Oxygen Transport and Haemoglobin Dissociation Curve (HUMB1001 Module 8 Part A)

Overview

  • The Respiratory System module covers the transport of oxygen via haemoglobin (Hb) in red blood cells (RBCs).
  • Oxygen is carried in two forms: dissolved in plasma and bound to Hb. The dissolved portion is very small because O2 is poorly soluble.
  • Most O2 is transported bound to Hb in a reversible chemical form; HbO2 is oxyhaemoglobin.
  • The primary determinant of Hb's O2 binding is the partial pressure of O2 (PO2).

Key quantitative facts

  • Oxygen content of blood:
    • 1000 mL of blood carries about 200 mL of O2 when bound to Hb, plus about 3 mL O2 dissolved in plasma (about 1.5%).
    • The dissolved portion is relatively small; Hb-bound O2 carries the majority.
  • Hb concentration in blood is approximately [Hb]≈150 extgtextHbtextper1000 extmL[Hb] \approx 150\ ext{g} \\text{Hb} \\text{per} \\ 1000\ ext{mL}, which approximates to about 200 mL O2 per liter of blood when Hb is fully saturated.
  • At normal cardiac output (CO) of 5.0Lmin5.0 \\ \frac{L}{min}, Hb can deliver about 1000mLO2min1000 \\ \frac{mL O2}{min}.
  • In numeric terms: 100 extmLbloodrightarrow20 extmLO2100\ ext{mL blood} \\rightarrow 20\ ext{mL O2}.
  • Hb contains 44 haem groups that act as binding sites for oxygen; Hb can be fully saturated with up to 4 O2 molecules per Hb molecule.
  • The percentage of Hb saturation in blood can vary from 0%0\% to 100%100\%.
  • Hb acts as both a transport carrier and a storage depot for O2; how much O2 is bound to Hb is determined by PO2.
  • If Hb levels are reduced to 50% of normal (e.g., anaemia), the O2-carrying capacity is reduced by 50%.
  • The O2-Hb system is influenced by several factors beyond PO2, including PCO2, acidity (Bohr effect), temperature, and 2,3-bisphosphoglycerate (BPG, also called DPG).

The Hb-O2 binding reaction

  • Chemical representation:
    ext{Hb} + ext{O}2 ightleftharpoons ext{HbO}2
  • Loading/unloading depends on PO2:
    • In the lungs, alveolar PO2 is high, shifting the reaction to the right (loading O2 onto Hb).
    • In tissues, tissue PO2 is low, shifting the reaction to the left (unloading O2 from Hb).
  • The reaction is driven by the PO2 gradient between alveolar air and pulmonary capillary blood in the lungs, and by the PO2 gradient between capillary blood and respiring tissues.
  • The most important factor affecting O2 binding to Hb is PO2.

Oxygen transport from lungs to tissues

  • O2 diffuses from alveoli into blood plasma, then into RBCs to combine with Hb (Hb + O2 ⇌ HbO2).
  • In the lungs, alveolar PO2 is higher than capillary blood PO2, promoting loading of O2 onto Hb.
  • In tissues, tissue PO2 is lower than capillary PO2, promoting unloading of O2 from Hb to tissues.
  • The gradient of PO2 determines the direction of O2 diffusion and HbO2 formation/unloading.

The O2-Hb dissociation curve

  • The O2-Hb relationship is represented by a dissociation curve with two distinct regions:
    • 0–40 mm Hg: steep slope (large changes in saturation with small PO2 changes).
    • 40–104 mm Hg: flat slope (large changes in PO2 produce small changes in saturation).
  • This shape ensures efficient loading in the lungs and unloading in tissues.
  • The curve’s shape is of great physiological significance for O2 delivery under varying physiological conditions.

Relationship between PO2 and Hb saturation (illustrative details)

  • When PO2 < 40 mmHg, small changes in PO2 lead to large changes in Hb saturation.
  • When PO2 > 40 mmHg, large changes in PO2 lead to only small changes in Hb saturation.

Oxygen delivery and Hb as a storage depot (resting vs exercising)

  • Hb binding capacity influences total O2 that blood can pick up in lungs and drop off in tissues.
  • Hb serves as a storage depot for O2; the amount of O2 bound to Hb is determined by the PO2.
  • If Hb concentration is reduced (e.g., anaemia),O2-carrying capacity falls proportionally.

Factors affecting Hb affinity for O2

  • Acidity (Bohr effect): increased acidity lowers Hb affinity for O2; H+ binds to Hb.
  • PCO2: higher PCO2 (as in exercising tissues) promotes O2 release from Hb; CO2 forms carbonic acid, which dissociates to H+ and HCO3-; the free H+ lowers pH.
  • Temperature: higher temperature promotes O2 release from Hb.
  • 2,3-BPG (DPG): higher levels promote O2 release from Hb; BPG is an glycolysis intermediate; its concentration increases with RBC metabolic activity and hypoxia; it is also influenced by hormones such as thyroxine and growth hormone.

Acidity, PCO2, temperature, and 2,3-BPG effects

  • Bohr effect: increased acidity (lower pH) reduces O2 affinity; H+ binding to Hb shifts dissociation curve to the right.
  • Higher PCO2 (as a product of respiration) shifts curve to the right, facilitating O2 release in tissues.
  • Temperature rise shifts the curve to the right (increased O2 delivery).
  • Increased BPG shifts the curve to the right (lower Hb affinity for O2, more O2 release).

Shifts of the O2-Hb dissociation curve

  • Right shift (decreased Hb affinity for O2):
    • Downward shift in pH (i.e., lower pH, more acidic)
    • Increased PCO2
    • Increased BPG
    • Increased temperature
  • Left shift (increased Hb affinity for O2):
    • Higher pH (alkaline)
    • Decreased PCO2
    • Decreased BPG
    • Decreased temperature

PCO2 and oxygen release: lungs vs tissues

  • At tissues: PCO2 rises due to ongoing cellular respiration; Hb-O2 curve shifts to the right, promoting O2 release.
  • At lungs: PCO2 falls as air is exhaled; Hb-O2 curve shifts to the left, promoting O2 loading.

A summary diagrammatic framing

  • From lungs to tissues: alveolar PO2 high -> HbO2 formation -> Hb releases O2 where PO2 is low enough to drive dissociation; then blood returns to lungs with CO2.
  • The entire system is governed by gradients in PO2, PCO2, pH, temperature, and BPG.

Quick numerical recap (reference points from the slides)

  • Dissolved O2 in plasma: approximately 3 mL O2 per 1000 mL blood3 \,\mathrm{mL}\,\mathrm{O_2}\ \text{per}\ 1000\,\mathrm{mL}\,\text{blood} (about 1.5%).
  • Hb-bound O2 per liter of blood: about 200 mL O2200 \,\mathrm{mL}\,\mathrm{O_2}.
  • Hb concentration: approximately 150 g Hb per 1000 mL150\ \mathrm{g}\,\mathrm{Hb}\ \text{per}\ 1000\ \mathrm{mL} of blood.
  • Oxygen delivery capacity at a typical cardiac output: CO=5.0 LminCO = 5.0\ \frac{L}{min}, delivering about 1000 mLmin⁡1000\ \frac{\mathrm{mL}}{\min} of O2.
  • Hb hem groups: Hb contains 44 haem groups capable of binding O2; fully saturated Hb binds 4 O2 molecules4\ \mathrm{O_2\ molecules} per Hb molecule.
  • Hb saturation range: 0%≤Hb sat≤100%0\% \le \mathrm{Hb~sat} \le 100\%.

The key equation (loading/unloading)

Hb+O<em>2⇌HbO</em>2\text{Hb} + \text{O}<em>2 \rightleftharpoons \text{HbO}</em>2

The broader significance

  • The O2 transport system is designed to maximize O2 loading in lungs and efficient O2 delivery to tissues under varying metabolic states (rest vs exercise).
  • The curve’s sigmoidal nature balances sensitivity to PO2 changes in tissues with saturation maintenance during loading in the lungs.
  • Pathophysiological states altering Hb concentration (anemia), Hb affinity (changes in pH, CO2, temperature, BPG), and PO2 gradients can markedly affect tissue oxygenation.

The end