Transport of Oxygen

The transport of oxygen from the atmosphere to the lungs is a mechanical and physiochemical process driven by pressure gradients, ensuring that oxygen reaches the respiratory membrane for gas exchange into the blood.

Transport Pathway: Atmosphere to Alveoli.

The journey of oxygen occurs through two distinct functional regions:

• The Conducting Zone: Oxygen enters through the nose or mouth and travels through the nasopharynx, larynx, trachea, bronchi, and bronchioles, reaching the terminal bronchioles. These passages function to filter, warm, and moisten the inspired air but do not participate in gas exchange.

• The Respiratory Zone: Air moves from the terminal bronchioles into the respiratory bronchioles, alveolar ducts, and finally the alveoli. The alveoli are the primary site for external respiration, where oxygen is transferred into the pulmonary capillary blood.

The Oxygen Pressure Gradient

The movement of oxygen is dictated by Dalton’s Law, which states that the partial pressure of a gas is the total pressure multiplied by its fractional concentration. Oxygen moves "downhill" from areas of high partial pressure to low partial pressure through the following stages:

1. Dry Inspired Air: At sea level (barometric pressure of 760 mm Hg), the fractional concentration of oxygen is 21%, resulting in a PO2 of approximately 160 mm Hg.

2. Humidified Tracheal Air: As air enters the conducting zone, it is fully saturated with water vapor (PH2O =47 mm Hg at 37°C). This dilutes the oxygen, reducing the PO2​ to approximately 150 mm Hg.

3. Alveolar Air (PAO2): By the time air reaches the alveoli, oxygen has been removed into the blood and CO2 has been added from the blood. This further reduces the PO2​ to approximately 100 mm Hg.

4. Mixed Venous Blood (PvO2): Deoxygenated blood returning to the lungs from the right heart has a PO2​

of 40 mm Hg.

5. Diffusion Gradient: The difference between alveolar gas (100 mm Hg) and mixed venous blood (40 mm Hg) creates a driving force of 60 mm Hg. This gradient powers the diffusion of oxygen across the thin respiratory membrane into the blood until equilibration is reached at 100 mm Hg.

Factors Influencing Transport

The efficiency of this transport is governed by Fick’s Law of Diffusion, which states that the rate of gas transfer is proportional to the surface area and the partial pressure difference, while being inversely proportional to the thickness of the membrane. Under normal conditions, oxygen transport is perfusion-limited, meaning equilibration occurs rapidly (within the first third of the pulmonary capillary), and the total amount of oxygen taken up is limited primarily by blood flow.

Analogy: Oxygen transport is like a descending staircase (the oxygen cascade). Oxygen starts at the highest step in the atmosphere and steps down at each stage—first when it is diluted by water vapor in the throat, then as it mixes with CO2

in the alveoli, and finally jumping across the "gap" into the blood because the blood's "step" is significantly lower

Oxygen transfer and transport are essential physiological processes that ensure the body's metabolic demands are met through a coordinated system of diffusion and convective flow.

I. Diffusion of Oxygen from Alveoli to Blood

The transfer of oxygen from alveolar gas to pulmonary capillary blood occurs via simple diffusion across the thin alveolocapillary barrier. This process is governed by the following steps:

• Driving Force: Diffusion is driven by a partial pressure gradient between alveolar air and mixed venous blood. Normally, alveolar PO2 (PAO2) is approximately 100 mmHg, while mixed venous PO2(P

vO2) is 40 mmHg, creating a driving force of 60 mmHg.

• Equilibration: Under normal resting conditions, oxygen transfer is perfusion-limited. This means that oxygen equilibrates so rapidly that the PO2 of pulmonary capillary blood reaches 100 mmHg within the first one-third of the capillary's length.

• The Barrier: Oxygen must pass through the respiratory membrane, which consists of the alveolar epithelium, a fused basement membrane, and the capillary endothelium. This membrane is extremely thin to facilitate rapid gas exchange.

II. Factors Determining the Diffusion of Oxygen

The rate of oxygen transfer is described by Fick’s Law of Diffusion, which identifies several critical determinants:

1. Partial Pressure Gradient (ΔP): The difference in PO2 between the two sides of the membrane; diffusion is directly proportional to this gradient.

2. Surface Area (A): Larger surface areas allow for more diffusion. This increases during exercise as more capillaries are recruited.

3. Membrane Thickness (ΔX): Diffusion is inversely proportional to the thickness of the barrier. Pathological states like fibrosis or pulmonary edema increase this distance, making oxygen transfer diffusion-limited.

4. Diffusion Coefficient (D): This combines the solubility of the gas with the inverse of the square root of its molecular weight.

5. Lung Diffusing Capacity (DL): A clinical parameter that combines the diffusion coefficient, surface area, and membrane thickness while also accounting for the time O2 takes to bind to hemoglobin.

III. Solubility of Oxygen in Blood

Oxygen has a very low solubility in aqueous solutions such as blood.

• Henry’s Law: This law states that the concentration of a dissolved gas is directly proportional to its partial pressure.

• Solubility Coefficient: For oxygen, the solubility in blood is 0.003 mL O2

/100 mL blood per mmHg.

• Dissolved Form: At a normal arterial PO2 of 100 mmHg, the concentration of dissolved oxygen is only 0.3 mL O2 /100 mL, which accounts for only 2% of the total oxygen content. This amount is grossly insufficient to meet tissue demands without an additional transport mechanism.

IV. Transport of Oxygen to Tissues

To compensate for its low solubility, the vast majority of oxygen (98%) is transported bound to hemoglobin within red blood cells.

• Hemoglobin Binding: One molecule of adult hemoglobin (HbA) can bind up to four molecules of oxygen. This binding increases the oxygen-carrying capacity of blood approximately 70-fold.

• Positive Cooperativity: The sigmoidal shape of the O2-hemoglobin dissociation curve is due to positive cooperativity; the binding of each O2 molecule increases the affinity of the remaining heme groups for the next molecule.

• Unloading at Tissues: In systemic tissues, where the PO2 is low (~40 mmHg), hemoglobin’s affinity for oxygen decreases, facilitating its unloading.

• Bohr Effect: Factors such as increased PCO2, decreased pH (acidosis), and increased temperature in active tissues further shift the curve to the right, raising the P50 and promoting the release of oxygen where it is needed most.

Analogy: Oxygen diffusion is like a crowd of people (gas molecules) moving from a packed room (alveoli) into a hallway (capillary). If the hallway doors are wide and the wall is thin (large surface area, thin membrane), they move quickly. However, the hallway floor is slippery (low solubility), so only a few can stand there. To move large numbers of people, they must jump into specialized "carts" (hemoglobin molecules) that can carry them efficiently to their final destination (tissues).

The oxygen-hemoglobin dissociation curve is a graphic representation of the relationship between the partial pressure of oxygen (PO2) and the percent saturation of hemoglobin with oxygen. This relationship is critical for understanding how blood picks up oxygen in the lungs and delivers it to systemic tissues.

I. Characteristics and Shape of the Curve

The curve typically exhibits a sigmoidal (S-shaped) appearance rather than a linear one. This specific shape is attributed to a phenomenon called positive cooperativity:

• Hemoglobin is a tetramer with four heme groups, each capable of binding one O2 molecule.

• The binding of the first O2 molecule increases the affinity of the remaining heme groups for the second, and this continues until the fourth molecule binds with the highest affinity.

• This ensures that once hemoglobin starts picking up oxygen, it quickly becomes fully saturated.

II. Phases of the Curve

The sigmoidal shape allows the curve to be divided into two functionally distinct portions:

A. The Plateau Phase (Upper Part: PO2 60–100 mm Hg) This "flat top" of the curve represents the loading of oxygen in the lungs.

• Safety Margin: Alveolar PO2 can drop from 100 mm Hg to 60 mm Hg (e.g., at moderate high altitudes or with mild lung disease) without a significant decrease in hemoglobin saturation; it only falls from roughly 97% to 90%.

• Diffusion Support: By tightly binding O2 in this range, hemoglobin keeps the concentration of free (dissolved) O2 in the plasma low, maintaining a steep partial pressure gradient that facilitates continued diffusion from the alveoli into the blood.

B. The Steep Phase (Lower Part: P

O2 0–40 mm Hg) This portion represents the unloading of oxygen at the systemic tissues.

• In metabolically active tissues, where PO2 is low (~40 mm Hg or less), hemoglobin’s affinity for O2

decreases sharply.

• This facilitates the rapid release of large quantities of oxygen to the cells even with small further drops in tissue PO2 (e.g., during heavy exercise).

III. The P50  Value

The P50 is the partial pressure of oxygen at which hemoglobin is 50% saturated. In a healthy adult, the normal P50 is approximately 25–30 mm Hg. It is used as a standard index to measure changes in hemoglobin's affinity for oxygen; an increase in P50 means affinity has decreased (right shift), while a decrease means affinity has increased (left shift).

IV. Factors Affecting Shifts of the Curve

A. Shift to the Right (Decreased Affinity)

A right shift means that for any given PO2, hemoglobin is less saturated, meaning it unloads oxygen more easily to the tissues. This occurs in response to:

• Increased PCO2 and Decreased pH: Known as the Bohr Effect, this occurs during exercise as tissues produce more CO2 and lactic acid.

• Increased Temperature: High metabolic activity generates heat, which triggers O2 release.

• Increased 2,3 Bisphosphoglycerate (2,3-BPG/DPG): This byproduct of glycolysis binds to the β-chains of deoxyhemoglobin and stabilizes them, reducing O2 affinity. Levels increase during chronic hypoxia or at high altitudes.

B. Shift to the Left (Increased Affinity)

A left shift means hemoglobin binds oxygen more tightly, making it harder to unload at the tissues (P50 decreases). Causes include:

• Decreased PCO2, Increased pH, and Decreased Temperature.

• Fetal Hemoglobin (HbF): HbF replaces the β-chains with γ-chains, which bind 2,3-BPG less avidly than adult hemoglobin. This higher affinity allows the fetus to "pull" oxygen from the maternal blood in the placenta.

• Carbon Monoxide (CO) Poisoning: CO binds to hemoglobin with 200–250 times the affinity of O2. It not only reduces the number of available O2 binding sites but also shifts the remaining curve to the left, preventing the release of the little oxygen that is bound.

Analogy: Imagine hemoglobin as a magnet for oxygen. In the lungs, the magnet is "extra strong" (high affinity), allowing it to pick up every scrap of oxygen available. When it reaches the tissues, the environment (acidity, heat) "weakens" the magnet (right shift), allowing the oxygen to easily drop off where it is needed most. Carbon monoxide is like a piece of iron that gets permanently stuck to the magnet and simultaneously makes it impossible for the remaining oxygen to be pulled away.