Respiratory Physiology

Parameter	Bronchi	Conducting Bronchioles
Smooth muscle	Present (many layers)	Present (1-3 layers)
Cartilage	Yes	No
Epithelium	Pseudostratified columnar	Simple cuboidal
Ciliated	Yes	Yes (less)
Diameter	Independent of lung volume	Depends on lung volume
Location	Intraparenchymal and extraparenchymal	Embedded directly within connective tissue of lung

Bronchi contain supportive cartilage rings that prevent airway collapse during expiration.

a. If not for these cartilage rings, the bronchi would be more likely to collapse during expiration, when intrathoracic pressures increase substantially.

• As the bronchi branch into successively smaller airways, they have fewer cartilage rings.

Bronchioles: lack cartilage

a. Bronchial branches that have no cartilage and are less than 1 mm in diameter are termed bronchioles.

• Bronchi are not physically embedded in the lung parenchyma; this allows them to dilate and constrict independently of the lung, which helps them stay open during expiration so the lungs can empty.

Clinical note: In asthma, the smooth muscle of the medium-sized bronchi becomes hypersensitive to certain stimuli (e.g., pollens), resulting in bronchoconstriction. This airway narrowing produces turbulent airflow, which is often appreciated on examination as expiratory wheezing.

4. Mucociliary tract

• Bronchial epithelium comprises pseudostratified columnar cells, many of which are ciliated, interspersed with mucus-secreting goblet cells.

• The mucus traps inhaled foreign particles before they reach the alveoli.

a. It is then transported by the beating cilia proximally toward the mouth, so that it can be swallowed or expectorated.

b. This process is termed the mucociliary escalator.

Mucociliary escalator: impaired by smoking, diseases such as cystic fibrosis, and intubation

Primary ciliary dyskinesia: immotile cilia; absent dynein arm (see clinical note)

Kartagener syndrome: ciliary dyskinesia in a setting of situs inversus, chronic sinusitis, and bronchiectasis (see clinical note)

Clinical note: Primary ciliary dyskinesia is an autosomal recessive disorder that renders cilia in airways unable to beat normally (absent dynein arm). The result is a chronic cough and recurrent infections. When accompanied by the combination of situs inversus, chronic sinusitis, and bronchiectasis, it is known as Kartagener syndrome. Cigarette smoke causes a secondary ciliary dyskinesia. Cystic fibrosis and ventilation-associated pneumonia are other examples of conditions associated with dysfunction of the mucociliary tract.

5. Conducting bronchioles (see Table 5-1)

• In contrast to the bronchi, these small-diameter airways are physically embedded within the lung parenchyma and do not have supportive cartilage rings.

• Therefore, as the lungs inflate and deflate, so too do these airways.

C. Respiratory airways (Table 5-2)

1. These include respiratory bronchioles, alveolar ducts, and alveoli, where gas exchange occurs.

TABLE 5-2 Comparison of Conducting and Respiratory Airways

Parameter	Conducting Airways	Respiratory Airways
Histology	Ciliated columnar tissue	Nonciliated cuboidal tissue
	Goblet cells (mucociliary tract)	No goblet cells
		Lacks smooth muscle
Presence of cartilage	Yes	No
Resistance	Large diameter	Small diameter
	Arranged in series	Arranged in parallel
	High resistance	Low resistance

Respiratory airways: site of gas exchange

2. Despite their smaller size, airway resistance is less than in conducting airways, because the respiratory airways are arranged in parallel, and airflow resistances in parallel are added reciprocally.

Respiratory airways: ↓ resistance because arranged in parallel

D. Pulmonary membrane: the “air-blood” barrier (Fig. 5-1)

1. This is a thin barrier that separates the alveolar air from the pulmonary capillary blood, through which gas exchange must occur.

2. It comprises multiple layers, including, from the alveolar space “inward”:

• A surfactant-containing fluid layer that lines the alveoli

• Alveolar epithelium composed of pneumocytes (both type I and type II)

• Epithelial and capillary basement membranes, separated by a thin interstitial space (fused in areas)

• Capillary endothelium

5-1 Microscopic structure of the alveolar wall.

(From Kumar V, Abbas A, Fausto N: Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia, Saunders, 2005, Fig. 15-1.)

Type II pneumocytes: synthesize surfactant; repair cell of lung

Pathology note: The alveolar epithelium is primarily populated by type 1 epithelial cells, which play an important role in gas exchange. Type 2 epithelial cells are much less numerous but are important in producing surfactant (stored in lamellar bodies). When the pulmonary membrane has been damaged, type 2 epithelial cells are able to differentiate into type 1 epithelial cells and effect repair of the pulmonary membrane.

III. Mechanics of Breathing

B. Inspiration

1. Overview

• Inspiration is an active process that requires substantial expansion of the thoracic cavity to accommodate the inspired air (Fig. 5-2).

a. This expansion occurs primarily as a result of diaphragmatic contraction and, to a lesser extent, contraction of the external intercostal muscles (see Fig. 5-2).

5-2 A, Muscles of inspiration. Note how contraction of the diaphragm increases the vertical diameter of the thorax, whereas contraction of the external intercostal muscles results in anteroposterior and lateral expansion of the thorax. B, Movement of thoracic wall during breathing. C, Muscles of expiration.

(From Boron W, Boulpaep E: Medical Physiology, 2nd ed. Philadelphia, Saunders, 2009, Fig. 27-3.)

Diaphragm: most important muscle of respiration

• During forceful breathing (e.g., exercise, lung disease), contraction of accessory muscles such as the sternocleidomastoid, scalenes, and pectoralis major may be necessary to assist in expanding the thorax (see Fig. 5-2A).

Accessory muscles: sternocleidomastoid, scalenes, pectoralis major; important in forceful breathing

Clinical note: During normal inhalation at rest, abdominal pressure increases secondary to diaphragmatic contraction. This is evident by watching a supine person’s abdomen rise during quiet breathing (as long as the person is not trying to “suck in their gut”). In patients with respiratory distress, the abdomen may actually be “sucked in” while the accessory muscles of inspiration are contracting. This is known as paradoxical breathing and is an indicator of impending respiratory failure.

2. Driving force for inspiration

• A negative intrapleural pressure is created by movement of the diaphragm downward and the chest wall outward.

a. This acts like a vacuum and “sucks open” the airways, causing air to enter the lungs.

Negative intrapleural pressure: responsible for pressure gradient driving air into lungs

• The relationship between intrapleural pressure and lung volume is expressed by Boyle’s law:

where

P₁ = intrapleural pressure at start of inspiration

P₂ = intrapleural pressure at end of inspiration

V₁ = lung volume at start of inspiration

V₂ = lung volume at end of inspiration

a. Boyle’s law shows that as lung volume increases during inspiration, the intrapleural pressure must decrease (become more negative).

Boyle’s law: V₂ = P₁V_1/P₂; i.e., as lung volume ↑ during inspiration the intrapleural pressure must ↓

b. The pressure and volume changes that occur during the respiratory cycle are shown in Figure 5-3.

5-3 Pressure and volume changes during the respiratory cycle. Note that alveolar pressure equals zero at the end of a tidal inspiration (when there is no airflow). In contrast, at the end of a tidal inspiration, the pleural pressure has decreased to its lowest value (approximately −7.5 cm H₂O). The difference between pleural and alveolar pressures is referred to as the transpulmonary pressure.

Transpulmonary pressure: difference between pleural and alveolar pressures

C. Expiration

3. Sources of resistance during expiration

• As the volume of the thoracic cavity decreases during expiration, the intrathoracic pressure increases (recall Boyle’s law—the inverse relationship of pressure and volume).

• The increased pressure compresses the airways and reduces airway diameter.

a. This reduction in airway diameter is the primary source of resistance to airflow during expiration.

Airflow resistance during expiration: primarily due to ↓ airway diameter from ↑ intrathoracic pressures

• Figure 5-4 shows a flow-volume curve recorded during inspiration and expiration in a normal subject.

• Note the linear decline during most of expiration.

• Note also the contribution of radial fibers, which exert traction on these small airways to help prevent collapse during expiration.

5-4 Flow-volume curve recorded during inspiration and expiration in a normal subject. Note the linear decline during most of expiration. PEF, Peak expiratory flow; RV, residual volume; TLC, total lung capacity; VC, vital capacity.

(From Goljan EF, Sloka K: Rapid Review Laboratory Testing in Clinical Medicine. Philadelphia, Mosby, 2008, Fig. 3-3.)

Clinical note: If the lung were a simple pump, its maximum attainable transport of gas in and out would be limited by exhalation. During expiration, the last two thirds of the expired vital capacity is largely independent of effort. The best way to appreciate this is to do it yourself. No matter how hard you try, you cannot increase flow during the latter part of the expiratory cycle. The reduction in small airway diameter with resultant increase in airway resistance is the major determinant of this phenomenon. In contrast, large airways are mostly spared from collapse by the presence of cartilage. One can imagine the difficulty asthmatic individuals face during exhalation with the addition of bronchoconstriction.

D. Work of breathing

2. Airway resistance

• As inspired air courses along the airways, friction, and therefore airway resistance, is generated between air molecules and the walls of conducting airways.

a. Airway resistance normally accounts for approximately 20% of the work of breathing.

• Because air is essentially a fluid of low viscosity, airflow resistance can be equated to the resistance encountered by a fluid traveling through a rigid tube.

Air: essentially a low-viscosity fluid, so airflow resistance can be approximated by Poiseuille’s equation

a. Poiseuille’s equation relates airflow resistance (R), air viscosity (η), airway length (l), and airway radius (r), assuming laminar rather than turbulent airflow:

Poiseuille’s equation: R = 8ηl/πr⁴

b. In the lung, air viscosity and airway length are basically unchanging constants, whereas airway radius can change dramatically.

• Even slight changes in airway diameter have a dramatic impact on airflow resistance because of the inverse relationship of resistance to the fourth power of radius, as demonstrated in Poiseuille’s equation.

Airway diameter: small changes can have dramatic impact on airflow resistance because of inverse relationship of resistance to the fourth power of radius

Pathophysiology note: Airway diameter can be reduced (and airway resistance thereby increased) by a number of mechanisms. For example, airway diameters are reduced by smooth muscle contraction and excess secretions in obstructive airway diseases such as asthma and chronic bronchitis. Work caused by airway resistance increases markedly as a result.

Note that this description is a simplification, because Poiseuille’s equation is based on the premise that airflow is laminar. Although this is true for the smaller airways, in which the total cross-sectional area is large and the airflow velocity is slow, airflow in the upper airways is typically turbulent, as evidenced by the bronchial sounds heard during auscultation.

• Contribution of large and small airways to resistance

a. Under normal conditions, most of the total airway resistance actually comes from the large conducting airways.

• This is because they are arranged in series, and airflow resistances in series are additive, such that

Large airways: contribute most to airway resistance; arranged in series with small total cross-sectional area

b. By contrast, the small airways (terminal bronchioles, respiratory bronchioles, and alveolar ducts) provide relatively little resistance.

• This is because they are arranged in parallel, and airflow resistances in parallel are added reciprocally, such that

c. Resistance is low in smaller-diameter airways despite the fact that Poiseuille’s equation states that resistance is inversely proportional to the fourth power of airway radius.

• This is because the branches of the small airways have a total cross-sectional area that is greater than that of the larger airways from which they branch.

• Additionally, flow in these small airways is laminar rather than turbulent, and it is very slow.

Small airways provide relatively little resistance: arranged in parallel; large total cross-sectional area; slow/laminar flow

Pharmacology note: Many classes of drugs affect large-airway diameter by affecting bronchial smooth muscle tone. For example, β₂-adrenergic agonists such as albuterol directly stimulate bronchodilation. Most other classes work by preventing bronchoconstriction or by inhibiting inflammation (which reduces airway diameter); these include steroids, mast cell stabilizers, anticholinergics, leukotriene-receptor antagonists, and lipoxygenase inhibitors.

E. Pulmonary compliance (C)

1. This is a measure of lung distensibility.

• Compliant lungs are easy to distend.

2. Defined as the change in volume (ΔV) required for a fractional change of pulmonary pressure (ΔP):

Lung compliance: compliant lungs are easy to distend

3. Compliance of the lungs (Fig. 5-6)

• In the schematic, note that the inspiratory curve has a different shape than the expiratory curve.

• The lagging of an effect behind its cause, in which the value of one variable depends on whether the other has been increasing or decreasing, is referred to as hysteresis.

• Hysteresis is an intrinsic property of all elastic substances, and the compliance curve of the lungs represents the difference between the inspiratory and expiratory curves.

5-6 Compliance curve of the lungs: lung volume plotted against changes in transpulmonary pressure (the difference between pleural and alveolar pressure). During inspiration, maximal compliance occurs in the midportion of the inspiratory curve. The difference between the inspiration curve and the expiration curve is referred to as hysteresis. Hysteresis is an intrinsic property of all elastic substances.

Compliance curve of the lungs: compliance greatest in midportion of curve; demonstrates hysteresis

• Note also that compliance is greatest in the midportion of the inspiratory curve.

4. Compliance of the combined lung–chest wall system (Fig. 5-7)

• In the schematic, note that at functional residual capacity (FRC), the lung–chest wall system is at equilibrium.

• In other words, at FRC, the collapsing pressure from the elastic recoil of the lungs is equal to the outward pressure exerted from the chest wall.

5-7 Compliance of the lungs and chest wall separately and together. FRC, Functional residual capacity.

(From West JB: Respiratory Physiology: The Essentials, 8th ed. Philadelphia, Lippincott Williams & Wilkins, 2008, Fig. 7-11.)

Lung–chest wall system: at equilibrium at FRC

Pathology note: In emphysema, destruction of lung parenchyma results in increased compliance and a reduced elastic recoil of the lungs because of destruction of elastic tissue by neutrophil-derived elastases. At a given FRC, the tendency is therefore for the lungs to expand because of the unchanged outward pressure exerted by the chest wall. The lung–chest wall system adopts a new higher FRC to balance these opposing forces. This is part of the reason patients with emphysema breathe at a higher FRC. Breathing at a higher FRC also keep more airways open, which decreases airway resistance and minimizes dynamic airway compression during expiration.

F. Pulmonary elastance

1. Elastance is the property of matter that makes it resist deformation.

• Highly elastic structures are difficult to deform.

2. Pulmonary elastance (E) is the pressure (P) required for a fractional change of lung volume (ΔV):

Elastance: elastic structures are difficult to deform, e.g., fibrotic lungs

3. As elastance increases, increasingly greater pressure changes will be required to distend the lungs.

Clinical note: In restrictive lung diseases such as silicosis and asbestosis, inspiration becomes increasingly difficult as the resistance to lung expansion increases in response to increased lung elastance, resulting in reduced lung volumes and total lung capacity. In obstructive lung diseases such as emphysema, there is reduced lung elastance secondary to destruction of lung parenchyma and loss of proteins that contribute to the elastic recoil of the lungs (e.g., collagen, elastin). Expiration may therefore become an active process (rather than a passive one), even while at rest, because the easily collapsible airways “trap” air in the lungs. “Pursed-lip breathing,” an attempt to expire adequate amounts of air, is often seen; it creates an added pressure within the airways that keeps them open and allows for more effective expiration.

G. Surface tension

1. The fluid lining the alveolar membrane is primarily water.

2. The water molecules are attracted to each other through noncovalent hydrogen bonds and are repelled by the hydrophobic alveolar air.

3. The attractive forces between water molecules generate surface tension (T), which in turn produces a collapsing pressure, which acts to collapse the alveoli.

Surface tension: created by attractive forces between water molecules; produces a collapsing pressure

4. Laplace’s law states that collapsing pressure is inversely proportional to the alveolar radius, such that smaller alveoli experience a larger collapsing pressure:

where

CP = collapsing pressure

R = alveolar radius

T = surface tension

5. Figure 5-8 demonstrates that saline-inflated lungs are more compliant that air-inflated lungs because of reduced surface tension and collapsing pressures.