Physiology

Gas Exchange and Transport (O₂ and CO₂)

A Comprehensive Article

Respiratory System

Every breath you take is an act of gas trade. You inhale oxygen to fuel your cells and exhale carbon dioxide — the waste product of metabolism. This exchange happens in your lungs and your tissues, all governed by pressure gradients and diffusion.

🫁 Overview: The Pathway of Gases

Process Location Description
Ventilation Lungs ↔ Atmosphere Movement of air in/out of alveoli
External respiration Alveoli ↔ Pulmonary capillaries O₂ in, CO₂ out
Transport Blood Gases carried to/from tissues
Internal respiration Systemic capillaries ↔ Cells O₂ diffuses into cells, CO₂ out
Cellular respiration Mitochondria Use of O₂ for ATP, production of CO₂
High-yield summary: Breathing is ventilation, but respiration is gas exchange and cellular utilization.

⚙️ 1️⃣ Gas Exchange in the Lungs (External Respiration)

Gas exchange occurs in the alveoli, across the respiratory membrane, which is only 0.5 μm thick — designed for rapid diffusion.

Respiratory Membrane Components:

  1. Alveolar epithelium (Type I cells)
  2. Fused basement membrane
  3. Capillary endothelium
Surface area: ~70 m² (about half a tennis court!)
Thickness: <1 μm — the thinner it is, the faster diffusion occurs.

Partial Pressures — The Driving Force

Gases move from high → low partial pressure (Dalton’s law). The difference in partial pressures between alveoli and blood drives diffusion.

Gas Alveolar (mmHg) Pulmonary Artery (mmHg) Pulmonary Vein (mmHg)
O₂ 104 40 100
CO₂ 40 45 40
So: O₂ diffuses from alveoli → blood; CO₂ diffuses from blood → alveoli.
Even though CO₂’s pressure gradient is small, it diffuses 20x faster than O₂ due to higher solubility.

🩸 2️⃣ Transport of Oxygen

Only a tiny fraction of oxygen travels freely in plasma — most is carried by hemoglobin (Hb) inside RBCs.

A. Oxygen in Blood

Form Percentage Description
Bound to Hb ~98.5% Each Hb molecule binds up to 4 O₂ molecules
Dissolved in plasma ~1.5% Creates PO₂ that drives diffusion

B. Oxygen–Hemoglobin Dissociation Curve

This famous S-shaped curve shows how Hb’s affinity for O₂ changes with PO₂.

PO₂ (mmHg) % Hb Saturation
100 (lungs) 97–100%
40 (tissues) ~75%
20 (active muscles) ~25%
Key principle: Hemoglobin loads O₂ easily in the lungs (high PO₂) and unloads it readily in tissues (low PO₂).

C. Factors Shifting the Curve

Shift Direction Cause Effect on Hb Affinity Physiological Example
Right shift ↑ CO₂, ↑ temperature, ↓ pH, ↑ 2,3-BPG ↓ Affinity → more O₂ released Exercise, fever
Left shift ↓ CO₂, ↓ temp, ↑ pH, ↓ 2,3-BPG ↑ Affinity → less O₂ released Fetal Hb, hypothermia
Mnemonic: “CADET, face Right!” — CO₂, Acid, DPG, Exercise, Temperature — all cause a right shift.

🧠 Bohr Effect

↑ CO₂ or ↓ pH (acidic blood) → Hb releases more O₂. Enhances oxygen unloading in metabolically active tissues.

🌬️ 3️⃣ Transport of Carbon Dioxide

CO₂ is continuously produced by tissues and must be carried to the lungs for exhalation. It’s transported in three forms:

Form Percentage Mechanism
As bicarbonate (HCO₃⁻) ~70% CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ (via carbonic anhydrase)
As carbaminohemoglobin (Hb–CO₂) ~23% Binds to Hb’s globin (not heme)
Dissolved in plasma ~7% Directly soluble in plasma
Main takeaway: Most CO₂ travels as bicarbonate, formed in RBCs and carried in plasma.

Haldane Effect

Deoxygenated Hb binds CO₂ more readily. So in tissues, where O₂ leaves Hb, CO₂ uptake is enhanced. In lungs, O₂ loading promotes CO₂ release.

Bohr = O₂ offloading enhanced by CO₂, Haldane = CO₂ offloading enhanced by O₂.

🫀 5️⃣ Gas Exchange in the Tissues (Internal Respiration)

At tissue level: PO₂ in tissues ≈ 40 mmHg; PCO₂ in tissues ≈ 45 mmHg → O₂ diffuses from blood → tissues, and CO₂ diffuses from tissues → blood.

The gradient is maintained by continuous cellular metabolism — as cells use O₂ and generate CO₂.

🧩 6️⃣ Factors Affecting Gas Exchange

Factor Effect if Altered Clinical Example
Surface area ↓ → ↓ diffusion Emphysema
Membrane thickness ↑ → ↓ diffusion Pulmonary fibrosis, edema
Diffusion coefficient ↓ → ↓ diffusion CO₂ diffuses 20× faster than O₂
Partial pressure gradient ↓ → ↓ diffusion High altitude
Ventilation–perfusion (V/Q) ratio Mismatch → hypoxemia Asthma, PE

⚖️ 7️⃣ Ventilation–Perfusion (V/Q) Ratio

Normal: ≈ 0.8 (ventilation 4 L/min, perfusion 5 L/min). V/Q mismatch → major cause of hypoxemia.

Condition V/Q Change Effect
Airway obstruction (shunt) ↓ V/Q (approaches 0) Blood passes unoxygenated
Pulmonary embolism (dead space) ↑ V/Q (approaches ∞) Ventilated but unperfused lung area
Mnemonic: “Shunt = no ventilation, Dead space = no perfusion.”

💡 Clinical Applications

Condition Key Change Effect
Anemia ↓ Hb concentration ↓ O₂ content, but normal PaO₂
Carbon monoxide poisoning Hb binds CO > O₂ ↓ O₂ delivery, cherry-red skin
COPD / asthma V/Q mismatch Hypoxemia, hypercapnia
High altitude ↓ atmospheric PO₂ Hypoxemia → hyperventilation
Emphysema ↓ surface area Impaired O₂ diffusion

🧠 Summary Table — Gas Transport

Gas Main Transport Form Important Concept
O₂ 98% as oxyhemoglobin Bohr effect
CO₂ 70% as bicarbonate Haldane effect
N₂ Insoluble → inert gas Diving decompression risk
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