Gas Transport

Principles of Gas Partial Pressures and Atmospheric Dynamics

Gas exchange between the alveoli and the pulmonary capillaries is driven by pressure gradients. Like ions moving across membranes, uncharged gas molecules move from areas of high pressure to low pressure. The concentration gradient determines the movement, described as the gas partial pressure.

• Atmospheric Pressure: This is the force exerted by the weight of the air column above the Earth's surface due to gravity.

  • At sea level, the standard atmospheric pressure is defined as $1\,\text{Atmosphere} = 760\,mm\,Hg$.

  • At high altitudes, such as the summit of Mt. Everest ($29,000\,\text{feet}$), the pressure drops to approximately $253\,mm\,Hg$.

• Composition of Air: Dry atmospheric air consists primarily of Nitrogen and Oxygen.

• Calculating Partial Pressures: The partial pressure of a specific gas is the product of its percentage concentration and the total atmospheric pressure.

  • Nitrogen ($PN_2$): $0.79 \times 760\,mm\,Hg = 600\,mm\,Hg$.

  • Oxygen ($PO_2$): $0.21 \times 760\,mm\,Hg = 160\,mm\,Hg$.

  • Carbon Dioxide ($PCO_2$) and Water Vapor ($PH_2O$) are near zero in dry atmospheric conditions.

Effects of Inhalation and Humidification

As air is inhaled, it undergoes humidification. This process adds water vapor to the air before it reaches the lungs, which alters the partial pressures of the other constituent gases while the total pressure remains $760\,mm\,Hg$.

• Water Vapor Pressure: At normal body temperature, water vapor exerts a partial pressure of $47\,mm\,Hg$.

• Modified Inhaled Air Pressures:

  • Oxygen ($PO_2$): $(760 - 47) \times 0.21 = 150\,mm\,Hg$.

  • Nitrogen ($PN_2$): $(760 - 47) \times 0.79 = 563\,mm\,Hg$.

Alveolar Ventilation and Gas Concentration Stability

The air moved in a single normal breath is the Tidal Volume, typically $500\,ml$. However, only a portion of this reaches the exchange surfaces.

• Alveolar Mixing: Out of the $500\,ml$ Tidal Volume, approximately $150\,ml$ stays in the anatomical dead space, meaning only $350\,ml$ reach the alveoli to mix with the air remaining from the previous breath (Functional Residual Capacity).

• Turnover Rate: With a Functional Residual Capacity of about $2.3\,L$ ($2300\,ml$), only about $15\%$ of the total lung gas is replaced with each breath ($350 / 2300$).

• Benefits of Slow Turnover: This slow replacement ensures that alveolar gas concentrations remain stable, preventing massive fluctuations in blood gas levels between inhalation and exhalation. This stability is critical for consistent respiratory monitoring and control.

  • PO2 shifts minimally from $104\,mm\,Hg$ to approximately $110\,mm\,Hg$ during the respiratory cycle.

Metabolic Gas Exchange Rates

• At Rest:

  • Alveolar ventilation: $4.2\,L/min$ ($350\,ml \times 12\,\text{breaths/min}$).

  • Oxygen uptake: $250\,ml/min$.

  • Carbon dioxide removal: $200\,ml/min$.

• Moderate Exercise:

  • Alveolar ventilation: Increases to approximately $17\,L/min$.

  • Oxygen uptake: Rises to $1000\,ml/min$.

  • Carbon dioxide removal: Rises to $800\,ml/min$.

  • Despite these increases, alveolar $PO_2$ and $PCO_2$ remain stable at $104\,mm\,Hg$ and $40\,mm\,Hg$ respectively, because the ventilation rate increases in tandem with metabolic demand.

Carbon Dioxide Transport in the Blood

Carbon dioxide is transported from systemic tissues back to the heart and lungs in three distinct forms:

1. Dissolved CO2 ($7\%$): This portion remains in free solution in the plasma, contributing to a venous $PCO_2$ of $45\,mm\,Hg$.

   1. 93% CO2 in different form

2. Carbaminohemoglobin ($23\%$): Inside red blood cells (RBCs), carbon dioxide binds to the hemoglobin protein. A negligible amount also binds to plasma proteins.

3. Bicarbonate ($70\%$): The majority of CO2 is converted into carbonic acid ($H_2CO_3$) by the enzyme Carbonic Anhydrase.

   • The reaction is: $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$.

   • The bicarbonate ($HCO_3^-$) is pumped out of the RBC into the plasma via a chloride-bicarbonate antiport protein.

   • Chloride Shift: This resulting increase in plasma bicarbonate and decrease in plasma chloride is a hallmark of venous blood.

   • Clinical Note: Inhibition of Carbonic Anhydrase (e.g., by the drug Acetazolamide) can cause venous $PCO_2$ to spike significantly to levels like $80\,mm\,Hg$.

Kinetics of Pulmonary Gas Exchange

In the pulmonary capillaries, blood must equilibrate with the alveolar gases quickly.

• Oxygen Equilibration: Venous blood enters the capillary with a $PO_2$ of $40\,mm\,Hg$ against an alveolar $PO_2$ of $104\,mm\,Hg$. The initial pressure gradient ($\Delta P$) is $64\,mm\,Hg$. Equilibration is reached within the first $1/3$ of the capillary length.

• Carbon Dioxide Equilibration: Venous blood enters with a $PCO_2$ of $45\,mm\,Hg$ against an alveolar $PCO_2$ of $40\,mm\,Hg$. The $\Delta P$ is only $5\,mm\,Hg$.

• The Diffusion Coefficient: Carbon dioxide equilibrates just as fast as oxygen despite the smaller gradient because its diffusion coefficient is $20\,\text{times}$ greater than that of oxygen.

• Safety Margin During Exercise: Because equilibration occurs early in the capillary at rest, the body can handle increased cardiac output during exercise. Even as blood travels faster through the capillary, there is still sufficient time to reach full saturation.

Systemic Gas Exchange and Arterial Shunts

• Arterial PO2 Drop: Blood leaving the alveolar capillaries is at $104\,mm\,Hg$, yet systemic arterial blood measures at $95\,mm\,Hg$. This is due to a $2\%$ physiological shunt, where deoxygenated blood used to nourish lung tissues mixes with oxygenated blood.

• Intracellular Gradients:

  • Interstitial fluid: $PO_2 \approx 40\,mm\,Hg$.

  • Intracellular: $PO_2 \approx 5\,mm\,Hg$.

  • Mitochondrial Matrix: $PO_2 \approx 0\,mm\,Hg$ (constant consumption).

  • Intracellular $PCO_2$: $46\,mm\,Hg$, creating a gradient to the interstitium ($45\,mm\,Hg$) and then the plasma ($40\,mm\,Hg$ in arteries).

Hemoglobin Dynamics and Allosteric Regulation

At a standard $PO_2$ of $95\,mm\,Hg$, hemoglobin is $97\%$ saturated. At a venous $PO_2$ of $40\,mm\,Hg$, it remains $75\%$ saturated.

• Oxygen Delivery:

  • Normal blood contains $15\,g\,Hb/dL$.

  • Each gram of Hb binds $1.34\,ml\,O_2$.

  • Total potential oxygen in circulation is roughly $1000\,ml\,O_2/min$ at a cardiac output of $5\,L/min$.

  • At rest, tissues consume about $250\,ml/min$, utilizing only $25\%$ of the available supply.

• The Bohr Effect: This describes the shift in the hemoglobin dissociation curve caused by carbon dioxide and acidity.

  • Right Shift (Reduced Affinity): High acidity (low pH), high $PCO_2$, high temperature, and increased 2,3-bisphosphoglycerate (2,3-BPG). This facilitates oxygen off-loading in metabolically active tissues.

  • Left Shift (Increased Affinity): Low acidity (high pH), low $PCO_2$, and lower temperatures. This occurs in the lungs to maximize oxygen loading.

• Fetal Hemoglobin: Exhibits a leftward shift compared to adult hemoglobin, allowing the fetus to effectively extract oxygen from maternal blood.

• The Haldane Effect: Oxygen binding to hemoglobin promotes the release of carbon dioxide. Conversely, deoxygenation of hemoglobin increases its ability to carry CO2. This effect essentially doubles many aspects of CO2 transport efficiency in physiological conditions.