Gas exchange and gas transport: comprehensive notes

Alveolar structure and diffusion

• Gas exchange occurs across the surface of about 300 million alveoli with a total surface area of about 100 m^2; branched morphology maximizes active surface area while minimizing transport distances.
• Overall gas exchange and nutrient exchange in the human vasculature occurs across ~600 m^2 of surface area with a branched morphology.
• Gas exchange happens in the alveoli (thin-walled air sacs at the tips of the bronchioles):
  • Oxygen diffuses through the moist film of the epithelium into the capillaries.
  • Carbon dioxide diffuses from the capillaries into the airspace.
• Mechanism: simple passive diffusion of O2 and CO2 down their partial pressure gradients.
• In the lung, blood arriving in the lungs has:
  • Low partial pressure of oxygen (PO₂)
  • High partial pressure of carbon dioxide (PCO₂)
    relative to the air in the alveoli.
• In the alveoli, O₂ diffuses into the blood and CO₂ diffuses into the alveolar air.
• In tissue capillaries:
  • Partial pressure gradients favor diffusion of O₂ into the interstitial fluid and cells.
  • CO₂ diffuses from the cells into the blood.
• Blood and gas exchange interplay with external respiration and internal respiration via diffusion across capillaries.
• The alveolar gas exchange depends on the properties of alveolar air (temperature, humidity) and residual volume.

Partial pressures and atmospheric composition

• The partial pressure of a gas in a mixture is given by the total pressure times the fraction of that gas in the mixture:
  Pi = P{ ext{total}} \, f_i
• Atmospheric composition at sea level (P_total ≈ 760 mmHg):
  • Nitrogen: f{N2} \,=\, 0.79 → P{N2} = 760 \times 0.79 = 600\text{ mmHg}
  • Oxygen: f{O2} \,=\, 0.21 → P{O2} = 760 \times 0.21 = 160\text{ mmHg}
  • Carbon dioxide: f{CO2} \,\approx\, 0.0003{-}0.0005 (very small) → P{CO2, ext{atm}} \approx 0.25\text{ mmHg}
• The partial pressure of oxygen in the atmosphere is 160 mmHg, but the partial pressure of oxygen in the alveoli is about 100 mmHg due to:
  • A residual volume of air remains in the lung that contains higher CO₂ than atmospheric air.
  • The air in the respiratory tract and alveoli is warm and moist, which affects gas partial pressures.
• Gas exchange occurs by diffusion down the partial pressure gradients:
  • In the alveoli, PO₂ is higher in the alveolar air than in the blood, so O₂ diffuses into the blood.
  • In the tissues, PO₂ is higher in the blood than in the interstitial fluid, so O₂ diffuses into tissues; CO₂ diffuses from tissues into blood.

Oxygen transport and the oxyhemoglobin dissociation curve

• Respiratory pigments (hemocytes in many animals; respiratory pigments) increase the amount of O₂ transported.
• The dominant pigment in vertebrates is hemoglobin (Hb):
  • A single Hb molecule can carry up to four O₂ molecules (one per iron-containing heme group).
  • Hemoglobin is contained in mature red blood cells.
• Hemoglobin binds O₂ reversibly and cooperatively:
  • Reversibly: Hb loads O₂ in the lungs/gills and releases O₂ in tissues.
  • Cooperatively: when one O₂ binds, Hb’s conformation changes to increase affinity for subsequent O₂ molecules.
• Hemoglobin states:
  • Deoxyhemoglobin (no O₂ bound)
  • Oxyhemoglobin (O₂ bound)
• Oxygen saturation, SO₂, is the fraction of Hb bound to O₂:
  SO2 = \frac{\text{O}2\text{-bound Hb}}{\text{O}2\text{ carrying capacity}} \quad\text{(often written as }SO2 = \frac{[O_2\text{-Hb}]}{[Hb]\cdot 4}\text{)}
• The oxyhemoglobin dissociation curve describes the relationship between PO₂ (x-axis) and Hb O₂ saturation (y-axis).
• Key points from normal physiology (at pH ≈ 7.4):
  • In the lungs, PO₂ ≈ 100 mmHg → Hb is ~100% saturated.
  • In resting tissues, PO₂ ≈ 40 mmHg → Hb is ~60–80% saturated (roughly 20–25% O₂ unloaded at rest).
  • In exercising tissues, PO₂ can fall below ≈ 20 mmHg → Hb saturation drops to
• Important note: the O₂ bound to Hb does not contribute to the dissolved O₂ partial pressure in blood.
• The curve also reveals how much O₂ can be delivered to tissues under different PO₂ conditions.
• The curve shifts with changes in pH and CO₂ (Bohr effect); more on this in the Bohr section.
• At normal PO₂ (lungs) Hb saturation reaches near maximum due to high affinity and abundant O₂.

Carbon dioxide transport in the blood

• CO₂ is transported in three main forms:
  • About 10% physically dissolved in plasma.
  • About 30% bound to hemoglobin as carbaminohemoglobin.
  • About 60% transported as bicarbonate ions (HCO₃⁻) in plasma.
• Hemoglobin can carry CO₂, binding at sites separate from the O₂-binding sites (carbaminohemoglobin).
• In red blood cells, carbonic anhydrase catalyzes the conversion of CO₂ to carbonic acid:
  \ce{CO2 + H2O
• The formation of bicarbonate in red blood cells leads to its diffusion into the plasma; to maintain electroneutrality, chloride ions move into the RBCs (the chloride shift).
• The carbon dioxide that is carried as bicarbonate contributes to the hydrogen ion load, lowering blood pH (acidifying the blood) and thereby influencing Hb’s O₂ affinity (Bohr effect).
• The overall CO₂ transport and buffering link to acid-base balance is essential for gas exchange efficiency and maintaining systemic homeostasis.

Acid-base balance and buffering (buffers and pH regulation)

• Maintaining a constant blood pH is critical for cellular function and metabolic processes.
• Buffers in blood primarily involve the bicarbonate buffering system:
  • Carbonic acid (H₂CO₃) and its conjugate base bicarbonate (HCO₃⁻) form the major extracellular buffer.
  • The buffer reaction can remove excess hydrogen ions or hydroxide ions to stabilize pH:
    \mathrm{HCO3^-} + \mathrm{H^+} \rightleftharpoons \mathrm{H2CO3} \rightleftharpoons \mathrm{CO2} + \mathrm{H_2O}
• If bicarbonate combines with free hydrogen ions, hydrogen ions are removed, moderating pH changes; excess carbonic acid can be converted to CO₂ and exhaled.
• If too many hydroxide ions are introduced, carbonic acid can combine with OH⁻ to form bicarbonate, which helps prevent pH rise.
• The respiratory system controls CO₂ levels by adjusting ventilation (increased ventilation lowers CO₂, raising pH; decreased ventilation raises CO₂, lowering pH).
• The urinary (kidneys) system regulates bicarbonate levels by retaining or excreting HCO₃⁻, providing longer-term pH regulation.
• The interplay between respiratory and renal systems maintains blood pH within a narrow range essential for life.

Bohr effect and factors shifting the oxyhemoglobin dissociation curve

• The Bohr effect describes how CO₂ and pH influence Hb’s affinity for O₂:
  • Higher CO₂ levels lower blood pH (more acidic), shifting the O₂-Hb dissociation curve to the right.
  • A rightward shift means decreased Hb affinity for O₂ at a given PO₂, promoting greater O₂ unloading in tissues.
  • Conversely, lower CO₂ levels raise pH, shifting the curve to the left and increasing Hb’s O₂ affinity (less unloading).
• Relationship between CO₂, carbonic acid, and pH:
  \mathrm{CO2} + \mathrm{H2O} \rightleftharpoons \mathrm{H2CO3} \rightleftharpoons \mathrm{H^+} + \mathrm{HCO_3^-}
• The Bohr effect links the acid-base status of the blood to the oxygen delivery to tissues, aligning gas exchange with metabolic demand.

Integrated perspective and practical implications

• Key relationships to remember:
  • Oxygen delivery depends on both the amount of O₂ transported by Hb and the PO₂ gradient between blood and tissues.
  • The majority of O₂ is carried bound to Hb; only a small fraction is dissolved in plasma to contribute to the PO₂ in blood.
  • The oxygen delivery to tissues is modulated by pH and CO₂ levels via the Bohr effect.
  • CO₂ transport in blood is efficient due to conversion to bicarbonate and its buffering role, influencing pH.
  • Maintaining acid-base homeostasis requires coordinated respiratory (CO₂ removal) and renal (HCO₃⁻ handling) control.
• Real-world relevance:
  • Exercise increases tissue CO₂ production and acid load, lowering pH and promoting O₂ unloading via the Bohr effect.
  • High-altitude or hypoxic conditions alter PO₂ gradients, impacting Hb saturation and tissue O₂ delivery.
  • Pathologies that affect acid-base balance can disrupt Hb-O₂ affinity and tissue oxygenation, underscoring the importance of buffering systems and ventilation control.

Quick reference: key equations and values

• Partial pressure definitions:
  Pi = P{\text{total}} \cdot f_i
• Atmospheric O₂ and N₂ partial pressures at sea level (P_total ≈ 760 mmHg):
  • P{N2} = 760 \times 0.79 = 600 \text{ mmHg}
  • P{O2} = 760 \times 0.21 = 160 \text{ mmHg}
  • P{CO2, ext{atm}} \approx 0.25 \text{ mmHg}
• Alveolar PO₂ and diffusion context:
  • Alveolar PO₂ ≈ 100 mmHg (lower than atmospheric due to residual volume and warming/moistening of air)
• Oxygen saturation relationship:
  SO2 = \frac{\text{O}2\text{-bound Hb}}{\text{O}2\text{ carrying capacity}} = \frac{[O2\text{-Hb}]}{[Hb] \cdot 4} \times 100\%
• Typical resting values (illustrative):
  • In lungs: PO₂ ≈ 100 mmHg → Hb ~ 100% saturated
  • In tissues at rest: PO₂ ≈ 40 mmHg → Hb ~ 60–80% saturated (≈20–25% O₂ unloaded at rest)
  • In tissues during exercise: PO₂ < 20 mmHg → Hb < 20% saturation ( >80% unloaded)
• CO₂ transport forms (approximate): 10% dissolved, 30% carbaminohemoglobin, 60% as bicarbonate (HCO₃⁻)
• Carbonic acid–bicarbonate buffering equilibrium:
  \mathrm{CO2} + \mathrm{H2O} \rightleftharpoons \mathrm{H2CO3} \rightleftharpoons \mathrm{H^+} + \mathrm{HCO_3^-}
• Buffering with bicarbonate in blood:
  \mathrm{HCO3^-} + \mathrm{H^+} \rightleftharpoons \mathrm{H2CO3} \rightleftharpoons \mathrm{CO2} + \mathrm{H_2O}