Pulmonary Physiology

Lecture 1: Lung Mechanics and Ventilation

The Purpose of the Respiratory System

Very simply put, the purpose of the respiratory system is twofold: 1) To get O2 out of the air, into the
blood, and on its way to the tissues of the body, 2) To clear CO2 from the blood as it is generated by
those tissues. The purpose of this section of the course is to describe how the lung is able to achieve
this remarkable feat and how it is affected by and responds to the demands of the body.

Basic Structure

Air flows from the environment to the alveoli of the lung via approximately 23
generations of progressively bifurcating airways extending from the naso- and
oropharynx, through the trachea (generation 0), the right and left mainstem
bronchi (generation 1), the upper/lower/middle lobe bronchi (generation 2),
through several generations of bronchioles and terminal bronchioles, several
more generations of respiratory bronchioles, and finally to the alveolar ducts
and sacs. An important fact to note is that gas exchange does not occur over
the whole system – gas exchange only occurs in the transitional and
respiratory zones (beyond about generation 17 where the cross sectional area
is very, very large). Bulk flow of air, but not gas exchange, occurs higher up in
the conducting zone (we will learn that this area is called “anatomic dead
space”).

In order to facilitate gas exchange, the

alveolar-capillary membranes in the respiratory zone (alveolar
ducts and sacs) are extremely thin. The “wall” between two
alveolar sacs consists of two layers of epithelium over two
basement membranes separated in the very center by the
“interstitium,” where the pulmonary capillary lies (along with other
necessaries like lymphatics, nerves, and other connective tissue).
O2 moves from the alveolus through each of these layers on its way
into the blood and CO2 moves through each in the opposite
direction on its way from the blood to the alveolus.
Lung Volumes and Capacities

Gas exchange at the alveolar level occurs by diffusion, but gas movement between the pharynx and the
alveoli occurs by bulk and convective flow. These volumes and capacities are defined (a capacity is the
combination of more than one volume) and are CRITICAL to diagnosing many lung diseases by
pulmonary function testing (PFTs). I can’t overemphasize how important the diagram below is. Do the
little breathing exercise I outline below, understand it all, and then just suck it up and memorize it.
Draw it ten times from memory and it’s yours for life.

Normal inspiration starts from a point that we call functional residual capacity (FRC). You can feel this
point on yourself if you exhale “normally” to the bottom of a typical breath. Don’t force anything…that
point is the natural balance between the tendency of your lungs to collapse and the tendency of your
chest wall to expand out; that’s FRC. A typical, normal, comfortable breath in (the kind you don’t think
about) would take you
up to your tidal volume
(VT, for reference, a
comfy tidal volume is
maybe about 500 ml).
If, at the top of the
comfortable typical
breath you breathed in
until you could breathe
in no more, you would
have added your
inspiratory reserve
volume (IRV) to the
breath, which makes
sense because it’s how much more you could breathe in above tidal volume if you really tried. The tidal
volume plus the inspiratory reserve volume is your inspiratory capacity (IC), which makes sense because
it is the total amount you can breathe in from your functional residual capacity. You are now at your
total lung capacity (TLC), the total amount of air that can be held in your lungs. Now, if at the top of that
enormous breath, you started to breathe out and kept going until you were blue in the face and couldn’t
possibly breathe out any more, you would go below your tidal volume and enter the expiratory reserve
volume (ERV, just like the IRV, it’s how much more you could expire if you really tried) and go all the way
down to your residual volume (RV, which is the amount of air that is always left in your lungs due to the
chest wall recoil pulling outwards – you just can’t squeeze it all out no matter how hard you try). You
just breathed out your vital capacity (VC), the difference between total lung capacity at the top of a FULL
breath and residual volume, the amount left over after a FULL exhale.
Static Lung Mechanics: Properties of Elastic Structures

Static lung mechanics describe the relationship between pressure and volume in the respiratory system
and its structures. On the other hand, dynamic lung mechanics describe the relationship between
pressure and flow in the respiratory system. We will discuss static mechanics now and then move on to
dynamic mechanics in the next section.

As you may know, the lung is an elastic structure. The chest wall is also an elastic structure. Intuitively,
this makes sense, but what does it really mean? It’s stretchy. True, but technically, an elastic structure
is one in which the volume of the structure is directly proportional to the pressure difference across the
wall of the structure (we call this the transmural pressure, PTM, trans- being across and mural being
wall). The PTM of an elastic structure is the difference between the pressure inside and the pressure
outside:

PTM = pressure inside – pressure outside

Think of a balloon: as you blow air into it, the pressure difference across the plastic wall increases as the
pressure inside builds up (from you blowing) and therefore it increases in volume. If you move the
blown up balloon into a high pressure chamber so that the pressure outside the balloon is now higher
than atmospheric pressure, it will get smaller, right? That’s because the PTM is now lower. The pressure
inside minus the pressure outside decreased.

Defining the precise relationship between the PTM and the volume of a particular structure is incredibly
important because it allows us to determine the compliance of that structure. Compliance is a word you
need to know and understand in pulmonary medicine. You can think of it as “stretchiness.” The more
compliant a structure is, the more easily it is stretched. (Incidentally, doctors often speak of patients as
“compliant” if they follow directions well, take their meds, etc. This has fallen out of favor because it
implies a “moldability” of the patient and a power structure in the relationship. Anyhow, it may help
you to remember what the word means in physiology!)

The opposite of compliance is elastance. You can think of elastance as “recoil-ness.” The more elastic a
structure is, the more easily it recoils, like an elastic band would. Take a moment to understand the
difference between the two terms. They are simply inverses of
elastic limit
one another, but it’s really important that you understand
which one is “stretchy” (compliance) and which one is “recoily”
(elastance).

To mathematically determine the compliance and elastance of unstressed (compliance)

a structure, you need to measure its PTM at various volumes volume
and then plot them on a graph like the one you see in the
figure. The slope of the curve at each point (which (compliance)
mathematically is the V/P) is the compliance. Elastance is
the inverse (1 over V/P, which is P/V). To recap, a
structure that has high compliance and low elastance is easily
Adapted from: Sinclair et al. BMC Pulm Med 2010
distended. One that has low compliance and high elastance is not easily distended. It is important to
note that a single structure may have different degrees of compliance at different volumes, in other
words, the relationship is not always linear as we will see in the example below.

Let’s look at the figure on the previous page and go back to the balloon analogy: The empty balloon is
completely unstressed. As you blow into it, at first not much happens, right, it doesn’t really stretch so
much? So you blow pretty hard to start and you can get an initial change in volume. So at low volumes,
the balloon has low compliance and high elastance – it was not very easily distended. Once you get it
going, though, it’s pretty easy to blow it up, right? The compliance has increased and the elastance has
decreased, it is more easily distended (which corresponds to the middle portion of the curve). At some
point, though, you just can’t get it get any bigger no matter how much you blow (it’ll pop). The
compliance is low again and the elastance is high – the elastic limit has been reached.

Static Lung Mechanics: Pressure-Volume Curves of the Lung and Chest Wall

A similar figure could be drawn for the lung because it is an elastic structure. The lowest volume of the
lung occurs at the end of a forced exhalation after as much air as possible has been expelled from the
lungs (we call this the residual volume, RV). The highest volume occurs at the top of a full inhalation
when as much air as possible has been inhaled (we call this total lung
capacity, TLC). The pressure-volume curve (i.e., the compliance curve)
for the lung might look something like the figure shown. What’s
transmural pressure again? The difference in pressure across the “wall,”
defined as the pressure inside minus the pressure outside. For the lung,
“pressure inside” is alveolar pressure (PALV) and “pressure outside” is
pleural pressure (PPL). So for the lung:

PTM = PALV – PPL

The lung is an elastic structure which means that (like all elastic structures) its compliance can be
described by the relationship between volume and pressure within it. The chest wall is also an elastic
structure, which means that it too can be described by the relationship between pressure and volume
within it. The curve describing the compliance of the chest wall looks different than the lung, though. It
might look something like the one shown. Wait a minute, it’s opposite?
And why is the transmural pressure of the chest wall a negative number?!
And why is the volume smaller at lower pressures? Is that even possible?

Whoa, slow down. Let’s take it step by step. The PTM for the chest wall is
the pressure inside minus the pressure outside, right? Pressure outside is
easy, that’s atmospheric pressure (which by convention is taken to be zero
so that all pressures are relative to it, and is denoted as “body surface” or
PBS). Determining the pressure inside requires us to first figure out the
anatomic limit of the chest wall. What is “inside?” The lung is encased by the visceral pleura and the
inner chest wall is covered by the parietal pleura. This is the dividing line. So the pressure “inside” the
chest wall is the pleural pressure. So, for the chest wall:

PTM = PPL – PBS

PTM = PPL – 0

PTM = PPL

PPL is negative right? And we said that PBS is zero by convention, so PTM of the chest wall is effectively
equal to PPL and is therefore negative. But I thought negative pleural pressures made us breathe in, so
then shouldn’t the chest wall have larger volumes at lower pleural pressures because air is rushing in? I
see why you are confused and I understand. What is confusing to you is that you are thinking about the
respiratory system as a whole, not the isolated chest wall. Take the lungs and the effect of the
respiratory muscles out of the process (think physics here, not physiology). What we are describing here
is the compliance curve for the isolated resting chest wall alone, no lungs. If you had the chest wall
alone in a lab and you applied negative pressure to the inside of it, it would get smaller, right? That’s
what this curve describes. The next section will add in the lungs.

In reality, as you know, neither the lung nor the

chest wall actually acts alone. They each have their
own compliance, but they are physically tethered to
one another and jointly they make up the respiratory
system. Changes in the compliance of the
respiratory system may be due to changes in the
compliance of the lungs (for example decreased
compliance due to fibrosis) or due to changes in the
compliance of the chest wall (for example, decreased
compliance due to obesity), which is why we must
understand each of them alone in addition to
understanding their effects on one another. The
combined compliance of the respiratory system has
its own curve which might look something like the
one shown here.

Note that the compliance of the respiratory system usually falls between the two individual curves. The
PTM of the respiratory system is again equal to the pressure inside (PALV) minus the pressure outside (PBS).
Since PBS is zero, the PTM of the respiratory system is equal to the PALV. You should note the volume
marked “FRC” for (functional residual capacity) on the chart above. That is a very important value which
we will descibe in more detail later. For now, the important thing to understand is that it is the volume
at which the transmural pressure of the respiratory system is zero. PALV is zero. It is where the positive
transmural pressure of the lungs is equal and opposite to the negative transmural pressure of the chest
wall. Where in the breathing cycle do you think that would be?
Use the chart here to better understand the relationship
between each of these pressures and the associated lung
volumes. You can see here that inspiration is initiated by a
drop in pleural pressure from a negative value to a more
negative value. That causes alveolar pressure to drop from
zero (which is equal to body surface pressure, right?) to a
negative value. Air then flows down the pressure gradient
filling the alveoli and increasing lung volume until alveolar
pressure again reaches body surface pressure and the
gradient is obliterated. Expiration is then initiated by a
relaxation of the respiratory muscles with an increase in
pleural pressure to a less negative value. This allows the
lungs to recoil and alveolar pressure increases above body
surface pressure. Air rushes down it’s gradient again (now in the opposite direction, decreasing lung
volume) until alveolar pressure reaches zero (body surface pressure) once again. So when is alveolar
pressure equal to zero? At the end of expiration right before inhalation is intitated. That’s FRC.

Static Lung Mechanics: Effects of Gravity on Ventilation

Assuming that pleural pressure is uniform over the lung surface makes our calculations simpler, but
unfortunately is not true. In reality, when we are standing, gravity causes the pleural pressure at the
bases of our lungs to be more positive (less negative) than the pleural pressure at the apices. The more
negative pleural pressure at the apices means that the alveoli at the apices are more distended than
those at the bases. The fact that these alveoli are more distended at
baseline means that they do not change in size as much with each
inspiration as the less distended alveoli at the bases do. They are
more distended, but less well ventilated. Luckily, gravity also affects
regional blood flow in the lungs such that more blood flows to the
bases than to the apices. This is important because it leads to a
relative matching of ventilation and perfusion throughout the regions
of the lung. What do you think happens to ventilation and perfusion
when we lie down? Stand on our heads?

CO2 and Ventilation

We know that the primary function of the lungs is gas exchange – bringing oxygen into the blood and
bringing CO2 out of the blood. These functions are respectively called oxygenation and ventilation. Here
we will talk about ventilation.
As it turns out, room air contains no significant amount of CO2. So all of the CO2 in our expired air comes
from the body’s metabolism, none of it was “breathed in” on inhalation. To achieve adequate
ventilation, i.e. clear the body’s CO2 and maintain the blood pH in an acceptable range, the lungs must
get CO2 out of the blood and into the alveoli, and then out of the alveoli and into the atmosphere. The
first part, getting the CO2 out of the blood and into the alveoli is usually not a problem because of the
very high diffusivity of CO2 (more on this later). On the other hand, getting the CO2 from the alveoli into
the atmosphere is a bit trickier. One reason for this is that not all of the air that moves into and out of
the lungs is even involved in gas exchange.

Think of it like this, the first air that comes into the lungs will go
the deepest, all the way down to the alveolar sacs, right? Then as
additional air comes in, it will fill the alveolar ducts, and so on up,
such that the last bit of air that comes in will fill the trachea and
then the upper respiratory tract and the pharynx. Similarly, on
exhalation, the first air to leave will come from the pharynx and
upper respiratory tract, then the trachea, all the way down in
reverse. We know that the air in these upper areas (down to
about generation 17) does not participate in gas exchange. It is
thus ventilating the areas of the lung that we call “dead space”
because those areas are ventilated (get air), but not perfused (no
capillary blood for gas exchange). The air that goes to these regions, the “dead space ventilation” (VD),
typically makes up as much as 150 ml of a normal 500 ml tidal volume (VT). The remaining 350 ml of
each breath does participate in gas exchange (because it made it below about generation 17) and is
called “alveolar ventilation,” (VA). In addition to the anatomic dead space like the trachea, etc., the
diseased lung may have additional areas of physiologic dead space where perfusion is absent and
therefore gas exchange cannot occur. The most common example of this is bullous emphysema. More
on this later.

The important thing to remember is that the elimination of CO2 is dependent on alveolar ventilation,
NOT tidal volume because dead space ventilation does not contribute to gas exchange:

Alveolar Ventilation = Respiratory Rate x (Tidal Volume – Dead Space Ventilation)

This equation is an important one! If you understand it, you won’t need to memorize it because it will
make sense. Make sure you can do that.

Under normal conditions, the brain controls minute ventilation (respiratory rate x tidal volume) such
that the body’s production of CO2 matches its elimination in order to maintain a partial pressure of CO2
in the arterial blood equal to the partial pressure of CO2 in the alveoli. (Yes, they are always the same,
and normally about 40 mmHg.) You’ll see later that the brain can also adjust ventilation to keep this
value higher or lower than 40 mmHg in response to (compensation for) metabolic acidosis or alkalosis in
order to maintain an adequate blood pH.
Static Lung Mechanics: Surface Tension

An air-fluid interface is a place at which a liquid comes into

contact with air – like water droplets on a car. We all know that
water has a tendency to “bead up” and contract on a flat surface
and that this is due to surface tension, but what does that really
mean and why? Surface tension is caused by the fact that
molecules exert attractive forces on one another. Think of it like
this…all of the liquid phase molecules are drawn to one another
and are quite close together. At the surface of the liquid,
though, the outermost molecules are drawn to the deeper ones (those not in contact with the air), but
they are not drawn nearly as strongly to the sparse gas phase molecules of the air that they are also in
contact with. So they are drawn down and into the rest of the liquid more than they are drawn up and
out into the air. The surface of the liquid contracts and you see “beading” on the car.

This is important for lung physiology because the alveoli are air-fluid interfaces. The alveolar walls are
covered with water (like all of our mucus membranes) but are filled with air. They have a tendency to
collapse down due to surface tension. This means that in order to expand the alveoli, surface tension
must be overcome. To aid in this, the lung makes a substance called surfactant. Surfactant is essentially
a detergent. It decreases surface tension in the lungs just like soap decreases surface tension in water
droplets on a car. (Detergents have hydrophilic and hydrophobic components so they interrupt the
normal interactions between the liquid molecules at the surface.) Lung surfactant is really, really
important. It decreases the amount of distending pressure necessary to open the alveoli and it
increases alveolar volume at each pressure. So surfactant essentially makes alveoli more compliant,
right?

The graph at the right demonstrates two important things. First, on the left, it shows the relationship
between pressure and volume in the lungs with inspiration (up arrows) and expiration (down arrows)
when the lung is filled with saline. The curve on the right is the same, but when the lung is filled with air
(like it normally is). Notice that when the lung is filled with saline
instead of air, it can be filled to much higher volumes (saline curve is
higher on the y-axis) and at much lower pressures (saline curve is
further to the left on the x-axis). It is more compliant. This is
because there is no surface tension to be overcome when you fill the
lungs with saline – there’s no air-fluid interface. And the difference is
quite large, right? This should help you understand why surface
tension is an important factor to consider.

The second thing that the figure demonstrates is a property called

hysteresis. You will hear that term again. It’s fancy physics talk but
pulmonary physiologists really like this one. For this part, you can
forget about the saline curve except to note that there is no
hysteresis when there is no surface tension. Hysteresis refers to the From: http://www.meddean.luc.edu/lumen/MedEd/
medicine/pulmonar/physio/pf8.htm
fact that there is a gap between the inspiratory and expiratory limbs of the curve when the lung is filled
with air. Higher pressures are required to achieve each volume during inspiration than during expiration
(translate this to compliance…the lung is less compliant during inspiration than during expiration,
right?). Why is that? Again, the issue is surface tension. Surfactant decreases surface tension, but it
doesn’t eliminate it (if it did, the curve would be the same as for saline). When the lung is filling with air,
surface tension needs to be overcome to expand the alveoli. During expiration, though, surface tension
doesn’t need to be overcome. In fact, it’s kind of working in your benefit because it has a tendency to
collapse the alveoli – there is less pressure pushing out at each volume. That’s hysteresis.

Surfactant deficiency is a major cause of morbidity and mortality in premature infants. The immature
lungs of a pre-term baby are not yet producing the substance. These babies often suffer from
“Respiratory Distress Syndrome,” characterized by poor lung compliance with resulting hypoxemia. As
you might guess, it is treated by the instillation of exogenous surfactant.

Dynamic Lung Mechanics: Airflow and Resistance

While static lung mechanics describe the relationship between pressure and volume in the respiratory
system and its structures, dynamic lung mechanics describe the relationship between pressure and air
flow in the respiratory system – i.e., breathing. As we already discussed, gas exchange requires that air
flows down about 17 generations of branching airways in the conducting zone, then through another 6
generations of branching airways of the respiratory zone all the way down to the alveoli at
approximately generation number 23. Then it has to go all the way back up!

We know that what makes the air move into and out of the lungs is pressure. Or rather, pressure
gradients. Once again, when the diaphragm contracts, pleural pressure becomes more negative and
causes the lungs to expand. This causes alveolar pressure to decrease (sort of like a vacuum effect).
When alveolar pressure drops below atmospheric pressure, air rushes down the
tracheobronchial tree into the alveoli until the alveolar pressure is again equal to
atmospheric pressure. When the diaphragm and other inspiratory muscles relax, the
pleural pressure becomes more positive, alveolar pressure increases above atmospheric,
and the air rushes back out until alveolar pressure is once again equal to atmospheric.

The pattern of air flow through the “tubes” of the lung is also important. Air flow may
be described as laminar, turbulent, or transitive. With laminar flow, air moves smoothly
in the direction of flow. With turbulent flow, the net movement of gas is in the direction
of flow but locally air movement is irregular. Finally, transitive flow is similar to laminar
flow, but with small eddies that tend to occur near obstructions or branches.

Just like air flowing through any other tube, air flowing through the “tubes” of the lung is limited by
friction between the air and the walls of the bronchi. This ultimately leads to a drop in pressure across
the length of the tube. Laminar flow through a straight tube can be described by Poiseuille’s Law which
tells us that the drop in pressure across the tube is proportional to the length of the tube, the viscosity
of the gas, and the flow of the gas. But it is also inversely proportional to the fourth power of the radius
of the tube – in English, pressure drops more for longer tubes, thicker gases, and faster flows, but it
drops a lot less when the tube is wide. You can see how this might be important for airflow in the lungs.

Another way to capture this, is to consider airway resistance (RAW) which is defined as the change in
pressure across a segment divided by the flow across it (R = P/Q like always). For a tube, R is also
inversely proportional to the fourth power of the radius – the wider the tube, the less the resistance.
(That makes sense, right? Wider tube, less contact with sides, less
friction…)

So, naturally, you’d think that RAW should be highest in the distal
(smallest) airways, right? Turns out that’s not true. Well, only kind of
true. There is higher resistance in each of those small airways than in
each of the larger ones, but there are many, many, many more of the
small airways and they are arranged in parallel (yes, back to the
physics), so the overall resistance in the distal airways is actually much
lower than the overall resistance in the proximal airways. In fact,
resistance increases through about the fourth generation of airways
and then steadily drops distally. http://www.indiana.edu/~msci531/lecture/lecnotes/Book%201%20Fall%20

One additional wrinkle. Airways tend to get wider as lung volume increases (due to radial traction – the
“tethering” from other adjacent airways) and narrower as lung volumes decrease (due to decreased
radial traction). This means that airway resistance also increases dramatically
towards the end of expiration. Radial traction is concept that lots of folks have
trouble wrapping their brains around. Look at the figure to the right and see how
the connective tissue all around an airway can actually stent it open. That’s because
all the connective tissue surrounding the airway (“radial”) is pulling out on the
airway in a bunch of different directions (“traction”) thus keeping it widely open.
When lung volumes are highest, all that connective tissue is stretched and in turn
pulls more on the airway to which it’s attached. From: Scichilone N,I nt J Chron Obstruct
Pulmon Dis (2006)

So, in summary: 1) Though resistance is higher in individual small airways than in individual large ones,
overall resistance is lowest in the smallest airways, and 2) Due to radial traction on airways, resistance is
lowest at high lung volumes.

Dynamic Lung Mechanics: Forced Expiration

From all that we’ve learned so far, you might expect that the rate of air flow out of the lungs during a
forced expiration would be highly dependent on effort – the harder you blow, the faster the air comes
out. Actually, that’s not entirely true either. In reality, if you push reasonably hard, you reach a maximal
expiratory flow rate that cannot be increased by further increases in effort. Huh? You can push and
push, but the air will only go out so fast, never faster.

The figure on the right looks complicated, but we can walk

through it together. Let’s start with the colorful left side.
This is a graph of expiratory flow rates (y-axis) vs. pleural
pressures (x-axis) with the different colored curves
identifying forced exhalation at different lung volumes
(green is exhalation from 80% of full TLC, orange from 60%
of full TLC, and so on). It’s important to note that these
colored lines are isovolume curves – that means that the
green curve is showing flow rates at different pleural
pressures while the lung volume remains unchanged at
Pleural Pressure Lung Volume (%VC)
80% of TLC, there is no change in volume along each of
those curves.

Let’s start with the green curve. The patient breathed in to 80% of TLC then is told to force it out. You
can see that as pleural pressure increases (becomes less negative and eventually positive because of the
“squeezing” of the respiratory muscles), the flow rate initially increases but then it plateaus. Once a
certain pleural pressure is reached, further increases in pleural pressure make no difference in terms of
flow – so the patient can “squeeze” harder, but flow won’t change. While the same thing is true for a
volume of 60% of TLC and so on, note that the maximal flow achievable is dependent on lung volume –
the plateau is higher at 80% of TLC than it is at 20%.

That brings us to the right side of the figure. If you translate the maximal flows at each volume to a flow
vs. volume graph, you see that flow steadily decreases as we approach residual volume, (the amount of
air left in the lungs when we can squeeze out no more). Voila.

This brings up two questions: 1) Why can we only achieve a certain expiratory flow rate at any particular
lung volume? 2) Why does the maximal flow rate decrease with decreasing lung volume.

Let’s start with the first question. Why can we only achieve a certain expiratory
flow rate at any particular lung volume? This takes us back to pressure gradients.
Looking at the figure to the right, you can see that at this lung volume, the alveolar
pressure is +40. The patient begins a forced exhalation and generates a positive
pleural pressure of +30. So there is a transmural pressure of +10 at the alveolus,
right? Air will leave the +10 alveolus and head for the pressure of 0 at the mouth.
Along the way to the mouth, though, airway resistance (friction, mucus, spasm,
etc.) will cause a steady drop in airway pressure. At some point along the pathway
from the alveolus to the outside world, the pleural pressure will match the airway
pressure (here, where airway pressure is 30 and pleural pressure is 30) and the
transmural pressure will become zero. Gradient gone, no more flow. You can
imagine that this “equal pressure point” would probably occur closer to the alveolus for smaller airways
because they have more resistance than larger airways. At this particular lung volume, a certain number
of airways have reached that equal pressure point and have collapsed, dropping out of the equation and
causing the maximal flow to have been reached for that particular volume.

Now to the second question, why does the maximal flow rate decrease with decreasing lung volume?
The answer is twofold. At lower volumes, the alveolar pressure is lower to start with (less distended
alveoli, less pressure). Also, remember that airway resistance increases at lower lung volumes due to
decreasing radial traction on the airways. Essentially, airways have more resistance at lower volumes
because they aren’t “stented open” by surrounding tissue. The increased resistance causes a quicker fall
in airway pressure on the way to the mouth.

So why is this all important? The rate of airflow out of the lungs is something that we measure clinically
all the time! Specifically, the FEV1 (forced expiratory volume in one second) and the FVC (forced vital
capacity), are critical in diagnosing obstructive lung diseases (which we will discuss later).

Pulmonary Function Tests: Spirometry and Lung Volumes

Measuring airflow rates is the most common thing we do in the

PFT lab. We call this spirometry. Basically, the patient breathes
into a mouthpiece connected to a computer and we measure
how fast the air is moving in or out while they perform different
maneuvers.

Spirometry is critical in diagnosing lung disease, especially

obstructive lung diseases like COPD and asthma. We spent a long
time discussing maximal expiratory flow rates in the previous
section, and this is exactly why. During spirometry, we often ask
patients to do forced expiratory maneuvers so that we can
measure how quickly they are able to force the air out of their
lungs. If they cannot get air out as quickly as expected, we say
that they have an “obstructive ventilatory defect,” that is, there is
an obstruction to air flow that is slowing down the works. All this
tells us is that there is increased airway resistance. It doesn’t tell
us why. In the case of asthma, it may be due to bronchospasm.
In the case of emphysema, it may be due to loss of radial traction
on airways. As physicians, we use the knowledge gained from spirometry in conjunction with the rest of
the clinical picture to arrive at a diagnosis.

Looking at the bottom pane of the figure, and starting from the right, you can see that the patient was
asked to breathe in and out normally (that’s the tidal volume). They were then asked to breathe all the
way in as much as possible (that takes them up to their TLC). They are then asked to breathe out as
quickly and forcefully as possible all the way down till they can breathe out no more (now they are at
their RV). The total amount they blew out from the top of TLC down to RV is their vital capacity (VC).
Since it was “forced,” we call it FVC. We can then look back at the tracing and measure how much air
they were able to blow out in the first second, we call that the “forced expiratory volume in one second”
or FEV1. Normally, we can blow out about 80% of our entire FVC in the first second, which means that
the normal FEV1/FVC ratio is 0.8, right? If spirometry reveals that our patient has a ratio less than 0.8,
we are concerned about an obstructive ventilatory defect. We will discuss this more when we talk
about obstructive lung disease.

All of the volumes and capacities that we have discussed can be measured by simple spirometry with
one important exception -- the residual volume. Since you physically can’t breathe out the air left at the
end of a full exhalation (the residual volume), my computer can’t possibly measure it. So I can directly
measure all volumes except residual volume and I can therefore calculate all capacities except which
ones? Anything that includes the residual volume – the FRC and the TLC. I want those numbers, they’re
clinically important. So how can I measure residual volume so I can know the TLC? There are three
common ways to do this, helium dilution, nitrogen washout, and body plethysmography. For the
budding pulmonologists out there, read on and enjoy the technicalities of how these tests are done. For
those who are less inclined, the point that you must take home is that you cannot determine TLC or RV
from spirometry alone. If you want these values, you have to do an additional test to measure lung
volumes. This is very important because an entire class of lung diseases (restrictive lung disease) is
defined by an abnormally low TLC. We will discuss this more when we talk about restrictive lung
disease.

For my pulmonologists:

The helium dilution technique involves the patient first breathing all the way out to residual volume and
then breathing in a mixture of gas containing a known fraction of helium, which is highly diffusive and
non-absorbable (so it mixes with the alveolar air quite easily but does not get taken up in to the blood).
They keep breathing this helium mix through a closed circuit until the helium concentration in their
exhaled air reaches a steady-state. Now, since I know the initial concentration of helium in the mix, the
final concentration of helium in the exhaled air, and the final volume of air in the system, I can calculate
the initial volume in their lungs, which was the residual volume because that’s where I had them start!

Another way to calculate the residual volume is by nitrogen washout (The Fowler Technique). By this
technique, the patient starts at residual volume (they breathe all the way out first) inhaling 100% oxygen
with each breath through a one way valve. All of their exhaled air is collected through a separate circuit
and analyzed for nitrogen content. Since typical room air is about 80% nitrogen, the first exhaled breath
contains a concentration of nitrogen about 80%. Each subsequent breath, however, has less and less
nitrogen because the patient is inhaling 100% oxygen. Once all of the nitrogen has been “washed out”
of the lungs, the total volume of all of the exhaled gas is measured and multiplied by the average
nitrogen concentration in the exhaled air to determine the volume of nitrogen that was in the lungs at
the start of the test. Since we know that this volume of nitrogen made up 80% of the total volume in
the lungs before we started any of this, we can multiply the volume of nitrogen by 1.25 and find out the
initial volume of the lungs, which was residual volume because that’s where they started!

The final way to do this is by body plethysmography, which we sometimes called the “body box”
because the patient sits in a glass box to perform the test. The idea here follows Boyle’s Law which tells
us that a closed container at a constant temperature will have a constant
pressure x volume. Knowing the initial pressures and volumes of the box,
and the initial pressure in the lungs and then measuring the final pressure
and volume of the box and the final pressure of the lung, we can calculate
the initial volume of the lungs.

Basically, the patient sits in an airtight box breathing through a mouthpiece.

The patient breathes normally for a few breaths, and then at the end of a
normal tidal exhalation (that’s FRC, right?), the shutter on the mouthpiece
is suddenly closed just as the patient begins to inhale. Take a moment to
simulate this in yourself – inhale against a closed glottis. Did you notice
how your chest still expanded even though no air entered your lungs?
That’s what we measure in the box. As the volume of the patient’s chest
increases, the volume of the air in the box must decrease (the volume, not
the “amount”). Is the volume of the air in the box decreases, the pressure
in the box must increase by Boyle’s Law. We can measure the volume in From Levitsky, MG.
Pulmonary Physiology, 2013.
the box and the pressure in the box. We can also measure the pressure at
the mouth, which must have decreased as the volume of air in the lungs increased (again, the volume,
not the amount). Recall that initial pressure x volume of the box must equal final pressure x volume of
the box. We can easily measure initial pressure and volume and we can measure final pressure and
volume. The final volume in the box must be equal to the initial volume minus the amount equal to how
much the chest expanded. So we can solve for the change in volume of the chest:

Initial box pressure x Initial box volume = Final box pressure x Final box volume

Initial box pressure x Initial box volume = Final box pressure x (Initial box volume – Volume chest
expanded)

Similarly, the initial volume x pressure of the lungs must be equal to the final volume x pressure of the
lungs. The initial lung volume must be the final lung volume plus the amount the chest expanded. So
here we can now plug in the change in volume of the chest that we solved for above and now solve for
initial lung volume:

Initial lung pressure x Initial lung volume = Final lung pressure x Final lung volume

Initial lung pressure x (Initial lung volume + volume of chest expansion) = Final lung pressure x
Final lung volume
The initial lung volume that we solve for is the FRC because this is all occurring at end expiration. We
can use the FRC to calculate the RV by subtracting out the expiratory reserve volume measured by
spirometry (go back to your diagram above).

Critical Points

1) The airways of the lung branch progressively to about 23 generations. Gas exchange only takes place
in the respiratory zone, which is after about generation 17.

2) Lung volumes and capacities are defined and knowable. You should know them.

3) PTM is the pressure difference across the wall of an elastic structure (PTM = P inside – P outside).

4) Compliance is “stretchiness” (V/P). Elastance is “recoil-iness” (P/V).

5) The lungs and chest wall are elastic structures which can be described by independent compliance
curves. When you combine them, you describe the compliance of the “respiratory system,” which is
somewhere in between.

6) FRC is the lung volume at which the transmural pressure of the respiratory system is zero and PALV is
zero. It is were the positive transmural pressure of the lungs is equal and opposite to the negative
transmural pressure of the chest wall.

7) Gravity causes pleural pressure to be more negative at the apices than the bases. This means that
apical alveoli are more distended but less well ventilated.

8) The clearance of CO2 from the body is dependent on alveolar ventilation. Alveolar ventilation =
repsiratory rate x (tidal volume – dead space).

9) Surfactant is a substance made by the lung to reduce surface tension at the air-fluid interface of the
alveoli. It makes the alveoli more compliant. Despite the presence of surfactant, the surface tension
remains and causes hysteresis, decreased lung compliance on inspiration compared with expiration.

10) Though resistance is higher in individual small airways than in individual large ones, overall
resistance is lowest in the smallest airways. But, due to radial traction on airways, resistance is lowest at
high lung volumes.

11) Maximal expiratory flow rate at any given lung volume is independent of excessive pleural pressure
generated by a forced expiration.

12) Spirometry measures air flow in and out of the lung. It is a common tool during PFTs and can be
used to diagnose obstructive lung disease which are characterized by a reduction in the ratio of
FEV1/FVC.
13) Spirometry alone is insufficient for the determination of TLC, RV, or FRC. To determine these values,
lung volumes must be obtained by nitrogen washout, helium dilution, or body plethysmography.