LUNG, AGING

The main function of the respiratory system is to secure gas exchange: oxygen, which fuels metabolism, is transported from the ambient air (which contains 21 percent oxygen) to the pulmonary capillaries, and carbon dioxide is transported from the pulmonary capillaries to the external atmosphere. The oxygen-enriched blood reaches (via the pulmonary veins) the left side of the heart and the peripheral arterial network, which distributes it to the various organs, according to their metabolic needs. Carbon dioxide, which is the end-product of the mitochondrial tissue metabolism, is brought to the lung through the systemic veins, then to the right side of the heart, and then to the pulmonary arteries.

In the blood, oxygen molecules are bound to the hemoglobin contained in the red blood cells, with only 3 percent being dissolved in plasma (100 millileters (ml) of normal blood are able to transport 20 ml of oxygen). The oxygen dissolved in arterial blood yields a partial pressure (PaO₂) of around 100 mm of mercury (Hg) in a young adult; in the mixed venous blood, the oxygen partial pressure is 40 mm Hg. At these pressures, the hemoglobin oxygen saturation is, respectively, 97 percent and 70 percent. At rest, one quarter of the oxygen arterial content is consumed by the tissues, so that 100 ml of mixed venous blood transports 15 ml of oxygen, and the arterio-venous difference between the arterial content in oxygen and the venous content in oxygen content is 5 volume percent (5 ml oxygen per 100 ml blood).

The carbon dioxide produced by tissue metabolism is collected by the peripheral veins, with 7 percent being dissolved in the plasma, and the rest being absorbed by the red blood cells. Seventy percent of the red-cell carbon dioxide content is transformed in bicarbonate and hydrogen ions through the action of the enzyme, carbonic anhydrase. In these conditions, 100 ml of blood can transport around 50 ml of carbon dioxide.

At rest, 250 ml of oxygen are absorbed by the lung per minute, eliminating 200 ml of carbon dioxide. The ratio between carbon dioxide excretion and oxygen absorption, called the respiratory quotient, is therefore equal to 0.8.

Gas transport from the mouth to the alveoli, and vice-versa, is only possible because of the inflation and deflation capability of the rib cage. At rest, the active phenomenon is called inspiration, which needs the coordinated contraction of three groups of muscles: the diaphragm muscle, the parasternals, and the scalenes. The rib cage distension results in an increased depression in the pleural space (the virtual space between the visceral and the parietal pleurae), which is followed by distension of the lung and transport of gas molecules from the mouth along the bronchial tree to the alveoli. When contraction of the inspiratory muscles ceases, the elastic energy stocked in the lung and chest wall is restored, and the volume of the respiratory system decreases, allowing expiration.

The volume of gas contained in the lungs at the end of an unforced, relaxed expiration is called the functional residual capacity (FRC). The volume of air that is inspired and expired during each respiratory movement is called the tidal volume (V_T), which is about 500 ml, at rest in a adult. There are around sixteen respiratory movments per minute, so that the per-minute ventilation is eight liters. The level of ventilation is adjusted to maintain PaO₂ and PaCO₂ in the normal range (PaCO₂ = 40 mm Hg) through a complex control system involving peripheral and central chemoreceptors situated in the carotid bodies and the medulla, respectively. During exercise, for example, the per-minute ventilation increases proportionally to the increase in oxygen consumption and carbon dioxide excretion. There is also an increase in the tidal volume and the respiratory frequency, and the expiration becomes active with the involvment of the expiratory thoracic (triangularis sterni) and abdominal (transverse abdominis) muscles. The same phenomenon is observed during forced expiratory maneuvers like sneezing or coughing.

The volume of gas contained in the lungs at the end of a maximal inspiration is called the total lung capacity (TLC), whereas the volume remaining in the lungs at the end of a maximal expiration is called the residual volume (RV). The volume mobilised between the TLC and RV levels is the vital capacity (VC). Together with the FRC, these three volumes determine the size of the lung. Taller people have proportionally larger lungs; women have smaller lungs than men (about 80 percent smaller); and there are also some differences linked to ethnic factors.

It is also of interest to look at the speed at which the vital capacity can be mobilized; the simplest way to determine this is to measure the volume of gas that can be expelled during the first second of a forced expiratory maneuver, starting at the TLC level (this is known as the one-second forced expiratory volume, or FEV₁). In a healthy middle-aged subject the FEV₁/VC ratio is about 75 percent. Another commonly measured index during a forced expiratory maneuver is the maximal instantaneous flow that can be attained after the onset of the maneuver; this is called the peak expiratory flow rate (PEFR).

In general, lung function declinces with age. Recent studies have also made clear that changes in function due to aging can be distinguished from those due to disease and environmental factors such as smoking. With age, structural changes occur in the respiratory system. The thoracic cage changes its form, becoming rounder, the intercostal cartilages become calcified, and there is some arthritis of the costovertebral joints. The large bronchi increase somewhat in size, whereas the caliber of the bronchioles decreases after the age of forty. The periphery of the lung changes consistently, with a progressive increase in the diameter of the respiratory bronchioles and of the alveolar ducts. By contrast, the alveolar sacs become shallower, so that the alveolar surface area decreases by 15 percent by the age of seventy, though the alveolar wall remains intact.

Morphological changes in the lung are associated with a progressive change in lung elasticity, particularly a loss of lung recoil pressure (pressure exerted by a distended lung) and a slight increase in lung distensibility. On the other hand, the chest-wall distensibility decreases, so that there is a slight increase in the functional residual capacity. The performance of the respiratory muscles, both in terms of force generation and endurance, decreases (which is also the case for the other skeletal muscles). The net effect of increased lung distensibility, combined with decreased thoracic compliance and inspiratory muscle force, is that the total lung capacity does not change over time. In contrast, the maximal expiration becomes limited, mainly because smaller peripheral airways in the dependent parts of the lung close, so that alveolar air remains trapped and the residual volume increases.

In older adults, contrasting changes in larger and smaller airways are such that the airway resistance associated with the transport of gas along the bronchial tree remains constant during normal breathing. However, during forced breathing both the maximal expiratory and inspiratory flow rates decrease. Changes in FEV₁ over time have been the most extensively studied. Cross-sectional studies of populations of different ages have conclusively shown a lower FEV₁ in older people (up to the age of eighty-five), the mean decline being 29 ml per year in males and 25 ml per year in females. Longitudinal studies, however, have shown that the decline is not rectilinear, with an acceleration in FEV₁ loss in older subjects.

Whether the loss in FEV₁ is linked to the aging process alone is difficult to know, since the lung is constantly exposed to many environmental stresses, with cigarette smoke being most important. Smokers have a steeper decline in FEV₁ than nonsmokers by a mean of 15 ml. per year, though following smoking cessation, the slope becomes normal again. Other factors that have a negative impact on lung function include occupational exposures to dusts and fumes, exposure to air pollutants, and respiratory infections (mainly during childhood).

In addition to the decreased alveolar surface area associated with aging, there is a limitation in the diffusion of oxygen molecules across the alveolar wall. This has been established through cross-sectional and longitudinal studies in both sexes, and in smokers and nonsmokers. However, this reduced diffusing capacity does not explain the arterial hypoxemia (reduced oxygen in the blood) that occurs with aging, at least up to the age of seventy-five. In older adults, hypoxemia results from a progressive imbalance between the perfusion and the ventilation of the alveoli, so that the difference between oxygen alveolar pressure and the oxygen arterial pressure widens progressively. Arterial carbon dioxide pressure (and its pH), however, does not change consistently.

The ability to perform physical tasks diminishes with age, with a progressive reduction of the amount of external work that can be performed and, consequently, of maximal oxygen consumption (a simple index of the fitness of an individual), both in men and in women. This reduction is closely linked to a progressive loss of muscle mass (which contrasts with an increase in the fat mass) and to a decrease in maximal cardiac frequency (which is aggravated by an increasing sedentary lifestyle and decreasing fitness). In healthy subjects, however, the ventilatory performance is never the limiting factor during exercise (the subject's cardiovascular and muscular states are), although an elderly person will approach his ventilatory limits during maximal exercise. This means that, after any slight impairment, the respiratory pump (i.e., the thoracic cagewith the respiratory muscles) may also become a limiting factor to exercise.

The physical ability of any individual can be estimated by a formal exercise test performed on a cycle ergometer or a treadmill, or by measuring the distance walked during a six or twelve-minute period, which decreases with age.

Enough information is now available on the performance of the respiratory system to properly identify common diseases such as asthma or chronic obstructive pulmonary disease, and to separate their effects from the physiological changes of aging and deconditioning that can also contribute to the occurrence of shortness of breath in up to half of an elderly population. Identifying specific diseases allows an efficient therapy, which has a major effect on a patient's quality of life and improves rates of survival.

Jean-Claude Yernault

See also Pneumonia; Smoking.

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