2007 defense of the lung.ho

8/14/2019 2007 Defense of the Lung.ho

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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





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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





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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



a. Glottic closure




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



a. Glottic closure



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


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


6th ed., McGraw Hill

2003, p. 221.


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Outline



a. Glottic closure



b. Cough reflex

c. Alveolar macrophage function

2007 defense of the lung.ho

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