Guyton and Hall Physiology Chapter 40 - Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane

Expired Air

• Expired air is a mixture of dead space air and alveolar air.
• Dead space air comes from the respiratory passageways, and is typical humidified air.
• Alveolar air is expired at the end of expiration after forceful expiration removes all the dead space air.

Respiratory Unit

• The respiratory unit is also called the respiratory lobule.
• The respiratory unit is composed of a respiratory bronchiole, alveolar ducts, atria, and alveoli.
• There are about 300 million alveoli in the lungs, each with an average diameter of about 0.2 millimeter.

Respiratory Membrane

• The respiratory membrane is the collective term for the membranes of all terminal portions of the lungs, including the alveoli.
• The respiratory membrane is also called the pulmonary membrane.
• The respiratory membrane is extremely thin, consisting of:
  • a layer of fluid containing surfactant
  • alveolar epithelium
  • epithelial basement membrane
  • interstitial space
  • capillary basement membrane
  • capillary endothelial membrane
• The total surface area of the respiratory membrane in healthy men is about 70 square meters.
• The total quantity of blood in the capillaries of the lungs at any given instant is 60 to 140 ml.

Diffusion of Gases

• Gas exchange between the alveolar air and pulmonary blood occurs through the respiratory membrane.
• The thickness of the respiratory membrane occasionally increases, for example, as a result of edema fluid.
• Increased thickness of the respiratory membrane can interfere with respiratory gas exchange.
• The surface area of the respiratory membrane can be greatly decreased by conditions like emphysema which cause many of the alveoli to coalesce, with dissolution of many alveolar walls.

Factors Affecting Alveolar O2 Concentration

• The rate at which O2 is absorbed into the blood
• The rate at which new O2 enters the lungs via ventilation

Normal Operating Point of Alveolar Po2

• A normal ventilatory rate of 4.2 L/min and an O2 consumption of 250 ml/min is the normal operating point for a young man

Moderate Exercise

• The rate of alveolar ventilation must increase fourfold to maintain alveolar Po2 at 104 mm Hg during moderate exercise

Maximum Alveolar Po2

• Extreme increases in alveolar ventilation cannot increase alveolar Po2 above 149 mm Hg when breathing normal atmospheric air at sea level because 149 mm Hg is the maximum Po2 in humidified air at this pressure

Factors Affecting Alveolar CO2 Concentration

• Rate of CO2 excretion from the blood
• Rate of alveolar ventilation

Effect of Increased CO2 Excretion on Alveolar Pco2

• Alveolar Pco2 increases directly with the rate of CO2 excretion
• Example: A fourfold increase in CO2 excretion elevates the alveolar Pco2 curve by four

Effect of Increased Ventilation on Alveolar Pco2

• Alveolar Pco2 decreases inversely with alveolar ventilation

Respiratory Membrane Composition

• Alveolar epithelium
• Epithelial basement membrane
• Interstitial space with connective tissue fibers
• Capillary basement membrane
• Capillary endothelial membrane

Respiratory Membrane Characteristics

• It's extremely thin, averaging approximately 0.6 micrometer in thickness, except where cell nuclei are present
• The total surface area is about 70 square meters in healthy men
• Contains 60 to 140 ml of blood

Diffusing Capacity for Oxygen

• Average diffusing capacity for O2 in a young man at rest is 21 ml/min per mm Hg
• During normal quiet breathing, the average O2 pressure difference across the respiratory membrane is about 11 mm Hg
• The diffusion capacity multiplied by the pressure difference equals approximately 230 ml of oxygen diffusing through the respiratory membrane each minute, which is the rate at which the resting body uses O2

Increased Oxygen Diffusing Capacity During Exercise

• Increased diffusing capacity for O2 during exercise is a result of:
  • Opening up of previously dormant pulmonary capillaries
  • Increased pulmonary blood flow
  • Increased alveolar ventilation

Diffusing Capacity of other Gases

• The diffusing capacity varies directly with the diffusion coefficient of the gas.
• The diffusion coefficient for CO2 is slightly more than 20 times that of O2

Measurement of Diffusing Capacity - Carbon Monoxide Method

• A small amount of CO is breathed into the alveoli
• The partial pressure of CO in the alveoli is measured from appropriate alveolar air samples
• The CO pressure in the blood is essentially zero because hemoglobin combines with it rapidly, preventing its pressure from building up
• The pressure difference of CO across the respiratory membrane is equal to its partial pressure in the alveolar air sample
• The volume of CO absorbed over a short period is divided by the alveolar CO partial pressure to determine the CO diffusing capacity
• The CO diffusing capacity is multiplied by 1.23 to convert it to O2 diffusing capacity, accounting for the difference in their diffusion coefficients
• The average diffusing capacity for CO in healthy young men at rest is 17 ml/min per mm Hg, while the diffusing capacity for O2 is 1.23 times this, or 21 ml/min per mm Hg

Venous Blood and Alveolar Gas Equilibration

• Venous blood returning from the systemic circulation perfuses the lungs' capillaries
• The gases in this venous blood equilibrate with the alveolar gases, influencing the alveolar partial pressures.
• Venous blood typically has a Po2 of 40 mm Hg and a Pco2 of 45 mm Hg.

Respiratory Gas Diffusion and Exchange

• Diffusion of gases across a membrane depends on several factors such as the difference in partial pressure between the two sides, the surface area of the membrane, the thickness of the membrane, and the solubility and molecular weight of the diffusing gas.

• The diffusion coefficient, a measure of how easily a gas diffuses, is proportional to the square root of its solubility divided by its molecular weight.

• Respiratory gases, including oxygen and carbon dioxide, are exchanged across the respiratory membrane, composed of multiple layers including the alveolar fluid, the alveolar epithelium, the interstitial space, the capillary endothelium, and the red blood cell membrane.

Factors Affecting Respiratory Gas Exchange

• The partial pressure difference between the alveolar air and the pulmonary capillary blood drives the diffusion of gases.

• The thickness of the respiratory membrane can be increased by various factors like interstitial edema or fibrosis, leading to increased diffusion distance and decreased gas exchange.

• Increased surface area of the respiratory membrane improves gas exchange. This surface area can be decreased by conditions like lung removal or emphysema, which can impair gas exchange.

• Ventilation-perfusion ratio, the ratio of airflow to blood flow, can influence gas exchange.

Diffusing Capacity of the Respiratory Membrane

• The diffusing capacity of the respiratory membrane refers to the volume of a gas that can diffuse across the membrane per minute for a given pressure difference.

• Increased ventilation during exercise enhances the diffusion of oxygen across the respiratory membrane.

• The diffusion capacity for carbon dioxide is not measurable due to its extremely rapid diffusion rate.

Physiological Shunt

• A small portion of blood flows through bronchial vessels, bypassing alveolar capillaries, representing 2% of cardiac output.
• This unoxygenated blood contributes to the physiological shunt.
• The physiological shunt is measured by analyzing oxygen concentrations in mixed venous blood and arterial blood, alongside cardiac output.
• The equation for calculating physiological shunt is: Q̇PS = (CiO2 - CaO2) / (CiO2 - CvO2), where Q̇PS is the shunt blood flow, Q̇T is cardiac output, and CiO2, CaO2, and CvO2 are oxygen concentrations in ideal arterial blood, measured arterial blood, and mixed venous blood, respectively.

Molecular Basis of Gas Diffusion

• Gases involved in respiratory physiology are simple molecules that move freely by diffusion.
• Diffusion requires energy, sourced from the kinetic motion of molecules.
• Molecules move randomly and continuously, colliding with each other, leading to a net diffusion from areas of higher concentration to lower concentration.
• Partial pressure of a gas in a mixture is proportional to its concentration.
• Partial pressures of nitrogen and oxygen in atmospheric air are 600 mm Hg and 160 mm Hg, respectively, totaling 760 mm Hg.

Pressures of Gases Dissolved in Water and Tissues

• Dissolved gases in water or tissues exert pressure due to their kinetic energy and random movement.
• When dissolved gas encounters a surface, it exerts its partial pressure, similar to gas in the gas phase.

Factors Affecting Rate of Gas Diffusion Through the Respiratory Membrane

• Rate of gas diffusion through the respiratory membrane is influenced by:
  • Thickness of the membrane
  • Surface area of the membrane
  • Diffusion coefficient of the gas in the membrane
  • Partial pressure difference of the gas across the membrane

Effects of Alveolar Ventilation on Alveolar Oxygen and Carbon Dioxide Concentrations

• Oxygen concentration in alveoli is controlled by rate of oxygen absorption into blood and rate of new oxygen entry from ventilation.
• Carbon dioxide is constantly formed in the body, transported to the alveoli by blood, and removed by ventilation.
• The alveolar partial pressure of carbon dioxide (PCO2) is affected by alveolar ventilation and the rate of carbon dioxide excretion from blood.