1. The Function of Respiration:

     In one celled animals, the respiratory gases are all exchanged freely between the organism and its medium. Oxygen moves into such cells by diffusion, and carbon dioxide leaves in the same way. In larger animals, the cells are in contact with the outside medium--water in the case of fish, air in the case of mammals--only indirectly. Gas exchange is between the cells and the blood; in motion, the blood acts as a fluid bridge to the outside medium, where a second exchange occurs in the respiratory organs. The blood which leaves the tissues is usually poor in oxygen and high in carbon dioxide. That which returns from the respiratory organs, having been exposed to the outside medium, is higher in oxygen and lower in carbon dioxide.

fig 252. Circulatory Gas Exchanges

     These relationships are shown schematically in Figure 252. From this figure it should be apparent that normal respiration requires four things:

(1) The blood must be in good contact with the medium in the respiratory organs, and the medium must be an adequate one.
(2) The blood must be in adequate motion.
(3) The transport function of the blood depends on the presence of proper transport agents in the blood.
(4) The tissues must be able to liberate the respiratory gases from the blood.

     To illustrate how these functions must be integrated, some of the most common types of respiratory disturbance will be outlined here:

(1) The outside air may be inadequate (as at very high altitudes), or the respiratory organs may be so damaged as to make effective gas transport difficult.
(2) The motion of the blood may be insufficient (as in shock).
(3) The oxygen carrying pigment hemoglobin may be abnormally low in concentration (as in anemia).
(4)The tissues may be chemically abnormal in such a way that they cannot liberate the gases carried by the blood (as in cyanide poisoning).

     This chapter will be concerned with the anatomy of the respiratory organs and the mechanics of the process by which the outside air is brought near the blood in the lungs. In Chapter 18, some of the factors involved in the transport of the respiratory gases will be considered. Chapter l9 will be concerned with the mechanisms which adjust respiratory activity to the activity of the body.

2. The Upper Respiratory Passageways and Associated Structures:

     In ordinary quiet respiration, the air which enters the lungs passes through the nose. The posterior part of the nasal cavity above the soft palate is called the nasopharynx. See Figure 253.

     The nasopharynx, the oropharynx, and the laryngopharynx make up the pharynx, the area in which the respiratory and digestive pathways cross. This crossing is illustrated in Figure 254 and will be considered again in Chapter 19. The pharynx is lined by mucous epithelium. Its walls are made of voluntary muscles, which by appropriate contractions can seal off one or the other of the pathways.

     During periods of increased activity, the mouth is also opened and breathing occurs through both the nasal pharynx and the oropharynx. Breathing through the oropharynx may substitute entirely for nasopharynged breathing when there is obstruction to the nasal passages, as in the common cold.

     The air which enters the pharynx during inspiration passes by way of the larynx into the trachea, or windpipe, and from the trachea into the bronchi. The subsequent distribution of the bronchi will be considered in part 3.

     The structures of the nasal cavity are shown in Figure 255. The entire nasopharynx is lined by a mucous membrane, as is the rest of the pharynx. The olfactory epithelium is at the top of the nasal cavity and not in the direct path of the air flow. Odors are more easily detected by "sniffing" than by ordinary breathing because "sniffed" air is brought into more direct contact with the olfactory mucosa than air which follows the respiratory pathway directly.

     The inside lining of the trachea consists of a pseudo-stratified columnar epithielium. These cells, like cells in the nose, contain hair like processes, cilia, on the air side. The cilia appear to alternate between a slow bending downward and a whiplike action upward. The effect of this action is to expel upward solid or semisolid matter which has been inhaled or formed lower in the respiratory tree.

     In mid-chest, the trachea divides into two main bronchi, which are more or less similar to the trachea, though somewhat smaller. Just above the level of division of the trachea is in intimate relation to the arch of the aorta (Figure 263). The bronchi are just behind the main pulmonary arteries. These relationships are also shown in the Dissectograph.

3. The Lungs and Other Intrathoracic Structures:

fig 264. Alveolar Structures

     The two main bronchi divide into three branches on the right and two on the left. Each of the five bronchi so formed serves one lobe of the lung. Each such branch, a lobar bronchus, serves one lobe of the lung. As the bronchi continue to branch they gain in muscle while losing cartilage; eventually their walls are purely muscular, and they are called bronchioles. The terminal bronchioles terminate in alveolar ducts; these go into alveolar ducts which finally end as alveolar air sacs or alveoli of the lung. Here the outside air is brought into contact with the blood. Of course, it is not truly outside air; this may be appreciated when it is considered that the respiratory passageway is a two way street; the blood gases leave by the same route as the gases of the air enter, with inevitable admixture. The gas of the alveoli is called alveolar air. Its composition will be considered in the next chapter. The overall anatomy of the structures just described are illustrated in Figure 264.

     The lungs lie in the thoracic cavity separated from each other by the mediastinum which contains non-respiratory intrathoracic structures. Its divisions are shown in Figure 265.

     The most important area of the mediastinum is the middle mediastinum. Here, within the pericardium, are the heart, the root of the ascending aorta, the root of the pulmonary artery, and the atrial attachments of the superior vena cava, as well as the first division of the trachea. Lying on the pericardium are the two phrenic nerves on their way to the diaphragm. The superior mediastinum contains the arch of the aorta and its main branches, the veins which form the superior vena cava, the vagus nerves, the thoracic duct, trachea and esophagus. The posterior mediastinum contains the descending aorta, the vagus nerves and esophagus. All portions of the mediastinum contain lymph nodes and loose connective tissue.

     In man, the mediastinum is relatively fixed and divides the chest into two hemithoraxes. This division is of great importance, for it enables either lung to function even when the other hemithorax is non-functional. Slight displacements, of the mediastinal structures to one side or the other are usually indicative of disease in one hemithorax.

     The lungs themselves fill the two hemithoraxes in a rather peculiar way. Each lung is smaller (when removed) than its corresponding hemithorax. In the body, however, it fills the hemithorax almost completely. This results from the fact that there is no air in the thorax to exert a counter pressure against the air of the lungs, which is continuous with the outside air. The lung is pushed by the outside air against the thoracic wall. Except at its root, where there is an indirect connection to the thoracic wall, there is no anatomical connection at all. Thus each lung conforms to changes in the size of its hemithorax not by means of direct attachment but through the pressure of the air inside it uncompensated by air on the outside of the lung.

     The pleura, a continuous membrane which lines the inside of the chest wall and also the outside of the lung, protects the lung structures from damage as they glide along the chest wall during respiration. The pleura also lines the outside of the mediastinum and the upper surface of the diaphragm. The parts of the pleura associated with the lung are called visceral pleura; the remainder is called parietal pleura. The parts of the latter associated with the chest wall are called costal, and the mediastinal and diaphragmatic pleura are related as their names indicate. These relationships are shown in Figure 266.

     Figure 266 also shows that there is a space between the visceral and parietal layers of the pleura. This space, called the pleural sac, is small and filled with fluid in health. There are some areas where the space is a little larger. Here the lung cannot quite fill the cavity available for it, which is bent at an acute angle. The two most important such spaces are at either side, where the diaphragmatic pleura becomes the costal pleura. These spaces are called the costodiaphragmatic recesses. Another space corresponds to the sharp angle made between the pericardium on the left and the sternum.

     The lungs within the visceral pleura are made of respiratory epithelium (the alveolar air sacs), and the passageways through which air must go to reach this epithelium (bronchial system). The blood supply of these two systems is different; the former receives its blood from the pulmonary artery and its branches, the latter from the bronchial arterial system. To a small extent these may intermingle in health, and their mixture may become of importance in disease. (See Figure 267).

     The alveolar air sacs are in the most intimate contact with the pulmonary capillaries which surround them in the same way as a gauze network sac surrounds a flying balloon. The combined thickness of the alveolar membrane, the capillary wall, and the interstitium which separates them is about 0.1 micra, rather less than the thickness of most capillary endothelium (Figure 267). It will be recalled from Chapter 15 that the interstitium is kept nearly dry in the pulmonary circulation. The total respiratory surface is about 70-80 square meters.

fig 269. Air Intake in the Lungs

4. Mechanics of Breathing:

     The combined acts of inspiration and expiration result in exchanges between the outside air and the air in the alveoli. As has been noted before, the respiratory passageways are a two way street, in which gases entering the alveolar air sacs from the arterial nd of the pulmonary capillaries are mixed with gases from the outside destined for the alveolar air sacs, where they will equilibrate with blood and leave the venular end of the alveolar capillaries. This arrangement, though it works, is less efficient than one in which air streams past the respiratory epithelium (see Figure 269). The inefficiency of the process is indicated by the fact that alveolar air contains only 2/3 as much oxygen as external air; its carbon dioxide content is 120 times as high as that of the outside air.

     Some understanding of the reasons for this may be obtained by a simple calculation. The lung volume is about 5L; the amount breathed per breath is about 0.4L. Some 0.15 of the latter amount simply moves to and fro in the respiratory passageways, and the residue of some 0.25L is brought to the alveoli. Thus, 0.25L (exchanged gases) / 5L (total volume), or 5%, of the alveolar air is exchanged with each breath. 95% remains as it was.

     This is such an inefficient process that one may wonder that it works at all. The fact that it does results from the fact that one breathes often, and that, when circumstances require, the volumes exchanged can be much larger. The role of frequency of breathing may be illustrated by the fact that at a normal breathing rate of 16 breaths / minute, although 95% of the alveolar air remain unchanged per breath, a little more than half the air (1 - 0.95¹⁶) is exchanged per minute. However, increases in rate of respiration, the depth remaining constant, produce more alveolar ventilation. The same changes just described may be brought about by 16 breaths taken in half a minute; in a minute the alveolar ventilation is enough to replace more than three quarters of the alveolar air. It is, however, much more effective to breathe deeply than to breathe rapidly. If, for example, the respiratory volume is doubled to 0.8 L, and 0.65 L reaches the alveoli per breath (the respiratory dead space remains constant in volume). Assuming 16 breaths / min, each breath replaces 0.65 L / 5 L, or 13%, of the alveolar air, 87% remaining as it was. In the course of a minute, 92% (1 - 0.87¹⁶) of the alveolar air is replaced. Both rate and depth increases are responsible for the increased alveolar ventilation of exercise.

     How little each breath matters may be conveyed to the reader by a simple experiment. Ordinarily 4 breaths are taken during a quarter minute at rest. Very few persons experience any discomfort at all from a 15 second period of breath holding, which is the time required to drink from a glass of water (it will be seen later that there is no respiratory activity during swallowing). In the quarter minute of breath holding, the alveolar air, unchanged by respiratory activity increases its carbon dioxide concentration less than 20% while its oxygen also falls less than 20%.

     The rate and depth of breathing are controlled by the central nervous system (See Chapter l9). The primary event in breathing is, however, a change in the size of the lung. Since the visceral pleura of the lung are in almost perfect contact with the parietal pleura, it follows that breathing will occur as the structures covered by the parietal pleura move. The structures principally involved are the chest walls and the diaphragm. Theoretically, the parietal pleura related to the pericardium are also involved, but since the pericardium is in almost the same position during systole and diastole of any of its chambers, respiratory function due to its movements can be neglected.

fig 270. Muscles and Breathing

     The movements of the diaphragm result in the most obvious volume changes in the lung. The diaphragm is dome shaped; when it contracts, flattening the dome, the space between the parietal pleura is increased. The visceral pleura, gliding freely along the parietal pleura, follow the increased volume, and the lung expands. Relaxation of the diaphragm results in a reduction in the volume of the lung. These volume changes can also occur as the result of changes in the configuration of the rib cage. This may be explaned by referring to Figure 270. This figure shows that in expiration, the sternum is sunk below the corresponding vertebra of the spinal column. The ribs angle downward from the spine to the sternum. If, by contraction of the external intercostal muscles, the ribs are brought upwards, there is an increase in the depth of the rib cage from front to back. This increases its volume and correspondingly the lungs expand. The internal intercostal muscles produce the opposite changes when they contract, increasing the downward slope of the ribs, the volume of the rib cage and the volume of the lung.

     In normal persons, diaphragmatic and intercostal breathing go on together. In certain circumstances, one or the other may predominate, but which predominates appears to be a matter of individual training and circumstances existing elsewhere in the body.

     Changes in lung volume involve all parts of the lung. For example, in inspiration, the bronchi and bronchioles dilate and lengthen, the amount of blood in the pulmonary venules and veins increases, and the alveolar air sacs increase in size and in number. These changes are all reversed on expiration. Some of them occur passively as the intrapleural pressure changes; others require active change (for example, inspiration is associated with a relaxation of the muscles of the bronchial system). One of the most interesting appears to occur passively, but it requires the presence of a chemical agent produced actively.

     This has to do with the fact that the alveoli, like soap bubbles, tend to shrink more rapidly the smaller they get. A familiar illustration of this is seen when a soap bubble is blown from a pipe but remains attached. The bubble contracts slowly at first, then much more rapidly until the bubble disappears entirely, being replaced by a flat soap film over the orifice of the pipe. This phenomenon is due to the surface tension of the bubble which produces a much greater pressure in a small bubble than a large one. That this is so can be seen readily when two soap bubbles are blown from two pipes which are then connected at the mouth end. Invariably, the small bubble empties into the larger one.

fig 271. Alveolar Structures

     Applying this to the lung, it would seem that as the lung deflated, the large alveoli should grow larger while the small ones disappeared. This may actually happen in lung disease. In the healthy lung, however, it does not happen because all the alveoli are lined with a substance (surfactant) which reduces their surface tension. As an alveolus becomes smaller, its surface tension becomes smaller too, since its surfactant is distributed over a smaller area. As the lungs are distended, the larger alveoli--with the smallest surfactant concentration and therefore the highest surface tension--tend to resist further distension, but the smaller alveoli--high surfactant concentration, low surface tension--are easily inflated. Thus, the volume changes in the lung during inspiration and expiration are evenly distributed through the alveoli as well as the other structures of the lung. See also Figure 271.

5. Lung Volumes:

     If one consciously suspends breathing activity in expiration, the lungs tend to assume a resting volume which is relatively constant for any one person. Normal inspiration increases the volume, the amount inspired being called the tidal air. It ordinarily amounts to about 400 ml.

     Further inspiratory effort can result in further expansion of the lung. The extra volume which can be inspired is called the inspiratory reserve volume. This ordinarily amounts to about 3000 ml. The expiratory reserve volume is that volume which can be expired by effort after normal expiration, about 1200 ml.

     After the most vigorous expiration, a volume of about 1200 ml remains in the lungs. This is called the residual volume.

     Taken from the deepest possible inspiration to the deepest possible expiration, the change in lung volume including the inspiratory reserve, the tidal air, and the expiratory reserve is called the vital capacity. This value does not include the residual volume or the anatomical dead space (150 ml). In healthy young men it is about 4800 ml. These relationships are summarized in Figure 272.

6. The Work of Breathing:

     The alternate increases and decreases of the volume of the chest require that work be done. Some of this work is used to overcome resistance to the movement of air in the respiratory passageway, some is required to deform the lung itself, some to move the chest wall, and some to move the organs which are displaced as the diaphragm moves. The exact value is not known but it has been speculated that the power involved in quiet breathing is about 5 watts. This is almost 4 times the work of the whole heart. This value may rise almost fifty times during maximum respiratory effort to about 250 watts. Man is capable of using oxygen at a rate which corresponds to the development of 1000 watts for short periods; over longer periods (such as an hour), a power consumption of 600 watts appears to be the limit of what man can use. However, respiratory effort is probably never more than 25% efficient, which means that the lungs would have to use almost the full 1000 watts of maximum output in order to generate 250 watts. This leads to the rather queer situation that the respiratory apparatus has greater capacity than can ever be used except for very short periods, and even during such periods the utilization of the full respiratory capacity to do work makes other work impossible.

     The answer to the apparent paradox probably lies in the fact that the total respiratory capacity is never used. Probably the limits of prolonged performance are set by the respiratory apparatus, but at lower levels than those seen in respiratory "sprints". This is probably not a significant factor in limiting the performance of normal men, but it may become very important in disease.

7. Diseases of the Respiratory Passageways:

     The list of respiratory diseases is almost endless. A few illustrative examples will be chosen from each of the above categories.

a. Upper Respiratory Tract Diseases:

     Pneumococcal pneumonia was once very common. The causative agent (pneumococcus), makes pulmonary capillaries permeable to proteins in the affected lobe or lobes. Pulmonary edema results (See also Chapters 15 and 16). With adequate antibiotic treatment, survival in this disease is close to 95%.

     Pulmonary tuberculosis: This disease is carried by the tubercule bacillus, an organism which can affect any part of the body. The first inhalation of the bacteria usually occurs without any symptoms at all. The bacteria are trapped, but usually not killed, in lymph nodes at the root of the main bronchus of the affected lobe. Most persons who have had one exposure to tubercle bacilli have no further trouble. They develop a kind of hyperimmunity to the bacteria (Chapter 32) which is displayed when bacterial extracts are injected in the skin, a tuberculis test. A positive tuberculis test, indicating that hyperimmunity exists, is an almost certain sign that there has been a previous exposure to the bacillus. The test is read as positive when the injected area becomes reddened, hardened, and edematous two to three days after injection.

     A person who is hyperimmune reacts very badly if reexposed to tubercle bacilli. Edema and swelling occur in the lung just as in the skin. Further, the lung tissue (including bronchial tissue and alveolar tissue) may be destroyed by the hyperimmune process. The destroyed tissue is usually expelled in part by coughing. Some is reinhaled and involves parts of the lung not involved before. The process may continue until both lungs are massively involved and may be terminated by the death of the patient. In the course of the disease, bronchitis, atelectasis, and tuberculous pneumonias may all appear.

     The decline in the death rate from tuberculosis in the last half century has been nothing short of spectacular. In 1900 the death rate from tuberculosis was 200 per 100, 000 population. By the l960s this figure had been reduced fifty fold. Part of the decrease is due to improvement of the nutritional status of the population, part is due to improved public health measures, and part to the advent of specific agents which suppress the growth of the bacillus (streptomycin, para amino salicylic acid, isoproniazid).

     In some cases, patients with tuberculous lung damage benefit from removal of a diseased lobe. Collapse therapy (in which the affected lung is collapsed by the introduction of air between the visceral and parietal pleura, by paralysis of one side of the diaphragm, or by removal of several ribs on the affected side) is hardly ever used, though it was once extremely popular in the treatment of tuberculosis. Treatment by sun (heliotherapy) or by moving to a high, dry climate (climate therapy) were both once in vogue, but both seem to be totally devoid of merit.

c. Diseases of the Pleura and Chest Wall:

     Inflammation of the pleura is usually a sign of underlying disease of the lung. It is characterized by a stabbing pain in the chest aggravated by respiration (pleurisy) The pain is due to involvement of the parietal pleura and can usually be localized very accurately. Such pleuritic pains should always be taken as evidence of serious disease unless proved otherwise even if the pains disappear, as it is quite likely to do if the involved pleural surfaces form fluid (pleurisy with effusion).

     Spontaneous pneumothorax is a condition, by no means rare, in which the visceral pleura ruptures in an overdistended area of lung. Air enters the intrapleural space and the lung collapses a little. Increased respiratory effort increases the amount of intrapleural air, bringing about further collapse. The process is usually halted when the lung collapses enough to seal off the perforation.

     The condition is rarely fatal, and ordinarily no treatment is required other than bed rest until the ruptured visceral pleura heals. The air in the chest is absorbed slowly and is usually gone by the time the pleura has healed.

     Perforating wounds of the chest wall can lead to dramatically sudden collapse of the lung. The respiratory distress experienced by the patient results in increasing the amount of the pneumothorax. Sealing the wound, whether by a dressing impermeable to air, or, in emergencies, by the application of the hand, may be life saving.

d. The lung in heart failure:

     When the left heart fails and enlarges, the pressure within its chambers rises. There is a corresponding rise in the pressure in the pulmonary veins and venules which become swollen with blood. Since the pulmonary venules make up part of the mass of the lung, their swelling, which makes the lung heavier, makes breathing sufficiently difficult to bring it to the level of awareness.

     The consciousness of labored breathing, called dyspnea, is one of the earliest signs of left heart failure. It may only occur on exertion; but it may also occur from an act as simple as lying down, which, by increasing the return of blood to the heart, may overload the left ventricle.

     In time, elevated pulmonary venous pressure may be translated into increased pulmonary capillary pressure and pulmonary edema. When pulmonary edema occurs the respiratory effectiveness of the lungs is compromised. The arterial blood may be deficient in oxygen, so that the heart suffers the further disadvantage of working in an unfavorable (negatively inotropic) chemical environment and dilates further, thus increasing venous pressure. The steps in this cycle usually follow each other inexorably; however, the cycle may be terminated by right heart failure (the right heart becoming unable to pump against the increased pulmonary capillary pressure). Vigorous and determined treatment may also interrupt the cycle. Bleeding diminishing the work of the heart, digitalis, improving the chemical status of the heart muscle, and the lessening of venous return by the application of loose tourniquets to arms and legs may be combined with oxygen administration, which gets more oxygen into the blood than is supplied by ordinary air in the presence of pulmonary edema.

     Almost all of the above changes can occur when the atrioventricular valves on the left side of the heart are stenotic (mitral stenosis) even though the left ventricle muscle is normal. This condition can be treated best by valve replacement; in some cases the stenotic valve can be forced open by pushing a finger through it after opening the chest. The finger need not enter the heart, but rather is pushed along with atrial tissue through the stenotic valve. This procedure, called closed mitral commissurotomy, is almost without risk in skilled hands and results in improvement in 80-90% of all cases. See also Chapter 16.

e. The work of breathing in disease:

     In Part 6 it was shown that quiet breathing in health required 5 watts of power. It was also noted that the respiratory muscles are at most 25% efficient. It will be shown in Chapter X than the energy available to a resting man is equivalent to 75-80 watts. Thus the respiratory muscles (which develop 5 watts at 25% efficiency) use no less than 20 watts at rest, about one quarter of the power available to the body.

     When part of the respiratory passageway is obstructed, the power demanded by the increased respiratory effort may increase faster than the oxygen supply made available through that effort. When this occurs, all the available oxygen may be spent in the respiratory endeavor while other organs suffer.

     The extent to which respiratory disease increases respiratory effort and exaggerates respiratory need is not known with any degree of certainty. It does, however, seem quite probable that minor disturbances in respiratory function may lead to major respiratory distress. This area deserves further study.

Continue to Chapter 18.