Guide — Fundamentals
Gas Exchange & Oxygen Transport
How oxygen moves from alveolus to mitochondria: diffusion across the alveolar-capillary membrane, the oxyhemoglobin dissociation curve and its shifts, oxygen content and delivery, and how carbon dioxide is carried back. Master this and the rest of cardiopulmonary physiology falls into place — every monitor and intervention traces back to these gradients and curves.
11 min read · Fundamentals
Written by Apex Respiratory Editorial Team
Educational use only. This material supports respiratory therapy education and exam review. It is not medical advice and is not a substitute for clinical judgment, institutional protocols, or physician orders. Always follow facility policies and current provider orders, and verify calculations independently before clinical use.
Overview
Gas exchange is the diffusion of O₂ and CO₂ across the alveolar-capillary membrane, driven by partial-pressure gradients (Fick’s law). Transport is how blood carries O₂ to the tissues and CO₂ back to the lungs. The two big jobs — oxygenation (PaO₂, SaO₂, oxygen content) and ventilation (CO₂ clearance) — are distinct problems and are assessed separately. Confusing one for the other is the root of most early bedside mistakes.
Key Concepts
- Diffusion (Fick’s law). The rate is proportional to surface area and the partial-pressure difference, and inversely proportional to membrane thickness. CO₂ is about 20 times more soluble than O₂, so diffusion defects cause hypoxemia well before hypercapnia.
- Oxygen content (CaO₂). CaO₂ = (1.34 × Hb × SaO₂) + (0.003 × PaO₂), about 20 mL O₂/dL in a normal adult. Almost all oxygen is carried bound to hemoglobin; the dissolved fraction (the 0.003 term) is tiny.
- Oxygen delivery (DO₂). DO₂ = CaO₂ × cardiac output × 10. Anemia or low cardiac output reduce delivery even when PaO₂ is normal — content is not the same as delivery.
- Oxyhemoglobin dissociation curve. A sigmoid relationship between SaO₂ and PaO₂. Landmark points: PaO₂ 27 = SaO₂ 50% (the P50), PaO₂ 40 = SaO₂ 75% (normal mixed venous), PaO₂ 60 = SaO₂ 90% (the steep “shoulder” and the usual supplemental-oxygen threshold), and PaO₂ 80–100 = SaO₂ 95–98%.
- Curve shifts. A rightshift means decreased affinity — hemoglobin releases O₂ to tissue — driven by increased temperature, increased PaCO₂ / decreased pH (acidosis, the Bohr effect), and increased 2,3-DPG. Mnemonic: “CADET, face Right” = CO₂, Acid, 2,3-DPG, Exercise, Temperature all increased. A left shift means increased affinity — hemoglobin holds O₂ — from decreased temperature, decreased PaCO₂ / increased pH (alkalosis), decreased 2,3-DPG, carbon monoxide, fetal hemoglobin, and methemoglobin.
- CO₂ transport. About 70% as bicarbonate (formed in the red cell by carbonic anhydrase, with the chloride shift), about 23% as carbamino compounds bound to hemoglobin, and about 7% dissolved. The Haldane effect: deoxygenated hemoglobin carries more CO₂.
The oxygen cascade traces PO₂ from inspired air down to the tissues, with the partial pressure stepping down at each stage (room air, sea level):
| Stage | PO₂ | Note |
|---|---|---|
| Dry inspired (PIO₂) | ~159 mmHg | Room air at sea level, before humidification |
| Humidified tracheal | ~150 mmHg | Water vapor added in the upper airway |
| Alveolar (PAO₂) | ~100 mmHg | After CO₂ dilution in the alveolus |
| Arterial (PaO₂) | ~95–100 mmHg | Small drop across the membrane and shunt |
| Mixed venous (PvO₂) | ~40 mmHg | After tissue extraction |
Assessment & Findings
| PaO₂ | SaO₂ | Landmark |
|---|---|---|
| 27 mmHg | 50% | P50 — the reference point for affinity |
| 40 mmHg | 75% | Normal mixed venous blood |
| 60 mmHg | 90% | Steep “shoulder”; usual supplemental-O₂ threshold |
| 80–100 mmHg | 95–98% | Normal arterial; flat upper plateau |
- Pulse oximetry reads saturation, not content. SpO₂ tells you the percentage of hemoglobin saturated, not how much oxygen the blood carries. A severely anemic patient can read SpO₂ 100% yet have dangerously low oxygen content.
- Carbon monoxide poisoning. SpO₂ reads falsely normal because a standard oximeter cannot distinguish carboxyhemoglobin from oxyhemoglobin — use co-oximetry.
- Cyanosis. Visible cyanosis requires about 5 g/dL of deoxygenated hemoglobin, so an anemic patient can be hypoxemic without obvious cyanosis.
RT Priorities & Interventions
- Optimize delivery, not just PaO₂. Oxygen delivery depends on hemoglobin, cardiac output, and SaO₂ together — address all three (transfuse when indicated, support the circulation, raise saturation), not the PaO₂ in isolation.
- Recognize when a reassuring SpO₂ hides poor delivery. Anemia, low cardiac output, and CO poisoning all leave saturation looking fine while tissue oxygen falls short.
- Use the curve to set targets. An SpO₂ around 90% (PaO₂ ~60) usually suffices; chasing 100% adds little content on the flat plateau and risks hyperoxia.
Common Pitfalls
- Treating SpO₂ or PaO₂ as if it equals oxygen content or delivery.
- Trusting SpO₂ in carbon monoxide poisoning, poor perfusion, motion, or with very low saturations where oximeter accuracy degrades.
- Forgetting that the dissolved term is negligible — hemoglobin carries essentially all the oxygen.
Board Exam Pearls
- The board mnemonic “40-50-60 → 70-80-90” (PaO₂ to SaO₂) is a handy approximation, but the precise saturations sit a little higher — PaO₂ 40 ≈ SaO₂ 75% (normal mixed venous), 50 ≈ 85%, and 60 ≈ 90%.
- Normal P50 = 27 mmHg.
- Right shift unloads O₂ to the tissues (CADET, face Right). Left shift = CO, fetal hemoglobin, alkalosis, hypothermia, low 2,3-DPG.
- Know CaO₂ = (1.34 × Hb × SaO₂) + (0.003 × PaO₂).
- Most CO₂ is transported as bicarbonate.
FAQ
Why can SpO₂ read 100% in an anemic or CO-poisoned patient who is still hypoxic?
Oximetry reports the percentage of available hemoglobin that is saturated, not how much hemoglobin there is or whether it is bound to oxygen versus carbon monoxide. Anemia lowers content despite full saturation; CO binds hemoglobin and reads as saturated. Both require content or co-oximetry, not just SpO₂.
What is the clinical meaning of a right shift?
Reduced hemoglobin affinity for oxygen, so hemoglobin releases more oxygen to the tissues. It is driven by fever, acidosis, hypercapnia, and high 2,3-DPG — the conditions of metabolically active or stressed tissue — and is generally helpful at the cellular level.
Why does a PaO₂ of 60 matter so much?
It corresponds to roughly SaO₂ 90%, sitting at the steep part of the curve where small further drops in PaO₂ cause large drops in saturation. It is the usual lower target and the common threshold for starting supplemental oxygen.
How is most carbon dioxide carried in the blood?
About 70% as bicarbonate (formed in red cells by carbonic anhydrase, with the chloride shift), about 23% bound to hemoglobin as carbamino compounds, and about 7% dissolved in plasma.
Put it to work
Work the alveolar air equation and the A-a gradient to see exactly how far oxygen falls between the alveolus and the artery.
Open the A-a Gradient calculator →Related Resources
Sources
- Kacmarek RM, Stoller JK, Heuer AJ. Egan's Fundamentals of Respiratory Care. 12th ed. Elsevier; 2021. Gas exchange and oxygen transport chapters.
- West JB, Luks AM. West's Respiratory Physiology: The Essentials. 11th ed. Wolters Kluwer; 2021.