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Chapter 39 Phys
Physics of Gas Diffusion and Gas Partial Pressures
 Partial pressure of a gas in solution is determined by its concentration and its solubility coefficient (how soluble
they are in water, in this case, body fluid), such that Henry’s law applies:
Partial Pressure = (concentration of dissolved gas)/(solubility coefficient)
 Partial pressure of each gas in alveolar respiratory gas mixture tends to force molecules of that gas into solution
in blood in alveolar capillaries, and molecules of the same gas that are already dissolved in blood can randomly
escape back into alveoli (directly proportional to partial pressure in blood)
 When non-humidified air is breathed in, water immediately evaporates from surfaces of respiratory passages
and humidifies air, resulting from going above vapor pressure of water
o Vapor pressure of water depends on temperature (higher temperature means greater vapor pressure
o Vapor pressure at body temperature is 47 mm Hg
 Factors that affect rate of gas diffusion in fluid are partial pressure difference of gas, solubility of that gas in the
fluid (higher solubility equals more gas into fluid), cross-sectional area of fluid (high SA means gas allowed to
escape fluid), distance through which gas must diffuse, molecular weight of the gas, and temperature of the
o Diffusion rate is directly proportional to partial pressure difference, cross-sectional area of pathway, and
solubility of gas
o Diffusion rate is indirectly proportional to distance of diffusion and the square root of the molecular
weight of the gas
 CO2 can diffuse 20x as rapidly as O2 in body fluid (all the other major gases diffuse at rates just under that of O2)
Differences in Composition of Alveolar Air and Atmospheric Air
 Alveolar air has different concentrations of gases than atmospheric air because alveolar air is only partially
replaced by atmospheric air with each breath, oxygen and carbon dioxide are constantly being exchanged
between pulmonary blood and alveolar air, and dry atmospheric air that enters respiratory passages is
humidified before it reaches alveoli
 Because inspired water vapor is far below vapor pressure of water at body temperature, water vapor reaches
vapor pressure and dilutes all other gases in inspired air (dilution of oxygen and nitrogen starts as soon as
inspired air is humidified in nose because these are the two most abundant air types in atmospheric air)
 Because humans don’t completely inflate and deflate lungs with each breath, several breaths are required to
replace alveolar air (usually takes about 16 breaths to replace majority of air in lungs) – slow replacement of
alveolar air important in preventing sudden changes in gas concentrations in blood, making respiratory control
mechanism much more stable than it would be otherwise (arterial and tissue blood gases more stable)
 Oxygen continually absorbed from alveoli into blood, and new oxygen continually breathed into alveoli from
o The more rapidly oxygen is absorbed, the lower its concentration in alveoli becomes
o The more rapidly new oxygen breathed into alveoli from atmosphere, the higher its concentration
o Oxygen concentration in alveoli (partial pressure) controlled by rate of absorption into the blood and
rate of entry of new oxygen into lungs by respiration
o Increased oxygen absorption during exercise is reason one must breathe faster to maintain alveolar PO2
at normal value
o Even if air contains higher PO2 than normal air, alveolar PO2 can only approach the higher partial
pressures at a high rate of ventilation
 CO2 continually formed by body and carried in blood to alveoli, where it is removed by ventilation
o Alveolar PCO2 increases in direct proportion to rate of CO2 excretion
o Alveolar PCO2 decreases in inverse proportion to alveolar ventilation
Expired Air
 Overall composition of expired air determined by amount of expired air that is dead space air and amount that is
alveolar air
 Collecting alveolar air for study is achieved by collecting last portion of expired air after forceful expiration has
removed all dead space air
Diffusion of Gases through Respiratory Membrane
 Respiratory (pulmonary) membrane – membranes of alveoli and respiratory bronchioles collectively
 Respiratory membrane consists of
o Layer of fluid lining alveolus and containing surfactant that reduces surface tension of alveolar fluid
o Alveolar epithelium composed of thin epithelial cells
o Epithelial basement membrane
o Thin interstitial space between alveolar epithelium and capillary membrane
o Capillary basement membrane that (in many places) fuses with alveolar epithelial basement membrane
o Capillary endothelial membrane
 RBC membrane usually touches capillary wall, so gases need not pass through significant amounts of plasma as
they diffuse between alveolus and the cell
Factors that Affect Rate of Gas Diffusion Through Respiratory Membrane
 Factors that determine how rapidly gas will pass through membrane are thickness of membrane, surface area of
membrane, diffusion coefficient of gas in membrane substance, and partial pressure difference of gas between
the two sides of the membrane
 Thickness of respiratory membrane can increase as a result of edema fluid in interstitial space of membrane or
o Some pulmonary diseases cause fibrosis of lungs, which can increase thickness of some portions of
respiratory membrane
 Surface area of respiratory membrane can be decreased by removing portions of lung or emphysema (where
alveoli coalesce, losing alveolar walls for exchange)
 Diffusion coefficient for transfer of each gas depends on gas’s solubility in the membrane and is inversely
proportional to square root of gas’s molecular weight
Diffusing Capacity of Respiratory Membrane
 Respiratory membrane’s diffusing capacity – ability of respiratory membrane to exchange gas between alveoli
and pulmonary blood; measured by volume of gas that will diffuse through membrane each minute for a partial
pressure difference of 1 mm Hg
o Diffusing capacity for oxygen is 21 mL/min/mm Hg – mean oxygen pressure difference across respiratory
membrane during normal quiet breathing is 11 mm Hg, so about 230 mL of O2 diffuses through
respiratory membrane each minute (equal to rate at which resting body uses oxygen)
 During strenuous exercise or other conditions that greatly increase pulmonary blood flow and alveolar
ventilation, diffusing capacity for oxygen increases to about 3 times that of resting – caused by:
o Opening up of previously dormant pulmonary capillaries or extra dilation of already open capillaries,
increasing surface area of blood into which oxygen can diffuse
o Better match between ventilation of alveoli and perfusion of alveolar capillaries with blood (ventilationperfusion ratio)
 Thus, during strenuous exercise, oxygenation of blood increased by increased alveolar ventilation AND greater
diffusing capacity of respiratory membrane
 Diffusing capacity of CO2 has never been measured because it diffuses through respiratory membrane so rapidly
that average PCO2 in pulmonary blood is not very different from PCO2 in alveoli – happens too fast and difference
is too small to be measured, but can be calculated by using oxygen diffusion rate and carbon dioxide’s diffusion
 Oxygen diffusing capacity can be calculated from measurements of alveolar PO2, PO2 in pulmonary capillary
blood, and rate of oxygen uptake by blood
o Measuring PO2 in pulmonary capillary blood so difficult and imprecise that it is not practical to measure
oxygen diffusing capacity directly except on an experimental basis
o Usually measure CO diffusing capacity instead and calculate oxygen diffusing capacity from this
 Small amount of CO breathed into alveoli, and partial pressure of CO is measured from
appropriate alveolar air samples
 PCO in blood is essentially zero because Hgb combines with gas so rapidly that its pressure never
has time to build up
 Pressure difference of CO across respiratory membrane is equal to its partial pressure in alveolar
air sample
By measuring volume of CO absorbed in short period and dividing this by alveolar PCO, diffusing
capacity of CO is determined
 To convert CO diffusing capacity to O2 diffusing capacity, value is multiplied by 1.23 because
diffusion coefficient of O2 is 1.23 times that of CO
Effect of Ventilation-Perfusion Ratio on Alveolar Gas Concentration
 Some areas of lungs are well ventilated but have almost no blood flow, whereas other areas may have excellent
blood flow but little or no ventilation – in both instances, gas exchange through respiratory membrane is
seriously impaired and person may suffer severe respiratory distress despite both normal total ventilation and
normal total pulmonary blood flow because ventilation and blood flow are going to different parts of lungs
 Ventilation-perfusion ratio used to understand respiratory exchange when there is imbalance between alveolar
ventilation and alveolar blood flow
o This ratio is alveolar ventilation per minute divided by blood flow per minute
o At a ratio of either zero or infinity, there is no exchange of gases through respiratory membrane in the
affected alveolus
 When ventilation-perfusion ratio is zero, air in alveolus comes to equilibrium with blood O2 and CO2 because
they diffuse between blood and alveolar air
o Because blood that perfuses capillaries is venous blood returning to lungs from systemic circulation, it is
gases in this blood with which alveolar gases equilibrate
 When ventilation-perfusion ratio is infinity, alveolar air becomes equal to humidified inspired air, so it loses no
oxygen to blood and gains no carbon dioxide from blood
 When there is both normal alveolar ventilation and normal alveolar capillary blood flow, exchange of O2 and CO2
through respiratory membrane is nearly optimal, and alveolar gases are between those of inspired air and that
of venous blood
 Whenever ventilation-perfusion ratio is below normal, there is inadequate ventilation to provide oxygen needed
to fully oxygenate blood flowing through alveolar capillaries, so only a certain fraction of venous blood passing
through the pulmonary capillaries does not become oxygenated
o Shunted blood – the fraction of venous blood that does not become oxygenated in pulmonary capillaries
as well as the blood that flows through bronchial vessels
o Physiologic shunt – total quantitative amount of shunted blood per minute; measured by analyzing
concentration of oxygen in both mixed venous blood and arterial blood, along with simultaneous
measurement of cardiac output; can be calculated by
QPS/QT = (CiO2 – CaO2)/(CiO2 – CvO2)
where QPS is the physiologic shunt blood flow per minute, QT is cardiac output per minute, CiO2 is
concentration of oxygen in arterial blood if there is ideal ventilation-perfusion ratio, CaO2 is measured
concentration of O2 in arterial blood, and CvO2 is measured concentration of oxygen in mixed venous
o The greater the physiologic shunt, the greater the amount of blood that fails to be oxygenated as it
passes through lungs
 When ventilation of some of alveoli is great but alveolar blood flow is low, there is far more available oxygen in
the alveoli than can be transported away from alveoli by flowing blood – ventilation of these alveoli is said to be
o Ventilation of anatomical dead space areas is also wasted
 Physiologic dead space is wasted ventilation of alveoli with poor blood flow plus ventilation of anatomic dead
space – found using the equation
VDphys/VT = (PaCo2 – PeCO2)/PaCO2
where VDphys is physiologic dead space volume per minute, VT is tidal volume per minute, PaCO2 is partial pressure
of CO2 in arterial blood, and PeCO2 is average partial pressure of CO2 in entire expired air
o When physiologic dead space is great, much of work of ventilation is wasted effort because so much of
ventilating air never reaches blood
 In normal person in upright position, both pulmonary capillary blood flow and alveolar ventilation are
considerably less in upper part of lung than in lower part, but blood flow is decreased considerably more than
ventilation is, so VA/Q is about 2.5 times as great as ideal value, which causes moderate degree of physiologic
dead space in this area of the lung
In bottom of lung in same person, there is slightly too little ventilation in relation to blood flow, with
VA/Q as low as 0.6 times ideal value, so small fraction of blood forms physiologic shunt
o Both of these slightly decrease lung’s effectiveness for exchanging gases
During exercise, blood flow to upper part of lung increases markedly, so far less physiologic dead space occurs,
and effectiveness of gas exchange approaches optimum
Most people who smoke for many years develop various degrees of bronchial obstruction, potentially to the
point of emphysema because of serious alveolar air trapping
o Because many small bronchioles are obstructed, alveoli beyond obstructions are unventilated, causing
VA/Q that approaches zero
o In those areas of lung where alveolar walls have been mainly destroyed, but there is still alveolar
ventilation, most of ventilation is wasted because of inadequate blood flow to transport blood gases
In chronic obstructive lung disease, some areas of lung exhibit serious physiologic shunt, and other areas exhibit
serious physiologic dead space
o This is most prevalent cause of pulmonary disability today