Oxygen Transport and Oxygen-Hemoglobin Dissociation Curve

Hemoglobin Basics - Iron's O2 Taxi

• Structure: Tetrameric protein; 4 globin chains (e.g., 2$\alpha$, 2$\beta$ in HbA) + 4 heme groups.
  • Heme: Iron-containing porphyrin; $Fe^{2+}$ (ferrous) at its core.
  • Each $Fe^{2+}$ reversibly binds one $O_2$; 1 Hb molecule carries 4 $O_2$ molecules.
• Types (Adult %):
  • HbA ($\alpha_2\beta_2$): >95%.
  • HbA2 ($\alpha_2\delta_2$): 1.5-3.5%.
  • HbF ($\alpha_2\gamma_2$): <2% (adults); higher $O_2$ affinity.
• Function: Primary: $O_2$ transport (lungs $\rightarrow$ tissues). Also $CO_2$ transport, blood buffer.
• Iron State for $O_2$ binding: Must be $Fe^{2+}$ (ferrous). $Fe^{3+}$ (ferric) in Methemoglobin (MetHb) cannot bind $O_2$.

⭐ HbF has higher oxygen affinity than HbA due to reduced binding of 2,3-BPG.

The O2-Hb Curve - Sigmoid Story

• Shape: Sigmoid (S-shaped) due to cooperative O2 binding.
  • One O2 binding ↑ affinity for more O2.
• Axes: Y-axis: % Hb Saturation, X-axis: $pO_2$.
• P50 Value: $pO_2$ for 50% Hb saturation.
  • Adult HbA: 26.6 mmHg.
• Significance:
  • Steep part: Efficient O2 unloading in tissues.
  • Plateau: Maintains O2 loading in lungs.
• Shifts:
  • Right Shift (↑P50, ↓Affinity): 📌 CADET, face Right! (↑$CO_2$, ↑Acid/H+, ↑2,3-BPG, ↑Exercise, ↑Temp). Promotes O2 release.
  • Left Shift (↓P50, ↑Affinity): Opposite factors (↓$CO_2$, etc.), HbF, CO, MetHb. Promotes O2 uptake.

⭐ Bohr effect: ↓ O2 affinity with ↑ $pCO_2$ or ↓pH, aiding O2 release in tissues.

Curve Shifters - Affinity Adjusters

Factors altering Hb-$O_2$ affinity. $P_{50}$: $O_2$ pressure for 50% Hb saturation (Normal: 26.6 mmHg). ↑ $P_{50}$ = ↓ affinity.

• 2,3-BPG: ↑ in hypoxia; stabilizes deoxyHb.
• CO: Binds Hb (~200x > $O_2$), forms COHb.
• HbF: ↑ affinity (poor 2,3-BPG binding).

⭐ CO poisoning: left shifts ODC for available sites (↓ $O_2$ unloading) + ↓ $O_2$ carrying capacity.

Clinical Curves - Patho Pointers

• P₅₀: O₂ partial pressure for 50% Hb saturation (Normal: 26.6 mmHg). ↑P₅₀ = Right shift; ↓P₅₀ = Left shift.
• Right Shift (↓O₂ Affinity): Facilitates O₂ unloading. 📌 Mnemonic: "CADET, face Right!"
  • Causes: ↑CO₂, ↑Acid (↓pH), ↑2,3-DPG, ↑Exercise, ↑Temperature.
  • Clinical: Anemia, Chronic high altitude.
• Left Shift (↑O₂ Affinity): Impairs O₂ unloading.
  • Causes: ↓CO₂, ↓Acid (↑pH), ↓2,3-DPG, ↓Temperature, HbF, CO, MetHb.
  • CO Poisoning: Cherry-red skin. Normal PaO₂, unreliable SaO₂ (pulse ox).
  • Methemoglobinemia (Fe³⁺): Chocolate blood. Tx: Methylene blue.

⭐ In CO poisoning, the O₂-Hb curve shifts left (impaired O₂ release) AND O₂ carrying capacity is reduced. Pulse oximetry is misleadingly normal.

• Hemoglobin's cooperative O2 binding creates a sigmoidal dissociation curve.
• P50 (~26.6 mmHg) indicates O2 affinity; ↑P50 means ↓affinity (right shift).
• Right shift factors (↑O2 release): ↑CO2, ↑H+ (↓pH), ↑2,3-BPG, ↑temperature. (CADET)
• Left shift factors (↓O2 release): ↓CO2, ↓H+ (↑pH), ↓2,3-BPG, ↓temperature, HbF, CO.
• Bohr effect: H+ and CO2 promote O2 release from Hb.
• CO poisoning: High Hb affinity for CO, left shift, ↓O2 carrying capacity.