Oxygen Dissociation Curve - MD Emergency Medicine Exam

The Curve

What the Curve Represents

• Fishman's Pulmonary Diseases, block3

Key Values to Memorize

Two Critical Zones of the Curve

1. Upper Flat Portion (PaO2 60-100 mmHg)

• Hemoglobin remains ~90-100% saturated
• Clinical advantage: Even with lung disease dropping PaO2 from 100 to 60 mmHg, SpO2 remains adequate (~90%)
• This is why you can tolerate moderate hypoxemia without catastrophic desaturation

2. Lower Steep Portion (PaO2 20-60 mmHg)

• Small drops in PaO2 cause large drops in saturation
• Clinical advantage for tissues: Large amounts of O2 are released per small drop in PO2, promoting efficient diffusion into metabolizing tissues
• At rest, only ~25% of delivered O2 is extracted; the remaining 75% is reserve
• The "slippery slope" - once PaO2 drops below 60 mmHg, rapid desaturation follows

Allosteric Effectors & Curve Shifts

Bohr Effect (pH and CO2)

• CO2 increased
• Acid (decreased pH)
• DPG (2,3-DPG/BPG) increased
• Exercise (increased temperature)
• Temperature increased

Table: Factors Shifting the ODC

• Mulholland & Greenfield's Surgery 7e, Guyton & Hall Physiology

2,3-BPG (2,3-Bisphosphoglycerate) - High-Yield

• Most abundant organic phosphate in RBCs; synthesized from glycolytic intermediates
• Binds exclusively to deoxyhemoglobin (T form) in the central pocket formed by the two β-globin chains
• Oxygenation narrows this pocket, expelling 2,3-BPG
• Effect: shifts ODC right → more O2 released to tissues

• Chronic hypoxia (COPD, high altitude)
• Chronic anemia
• Compensatory response to improve tissue O2 delivery

• Stored blood (blood bank) - acts as an O2 "trap" rather than delivery system; replenished within 6-24 hours post-transfusion
• Transfusing large volumes of old blood is dangerous in critically ill patients
• Lippincott Biochemistry 8e

Bohr Effect - Mechanism (Exam Depth)

1. CO2 is produced → converted by carbonic anhydrase to H2CO3 → HCO3- + H+
2. ↑ H+ lowers pH in tissue capillaries
3. H+ binds histidine residues on deoxyhemoglobin (higher pKa than oxyhemoglobin) → forms salt bridges → stabilizes T (deoxy) form
4. Result: O2 is released in tissues

• CO2 is exhaled → pH rises → equilibrium shifts toward oxyhemoglobin → O2 is loaded

Fetal Hemoglobin (HbF) - Left Shift

• HbF has γ-chains instead of β-chains
• 2,3-BPG binds poorly to γ-chains → HbF has lower affinity for 2,3-BPG → higher O2 affinity
• ODC is left-shifted relative to adult HbA
• Physiological advantage: allows fetus to extract O2 from maternal blood at the placenta
• Clinical note: HbF's P50 is ~20 mmHg vs ~26.5 mmHg for HbA

Carbon Monoxide (CO) - Left Shift + Haldane Effect

• CO binds hemoglobin with 240x greater affinity than O2 → forms carboxyhemoglobin (COHb)
• Dual problem:
  1. Reduces O2-carrying capacity (fewer sites for O2)
  2. Left-shifts the ODC for remaining Hb sites - O2 that is bound is not released to tissues
• This is why CO poisoning is so deadly even at moderate COHb levels
• SpO2 on pulse oximetry reads falsely normal (cannot distinguish OxyHb from COHb)

Myoglobin vs Hemoglobin

Clinical Emergency Scenarios (High Yield)

1. Septic Shock / Lactic Acidosis

• ↓ pH + ↑ CO2 + ↑ temperature → right shift → facilitates O2 unloading to ischemic tissues
• Compensatory but may be overwhelmed if cardiac output fails

2. Massive Transfusion

• Stored RBCs are 2,3-BPG depleted → left shift → O2 remains bound, not delivered to tissues
• Use fresh blood or "rejuvenated" blood when possible; 2,3-BPG restores in 6-24 hrs

3. CO Poisoning

• SpO2 falsely normal on pulse ox - always measure COHb directly with co-oximetry
• Left-shifted ODC + reduced capacity = tissue hypoxia despite apparent normal sats
• Treatment: 100% O2 (displaces CO), hyperbaric O2 in severe cases

4. High Altitude / COPD (Chronic Hypoxia)

• Compensatory ↑ 2,3-BPG → right shift → improves O2 delivery to tissues
• Guyton & Hall: BPG mechanism allows O2 release at up to 10 mmHg higher tissue pO2

5. Alkalosis (Hyperventilation / Over-correction of Acidosis)

• ↑ pH → left shift → Hb holds O2 → tissue hypoxia despite adequate PaO2
• Clinically relevant during aggressive bicarbonate administration or excessive ventilation

6. Hypothermia

• ↓ Temperature → left shift → reduced O2 delivery, but also reduced metabolic demand (protective in therapeutic hypothermia post-cardiac arrest)

Quick Memory Frame

RIGHT shift = "HEAT" releases O2
  ↑ H+   ↑ CO2   ↑ Temperature   ↑ 2,3-DPG
  → more O2 to tissues (P50 goes UP)

LEFT shift = "COLD stored fetal blood"
  ↓ H+   ↓ CO2   ↓ Temperature   ↓ 2,3-DPG
  HbF, COHb, MetHb
  → Hb holds O2 (P50 goes DOWN)