Physiology
Oxygen Transport
Hemoglobin loading, dissolved O2, and the curve that gets oxygen from lungs to tissues
Oxygen travels in blood two ways — bound to hemoglobin (~98.5% of total O2 at sea level) and dissolved in plasma (~1.5%). Each hemoglobin molecule carries 4 O2 via Fe2+ in heme; saturation curve is sigmoidal due to cooperative binding. Arterial O2 content (CaO2) = (Hb × 1.34 × SaO2) + (0.003 × PaO2). Right shifts (high CO2, H+, temperature, 2,3-BPG) release O2 to tissues — the Bohr effect. Left shifts retain O2 (carboxyhemoglobin, fetal Hb, alkalosis). Anemia, CO poisoning, and methemoglobinemia all reduce O2 delivery despite normal PaO2 — pulse oximetry can mislead.
- Hb O2 capacity1.34 mL O2 per gram Hb
- Normal CaO2~20 mL O2/dL blood
- P50~26.6 mmHg (PaO2 at 50% saturation)
- Bohr effectAcidosis/CO2 shift curve right (release O2)
- CO affinity240x O2 affinity for hemoglobin
- Fetal Hb (HbF)Higher O2 affinity (P50 ~19 mmHg)
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Why oxygen transport matters
- Hypoxemia diagnosis. Distinguishing hypoxemia from anemia requires understanding both PaO2 and CaO2.
- CO poisoning. Pulse ox lies — must check carboxyhemoglobin level.
- Sickle cell disease. Hydroxyurea reactivates HbF, reducing crisis frequency.
- Altitude medicine. 2,3-BPG and Hb mass adapt for chronic hypoxia.
- Transfusion decisions. Hb thresholds based on physiologic understanding.
- Anesthesia. Pre-oxygenation creates O2 reserve for apneic intubation.
- Critical care. Mixed venous SaO2 monitors tissue O2 extraction.
Common misconceptions
- SpO2 measures oxygen content. SaO2 is just saturation — anemia drops content even at 100%.
- PaO2 100 mmHg means good oxygenation. CO poisoning, methemoglobinemia, anemia all bypass PaO2.
- Curves are linear. Sigmoidal — small SpO2 drop below 90% means big PaO2 drop.
- Pulse ox detects CO. It can't distinguish COHb from HbO2; reads falsely normal.
- Acidosis is always bad for O2. Bohr effect promotes tissue O2 release in metabolic stress.
- Stored blood transfuses normally. Lost 2,3-BPG impairs O2 release for 24-48 hours after transfusion.
Frequently asked questions
Why is the O2-Hb curve sigmoidal?
Cooperative binding. Hemoglobin has 4 subunits — binding O2 to one subunit changes conformation (T to R state), increasing affinity at remaining sites. This produces the steep middle of the curve, allowing efficient unloading at tissue PaO2 (~40 mmHg) while remaining nearly fully saturated at lung PaO2 (100 mmHg). Myoglobin (single subunit, no cooperativity) has a hyperbolic curve and only releases O2 at very low PO2.
What's the Bohr effect?
Increased CO2 and H+ shift the O2-Hb curve right, decreasing affinity and promoting O2 release. Tissue metabolism produces CO2 and lactate, lowering pH locally — hemoglobin releases more O2 right where it's needed. In lungs, the reverse: low CO2 raises affinity, loading O2. Discovered by Christian Bohr (1904). Counterpart: Haldane effect — deoxyhemoglobin binds CO2 better, helping CO2 transport from tissues to lungs.
Why does CO poisoning cause hypoxia despite normal PaO2?
Carbon monoxide binds Fe2+ with 240x affinity of O2, forming carboxyhemoglobin which can't carry O2. Worse, CO left-shifts the dissociation curve of remaining HbO2, impairing O2 release to tissues. PaO2 (dissolved O2) stays normal — pulse oximetry reads falsely normal because it can't distinguish HbO2 from COHb. Diagnosis requires co-oximetry. Treatment: 100% O2 (half-life CO 80 min) or HBO (23 min).
How does 2,3-BPG affect oxygen delivery?
2,3-bisphosphoglycerate is produced by RBCs in glycolysis. It binds the central cavity of deoxyhemoglobin, stabilizing the T (low-affinity) state and shifting the curve right. Increases at high altitude, anemia, chronic hypoxemia — boosts O2 unloading to tissues. Stored blood loses 2,3-BPG within days, reducing O2 release; warmed and reperfused before transfusion in critical settings. Fetal Hb doesn't bind 2,3-BPG — explaining its higher affinity.
What is methemoglobinemia?
Iron in heme is normally Fe2+ (ferrous). Oxidation to Fe3+ (ferric) creates methemoglobin, which can't bind O2 and left-shifts the curve. Causes: dapsone, benzocaine, nitrites, aniline dyes, congenital cytochrome b5 reductase deficiency. Cyanosis appears at MetHb > 15% with chocolate-brown blood. Pulse ox reads ~85% regardless of true saturation. Treatment: methylene blue 1-2 mg/kg IV (reduces Fe3+ back to Fe2+).
Why does fetal hemoglobin have higher O2 affinity?
HbF has two gamma chains instead of beta chains. The gamma chain's amino acid sequence binds 2,3-BPG less effectively, leaving HbF in higher-affinity state. P50 ~19 mmHg vs adult 27 mmHg. This left-shift lets fetal blood extract O2 from maternal blood across the placenta despite low fetal PO2 (~30 mmHg). HbF persists for ~6 months post-birth before being replaced by HbA. Hydroxyurea reactivates HbF in sickle cell disease.
How does anemia affect oxygen delivery?
O2 delivery (DO2) = cardiac output × CaO2. Anemia reduces Hb, cutting CaO2 proportionally — at Hb 7 g/dL, CaO2 is ~9.4 mL/dL versus 20 mL/dL normal. Compensations: increased cardiac output, rightward curve shift via 2,3-BPG, increased O2 extraction. Symptoms appear when compensation fails — fatigue, dyspnea, angina. Transfusion thresholds: Hb < 7 g/dL in stable patients, < 8 g/dL in cardiac disease (TRICC trial).