2007 Defense Of The Lung.ho

Defense of the Lung

James E. Johnson, M. D.

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function 1. 2.

Special Defense Problems of the Lung 1. Gravity and swallowing 2. Airborne particles and toxins

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 lung is 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 very important to deal with what gets past the other defenses that we will discuss below.

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 up and 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 are at 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.

Entry of Noxious Substances into the Lung  Aspiration  Inhalation

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function • •

2. Upper airway defense a. Glottic closure—To function effectively, the airways need to be kept free of particulate matter or liquids that could occlude them. Also, liquids and large objects usually 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 next slide shows the appearance of the glottic opening from above in a dissected specimen.

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 the bronchoscope 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 local anesthetics. The muscles moving these structures rapidly close the glottis when swallowing occurs in a similar manner.

Glottic Opening

Grant’s Atlas of Anatomy 6th ed. 1972, Williams & Wilkings.

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function • •

2. Upper airway defense—b. 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 mucous secreted 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 swallowed or expectorated (see next slide).

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 upper airway 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 toward the nose with a sneeze than with a cough. This tends to clear nasal obstruction.

Upper Airway Anatomy

Levitsky MG, Pulmonary Physiology 6th ed., McGraw Hill 2003, p. 217.

Particle Penetration into the Airway Larger than 10 microns—above the glottis (sometimes activating the sneeze reflex) 2. 2-10 microns—trachea through bronchioles 3. Less than 2 microns—alveoli (most less than 0.5 microns stay suspended and are exhaled) 4. Gases—effects depend on solubility and chemical reactivity 1.

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 heavier particles 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 they tend 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.

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 the blood. Gases that are well absorbed can have distant effects. Inhaled anesthetics are examples of gases with distant effects (CNS suppression)

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function 1. 2.

3. Lower airway defense—Because many particles get past upper airway defense, lower airway defense mechanisms are needed. The first of these we will consider is the mucociliary escalator. This is an extremely important mechanism that we take for granted. Both patients with ciliary defects (immotile cilia syndromes) and those with mucous formation abnormalities (eg. cystic fibrosis) get recurrent life threatening lung infections. These patients get abnormally dilated, mucous-filled, chronically infected airways (a condition referred to as bronchiectasis).

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 the central airways (about 1 mm/min in small airways with up to 5-20 mm/min in the trachea).

Scanning EM of Respiratory Cilia

Levitsky MG, Pulmonary Physiology 6th ed., McGraw Hill 2003, p. 217.

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 of mucopolysaccharides. Persons exposed chronically to irritants such as cigarette smoke often get hypertrophy of mucous glands with increased amount and viscosity of mucous (these changes 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 of particles in the lung. Infecting organisms then have more time to reproduce increasing the risk of clinical infection.

Composition of Airway Mucous  Water  Electrolytes  Mucopolysaccharides

Short-Term Effects of Smoking on Lung Defense  Increased amount of mucous  Increased viscosity of mucous  Reduced ciliary movement  Alveolar macrophage dysfunction

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function 1. 2.

The reason for the synchrony between cilia is not known with certainty. The mechanical linkage between the cilia due to the overlying blanket of mucous seems to play a role. Another very effective airway clearance mechanism is the cough reflex which is used for larger particles that impact the airways and stimulate irritant receptors. A cough has 3 phases as given on the next slide. It differs from a forced vital capacity maneuver in that the glottis is closed initially as expiratory muscles are activated. The glottis is then rapidly opened so that air escapes explosively. This is analogous to revving the engine of a car and “popping” the clutch. If the tires get good traction on the road, the car will accelerate more rapidly than with smoothly letting off the clutch

With a cough, a breath is inhaled (inspiratory phase), the glottis is closed and pressure as high as 200300 cmH2O is generated in the chest (compressive phase) and then the glottis is opened (expulsive phase). Air acceleration is rapid producing air velocities transiently as high as 500 miles per hour in the central airways (80-85% of the speed of sound). This will shear mucous, particles and objects off the wall of the airway and blow them out of the glotti opening. The cough mechanism is most effective in the central airways where velocities of air are greatest. Inadequate cough predisposes to pneumonia (eg. low cervical spinal cord quadraplegia, which spares the diaphragm but paralyses expiratory muscles).

Phases of a Cough Inspiratory phase 2. Compressive phase* 3. Expulsive phase* 1.

*Compressive

and expulsive phases usually occur more than

once with a given exhalation; cough is dependent on active exhalation.

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 muscles contract. 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 to the resistance of the airway.

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. This is 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.

Forced Expiration with Pleural Pressure of 30 cm H2O

Netter FH, CIBA Collection of Medical Illustrations 1st ed. 1979 vol.7, p. 60..

Cough, Compressive Phase 200 Closed glottic opening (not shown)

200 200 cmH2O

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function 1. 2.

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 division bronchus 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 being lymphocytes). 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. Particles that reach the distal airways are recognized as being not the usual milieu and are phagocytized.

Organisms are usually killed by the impressive destructive weapons these cells have. Particles that cannot be destroyed are carried with the cell. Its usual fate is migration into the bronchioles where the mucociliary escalator carries the cell and the particle up and out. Healthy smokers have 2-3 times as many of these cells in their bronchoalveolar lavage material as normals. They are filled with a black oily material.

Netter FH, CIBA Collection of Medical Illustrations 2nd ed. 1980 vol.7, p. 29.

Alveolar Macrophage

Levitsky MG, Pulmonary Physiology 6th ed., McGraw Hill 2003, p. 220.

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

Macrophage Migration

Levitsky MG, Pulmonary Physiology 6th ed., McGraw Hill 2003, p. 221.

Outline Defense problems unique to the lung Upper airway defensive functions a. Glottic closure b. Warming and filtering of air 5. Lower airway defense a. Mucociliary Escalator b. Cough reflex c. Alveolar macrophage function 1. 2.