Essentials of Pulmonology

Respiratory Physiology

The morphologic development of the lung begins at several weeks after conception and continues into the first decade of postnatal life. Intrauterine gas exchange occurs via the placenta, but the respiratory system develops in preparation for extrauterine life, when gas exchange transfers abruptly to the lungs at birth.

Development of the lung, which begins as an outgrowth of the foregut ventral wall, can be divided into several stages ( Fig. 13.1 ). During the embryonic period, in the first few weeks after conception, lung buds form as a projection of the endodermal tissue into the mesenchyme. The pseudoglandular period extends to the 17th week of life, during which rapid lung growth is accompanied by formation of the bronchi and branching of the airways down to the terminal bronchioli. Further development of bronchioli and vascularization of the airways occurs during the canalicular stage of the second trimester. The saccular stage begins at approximately 24 weeks, when terminal air sacs begin to form. The capillary networks surrounding these air spaces proliferate, allowing sufficient pulmonary gas exchange for extrauterine survival of the premature neonate by 26 to 28 weeks. Formation of alveoli occurs by lengthening of the saccules and thinning of the saccular walls and has begun by the 36th week after conception in most human fetuses. The vast majority of alveolar formation occurs after birth, typically continuing until 8 to 10 years postnatally. At birth, the neonatal lung usually contains 10 to 20 million terminal air sacs (many of which are saccules rather than alveoli), one-tenth the number in the mature adult lung. After birth, growth of the lungs occurs primarily as an increase in the number of respiratory bronchioles and alveoli rather than an increase in the size of the alveoli.

The abrupt transition to extrauterine gas exchange at birth involves the rapid expansion of the lungs, increased pulmonary blood flow, and initiation of a regular respiratory rhythm. The development of a respiratory rhythm, detectable initially by intermittent rhythmic fetal thoracic movements, begins well before birth and may be necessary for normal anatomic and physiologic lung development. Interruption of umbilical blood flow at birth initiates continuous rhythmic breathing. Amniotic fluid is expelled from the lungs via the upper airways with the first few breaths, with residual fluid draining through the lymphatic and pulmonary channels in the first days of life. Changes in the partial pressures of oxygen (P o ₂ ) and carbon dioxide (P co ₂ ) and in hydrogen ion concentration (pH) cause an acute decrease in pulmonary vascular resistance and a consequent increase in pulmonary blood flow. Increased left atrial and decreased right atrial pressures reverse the pressure gradient across the foramen ovale, causing functional closure of this left-to-right one-way flap valve. Ventilatory rhythm is augmented and maintained in part by the increased arterial oxygen relative to the prior intrauterine levels.

Breathing is controlled by a complex interaction involving input from sensors, integration by a central control system, and output to effector muscles. Afferent signaling is provided by peripheral arterial and central brainstem chemoreceptors, upper airway and intrapulmonary receptors, and chest wall and muscle mechanoreceptors.

The peripheral arterial chemoreceptors consist of the carotid and aortic bodies, with the carotid bodies playing the greater role in arterial chemical sensing of both arterial O ₂ tension (Pao ₂ ) and pH. The central chemoreceptors, responsive to arterial CO ₂ tension (Pa co ₂ ) and pH, are thought to be located at or near the ventral surface of the medulla.

The nose, pharynx, and larynx have a wide variety of pressure, chemical, temperature, and flow receptors that can cause apnea, coughing, or changes in ventilatory pattern. Pulmonary receptors lie in the airways and lung parenchyma. The airway receptors are subdivided into the slowly adapting receptors, also called pulmonary stretch receptors, and the rapidly adapting receptors. The stretch receptors, found in the airway smooth muscle, are thought to be involved in the balance of inspiration and expiration. These receptors may be the sensors in the Hering-Breuer reflexes, which prevent overdistention or collapse of the lung. The rapidly adapting receptors lie between the airway epithelial cells and are triggered by noxious stimuli such as smoke, dust, and histamine. Parenchymal receptors, also known as juxtacapillary receptors, are located adjacent to the alveolar blood vessels; they respond to hyperinflation of the lungs, to various chemical stimuli in the pulmonary circulation, and possibly to interstitial congestion. Chest wall receptors include mechanoreceptors and joint proprioreceptors. Mechanoreceptors in the muscle spindle endings and tendons of respiratory muscles sense changes in length, tension, and movement.

Central integration of respiration is maintained by the brainstem (involuntary) and by cortical (voluntary) centers. Although the precise mechanism of the neural ventilatory rhythmogenesis is unknown, the pre-Bötzinger complex and the retrotrapezoid nucleus/parafacial respiratory group, neural circuits in the ventrolateral medulla, are thought to be the respiratory rhythm generators. These neuron groups fire in an oscillating pattern, an inherent rhythm that is moderated by inputs from other respiratory centers. Involuntary integration of sensory input occurs in various respiratory nuclei and neural complexes in the pons and medulla that modify the baseline pacemaker firing of the respiratory rhythm generators. The cerebral cortex also affects breathing rhythm and influences or overrides involuntary rhythm generation in response to conscious or subconscious activity, such as emotion, arousal, pain, speech, breath-holding, and other activities.

The effectors of ventilation include the neural efferent pathways, the muscles of respiration, the bones and cartilage of the chest wall and airway, and elastic connective tissue. Upper airway patency is maintained by connective tissue and by sustained and cyclic contractions of the pharyngeal dilator muscles. The diaphragm produces the majority of tidal volume during quiet inspiration, with the intercostal, abdominal, and accessory muscles (sternocleidomastoid and neck muscles) providing additional negative pressure. The elastic recoil of the lungs and thorax produces expiration. Inspiration is an active and expiration a passive action in normal lungs during quiet breathing. During vigorous breathing or with airway obstruction, both inspiration and expiration become active processes.

Another effect of age is a change in chest wall compliance. In adults the end-expiratory volume is equivalent to the functional residual capacity (FRC). In infants the chest wall is more compliant, so the tendency of the lung to collapse is not adequately counterbalanced by chest wall rigidity. Infants stop expiration at a lung volume greater than FRC, with the inspiratory muscles braking expiration. When this braking mechanism is impaired, as occurs with general anesthesia, the infant has a tendency to develop atelectasis.

Preoperative Assessment

The preoperative assessment of the respiratory system in a child is based on the history, physical examination, and evaluation of vital signs. Because ventilation is a complex process involving many systems besides the lung, the pulmonary appraisal must also include an assessment of airway, musculoskeletal, and neurologic pathology that might affect gas exchange under anesthesia or in the postoperative period. The potential impacts of esophageal reflux and cardiac, hepatic, renal, or hematologic disease on gas exchange and pulmonary function should be considered. Further investigations, such as laboratory, radiographic, and pulmonary function studies, may be indicated if there is doubt as to the diagnosis or severity of the pulmonary disease.

Because children may be unwilling or unable to give a reliable history, parents or caregivers are often the sole source or an important supplemental source of information during initial evaluation. Risk factors in the history that are associated with an increased risk of perioperative events include a respiratory tract infection within the preceding 2 weeks, wheezing during exercise, more than three wheezing episodes in the past 12 months, nocturnal dry cough, eczema, and a family history of asthma, rhinitis, eczema, or exposure to tobacco smoke. Viral upper respiratory tract infections (URIs) are common in children, and the time, frequency, and severity of infection should be established. If wheezing is present, the precipitating causes, frequency, severity, and relieving factors should be determined. Chronic pulmonary diseases often have a variable clinical course, and the details of acute exacerbations of chronic problems should be elicited.

In younger children the gestational age at birth, the current postmenstrual age, neonatal respiratory difficulties, and prolonged intubation in the neonatal period are particularly important to ascertain. Apneic episodes, subglottic stenosis, and tracheomalacia are possible complications of prematurity and prolonged intubation that may be exacerbated in the perioperative period. Whereas congenital lesions often manifest at birth, symptoms of airway collapse or stenosis may become evident only later in life.

Physical examination begins when you enter the room. Particularly with young children, your best opportunity to observe them before they react to your presence is from across the room, and inspection from a distance can provide useful information. The respiratory rate is a sensitive marker of pulmonary problems, and scrutiny of the rate before a young child becomes agitated and hyperventilates is an important metric. Pulse oximetry is a useful baseline indicator of oxygenation. Nasal flaring, intercostal retractions, and the marked use of accessory respiratory muscles are all signs of respiratory distress. General appearance is also important. Apathy, anxiety, agitation, or persistent adoption of a fixed posture may indicate profound respiratory or airway difficulties, and intense cyanosis can also be detected from a distance. Weight may relate to pulmonary function; children with chronic severe pulmonary disease are often underweight owing to retarded growth or malnourishment, whereas severe obesity can produce airway obstruction and sleep apnea. Inspection of the chest contour may reveal hyperinflation or thoracic wall deformities.

Closer physical examination adds further information. Atopy and eczema may be associated with hyperreactive airways. Auscultation may reveal wheezes, rales, fine or coarse crepitus, transmitted breath sounds from the upper airway, altered breath sounds, or cardiac murmurs. Chest percussion can provide an estimate of the position of the diaphragm and serve as a useful marker of hyperinflation. Patience, a gentle approach, and warm hands improve diagnostic yield and patient satisfaction.

Pulmonary Function Tests

Further pulmonary investigations include chest imaging, measurement of hematocrit, arterial blood gas analysis, pulmonary function tests, and sleep studies. Special investigations are not routinely indicated preoperatively and should be reserved for cases in which the diagnosis is unclear, the progression or treatment of a disease needs to be established, or the severity of impairment is not evident. In most cases a comprehensive history and careful physical examination are adequate to establish an appropriate anesthetic plan. Before requesting a new investigation, the clinician should have a clear idea of the question the test is expected to answer and how the answer will modify anesthetic management and outcome. Many tests are difficult to perform in children who have short attention spans and who cannot sit still for any length of time. Judgment must be exercised when ordering these tests for young children, and due consideration must be given to the child's age and level of maturity and the influence of the parents.

Pulmonary function tests include dynamic studies, measurement of static lung volumes, and diffusing capacity. Pulmonary function tests enable clinicians to (1) establish mechanical dysfunction in children with respiratory symptoms, (2) quantify the degree of dysfunction, and (3) define the nature of the dysfunction as obstructive, restrictive, or mixed obstructive and restrictive. Table 13.1 presents common indications for pulmonary function testing in children.

The dynamic studies, which are the most commonly used tests, include spirometry, flow–volume loops, and measurement of peak expiratory flow. Spirometry measures the volume of air inspired and expired as a function of time and is by far the most frequently performed test of pulmonary function in children. With a forced exhalation after a maximal inhalation, the total volume exhaled is known as the forced vital capacity (FVC), and the fractional volume exhaled in the first second is known as the forced expiratory volume in 1 second (FEV ₁ ). Fig. 13.2 illustrates a normal pulmonary function test (normal flow–volume loop and spirometry parameters).

An obstructive process is characterized by decreased velocity of airflow through the airways ( Fig. 13.3 ), whereas a restrictive defect produces decreased lung volumes ( Fig. 13.4 ). Examination of the ratio of airflow to lung volume assists in differentiating these components of lung disease. Normally, a child should be able to exhale more than 80% of the FVC in the first second. Children with obstructive lung disease have decreased airflow in relation to exhaled volume. If the volume exhaled in the first second divided by the volume of full exhalation (FEV ₁ /FVC) is less than 80%, then airway obstruction is present ( Table 13.2 ; Fig. 13.3 ).

The FEV ₁ needs to be interpreted in the context of the FVC. A small FEV ₁ alone is insufficient evidence on which to make a diagnosis of airflow obstruction. Those with restrictive lung disease have both decreased FEV ₁ and FVC—decreased flow rate and reduced total exhaled volume. Restrictive lung disease is associated with a loss of lung tissue or a decrease in the lung's ability to expand. A restrictive defect is diagnosed when the FVC is less than 80% of normal with either a normal or an increased FEV ₁ /FVC (see Table 13.2 and Fig. 13.4 ).

Most children with respiratory problems have an obstructive pattern; isolated restrictive diseases are far less common. Asthma is the most common obstructive pulmonary disease in children. Rare causes of obstruction include airway lesions, congenital subglottic webs, and vocal cord dysfunction. Restrictive lung disease can arise from limitations to chest wall movement, such as chest wall deformities, scoliosis, or pleural effusions, or from space-occupying intrathoracic pathology such as large bullae or congenital cysts. Alveolar filling defects (e.g., lobar pneumonia) also reduce lung volume and can be considered as restrictive processes. Although the diseases arise from specific isolated genetic disorders, children with cystic fibrosis (CF) and sickle cell disease (SCD) can have highly variable pulmonary pathologic processes with both obstructive and restrictive components of lung disease. Bronchopulmonary dysplasia may also result in both obstructive and restrictive pathology.

Pulmonary function tests can also be used to differentiate fixed from variable airway obstruction and to localize the obstruction as above or below the thoracic inlet ( Figs. 13.5 through 13.7 , E-Fig. 13.1 ). This information can be gleaned from distinctive changes in the configuration of the flow–volume loop, a graphic representation of inspiratory and expiratory flow volumes plotted against time. A fixed central airway obstruction, such as a tumor or stenosis, may obstruct both inspiration and expiration, flattening the flow–volume curve on both inspiration and expiration (see Video 14.1 ). The child with tracheal stenosis, for example, has flattening of both inhalation and exhalation curves (see Fig. 13.6 ). A variable obstruction tends to affect only one part of the ventilatory cycle. On inhalation, the chest expands and draws the airways open. On exhalation, as the chest collapses, the intrathoracic airways collapse. Variable extrathoracic lesions tend to obstruct on inhalation more than exhalation, whereas variable intrathoracic lesions tend to obstruct more on exhalation. This produces the characteristic flow–volume patterns.

In addition to diagnostic uses, spirometry is used to assess the indication for, and efficacy of, treatment. For example, the obstruction in patients with asthma is usually reversible, either gradually over time without intervention or much more rapidly after treatment with a short-acting bronchodilator. An improvement in FEV ₁ of 12% and 200 mL in adults or approximately 3 mL/kg is considered a positive response. In addition to confirming the diagnosis of asthma, the degree of airflow obstruction, as indicated by the FEV ₁ , is one measure of asthma control. A low FEV ₁ or an acute decrease from baseline may indicate a child whose asthma is not under good control and therefore who potentially is at greater risk for a perioperative exacerbation (see Fig. 13.3 ).

Because it measures the amount of air entering or leaving the lung rather than the amount of air in the lung, spirometry cannot provide data about absolute lung volumes. Information about FRC and lung volumes calculated from FRC, such as total lung capacity and residual volume, must be obtained by different means, such as gas dilution or body plethysmography. Gas dilution is based on measuring the dilution of nitrogen or helium in a circuit in closed connection to the lungs, whereas body plethysmography calculates lung gas volumes based on changes in thoracic pressures.