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Defense of the Lung
James E. Johnson, M. D.
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Outline
1. Defense problems unique to the lung
2. Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflexc. Alveolar macrophage function
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The lung has the same defensive needs as other
organs in terms of immunological and inflammatory
responses to infecting organisms. By virtue of the
constant airflow into and out of the airway, the lungis a major portal for entry of infection much like the
skin and GI tract which also contact infecting
organisms regularly. We will not cover immune
defense any further except to say that it is veryimportant to deal with what gets past the other
defenses that we will discuss below.
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The respiratory system has the special problem of
needing to defend against foreign materials entering
the airway. It is at risk of solids and liquids entering
by aspiration since the airway is oriented in an upand down configuration and swallowed materials go
right over the opening, referred to as the glottis
(specifically the glottis is defined as the vocal cords
and the space between them). Also, the lungs areat risk from inhaled particles and toxins given that
10,000 liters of air move in and out each day. These
substances enter by inhalation. The mechanisms
below reduce the risks of both of these problems.
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Entry of Noxious Substances into the
Lung
Aspiration
Inhalation
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Outline
Defense problems unique to the lung
Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflexc. Alveolar macrophage function
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2. Upper airway defense a. Glottic closureTo
function effectively, the airways need to be kept
free of particulate matter or liquids that could
occlude them. Also, liquids and large objectsusually carry bacteria which are likely to produce
lung infection. The upper airway needs (and has)
an effective mechanism for preventing aspiration
of liquids and solids into the trachea. The nextslide shows the appearance of the glottic opening
from above in a dissected specimen.
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I have witnessed this apparatus in action many times
during bronchoscopy, and the closed glottis
resembles a closed fist with complete obliteration of
any opening. Eliciting a gag reflex with thebronchoscope produces this glottic closure. I can
assure you that this mechanism works quite well, so
well that we sometimes have difficulty getting the tip
of the bronchoscope into the trachea despite localanesthetics. The muscles moving these structures
rapidly close the glottis when swallowing occurs in a
similar manner.
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Glottic Opening
Grants Atlas of Anatomy 6th ed. 1972, Williams & Wilkings.
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Outline
Defense problems unique to the lung
Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflexc. Alveolar macrophage function
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2. Upper airway defenseb. Warming and filtering
The nasal turbinates have a surface area of about
160 cm^2. As air moves through them, large
particles impact there and are caught in mucoussecreted onto the epithelial lining cells. Also, the
sharp turn from the upper airway to the glottis
causes particles larger than 10 microns to impact
on the upper airway wall where they are swallowedor expectorated (see next slide).
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Air is also warmed and humidified as it moves through
the upper airway. Both of these mechanisms are
more effective with nose breathing. Some irritants,
especially larger particles impacting in the upperairway stimulate irritant receptors producing the
sneeze reflex. The sneeze reflex is similar in many
ways to the cough reflex, but is under less voluntary
control. Expiratory gas flow is directed more towardthe nose with a sneeze than with a cough. This
tends to clear nasal obstruction.
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Upper Airway Anatomy
Levitsky MG, Pulmonary Physiology
6th
ed., McGraw Hill2003, p. 217.
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Particle Penetration into the Airway
1. Larger than 10 micronsabove the glottis
(sometimes activating the sneeze reflex)
2. 2-10 micronstrachea through bronchioles
3. Less than 2 micronsalveoli (most lessthan 0.5 microns stay suspended and are
exhaled)
4. Gaseseffects depend on solubility andchemical reactivity
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The slide above shows the penetration of particles into
the airway based on size. The larger the particle,
the higher in the airway it tends to impact. This
occurs because of inertia such that the heavierparticles cannot make the turns with airway
branching. Lighter particles will penetrate further.
Extremely light particles (< 0.5 microns in size) are
not deposited efficiently in the lung because theytend remain suspended in air and get exhaled.
Brownian motion will push some of these against the
alveolar wall however, so exhalation will not clear
100% of these particles from the lung.
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Gases will, of course, penetrate all the way to the
alveolus. What happens to various inhaled gases
will depend on chemical reactions with cellular
components in the lung and on their solubility in theblood. Gases that are well absorbed can have
distant effects. Inhaled anesthetics are examples of
gases with distant effects (CNS suppression)
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3 L i d f B ti l
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3. Lower airway defenseBecause many particlesget past upper airway defense, lower airwaydefense mechanisms are needed. The first ofthese we will consider is the mucociliary escalator.This is an extremely important mechanism that wetake for granted. Both patients with ciliary defects(immotile cilia syndromes) and those with mucousformation abnormalities (eg. cystic fibrosis) get
recurrent life threatening lung infections. Thesepatients get abnormally dilated, mucous-filled,chronically infected airways (a condition referred toas bronchiectasis).
Th lid b l h i EM f h
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The slide below shows a scanning EM of the
respiratory epithelium that is present from the
trachea through the terminal bronchioles (in fact,
much of the nasal epithelium looks like this also).These cilia beat at a frequency of 10-15 beats per
second, and they move in a coordinated fashion
such that mucous is continually swept up the
airway. Mucous movement gets more rapid in thecentral airways (about 1 mm/min in small airways
with up to 5-20 mm/min in the trachea).
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Th li i th i i d d b bl t
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The mucous lining the airways is produced by goblet
cells and by mucous glands which are located in
the submucosa. The mucous is a mixture of water,
electrolytes and a complex polymer ofmucopolysaccharides. Persons exposed
chronically to irritants such as cigarette smoke
often get hypertrophy of mucous glands with
increased amount and viscosity of mucous (thesechanges make mucous clearance more difficult).
Also, cigarette smoke is known to inhibit ciliary
function slowing mucous clearance. Slowing of
mucous clearance increases the contact time ofparticles in the lung. Infecting organisms then have
more time to reproduce increasing the risk of
clinical infection.
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Composition of Airway Mucous
Water
Electrolytes
Mucopolysaccharides
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Short-Term Effects of Smoking on
Lung Defense
Increased amount of mucous
Increased viscosity of mucous
Reduced ciliary movement
Alveolar macrophage dysfunction
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Outline
1. Defense problems unique to the lung
2. Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflexc. Alveolar macrophage function
The reason for the synchrony between cilia is not
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The reason for the synchrony between cilia is notknown with certainty. The mechanical linkagebetween the cilia due to the overlying blanket ofmucous seems to play a role.
Another very effective airway clearance mechanism isthe cough reflex which is used for larger particlesthat impact the airways and stimulate irritantreceptors. A cough has 3 phases as given on thenext slide. It differs from a forced vital capacitymaneuver in that the glottis is closed initially asexpiratory muscles are activated. The glottis is thenrapidly opened so that air escapes explosively. Thisis analogous to revving the engine of a car and
popping the clutch. If the tires get good tractionon the road, the car will accelerate more rapidlythan with smoothly letting off the clutch
With a cough a breath is inhaled (inspiratory phase)
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With a cough, a breath is inhaled (inspiratory phase),the glottis is closed and pressure as high as 200-300 cmH2O is generated in the chest (compressivephase) and then the glottis is opened (expulsivephase). Air acceleration is rapid producing airvelocities transiently as high as 500 miles per hourin the central airways (80-85% of the speed ofsound). This will shear mucous, particles and
objects off the wall of the airway and blow them outof the glotti opening. The cough mechanism is mosteffective in the central airways where velocities of airare greatest. Inadequate cough predisposes to
pneumonia (eg. low cervical spinal cordquadraplegia, which spares the diaphragm butparalyses expiratory muscles).
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The next two slides are presented to help illustrate the
difference between forced exhalation and cough.
During forced exhalation, maximal alveolar pressures
are 30 to 50 cmH2O at total lung capacity, but with
the cough maneuver they can be as high as 200 to
300 cmH2O. With forced exhalation, the glottis is
open so air moves as the expiratory musclescontract. With the compressive phase of a cough, the
glottis is closed and very high pressures can be
generated and all of it is transmitted up the airway.
No air is moving, so no pressure drop occurs due tothe resistance of the airway.
Th f th f ll i t i ht d th
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Therefore, the full pressure is present right under the
vocal cords and there is an explosive release as
they open. The transient high flow velocities in the
central airways blast out mucous, particles, etc. Thisis why your mother told you to put your hand over
your mouth when you cough.
If you leave your vocal cords open, all the same
principles that we studied during forced exhalation
will apply as the pressure drops and an equal
pressure point develops at a given lung volume. As
you know that is not what you do when you cough.You close your glottis again and build the central
airway pressure and repeat the explosion at a lower
lung volume. The result is a stair stepping process
down to FRC or even RV.
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Cough, Compressive Phase
200 cmH2O
200
200
Closed glottic
opening (not shown)
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Outline
1. Defense problems unique to the lung
2. Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflex
c. Alveolar macrophage function
The next four slides deal with alveolar macrophage
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The next four slides deal with alveolar macrophage
function. These cells are present in abundance in
the alveolus. If one does a bronchoalveolar lavage
by passing a bronchoscope into a 4th
or 5th
divisionbronchus and washing saline into the distal airway,
the material suctioned back through the scope will
have mainly alveolar macrophages in it (> 90% of
the cells with most of the remainder beinglymphocytes). These cells have many functions in
lung defense fulfilling the role that cells from the
monocyte lineage have in the immune response.
They are also major garbage collectors. Particlesthat reach the distal airways are recognized as
being not the usual milieu and are phagocytized.
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Netter FH, CIBA Collection of
Medical Illustrations 2nd
ed. 1980vol.7, p. 29.
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Alveolar Macrophage
Levitsky MG, Pulmonary Physiology
6th ed., McGraw Hill
2003, p. 220.
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Alveolar Macrophages
Amoeba-like mononuclear phagocytic cells
Ingest and kill organisms
Ingest and migrate upward with inert particles
Live 1-5 weeks
From monocyte lineage; participate in
immune response
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Macrophage Migration
Levitsky MG, Pulmonary Physiology
6th ed., McGraw Hill
2003, p. 221.
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Outline
1. Defense problems unique to the lung
2. Upper airway defensive functions
a. Glottic closure
b. Warming and filtering of air5. Lower airway defense
a. Mucociliary Escalator
b. Cough reflex
c. Alveolar macrophage function