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Diffusion of Gases Through the Respiratory Membrane

 The respiratory membranes of the lungs are in the respiratory bronchioles, alveolar ducts, and al­veoli. Approximately 300 million of these units are in the two lungs. The average diameter of each al­veolus is approximately 0.25 mm, and its walls are extremely thin. Surrounding each alveolus is a net­work of capillaries arranged so that air within the alveoli is separated by a thin respiratory membrane from the blood contained within the alveolar capil­laries.

 

Figure 1.

 

The respiratory membrane (see Figure 1.) consists of

• A thin layer of fluid lining the alveolus,

• The alveolar epithelium comprised of simple squamous epithelium,

• The basement membrane of the alveolar epithelium,

• A thin in­terstitial space,

• The basement membrane of the capillary endothelium, and the capillary endo­thelium comprised of simple squamous epithelium.

 

The factors that influence rate of gas diffusion across the respiratory membrane include

• The thickness of the membrane,

• The diffusion coeffi­cient of the gas in the substance of the membrane, which is approximately the same as the diffusion coefficient for gas through water,

• The surface area of membrane, and the partial pressure difference of the gas between the two sides of the membrane.

 

Respiratory membrane thickness

 Increasing the thickness of the respiratory membrane decreases the rate of diffusion. In healthy lungs, the respiratory membrane (alveolar membrane + endothelial membrane + fused basement membranes) is 0.5-1.0um thick, but the thickness can be increased by respiratory diseases. For example, in patients with pulmonary oedema fluid accumulates in the alveoli, and gases must diffuse through a thicker-than-normal layer of fluid. If the thickness of the respiratory membrane is increased two or three times, the rate of gas exchange is markedly decreased.

  

Diffusion coefficient

 The diffusion coefficient is a measure of how easily a gas will diffuse through a liquid or tissue, taking into account the solubility of the gas in the liquid and the size of the gas molecule (molecular weight). If the diffusion coefficient of oxygen is as­signed a value of 1, then the relative diffusion co­efficient of carbon dioxide is 20 (i.e., carbon dioxide will diffuse through the respiratory membrane 20 times more rapidly than oxygen).  When the respiratory membrane becomes pro­gressively damaged as a result of disease, its capacity for allowing the movement of oxygen into the blood is often impaired enough to cause death from oxygen deprivation before the diffusion of carbon dioxide is dramatically reduced. However, if life is being main­tained by extensive oxygen therapy, which increases the concentration of oxygen in the lung alveoli, the reduced capacity for the diffusion of carbon dioxide across the respiratory membrane can result in sub­stantial increases of carbon dioxide in the blood.

  

Surface area 

The total surface area of the respiratory mem­brane is approximately 70 m2 (approximately the area of one half of a tennis court) in the normal adult. The surface area of the respiratory membrane is decreased by several respiratory diseases, including emphy­sema and lung cancer. Even small decreases in this surface area adversely affect the respiratory exchange of gases during strenuous exercise. When the total surface area of the respiratory membrane is decreased to one third or one fourth of normal, the exchange of gases is significantly restricted even under resting conditions.

  

Partial pressure difference 

The partial pressure difference of a gas across the respiratory membrane is the difference between the partial pressure of the gas in the alveoli and the par­tial pressure of the gas in the blood of the alveolar capillaries. When the partial pressure of a gas is greater on one side of the respiratory membrane than on the other side, net diffusion occurs from the higher to the lower pressure. Normally the partial pressure of oxygen (P02) is greater in the alveoli than in the blood of the alveolar capillaries, and the partial pres­sure of carbon dioxide (Pco2) is greater in the blood than in the alveolar air.  The partial pressure difference for oxygen and carbon dioxide can be increased by increasing the alveolar ventilation rate. The greater volume of at­mospheric air exchanged with the residual volume raises alveolar Po2, lowers alveolar Pco2, and thus promotes gas exchange. Conversely, inadequate ven­tilation causes a lower-than-normal partial pressure difference for oxygen and carbon dioxide, resulting in inadequate gas exchange.

 

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DIFFUSION 

There are Two Mechanisms for the Gas Flows Associated with Respiration

·         Bulk flow - The movement of a gas or gas mixture from a region of high to low net pressure.  All components of the gas mixture are subjected to the same net pressure gradient and they move together.

o    Inspiration:  The volume of the lungs increases and intrapulmonary pressure falls below atmospheric pressure.  The resultant pressure gradient forces air into the lungs.

o    Expiration:  The volume of the lungs decreases and intrapulmonary pressure rises above atmospheric pressure.  The resultant pressure gradient forces air out of the lungs.

·         Diffusion - In the respiratory bronchioles and alveoli of the lung, movement by bulk flow slows to the point where diffusion becomes the mode for gas movement.  In this region diffusion forces promote the net movement of O₂ from alveoli to blood and CO₂ from blood to alveoli across the alveolar-capillary membrane.

·         Diffusion of a Gas within a Gas

o    General principles

o    Molecules of gas are in constant random motion.  Diffusion is from a region of higher concentration to a region of lower concentration.

o    Rate of diffusion related to density of gas

Graham’s Law:  The relative diffusion of a gas (Dgas) within a gas is inversely proportional to the square root of its molecular weight.

For CO₂ and O₂ (P and T constant) MW CO₂ = 44; MW O₂ = 32

Which gas moves more quickly within the alveoli?  Lighter molecules travel faster, have more frequent collisions and thus diffuse more rapidly?

Therefore, alveolar oxygen would diffuse 1.2 times more rapidly than alveolar carbon dioxide.

 

Diffusion of O₂ and CO₂ Across the Alveolar Capillary Membrane

Click here to see a Flash presentation on diffusion of gas into another gas

·         Factors which influence diffusion rates across the alveolar-capillary wall.

o    Graham’s Law applies.  O₂ and CO₂ are gases diffusing within the alveolar gas next to the alveolar-capillary membrane.  Graham’s law gives us the relative rate of this diffusion.

o    Therefore within the gaseous phase in the alveoli O₂ diffuses 1.2 times as fast as CO₂.

o    Effect of water solubility on diffusion across the alveolar - capillary membrane.

Regardless of whether gases diffuse from blood to alveolus or from alveolus to blood, they pass into the membranes from an aqueous environment because on the alveolar side a thin layer of water covers the alveolar wall.  The solubility coefficient for CO₂ (0.57) is 24 x that for O₂ (0.024).  For the same partial pressures of the two gases the aqueous concentration of CO₂ will be 24 x that of O₂, and CO₂ will diffuse 24 x faster.  Combining this observation with Graham’s Law:

For a given partial pressure gradient CO₂ diffuses across the alveolar-capillary membrane about 21 x as fast as O₂.

·         Fick’s Law for diffusion of gases across the alveolar-capillary membrane.

Click here to see a Flash presentation on Fick’s law of diffusion of gas into a liquid.

The rate of diffusion of a gas through a sheet of tissue (Vgas)is directly proportional to the tissue area (A), a diffusion constant (also called Diffusivity, D), a difference in the partial pressure of the gas across the tissue barrier (P₁-P₂), and inversely proportional to tissue thickness (T).

 

 

Figure 1

A = average 70 m2 (50-100); T = 0.1-0.5 microns

D (diffusivity) is directly proportional to the solubility of the gas and inversely proportional to the square root of the molecular weight.

·         Diffusing capacity of the lung (DL)

o    Diffusing Capacity (DL) lumps together the terms for area, thickness, and diffusivity.

                            

                            

o    From Fick’s Law, DL can be measured:

o    Area and thickness may both change in pulmonary disease.  Measurement of DL is of use in the diagnosis of pulmonary disease.

·         Measuring DLCO:

o    Carbon monoxide is used for the measurement of diffusing capacity because carbon monoxide is so avidly bound to hemoglobin upon entering arterial blood that PaCO remains essentially zero for a significant time.  The above equation then simplifies to:

                             

o    In other words, the unidirectional diffusion rate from alveolus to blood can easily be measured in the case of carbon monoxide.

o    The single breath method:  A single inspiration of a dilute mixture of carbon monoxide is made, and the disappearance of carbon monoxide from alveolar gas during a 10 second breath hold is calculated.  This is usually done by measuring the inspired and expired concentrations of carbon monoxide with an infrared analyzer.  The normal value for the diffusing capacity for carbon monoxide is 25 ml/min/mmHg and it increases to two or three times this value upon exercise.

o    The diffusing capacity for oxygen DLO₂ can be calculated by knowing DLCO and the relative diffusivities of oxygen and carbon monoxide.

o    Clinical Interpretation.  Measured DLCO is affected by ventilation/perfusion mismatching as well as membrane thickness and surface area.  Therefore, it is better to think of DLCO as an index of overall lung function rather than an index of diffusion capabilities per se.

Diffusion-Perfusion Relationships

·         The amount of a gas which is transferred across the alveolar-capillary membranes of the lungs can be influenced by two factors:

o    The diffusion rate of the gas, and

o    The rate at which the lungs are perfused with blood (pulmonary blood flow).  Gases which have diffused into blood must be carried away if favorable diffusion gradients are to be maintained.

Figure 2

·         Diffusion - limited transfer.  Recognized by the presence of an end capillary partial pressure difference between blood and alveolus.  Carbon monoxide (CO) is the best example of this.  When CO diffuses from alveolus to blood, it is so rapidly removed by reaction with hemoglobin that the partial pressure of CO in blood remains essentially zero  PCO during the normal transit time of blood through a pulmonary capillary (0.75 sec).  The possibility of back flux from blood to alveolus is thus eliminated, and net transfer from alveolus to blood is a function of diffusion rate only.  This makes CO useful in the measurement of pulmonary diffusion capacity.

·         Perfusion-limited transfer.  Recognized by the absence of an end capillary partial pressure difference between blood and alveolus.  Nitrous oxide (N₂0) is a good example of this.  As N₂0 diffuses from alveolus to blood, the partial pressure of N₂0 in blood PCN₂O rapidly rises to equal the alveolar partial pressure PAN₂O and net transfer ceases.  This occurs well within the normal transit time of blood through a pulmonary capillary (0.75 sec).  An increase in blood flow lowers PCN₂O by washout, a favorable diffusion gradient is maintained, and net diffusion continues.  The amount of N₂0 transferred from alveolus to blood is limited by perfusion rate, not diffusion rate.

·         Diffusion-and perfusion-limited transfer - O₂ is an example of this.  Normally, O₂ reaches diffusion equilibrium early in the pulmonary capillary (in less than 0.25 sec).  Net transfer is thus largely perfusion-limited.  In some abnormal situations diffusion equilibrium is not attained even at the end of the pulmonary capillary in a normal transit time of 0.75 sec.  There is then a significant diffusion limitation to net transfer.  The diffusion limitation can then become even more severe during exercise, when transit time through the capillary is reduced still further.

·         In the following pair of graphs “abnormal” and “grossly abnormal” represent the pattern of capillary O₂ exchange when there is increasing diffusion impairment due to pulmonary disease.  The problem becomes exacerbated during exercise when transit time may be reduced to 0.25 sec, or when the PO₂ in inspired air is reduced, as in the graph on the right.  Hypoxemia develops (PaO₂ < 100 mm Hg) when there is failure of gas equilibration in the pulmonary capillaries.

Figure 3

Figure 4

·         CO₂ transfer.  The following graph shows the pattern of CO₂ exchange along the length of the pulmonary capillaries.  “Abnormal” represents impaired diffusion.  Failure of gas equilibrium by the end of the capillary results in some degree of CO₂ excess (hypercapnia) in arterial blood(PaCO₂ > 40 mm Hg) .  The problem is exacerbated during exercise when transit time may be reduced to 0.25 seconds.

Figure 5

Summary of Partial Pressures Important in Pulmonary Exchange of O₂ and CO₂

·         Partial pressures in mixed venous blood  delivered to the lung in the pulmonary artery:

o    PVO₂ = 40 mm Hg

o    PVCO₂ = 45 mm Hg

·         Partial pressures in alveolar gas (A)

o    PAO₂ = 100 mm Hg

o    PACO₂ = 40 mm Hg

·         Partial pressures in blood leaving the lungs in the pulmonary vein.  These values are essentially the same as in arterial blood (a).

o    PaO₂ = 100 mm Hg*

o    PaCO₂ = 40 mm Hg

§  *Actually, PaO₂ is normally less than PAO₂ by 5-20 mmHg.  This is the A-a difference.  The reasons for this will be discussed in detail later, and are unrelated to diffusion.  Therefore, it would not be unusual to measure a patient PaO₂ of 95 mmHg.

§  Diffusion equilibrium is normally reached well before the end of the pulmonary capillaries. There is a substantial diffusion reserve for both O₂ and CO₂.  Even during exercise when transit time may be reduced to 0.25 sec; PaO₂ and PaCO₂ are unaltered from resting values.

·         Gradients for diffusion at the beginning of the pulmonary capillaries.

o    For O₂: PAO₂ - PvO₂ = 60 mm Hg

o    For CO₂: PvCO₂ - PACO₂ = 5 mm Hg

·         As discussed above, gradients at the end of the capillary for O₂ and CO₂ are normally zero. Therefore, alveolar partial pressures for O₂ and CO₂ can be used to estimate end-capillary partial pressures.

 

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Gas Transport

Gas Exchange Disorders

Gas Exchange

Gas Exchange Notes