin
    • Hb is synthesize in the RBC
    • Hb allows transportation of much greater amounts of oxygen than if oxygen were to be dissolved in plasma alone. 1 molecule of Hb can carry 4 molecules O2. At atmospheric pressure, 98% of O2 in blood is carried by Hb
    • Hb-Adair effect – positive cooperativity whereby reaction of the 4 subunits of Hb and O2 occur sequentially, each facilitating the next so that the 4th unit reaction is the fastest despite less binding areas for O2
    • Hb has high affinity for oxygen – modifying factors include Bohr effect (increased in H+, temperature and pCO2.) and 2,3-DPG will increase release of O2. in the tissues
    • Relationship of pO2 and % saturation of HbO2 is sigmoid-shape and the p50 (usual is 26 mmHg) can be used to define the position of the curve, moving it to the left or right on oxygen-dissociation curve: p50 is the pO2 at which the blood is 50% saturated with oxygen
    • RBC needed in O2 transport rather than Hb alone as free Hb can be toxic: free Hb will increase the plasma osmolality, globin chains can blocked renal tubules and cause renal failure
  • RBC shape
    • Biconcave disc that allows a large surface area relative to its volume. This promotes gaseous diffusion into cell
    • Flexibility – able to squeeze into the capillaries to allow oxygen delivery to the tissues
  • 2,3-diphosphoglycerate (DPG) synthesis from RBC
    • Allows Hb to unload O2  by reducing affinitry of Hb for O2
    • 2,3-DPG is synthesize from the Rapaport-Luebering shunt


2. CO2 removal

  • In the tissue capillaries, oxyHb releases O2 and becomes deoxyHb
  • DeoxyHb is a better buffer than oxyHb as it dissociates more
  • DeoxyHb then helps remove the CO2 and H+ that is produced in the tissues with the help of carbonic anhydrase
  • H+ is taken up by the  deoxyHb and CO2 can enter venous blood
  • As a result, venous blood is only slightly acidic than arterial blood despite large amounts of CO2 being produced/day. This process is referred to as  “isohydric buffering”
  • 30% or CO2 is carried in venous blood as carbamino-Hb compounds in the RBC
  • Carbamino compounds are formed by CO2 and carbonic acid combine with terminal amino groups of the amino acids of Hb

HbNH2 + CO2 ® HbNHCOO - + H+

HbNH2 + H2CO3 ® HbNH3 + + HCO3-

  • The Haldane effect allows deoxyHb to carry more CO2 and increase the formation of carbamino compounds


3. Hb in the RBC acts as a buffer

  • This is a powerful buffering system. It is the primary non-bicarbonate buffer of blood for both respiratory and metabolic acids
  • Hb is present in high concentration inside RBC and Hb in turn has a high concentration of imidazole side chains that are responsible for its buffering activity
  • Hb in RBC is present as a weak acid (HHb) and its potassium salt (KHb)
  • H+ is buffered by Hb and HCO3- is produced in the RBC. The bicarbonate in the RBC diffuse out of RBC into plasma to maintain electrical neutrality


4. Red cell metabolism

  • Energy generation
    • Generates ATP for energy to maintain RBC shape and flexibility
    • Via anaerobic glycolytic pathway (Embden-Meyerhof pathway)
    • 2 ATP for each molecule glucose


  • NADPH and NADH generation
    • Iron in Hb must be maintained in the ferrous state in order to bind O2. Ferric form of Hb = Met Hb and is unable to bind O2
    • NADPH is a major reducing agent in the RBC and protects against oxidation. NADPH is generated for the hexose monophosphate shunt and is required by the RBC to maintain reduced glutathione
    • NADH is a cofactor in the metHb reductase reaction to reduce MetHb to Hb


5. Iron metabolism – role of RBC as a transporter for iron

  • Hb contains 65-70% of total body iron
  • Old RBCs are removed by the reticuloendothelial system mainly spleen and haem is reutilized by the marrow to make Hb


6. Other functions

  • RBC esterases involved in metabolism of some drugs
  • Binding of nitric oxide to form S-nitrosohemoglobin (SNO-Hb) with function in linking regulation of vascular tone to tissue oxygenation
  • ABO compatibility – antigen present on the surface of RBC


Ó Claudia Cheng August 2006

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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