PATHOPHYSIOLOGY OF AIRWAY OBSTRUCTION



The mechanism of the airway obstruction in these disorders is always multifactorial, although in any individual patient one mechanism may play a dominant role. Air flow in the lungs is di­rectly proportional to the driving pressure and in­versely related to the airway resistance. During most of a forced expiration, the effective driving pressure is the elastic recoil pressure of the lung.

Thus, reduction in elasticity, as in emphysema, decreases the maximum expiratory flow. De­creased elasticity also increases airway resistance, since the elastic recoil pressure exerts radial trac­tion on the airways, which limits their dynamic compression during expiration.

A second cause of increased airway resistance is bronchoconstriction. The airways are lined by smooth muscle that is innervated by both adre­nergic (bronchodilating) and cholinergic (bron-choconstricting) pathways. Cholinergic control is mediated by a vagal reflex, via irritant receptors lying just beneath the mucosa of the large airways, trachea, and upper respiratory tract. Stimulation of these receptors by inhaled irritants or inflam­mation produces bronchoconstriction. In addi­tion, endogenous mediators such as histamine and prostaglandins may dilate or constrict bron­chial smooth muscle directly or reflexly by ex­citing the irritant receptors. Such mechanisms function to protect the lungs of normal subjects from noxious agents, but hyperreactivity of these pathways exists in patients with obstructive lung disease.

A third cause of increased airway resistance is chronic inflammation. In response to irritation in the form of external pollutants, recurrent infec­tion, or chronic immunological stimulation, there is hyperplasia and hypertrophy of the bronchial glands, inflammatory narrowing of the airways, and the production of excessive, thick secretions. If this process is allowed to continue it often re­sults in the loss of ciliated epithelium, squamous metaplasia, and eventual peribronchial fibrosis.

Airway obstruction leads to characteristic changes in lung volumes, with an increase in re­sidual volume (RV) and functional residual ca­pacity (FRC) and a normal or increased total lung capacity (TLC). The vital capacity (VC) is de­creased as the RV takes up more and more of the thoracic gas volume. The mechanism of the in­crease in RV and FRC is not completely understood, although several factors are likely to con­tribute to a variable degree depending on the specific etiology involved. Decrease in the elastic recoil of the lungs moves the FRC closer to the relaxed volume of the chest wall (about two thirds of TLC). A second factor is the greater tendency for abnormal airways, particularly at the lung base, to collapse during expiration, trapping air behind the closed airways. Finally, certain pa­tients with asthma have persistent activity of the inspiratory muscles during expiration, which ac­tively maintains a high FRC.

There are three major consequences of these changes in lung volume. Because of the nonlinear nature of the pressure-volume relationship of the lung, breathing at high lung volumes along the flat portion of the curve requires a greater pressure for the same change in volume , further increasing the work of breathing, which is already high owing to the abnormal airway resistance. In addition, the higher the resting lung volume, the shorter the inspiratory muscles are at the begin­ning of the breath . This places them at a disadvantageous position on their length-tension curve and predisposes them to fa­tigue. Hyperinflation, however, has one beneficial effect. Owing to the tethering effect of the lung parenchyma on the airways, there is an inverse relationship between lung volume and airway re­sistance. Thus, hyperinflation is the one strategy immediately available in asthmatics to minimize sudden changes in airway caliber.

Abnormal pulmonary gas exchange is an in­evitable consequence of obstructive lung disease. Airway obstruction and the breakdown of alveolar walls produce ventilation-perfusion mismatch, which interferes with the efficient transfer of both 02 and C02. Up to a certain point, patients with obstructive lung disease can increase their minute ventilation sufficiently to prevent the develop­ment of hypercapnia despite worsening hypox­emia . However, with continued progression of the disease a point is reached be­yond which further increase in ventilation is im­practical because of either the high energy re­quirements or the development of muscle fatigue. At that point, it is more efficient, physiologically, to allow Paco2 to rise, thus eliminating it at both a lower minute ventilation and metabolic cost but at a higher concentration. The onset of hypercap-nia is not always clearly related to the degree of mechanical impairment, and it appears that some patients prefer to work harder to maintain nor­mocapnia, while others with the same degree of impairment are satisfied to breathe less and allow worse gas exchange .

Acute exacerbations of the chronic process brought on by infection or congestive heart failure may lead to the development of intrapulmonary shunt and further worsen gas exchange. During sleep, gas exchange is also usually worse owing to a characteristic reduction in minute ventila­tion. A patient with adequate arterial blood gases during the day may develop significant hyper-capnia and arterial desaturation at night.