NROSCI-BIOSC-MSNBIO
1070-2070
Respiration 2
October 13, 2015
Pulmonary
Pressures
 When discussing ventilation, it is
important to differentiate pleural
pressure, alveolar pressure, and
transpulmonary pressure.
 Pleural pressure is the pressure
of the fluid in the narrow space
between the lung pleura and the
chest wall pleura. Pleural
pressure is normally slightly
negative, as the lung tends to
“stick” to the thoracic wall.
 Alveolar pressure is the pressure
in the alveoli.
 Transpulmonary pressure is the
difference between the two
values. Transpulmonary
pressure is mainly generated by
the elastic forces in the lung,
and is a measure of recoil
pressure available to help
collapse the lungs at the end of
inspiration.
Pulmonary
Pressures
 Note that alveolar
pressure reaches its most
negative value about
halfway into inspiration.
Pleural pressure decreases
as long as the thoracic
cavity continues to
expand, but air flow into
the alveoli offsets the
negative pressure that is
being generated.
 Air flow into the lungs
continues until alveolar
pressure equals
atmospheric pressure,
which occurs at the end of
the inspiratory cycle.
Pulmonary Pressures
Note that pleural pressure becomes more negative during
inspiration, as the recoil tendency for the lungs is higher (the
elastic elements are stretched), which tends to cause
transpulmonary to increase as well.
Passive vs. Active Expiration
• Passive recoil is mainly responsible for forcing air
out of the lungs during expiration, which occurs
when alveolar pressure exceeds atmospheric
pressure. This passive recoil is generated by the
elastic forces in the lungs, and also by the chest
wall (muscle and bone).
• If ventilation exceeds 30 breaths per minute (the
average in resting is 12-20 breaths per minute), the
contraction of the expiratory muscles also
contributes to expiration. Contraction of the
abdominal muscles during active expiration pulls
the lower ribcage inward and decreases abdominal
volume. This causes the visceral contents to be
pushed up into the diaphragm, thereby decreasing
chest volume and forcing air out of the lungs. The
internal intercostal muscles also contribute to active
expiration, in that they act to compress the ribcage.
Pneumothorax
• It is interesting that respiration depends on such a
fragile thing as the lung and thoracic cavity pleural
membranes sticking together. This “bond” assures
that the lung expands with the ribcage, so that air will
be inspired, and that recoil after the inspiration can
produce expiration.
• Thus, it is tragic when air gets into the thoracic cavity,
as it breaks the bond between the pleural membranes.
This is what happens when a penetrating wound
makes a hole in the thoracic cavity. This condition,
called pneumothorax, results in a collapsed lung that
is unable to work properly. A pneumothorax can also
be created if the lung ruptures, allowing air into the
thoracic cavity.
Lung Compliance
• The process of respiration also depends on the lungs
being able to stretch properly. In fact, most of the
“work” of breathing goes into overcoming the
resistance of the elastic lungs and the respiratory
muscles. Thus, if the compliance (the inverse of
stiffness) of the lungs changes, breathing can be
impaired.
• Too much compliance is just as bad as too little, as
there is no elastic recoil to help force air out of the
lungs during expiration.
• Emphysema is a disease in which the elastin fibers in
the lungs break down; people with this disease find it
very difficult to achieve gas exchange. In addition,
many alveoli are lost in emphysema patients, as we
will see later in this lecture.
Restrictive Lung Disease
• Restrictive lung diseases occur when
lung compliance drops markedly.
• One example of such as disease is
fibrotic lung disease, which results when
prolonged exposure to irritants such as
asbestos leads to an accumulation of
scar tissue in the lungs.
Lung Compliance
• The pressure-volume curves
to the left show how
alterations in lung
compliance in different
pulmonary diseases affects
filling of the lungs during
breathing.
• In emphysema, the
compliance of the lungs is
high, so it is easy to distend
the lungs.
• In restrictive lung diseases,
the compliance of the lungs
is low, so expanding the
lungs is very difficult.
Surfactant
• Another condition that leads to a reduction of
lung compliance is a loss of surfactant.
• The fluid that moisturizes the alveolar wall
tends to produce surface tension, which
increases the resistance of the lung to stretch.
This is due to a natural tendency of water
molecules to aggregate, and to form a sphere.
• If surface tension went unchecked, it would be
very difficult to expand the lung. Fortunately,
the lung secretes surfactants that disrupt
cohesive forces between water molecules.
• Surfactants are typically lipoproteins.
Surfactant
• If surfactant production does not occur, many alveoli
would collapse. This is explained by the Law of
LaPlace, which describes the physics of a fluid sphere
or bubble. LaPlace’s law states that the pressure
inside a fluid-filled alveolus is dependent on surface
tension of the fluid and radius of the alveolus:
P=2 * T/r
P=pressure of alveolus
T=surface tension
r=radius of alveolus
Thus, if surface tension is high, then pressure inside small
alveoli would be great, and they would collapse as air flowed to
lower-pressure larger alveoli. Surfactants are not produced
until about 8 weeks before birth, which explains why premature
infants have a hard time in breathing.
Surfactant
Surfactant
Resistance of the Airways
• It is also essential that airway resistance be
minimized. Normally, the respiratory effort required
to overcome this resistance is trivial compared to
that required to overcome elastic forces of the lungs
and thoracic cavity.
• However, during pathological states this situation
can change. As you may recall, Poiseuille’s Law
states the following:
Q=
4
π∆Pr /
8ηl or R = 8ηl /
4
πr
Thus, if the radius of the airway diminishes, there
can be a huge change in resistance and flow. Mucus
accumulation in the airway passages during infection
can require tremendous respiratory effort to
overcome.
Resistance of the Airways
• Another factor that can affect airway
resistance is constriction of smooth muscle of
the bronchioles.
• This constriction can be induced neurally, by
activation of the parasympathetic nervous
system. This response helps to protect the
alveoli from inhaled irritants.
• The smooth muscle of bronchioles receives
practically no sympathetic innervation.
However, this smooth muscle possesses β2
receptors, and dilates when exposed to
circulating epinephrine. It is for this reason
that epinephrine is sometimes injected to
reduce respiratory resistance.
Resistance of the Airways
• A number of paracrine factors also affect the
constriction of smooth muscles of bronchioles:
– Carbon dioxide is the most potent agent, and acts
to induce vasodilation.
– Histamine, released during allergic reactions, acts
to produce bronchoconstriction.
– Asthma occurs in persons who are subject to
bronchoconstriction during exposure to particular
conditions that lead to release of appropriate
paracrine factors.
– As you might expect, β2 adrenergic agonists have
been used to treat asthma.
Lung Volumes
• Clinically, measures of lung volumes
can be useful. A spirometer measures
the volume of air moving during each
breath. It is useful to know the terms
that refer to lung volumes, and their
typical values.
Lung Volumes
maximal
amount
airtotal
that
••••Total
lung
capacity
is of
the
The
amount
of
additional
air can
••The
Even
The
after
term
a
expiratory
maximal
expiration,
reserve
The
amount
of
air
that
moves
normally
be
moved
islungs,
called
vital
amount
of
air
in
the
and a
that
you
can
inspire
following
some
volume
air
is
(ERV)
left
in
refers
the
lungs.
to
the
in a single
normal
inspiration
capacity,
and
is
the
summation
of
normal
tidal
inspiration
is
called
isThis
about
5.7L
(summation
of
amount
volume
of inspiratory
additional
is called
residual
air
that
or volume,
expiration
is called
tidal
tidal
reserve
inspiratory
reserve
volume
vital
capacity
and
residual
volume
can
beand
(RV),
exhaled
and
after
isan
about
a normal
1.2
volume
(VT).
In
averagevolume
expiratory
reserve
(IRV).
In you
a normal
male,isthis
volume).
volume.
As
can
calculate,
the
sized male,
this
volume
L.volume
expiration,
and
is
about
1
L.
is ~ 3L.
approximately
5004.5
ml.L.
vital capacity is about
Pulmonary Ventilation
• The term “total pulmonary ventilation” refers to the
amount of air moved into and out of the lungs per
minute. As you might imagine, total pulmonary
ventilation is calculated by the following formula:
• VT * Ventilation Rate = Total Pulmonary ventilation
• In an “average” male, tidal volume is 500 ml and
Ventilation Rate is 12 breaths/min.
Thus:
Total pulmonary ventilation = 500 ml/breath *
12 breaths/min = 6000 ml/min
Pulmonary Ventilation
• Total pulmonary ventilation is a misleading quantity,
as not all of this volume reaches the exchange
surface. Part of the air remains in the conducting
passageways, which are referred to as dead space
(because they are not involved in gas exchange).
Thus, to determine total alveolar ventilation, dead
space volume should be subtracted from tidal volume.
• In other words:
Alveolar Ventilation = Ventilation rate * (Tidal Volume Dead Space Volume)
• In an “average” man, dead space volume = 150 ml,
so:
Alveolar Ventilation = 12 breaths/min * (500 ml/breath 150 ml/breath) = 4200 ml/min
Question for
Discussion
• How is alveolar
ventilation affected
by breathing through
a tube (e.g.,
snorkel)?
Alveolar Gas Exchange
•• Two
factors
contribute
During
increases
and to the
decreases inof
alveolar
maintenance
constant
ventilation,
the and
partial
levels
of oxygen
carbon
pressure
of oxygen
dioxide
in the
alveoli:and
carbon
dioxide
in of
theoxygen
- First,
the
amount
alveoli can change
that enters an alveolus during
markedly.
each breath is approximately
• equal
However,
normal
to theduring
amount
that
tidal breathing, the partial
enters the blood.
pressures of these gases
- Second,
amount
of fresh
remainsthe
stable
in the
air
broughtThis
intomay
the seem
alveoli
alveoli.
during
each breath
is only
a
contradictory,
as you
might
fraction
totaltoair
in the
expect of
thethe
levels
change
markedly between
lungs.
inspiration and expiration.
Matching of Ventilation & Alveolar Blood Flow
• Bringing oxygen into the alveoli does little good unless the
circulatory system can pick-up the inspired gas. There is a
precise matching between air and blood flow to the alveoli for this
purpose.
• In the lungs, local factors are mainly responsible for this
matching. Arterioles in the lungs, unlike those in most other
vascular beds, are not extensively regulated by the autonomic
nervous system.
• Furthermore, capillaries in the lungs are collapsible. Near the
apex (top) of the lung, the capillaries are normally collapsed, and
blood flow is diverted to the base of the lung where gravity
causes hydrostatic pressure to be higher. During exercise,
when mean arterial pressure increases, the apex capillaries open,
and gas exchange takes place in a larger area of the lung. This
process is part of the reserve capacity of the lung.
• Pulmonary arterioles are mainly sensitive to local levels of
oxygen. When oxygen levels rise, the capillaries dilate to permit
more gas exchange. In contrast, the bronchiole smooth muscle is
most affected by carbon dioxide levels. When carbon dioxide
levels rise, then the smooth muscle relaxes to permit more
ventilation of the alveoli.
Matching of Ventilation & Alveolar Blood Flow
How Much
Gas is
Exchanged?
Gas Exchange in the Lungs
•
•
Simple diffusion governs the exchange of materials
between the blood and alveoli
Diffusion is limited by the following conditions:
➡ The rate of diffusion across membranes is directly
proportional to the partial pressure (concentration)
gradient.
➡ The rate of diffusion across membranes is directly
proportional to the available surface area.
➡ The rate of diffusion across membranes is inversely
proportional to the thickness of the membrane.
➡ Diffusion is most rapid over short distances.
Movement of O2 from Alveoli to Blood
• The gas laws state that gases move from regions of
higher partial pressure to regions of lower partial
pressure. Also recall that
in the alveoli is near
O2 the PO2
Alveolus
100 mm Hg. The PO2 in the blood returning to the lungs
is near 40 mm Hg. Thus, diffusion will cause oxygen to
move from the alveolus to the blood.
PO2=40 mm Hg
Plasma
O2
O2
PO2=100 mm Hg
RBC
Elimination of CO2
• Carbon dioxide
returning to the
lungs from the
systemic
circulation has a
partial pressure
of ~45 mm Hg,
whereas the
partial pressure
in the alveolus
is ~40 mm Hg.
Thus, diffusion
causes CO2 to
be eliminated
from the blood.
Diffusion and Gas Exchange
• Normally, diffusion between the alveolus and
blood occurs rapidly and efficiently, because
both oxygen and carbon dioxide are small
molecules that are both lipid and water
soluble. Furthermore, the specializations
that we discussed earlier (much of the
surface area of the alveolus is covered with
capillaries; the interstitial space is small) will
serve to maximize the diffusion process.
Impairment of Gas Exchange
• If the partial pressure of oxygen in an alveolus drops,
then oxygenation of the blood will be impaired. This
will occur if ventilation is impaired by diseases (e.g.,
asthma, which increases resistance in the
bronchioles), or if atmospheric pressure drops (as
occurs at high altitudes).
• For example, on the top of Mount Everest,
atmospheric pressure is 253 mm Hg, and so the
partial pressure of oxygen in the air is (0.21 * 253 =
53 mm Hg). Because air inspired during each breath
is only a fraction of air in lungs, the partial pressure of
air in the alveolus would only be 35 mm Hg (a value
less than that normally in venous blood). Obviously,
then, it would be impossible for a person to achieve
proper blood oxygenation if living on Mount Everest.
Impairment of Gas Exchange
• The principles of diffusion also
indicate that gas exchange
between the alveoli and lungs will
be impaired if there is a decrease
in the surface area available for gas
exchange, or if there is an increase
in the diffusion distance between
air and the blood. Emphysema is
associated with both the loss of
alveoli and connective tissue from
the lungs. As a result, surface area
available for diffusion of oxygen
into the blood is low, and PO2 in
blood will be low.
Impairment of Gas Exchange
• Diseases such as fibrosis can lead to a
thickening of the alveoli, which will affect
diffusion of gases into the blood, and PO2
will be low.
Impairment of Gas Exchange
• Pulmonary edema, which results from left
ventricular failure, will result in an expansion of
fluid volume in the interstitial space of the lung
and have the same effect (YOU SHOULD BE ABLE
TO EXPLAIN WHY THIS OCCURS).
Impairment of Gas Exchange
• Diseases such as asthma, in which alveolar
ventilation decreases, will result in low PO2 in the
alveoli, which translates to low PO2 in the blood.
Impairment of Gas Exchange
• If too little oxygen is in the blood, then
the cells will be deprived. This condition
is referred to as hypoxia. Often, hypoxia
goes hand-in-hand with hypercapnia, or
elevated concentrations of carbon
dioxide.
Effects of Pulmonary Disease
on Pulmonary Blood Flow
• Hypoxia results in a constriction of
pulmonary arterioles.
• As a consequence:
– the resistance in the pulmonary circulation
(afterload) increases
– ejection fraction decreases for the right
heart
– end systolic volume increases.
Effects of Pulmonary Disease
on Pulmonary Blood Flow
• Normal cardiac return adds to the
increased end systolic volume, such that
end diastolic volume is also larger.
• Hence, preload increases, and this
induces larger right ventricular
contractions.
• In the left heart, diminished blood return
through the pulmonary veins causes
preload to drop, and thus left ventricular
contractions are weaker.
Effects of Pulmonary Disease
on Pulmonary Blood Flow
• Accordingly, the Frank-Starling
mechanism serves to equalize left and
right ventricular cardiac output when
hypoxia is moderate.
• However, prolonged hypoxia results in
more severe changes in pulmonary blood
flow.