Embryology of the Lung

The respiratory system begins to develop by the fourth week of gestation. A lung bud branches from the primitive esophagus and eventually forms the airways and alveolar spaces. The pulmonary arteries form near the branching airways and their growth matches the growth of the airways. Although virtually all other body systems are physiologically ready for extrauterine life by as early as 25 weeks’ gestation, the lungs require more time to mature. Thus lung maturity is the single most important factor that determines whether a premature infant can survive extrauterine life. Table 9-1 summarizes development of the respiratory system. Although the number of airway branches is fixed at birth, airway dimensions increase until the child is approximately 8 years old.²⁰² Alveoli multiply rapidly from an estimated 20 million alveoli at birth to 200 million by 3 years of age, and the number decreases thereafter. The alveolar surface is lined with type I and type II epithelial cells that are well developed at birth.⁹⁹

Table 9-1 Fetal Respiratory System Development

Anatomy of the Chest

The thoracic cavity is formed by the ribs, intercostal muscles, and diaphragm, and it contains both lungs and the mediastinal structures. The right lung is composed of three lobes, and the left lung is composed of two lobes.⁴⁹ The heart, great vessels, nerves, trachea, and esophagus are located within the mediastinum. Pleural tissue covers each lung and adheres to the surface of the diaphragm and inner surface of the chest wall.

The diaphragm is the principal muscle of inspiration. If the chest wall is sufficiently stiff and expands during inspiratory contraction of the diaphragm, thoracic volume increases in both longitudinal and transverse dimensions, and thoracic cavity pressure decreases.

The diaphragm is innervated on each side of the chest by the phrenic nerve, which is formed by the third, fourth, and fifth cervical spinal nerves. In older children and adults, the chest wall is relatively rigid compared with the chest wall of the neonate and infant. Therefore, when the diaphragm contracts in older patients, intrathoracic pressure falls in proportion to the movement of the diaphragm, and air moves into the lungs (Fig. 9-1).

Fig. 9-1 Chest cavity and related structures. A, Anterior view. B, Cross section.

(From Thompson JM, et al: Mosby’s manual of clinical nursing, ed 2, St Louis, 1989, Mosby.)

The ribs angle downward, from back to front, so that contraction of the external intercostal muscles will elevate the rib cage. The chest wall of an infant is compliant, and the external intercostal muscles stabilize the chest wall. When respiratory disease develops, pulmonary compliance is reduced. When the diaphragm contracts and produces a decrease in intrathoracic pressure, intercostal and sternal retractions develop rather than inflation of the lungs (Fig. 9-2). The more the chest wall retracts, the less the lungs inflate.

Fig. 9-2 Interaction of forces during inspiration and expiration. Equilibrium between recoil tendencies of lungs (to move inward) and chest wall (to move outward) is reached at the end of each normal expiration (A) and inspiration (C). During inspiration (B), the equilibrium is disrupted, with the chest wall tendency to move outward dominant (large arrows indicate chest wall tendencies). During expiration (D), the lung’s recoil tendencies are dominant (large arrows indicate recoil tendencies). The chest wall and lungs tend to expand and recoil together as the result of the subatmospheric pressure present in the pleural space.

(From Brashers VL: Structure and function of the pulmonary system. In McCance KL, Heuther SE: Pathophysiology: the biologic basis for disease in adults and children, ed 6, St Louis, 2010, Mosby.)

The diaphragm inserts more horizontally in infants than in older children or adults, and diaphragm contraction can contribute to subcostal retractions, particularly when the infant is supine.⁴⁹ The greater the retractions present, the more the diaphragm will need to contract or shorten to generate an adequate V_T. Retractions make ventilation inefficient, with the result that the diaphragm must shorten and move as much as 130% of normal to generate a V_T; this increases the work of breathing and can lead to respiratory muscle fatigue.

The airways distribute gas to all parts of the lung. As air passes through the nose and mouth it is warmed, humidified, and filtered. The upper airway thus serves as an air filter and an “air conditioner,” so air that reaches the trachea has been warmed to body temperature, is fully saturated with water, and is freed of small particles.

The amount of water vapor a volume of gas can contain depends on the temperature of the gas. The higher the temperature of the inspired gas, the greater the amount of water vapor contained in the gas. Heat is transmitted to inspired air by convection, whereas water is added by evaporation from the airway surface. Therefore there is usually a loss of heat and water from the body during breathing. Although a healthy child copes well with this loss, a small infant with lung disease can lose a substantial amount of heat and water when tachypnea develops. When water is lost from the airway surface, ciliary activity and mucociliary clearance are impaired, which can lead to the formation of mucous plugs, atelectasis, air trapping, or infection. When the upper airway is bypassed with an endotracheal tube (ETT) or tracheostomy, inspired gas must be humidified to avoid damage to the airway surface by mucosal drying.

The Upper Airway

The neonate (0-4 weeks of age) breathes predominantly through the nose, so any obstruction in the nose or nasopharynx will increase upper airway resistance and increase the work of breathing. For example, respiratory failure can be exacerbated in neonates by the insertion of a nasogastric tube or obstruction of the nares by secretions.

The airways of infants and children are much smaller than the airways of adults. Resistance to air flow in any airway will increase exponentially if the airway radius is compromised (see Box 9-1 and Fig. 9-3). This means that any decrease in airway radius can significantly compromise effective gas flow or increase the work of breathing. Relatively small amounts of mucus accumulation, airway constriction, or edema can substantially reduce airway radius in the infant or child, resulting in an increase in the resistance to air flow and the work of breathing.

Fig. 9-3 Relative effects of 1   mm of circumferential airway edema in a infant and young adult. A, The infant’s larynx is approximately 4   mm diameter, with a 2-mm radius. If 1   mm of circumferential edema develops, it will halve the airway radius and increase resistance to air flow by a factor of 16 if airflow is laminar, and it will increase resistance to turbulent airflow by up to 32 times. B, The young adult possesses a larynx approximately 10   mm in diameter and 5   mm in radius. Development of 1   mm of circumferential edema in the young adult will reduce the radius by approximately 20% (from 5 to 4   mm) and increase resistance to laminar air flow by a factor of 2.4.

Upper airway patency is maintained by the active contraction of muscles in the pharynx and larynx. Airway obstruction can develop if these muscles do not function properly or if the neck of an infant is flexed or extended. Airway obstruction can also develop during rapid-eye-movement sleep, when muscle tone is markedly reduced. The upper airway of the infant is fairly pliable and it can narrow during inspiration.

The infant upper airway is shaped like a funnel, whereas the upper airway of the older child and adult is more tubular. The glottis of an infant is located more anteriorly and more cephalad than in an older child, and the epiglottis is longer, making intubation of the trachea more difficult in the small infant, especially when the neck is hyperextended. The narrowest portion of the infant’s airway is at the level of the cricoid, whereas the narrowest portion of the airway in the adult is at the level of the vocal cords. Small amounts of edema or obstruction in the cricoid (subglottic) area will produce an increase in airway resistance and can lead to respiratory failure. Postnatally the airways increase in both length and diameter and major changes occur in the terminal respiratory units as the number and size of the alveoli increase.^49,182

Compliance and Resistance

From the time of the first breath, elastic fibers in the lung tissue create a tendency for the lungs to recoil inward (away from the chest wall). This recoil tendency is balanced by the propensity of the chest wall to spring outward. The net effect of these two opposing forces is to create a subatmospheric pressure in the intrathoracic space at the end of a normal breath (Fig. 9-2). During inspiration, the volume of the thoracic cavity is increased, and intrathoracic pressure becomes more negative with respect to atmospheric pressure. As a result, air moves from the mouth to the alveolar spaces. At the end of inspiration, the elastic recoil of the lungs and chest wall cause alveolar pressure to rise above atmospheric pressure, producing expiratory flow. In a person with normal lungs, expiration is passive and requires no muscular work.⁹²

The ratio of lung volume to transpulmonary pressure is called compliance. Compliance of the lung (C_L) is a measure of the distensibility of the lungs and is defined as the volume change (ΔV) produced by a transpulmonary pressure change (ΔP):

Compliance is high when the volume change produced by a given pressure change is large. Compliant lungs will inflate with very low pressure (i.e., the volume change produced by 1   cm H₂O pressure is large).

If the volume change produced by a given pressure change is small, the lungs are stiff and less compliant. When lung compliance is low, the work of breathing is increased. Compliance is increased in diseases such as emphysema and asthma, and it is decreased by pulmonary edema, pneumothorax, atelectasis, and pulmonary fibrosis. Compliance is difficult to measure, but effective compliance or dynamic compliance of the lung and chest wall can be measured in the intubated child during mechanical ventilation (see sections, Optimal PEEP and Common Diagnostic Tests).

Lung compliance is determined primarily by two factors: surfactant and the elasticity of lung tissue. Surfactant is a lipid material that spreads on the alveolar surface and prevents alveolar collapse as the alveoli get smaller during expiration. Surfactant lowers surface tension at low lung volumes.

Just as compliance is determined by lung tissue factors, resistance is determined primarily by airway size (diameter or radius). Airway resistance is defined as the driving pressure divided by the airflow rate. In the lung, the driving pressure for flow is the transairway pressure, which is equal to mouth pressure minus alveolar pressure during inspiration and alveolar pressure minus mouth pressure during expiration.

Resistance to air flow is directly proportional to three variables: flow rate, the length of the airway, and the viscosity of the gas. If any of these variables increases, resistance to air flow will increase.

In addition, resistance to air flow is inversely proportional to the fourth power of the airway radius (Box 9-1) when flow is laminar.¹¹⁰ Any reduction in the infant’s airway radius will result in exponential increases in the resistance to air flow and work of breathing (Fig. 9-3). Resistance to airflow is inversely related to the fifth power of the airway radius when air flow is turbulent (e.g., with upper airway obstruction).

For example, if the 4-mm airway of the infant is compromised by 1   mm of circumferential edema, the airway radius is reduced by 50% from 2 to 1   mm. The decrease in circumference will increase resistance to air flow by a factor of 16 if airflow is laminar, and by a factor of as much as 32 if airflow is turbulent. If the adult with a 10-mm airway develops the same 1   mm of circumferential edema, the adult’s airway radius will be reduced by 20% from 5 to 4   mm, and resistance to laminar air flow will be slightly more than doubled.

The small caliber of the pediatric airway increases the potential significance of any disorder that compromises airway size. Airway resistance is highest in the nasopharynx and lowest in the small bronchioles. Airway resistance is substantially increased in diseases such as asthma, cystic fibrosis, chronic lung disease, bronchiolitis, and tracheal stenosis and conditions with increased respiratory secretions. High airway resistance increases the work of breathing and creates respiratory distress. If a child with increased airway resistance develops respiratory muscle fatigue, respiratory failure will ensue.

Ventilation

The process of gas movement in and out of the lungs is defined as ventilation. Minute ventilation (volume per minute ) is the product of respiratory frequency and tidal volume:

For example, a patient breathing 30 times per minute, with a tidal volume of 100   mL, has a minute ventilation of 30  ×  100   mL, or 3000   mL/min.

Normal tidal volume during spontaneous respiration is approximately 6 to 7   cc/kg. Approximately 70% of tidal volume reaches the alveolar space, and 30% fills the conducting airways. The latter volume is called the anatomic dead space (V_D) and is typically approximately 2 to 3   cc/kg body weight. The anatomic dead space is the gas that remains in the conducting airways and does not participate in gas exchange. The remaining 70% of the volume that actually reaches the alveolar space is referred to as alveolar ventilation (V_A). Alveolar ventilation can be estimated by subtracting the anatomic dead space from the tidal volume (V_T):

For example, if the tidal volume is 100   mL, respiratory rate is 30/min, and the anatomic dead space is 20   mL, then alveolar ventilation would equal 30  ×  (100  −  20), or 2400   mL/min. Alveolar ventilation is always less than minute ventilation.

The rate of removal of carbon dioxide from alveoli and the rate of oxygen delivery to the alveoli are directly related to alveolar ventilation. Normal alveolar ventilation is defined as the level of ventilation that results in normal partial pressures of oxygen and carbon dioxide in arterial blood.¹⁰³

Anatomic dead space is just one part of the total dead space ventilation. A more clinically significant portion of dead space is the physiologic dead space. This space represents the volume of ventilation that reaches the alveoli that do not receive any pulmonary blood flow; therefore it is ventilation that does not participate in gas exchange. Ventilation of this portion of the lung is wasted. This concept is illustrated in Fig. 9-4. Normally, physiologic and anatomic dead space volumes are similar, but physiologic dead space can be significant in patients with pulmonary vascular disease or when positive end-expiratory pressure (PEEP) reduces pulmonary blood flow or whenever right ventricular output is reduced.

Fig. 9-4 The theoretical respiratory unit with graphic representation of the relationship between ventilation and perfusion in different clinical conditions. A, The ideal ventilation-perfusion ratio is . B and C, Lung diseases characterized by a loss of alveolar volume (e.g., acute respiratory distress syndrome) create V/Q ratios that are either low ()—shown in B—or zero ( which is the definition for intrapulmonary shunt)—shown in C. Importantly, low alveolar units are responsive to oxygen administration (i.e., results in an increase in PaO₂), whereas alveolar units (intrapulmonary shunt) are not responsive to oxygen administration. D, High units (dead space ventilation) are created under any circumstances in which pulmonary perfusion is reduced while alveolar ventilation is maintained. Thus any clinical condition that decreases right ventricular output (e.g., full cardiac arrest) or increases pulmonary vascular resistance (e.g., excessive PEEP) will result in increased dead space ventilation.

Lung Volumes

Lung volume measurements require patient effort; therefore accuracy is affected by patient cooperation. Such measurements are difficult or impossible to obtain in children who are uncooperative or who are younger than 5 years.

The total volume of the gas contained in the lung at maximum inspiration is the total lung capacity, Fig. 9-5. The volume that can be expired after a maximal inspiratory effort is the vital capacity (VC). This important and useful measurement of lung function is discussed in detail later in this chapter. VC can be reduced by any acute or chronic lung disease that increases lung stiffness (i.e., reduces lung compliance) or by conditions that limit available intrathoracic space (e.g., scoliosis, pneumonia, pleural effusion).

Fig. 9-5 Divisions of total lung capacity. A and B, Total lung capacity (TLC) is the maximum amount of air contained in the lungs. The total lung capacity is divided into four primary volumes: inspiratory reserve volume (IRV), tidal volume (V_T), expiratory reserve volume (ERV), and residual volume (RV). Capacities are combinations of two or more lung volumes; these include inspiratory capacity (IC), functional residual capacity (FRC), and VC. The IC is the IRV plus the V_T. The FRC is ERV plus the RV. The VC is depicted. Normal adult volumes are shown.

(From Patton KT, Thibodeau GA: Anatomy and physiology, ed 7, St Louis, 2010, Mosby.)

The volume of gas remaining in the lungs at the end of a normal expiration is the functional residual capacity (FRC). An increase in functional residual capacity usually indicates hyperinflation of the lung, or gas trapping, which is generally found in disorders characterized by decreased expiratory flow, such as chronic lung disease, cystic fibrosis, or asthma. A decrease in FRC may be seen in patients with pulmonary fibrosis or scoliosis.

Ventilation-Perfusion Relationships

As atmospheric air reaches the lungs (ventilation), it is exposed to pulmonary capillary blood perfusing the lungs. The distribution of perfusion and ventilation is not uniform in normal lungs. Because gravity affects blood flow, blood flow is greatest in dependent portions of the lungs. When the patient is supine, blood flow is greatest in the posterior portions of the lungs. When the patient is standing or sitting, blood flow is greatest in the inferior portions of the lung.

Pleural pressure is not uniform, so the upper lobes of the lungs receive more ventilation than the lower lobes. As a result of the effects of gravity and pleural pressure, some portion of pulmonary blood flow will not reach ventilated alveoli (i.e., there will be some dead space ventilation).

Intrapulmonary shunting exists in areas of the lung where alveolar ventilation is absent, but blood flow to the nonventilated alveoli persists (i.e., alveoli are not ventilated but are perfused, so is 0; see Fig. 9-4, C). Intrapulmonary shunting is the cause of reduced PaO₂ (hypoxemia) in diseases such as cardiogenic and noncardiogenic pulmonary edema (acute respiratory distress syndrome [ARDS]). By definition, hypoxemia associated with intrapulmonary shunting does not respond to supplementary oxygen administration, because the oxygen does not reach the nonventilated alveoli. This finding is in contrast to hypoxemia caused by partially ventilated alveoli (), which do respond to administration of supplementary oxygen (i.e., the PaO₂ increases). An important distinction is that alveoli that are not ventilated (i.e., ) must be recruited (opened) for supplementary oxygen to improve oxygenation. With treatment, the ratio is converted from zero (shunt) to low or normal (i.e., to oxygen-responsive hypoxemia).

Intrapulmonary shunt and low match are the most common causes of hypoxemia in pediatric lung disorders. These physiologic or abnormal intrapulmonary shunts do not result in hypercapnia (increased PaCO₂), because CO₂ is highly soluble in capillary blood and rapidly diffuses into the alveoli, and it is eliminated during expiration (exhalation).

During the first days of life, neonates demonstrate both cardiac and intrapulmonary shunting of blood. The cardiovascular shunt is caused by the patent ductus arteriosus with some desaturated pulmonary arterial blood shunted through the ductus into the arterial circulation (the aorta) without passing through the lungs. This right-to-left shunt occurs because pulmonary vascular resistance is high at birth. Once pulmonary vascular resistance begins to fall, the volume of right-to-left shunt falls. In infants with a patent ductus arteriosus, a PaO₂ of 60 to 80   mm Hg may be normal in the first day of life, but the PaO₂ typically exceeds 80   mm   Hg within 2 or 3 days after birth (Table 9-2) as pulmonary vascular resistance falls and the right-to-left shunt ceases. A small amount of right-to-left shunting can also occur in the immediate newborn period through a patent foramen ovale.

Table 9-2 Normal Arterial Blood Gas Values in Children

Gas Transport

The exchange of O₂ and CO₂ occurs in the alveolus. The gases diffuse through the alveolar-capillary membranes. The pressure gradient for CO₂ causes CO₂ to diffuse from the blood into the alveolar space, whereas the pressure gradient for oxygen causes oxygen to diffuse from the alveolar space to the blood. The amount of oxygen that diffuses through the alveolar-capillary membrane is determined by both the pressure gradient and the amount of functional alveolar membrane.

The Oxyhemoglobin Dissociation Curve

The relationship between the PaO₂ and the hemoglobin saturation is expressed by the oxyhemoglobin dissociation curve, as shown in Fig. 9-6, with the PaO₂ on the horizontal axis and the hemoglobin saturation on the vertical axis. The curve is not linear but S-shaped, with a large plateau at the higher levels of PaO₂. There are several important things to note about the oxyhemoglobin dissociation curve. As noted, the curve flattens when the PaO₂ exceeds 80 to 100   mm   Hg; this means that although the PaO₂ continues to rise beyond 100   mm   Hg, the hemoglobin cannot become more saturated than 100%, and it cannot carry any more oxygen. Any additional rise in the PaO₂ will result only in increases in the amount of dissolved oxygen in the blood, which contributes only 0.003   mL O₂ per mm   Hg rise in PaO₂. Therefore a rise in PaO₂ from 100 to 700 torr does not mean that sevenfold more oxygen is carried in the blood; it is associated with an approximately 10% increase in oxygen content. Because the hemoglobin is fully saturated once the PaO₂ reaches 100   mm   Hg, there is usually no advantage to maintaining the patient’s PaO₂ any higher than this value.

Fig. 9-6 Oxyhemoglobin dissociation curve. The horizontal or flat segment of the curve at the top of the graph is sometimes called the arterial portion, or that part of the curve where oxygen is bound to hemoglobin. This portion of the curve is flat because partial pressure changes of oxygen between 60 and 100   mm   Hg do not significantly alter the percent saturation of hemoglobin with oxygen. The wide range of partial pressures of oxygen (PaO₂  =  60-100   mm Hg) represented by the flat part of the curve, allows adequate hemoglobin saturation at a variety of altitudes. For example, a PaO₂ of 100   mm   Hg at sea level results in a hemoglobin saturation with oxygen of 98%. The steep part of the oxyhemoglobin dissociation curve occurs after the PaO₂ drops below 60   mm   Hg and represents the rapid dissociation of oxygen from hemoglobin. During this phase, oxygen diffuses rapidly from the blood into tissue cells. Conditions associated with altered affinity of hemoglobin for O₂ are listed. P50 is the PaO₂ at which hemoglobin is 50% saturated, normally 26.6   mm   Hg. A lower-than-normal P50 represents increased affinity of hemoglobin for O₂, such as is present in conditions such as alkalosis, hypocarbia, hypothermia. The lower P50 means that the hemoglobin will be better saturated at lower PaO₂ (e.g., at normal pH, a 90% oxyhemoglobin saturation is associated with PaO₂ of approximately 60   mm   Hg; at an alkalotic pH, a 90% oxyhemoglobin saturation will be associated with a lower PaO₂, probably nearer 50   mm   Hg). The increased affinity means that the hemoglobin does not release O₂ to the tissues as readily. A higher P50 is seen with decreased hemoglobin affinity for O₂. With decreased affinity for O₂, the hemoglobin is less saturated at a given PaO₂, but will release the oxygen more readily to the tissues. Note that variation from normal is associated with decreased (low P50) or increased (high P50) availability of O₂ to tissues (dotted lines). The shaded area shows the entire oxyhemoglobin dissociation curve under the same circumstances. 2,3-DPG, 2,3-diphosphoglycerate present in higher quantities in children with cyanotic heart disease and in lower quantities in neonates with large amounts of fetal hemoglobin.

(From Lane EE, Walker JF: Clinical arterial blood gas analysis, St Louis, 1987, Mosby.)

As shown in Fig. 9-6, the slope of the oxyhemoglobin dissociation curve becomes extremely steep once the PaO₂ is less than 60   mm   Hg. Thus when the patient’s PaO₂ falls below 60   mm   Hg, even small additional decreases in the PaO₂ will be associated with a significant fall in the hemoglobin saturation and arterial oxygen content. Therefore the patient’s PaO₂ should be maintained above 60   mm   Hg, if possible.

The position of the oxyhemoglobin curve can be altered by several factors (Table 9-3). If the curve is shifted to the right, then hemoglobin has less affinity for oxygen (it is less well saturated) at any partial pressure of oxygen (PaO₂). Conversely, if the curve is shifted to the left, then hemoglobin has a higher affinity for oxygen (the hemoglobin is better saturated) at any given PaO₂.

Table 9-3 Shifts in Hemoglobin Dissociation Curve

Shift to Left (Higher oxygen affinity)	Shift to Right (Lower oxygen affinity)
Alkalosis	Acidosis
Hypocapnia	Hypercapnia
Hypothermia	Hyperthermia
Fetal hemoglobin (decreased 2,3 DPG)	Increased 2,3 DPG
Methemoglobinemia	Adult hemoglobin

Factors that shift the curve to the right include acidosis, hypercapnia, and hyperthermia. Under these conditions the oxyhemoglobin saturation and oxygen content is lower at any given PaO_2, but within the normal range the amount of oxygen released to tissues is enhanced, which is an adaptive response that makes oxygen more available in the tissue beds of patients who are likely to need it (e.g., those who are acidotic, hypercapnic, febrile).²⁷¹ Factors that shift the oxyhemoglobin dissociation curve to the left include alkalosis, hypocapnia, and hypothermia. Although these factors increase oxyhemoglobin saturation at any given PaO₂, oxygen will not be as readily released to the tissues,²⁷¹ because oxygen is more tightly bound to the hemoglobin molecule.

The hemoglobin dissociation curve for fetal hemoglobin is located to the left of the adult hemoglobin curve. Thus at a given PaO₂ and hematocrit, fetal blood contains more oxygen than adult blood. This higher affinity of fetal hemoglobin for oxygen provides adequate fetal arterial oxygen content and delivery, despite the relatively low PaO₂ in the placenta and fetal circulation. Fetal hemoglobin, however, releases oxygen less readily to the tissues than does adult hemoglobin. Fetal hemoglobin usually disappears within 4 to 6 weeks after birth and is replaced by adult hemoglobin.

Stay updated, free articles. Join our Telegram channel

Join