Gas Transport – Oxy-Hb

Master answer

Oxyhaemoglobin dissociation curve

• OHDC describes the relationship between S_aO₂ and P_aO₂ at 37 degrees
• Demonstrates cooperative binding of Hb:
  • ↑ in O₂ affinity of Hb with each successive O₂ binding
    • 1st O₂ molecule = difficult to bind – 2° strong electrostatic charges to be overcome to achieve conformational changes in Hb molecule: tense conformation → β chains far apart
    • once 1st O₂ has bound confirmation of Hb changes → β chains closer together → 2nd O₂ has ↑ binding affinity → ↓ energy to bind
    • 4th molecule binds 300 times more easily than 1st
    • once 4th O₂ bound → Hb in relaxed state
  • The max amount of O₂ that can be combined with Hb is the O₂ capacity → all available binding sites are occupied by O₂
• Importance of sigmoidal shape
  • Upper portion is flat: if PO₂ in alveolar gas ↓s slightly, loading of O₂ will be little affected. I.e. a small ↓ in PO₂ at normal O₂ levels → causes only a slight ↓ in arterial saturation
  • However, where O₂ levels are already low, and on the steep part of the curve, the same small ↓ in PO₂ will cause a sharp ↓ in S_aO₂

• Oxygen saturation of Hb = the % of the available binding sites that have O₂ attached:
  • (O₂ combined wit Hb / O₂ capacity) x 100
  • In arterial blood, O₂ sats are usually >97%. This corresponds to a PO₂ of 100mmHg and is on the flat part of the curve
  • In venous blood, the saturations are ~75%. This corresponds to the start of the steep part of the curve and a PO₂ of ~40mmHg
    

Factors that may alter the OHDC

• Position of OHDC is described by P50 value = the PO₂ at which 50% of Hb is bound to O₂; corresponds to PaO₂ of 26mmHg
• Right shift
  • ↓ affinity of O₂ for Hb → O₂ ↑ easily offloaded (i.e. for a given PO₂, S_aO₂ is lower)
  • ensures ↑ tissue oxygenation in states of ↓ perfusion
  • Causes: ↑ PCO₂; acidosis; ↑ 2, 3, DPG; exercise; ↑ temp; HbS
  • Bohr effect: ∆ PCO₂ and pH affect O₂ transport → ↑ PaCO₂ and ↓ pH sabilises deoxyHb → facilitates release of O₂ → right shift
• Left shift
  • Left shift → ↑ O₂ binding affinity
  • Causes; ↓P_aCO₂; alkalosis; ↓2, 3, DPG; hypothermia; methaemoglobin; HbF

2,3 DPG

• Formed by RBC during glycolysis
• Binds to beta chains of deoxy-Hb
• DPG binds strongly with beta chains → changing protein conformation → ↓O2 affinity
• ↑2,3DPG → ↑unloading of O2 from Hb → ↑ tissue supply
• Factors ↑ DPG:
  • High altitude: aclimatisation response
  • Anaemia
  • Alkalosis
  • Chronic hypoxaemia
  • Exercise
  • Pregnancy
  • Hyperthyroidism
• Factors ↓DPG
  • Stored blood: DPG ↓ in stored blood: storage ↓ glycolysis (only issue with MTP); levels return to normal after 24-48hr

Kerr