Diagnosis and treatment of most respiratory disorders depend heavily on understanding the basic physiologic principles of respiration and gas exchange. Some respiratory diseases result from inadequate ventilation. Others result from abnormalities of diffusion through the pulmonary membrane or abnormal blood transport of gases between the lungs and tissues. Therapy is often entirely different for these diseases, so it is no longer satisfactory simply to make a diagnosis of “respiratory insufficiency.”
Useful Methods for Studying Respiratory Abnormalities
In the previous few chapters, we have discussed several methods for studying respiratory abnormalities, including measuring vital capacity, tidal air, functional residual capacity, dead space, physiologic shunt, and physiologic dead space. This array of measurements is only part of the armamentarium of the clinical pulmonary physiologist. Some other tools are described here.
Study of Blood Gases and Blood pH
Among the most fundamental of all tests of pulmonary performance are determinations of the blood PO2, CO2, and pH. It is often important to make these measurements rapidly as an aid in determining appropriate therapy for acute respiratory distress or acute abnormalities of acid-base balance. Several simple and rapid methods have been developed to make these measurements within minutes, using no more than a few drops of blood. They are the following.
Determination of Blood pH
Blood pH is measured using a glass pH electrode of the type used in all chemical laboratories. However, the electrodes used for this purpose are miniaturized. The voltage generated by the glass electrode is a direct measure of pH, and this is generally read directly from a voltmeter scale, or it is recorded on a chart.
Determination of Blood CO2
A glass electrode pH meter can also be used to determine blood CO2 in the following way: When a weak solution of sodium bicarbonate is exposed to carbon dioxide gas, the carbon dioxide dissolves in the solution until an equilibrium state is established. In this equilibrium state, the pH of the solution is a function of the carbon dioxide and bicarbonate ion concentrations in accordance with the Henderson-Hasselbalch equation that is explained in Chapter 30; that is,
When the glass electrode is used to measure CO2 in blood, a miniature glass electrode is surrounded by a thin plastic membrane. In the space between the electrode and plastic membrane is a solution of sodium bicarbonate of known concentration. Blood is then superfused onto the outer surface of the plastic membrane, allowing carbon dioxide to diffuse from the blood into the bicarbonate solution. Only a drop or so of blood is required. Next, the pH is measured by the glass electrode, and the CO2 is calculated by use of the previously given formula.
Determination of Blood PO2
The concentration of oxygen in a fluid can be measured by a technique called polarography. Electric current is made to flow between a small negative electrode and the solution. If the voltage of the electrode is more than −0.6 volt different from the voltage of the solution, oxygen will deposit on the electrode. Furthermore, the rate of current flow through the electrode will be directly proportional to the concentration of oxygen (and therefore to PO2 as well). In practice, a negative platinum electrode with a surface area of about 1 square millimeter is used, and this is separated from the blood by a thin plastic membrane that allows diffusion of oxygen but not diffusion of proteins or other substances that will “poison” the electrode.
Often all three of the measuring devices for pH, CO2, and PO2 are built into the same apparatus, and all these measurements can be made within a minute or so using a single, droplet-size sample of blood. Thus, changes in the blood gases and pH can be followed almost moment by moment at the bedside.
Measurement of Maximum Expiratory Flow
In many respiratory diseases, particularly in asthma, the resistance to airflow becomes especially great during expiration, sometimes causing tremendous difficulty in breathing. This has led to the concept called maximum expiratory flow, which can be defined as follows: When a person expires with great force, the expiratory airflow reaches a maximum flow beyond which the flow cannot be increased any more, even with greatly increased additional force. This is the maximum expiratory flow. The maximum expiratory flow is much greater when the lungs are filled with a large volume of air than when they are almost empty. These principles can be understood by referring to Figure 42-1.
Figure 42-1 A, Collapse of the respiratory passageway during maximum expiratory effort, an effect that limits expiratory flow rate. B, Effect of lung volume on the maximum expiratory air flow, showing decreasing maximum expiratory air flow as the lung volume becomes smaller.
Figure 42-1A shows the effect of increased pressure applied to the outsides of the alveoli and air passageways caused by compressing the chest cage. The arrows indicate that the same pressure compresses the outsides of both the alveoli and the bronchioles. Therefore, not only does this pressure force air from the alveoli toward the bronchioles, but it also tends to collapse the bronchioles at the same time, which will oppose movement of air to the exterior. Once the bronchioles have almost completely collapsed, further expiratory force can still greatly increase the alveolar pressure, but it also increases the degree of bronchiolar collapse and airway resistance by an equal amount, thus preventing further increase in flow. Therefore, beyond a critical degree of expiratory force, a maximum expiratory flow has been reached.
Figure 42-1B shows the effect of different degrees of lung collapse (and therefore of bronchiolar collapse as well) on the maximum expiratory flow. The curve recorded in this section shows the maximum expiratory flow at all levels of lung volume after a healthy person first inhales as much air as possible and then expires with maximum expiratory effort until he or she can expire at no greater rate. Note that the person quickly reaches a maximum expiratory airflow of more than 400 L/min. But regardless of how much additional expiratory effort the person exerts, this is still the maximum flow rate that he or she can achieve.
Note also that as the lung volume becomes smaller, the maximum expiratory flow rate also becomes less. The main reason for this is that in the enlarged lung the bronchi and bronchioles are held open partially by way of elastic pull on their outsides by lung structural elements; however, as the lung becomes smaller, these structures are relaxed so that the bronchi and bronchioles are collapsed more easily by external chest pressure, thus progressively reducing the maximum expiratory flow rate as well.
Abnormalities of the Maximum Expiratory Flow-Volume Curve
Figure 42-2 shows the normal maximum expiratory flow-volume curve, along with two additional flow-volume curves recorded in two types of lung diseases: constricted lungs and partial airway obstruction. Note that the constricted lungs have both reduced total lung capacity (TLC) and reduced residual volume (RV). Furthermore, because the lung cannot expand to a normal maximum volume, even with the greatest possible expiratory effort, the maximal expiratory flow cannot rise to equal that of the normal curve. Constricted lung diseases include fibrotic diseases of the lung itself, such as tuberculosis and silicosis, and diseases that constrict the chest cage, such as kyphosis, scoliosis, and fibrotic pleurisy.
Figure 42-2 Effect of two respiratory abnormalities—constricted lungs and airway obstruction—on the maximum expiratory flow-volume curve. TLC, total lung capacity; RV, residual volume.
In diseases with airway obstruction, it is usually much more difficult to expire than to inspire because the closing tendency of the airways is greatly increased by the extra positive pressure required in the chest to cause expiration. By contrast, the extra negative pleural pressure that occurs during inspiration actually “pulls” the airways open at the same time that it expands the alveoli. Therefore, air tends to enter the lung easily but then becomes trapped in the lungs. Over a period of months or years, this effect increases both the TLC and the RV, as shown by the green curve in Figure 42-2. Also, because of the obstruction of the airways and because they collapse more easily than normal airways, the maximum expiratory flow rate is greatly reduced.
The classic disease that causes severe airway obstruction is asthma. Serious airway obstruction also occurs in some stages of emphysema.
Forced Expiratory Vital Capacity and Forced Expiratory Volume
Another exceedingly useful clinical pulmonary test, and one that is also simple, is to record on a spirometer the forced expiratory vital capacity (FVC). Such a recording is shown in Figure 42-3A for a person with normal lungs and in Figure 42-3B for a person with partial airway obstruction. In performing the FVC maneuver, the person first inspires maximally to the total lung capacity and then exhales into the spirometer with maximum expiratory effort as rapidly and as completely as possible. The total distance of the downslope of the lung volume record represents the FVC, as shown in the figure.
Figure 42-3 Recordings during the forced vital capacity maneuver: A, in a healthy person and B, in a person with partial airway obstruction. (The “zero” on the volume scale is residual volume.)
Now, study the difference between the two records (1) for normal lungs and (2) for partial airway obstruction. The total volume changes of the FVCs are not greatly different, indicating only a moderate difference in basic lung volumes in the two persons. There is, however, a major difference in the amounts of air that these persons can expire each second, especially during the first second. Therefore, it is customary to compare the recorded forced expiratory volume during the first second (FEV1) with the normal. In the normal person (see Figure 42-3A), the percentage of the FVC that is expired in the first second divided by the total FVC (FEV1/FVC%) is 80 percent. However, note in Figure 42-3B that, with airway obstruction, this value decreased to only 47 percent. In serious airway obstruction, as often occurs in acute asthma, this can decrease to less than 20 percent.
Pathophysiology of Specific Pulmonary Abnormalities
Chronic Pulmonary Emphysema
The term pulmonary emphysema literally means excess air in the lungs. However, this term is usually used to describe complex obstructive and destructive process of the lungs caused by many years of smoking. It results from the following major pathophysiologic changes in the lungs:
1. Chronic infection, caused by inhaling smoke or other substances that irritate the bronchi and bronchioles. The chronic infection seriously deranges the normal protective mechanisms of the airways, including partial paralysis of the cilia of the respiratory epithelium, an effect caused by nicotine. As a result, mucus cannot be moved easily out of the passageways. Also, stimulation of excess mucus secretion occurs, which further exacerbates the condition. Inhibition of the alveolar macrophages also occurs, so they become less effective in combating infection.
2. The infection, excess mucus, and inflammatory edema of the bronchiolar epithelium together cause chronic obstruction of many of the smaller airways.
3. The obstruction of the airways makes it especially difficult to expire, thus causing entrapment of air in the alveoli and overstretching them. This, combined with the lung infection, causes marked destruction of as much as 50 to 80 percent of the alveolar walls. Therefore, the final picture of the emphysematous lung is that shown in Figures 42-4 (top) and 42-5.
Figure 42-4 Contrast of the emphysematous lung (top figure) with the normal lung (bottom figure), showing extensive alveolar destruction in emphysema.
(Reproduced with permission of Patricia Delaney and the Department of Anatomy, The Medical College of Wisconsin.)
Figure 42-5 Lung alveolar changes in pneumonia and emphysema.
The physiologic effects of chronic emphysema are variable, depending on the severity of the disease and the relative degrees of bronchiolar obstruction versus lung parenchymal destruction. Among the different abnormalities are the following:
1. The bronchiolar obstruction increases airway resistance and results in greatly increased work of breathing. It is especially difficult for the person to move air through the bronchioles during expiration because the compressive force on the outside of the lung not only compresses the alveoli but also compresses the bronchioles, which further increases their resistance during expiration.
2. The marked loss of alveolar walls greatly decreases the diffusing capacity of the lung, which reduces the ability of the lungs to oxygenate the blood and remove carbon dioxide from the blood.
3. The obstructive process is frequently much worse in some parts of the lungs than in other parts, so some portions of the lungs are well ventilated, whereas other portions are poorly ventilated. This often causes extremely abnormal ventilation-perfusion ratios, with a very low 
in some parts (physiologic shunt), resulting in poor aeration of the blood, and very high 
in other parts (physiologic dead space), resulting in wasted ventilation, both effects occurring in the same lungs.
4. Loss of large portions of the alveolar walls also decreases the number of pulmonary capillaries through which blood can pass. As a result, the pulmonary vascular resistance often increases markedly, causing pulmonary hypertension. This in turn overloads the right side of the heart and frequently causes right-sided heart failure.
Chronic emphysema usually progresses slowly over many years. The person develops both hypoxia and hypercapnia because of hypoventilation of many alveoli plus loss of alveolar walls. The net result of all these effects is severe, prolonged, devastating air hunger that can last for years until the hypoxia and hypercapnia cause death—a high penalty to pay for smoking.
Pneumonia
The term pneumonia includes any inflammatory condition of the lung in which some or all of the alveoli are filled with fluid and blood cells, as shown in Figure 42-5. A common type of pneumonia is bacterial pneumonia, caused most frequently by pneumococci. This disease begins with infection in the alveoli; the pulmonary membrane becomes inflamed and highly porous so that fluid and even red and white blood cells leak out of the blood into the alveoli. Thus, the infected alveoli become progressively filled with fluid and cells, and the infection spreads by extension of bacteria or virus from alveolus to alveolus. Eventually, large areas of the lungs, sometimes whole lobes or even a whole lung, become “consolidated,” which means that they are filled with fluid and cellular debris.
In pneumonia, the gas exchange functions of the lungs decline in different stages of the disease. In early stages, the pneumonia process might well be localized to only one lung, with alveolar ventilation reduced while blood flow through the lung continues normally. This causes two major pulmonary abnormalities: (1) reduction in the total available surface area of the respiratory membrane and (2) decreased ventilation-perfusion ratio. Both these effects cause hypoxemia (low blood oxygen) and hypercapnia (high blood carbon dioxide).
Figure 42-6 shows the effect of the decreased ventilation-perfusion ratio in pneumonia, showing that the blood passing through the aerated lung becomes 97 percent saturated with oxygen, whereas that passing through the unaerated lung is about 60 percent saturated. Therefore, the average saturation of the blood pumped by the left heart into the aorta is only about 78 percent, which is far below normal.
Figure 42-6 Effect of pneumonia on percentage saturation of oxygen in the pulmonary artery, the right and left pulmonary veins, and the aorta.
Atelectasis
Atelectasis means collapse of the alveoli. It can occur in localized areas of a lung or in an entire lung. Common causes of atelectasis are (1) total obstruction of the airway or (2) lack of surfactant in the fluids lining the alveoli.
Airway Obstruction Causes Lung Collapse
The airway obstruction type of atelectasis usually results from (1) blockage of many small bronchi with mucus or (2) obstruction of a major bronchus by either a large mucus plug or some solid object such as a tumor. The air entrapped beyond the block is absorbed within minutes to hours by the blood flowing in the pulmonary capillaries. If the lung tissue is pliable enough, this will lead simply to collapse of the alveoli. However, if the lung is rigid because of fibrotic tissue and cannot collapse, absorption of air from the alveoli creates very negative pressures within the alveoli, which pull fluid out of the pulmonary capillaries into the alveoli, thus causing the alveoli to fill completely with edema fluid. This almost always is the effect that occurs when an entire lung becomes atelectatic, a condition called massive collapseof the lung.
The effects on overall pulmonary function caused by massive collapse (atelectasis) of an entire lung are shown in Figure 42-7. Collapse of the lung tissue not only occludes the alveoli but also almost always increases the resistance to blood flow through the pulmonary vessels of the collapsed lung. This resistance increase occurs partially because of the lung collapse itself, which compresses and folds the vessels as the volume of the lung decreases. In addition, hypoxia in the collapsed alveoli causes additional vasoconstriction, as explained in Chapter 38.
Figure 42-7 Effect of atelectasis on aortic blood oxygen saturation.
Because of the vascular constriction, blood flow through the atelectatic lung is greatly reduced. Fortunately, most of the blood is routed through the ventilated lung and therefore becomes well aerated. In the situation shown in Figure 42-7, five sixths of the blood passes through the aerated lung and only one sixth through the unaerated lung. As a result, the overall ventilation-perfusion ratio is only moderately compromised, so the aortic blood has only mild oxygen desaturation despite total loss of ventilation in an entire lung.
Lack of “Surfactant” as a Cause of Lung Collapse
The secretion and function of surfactant in the alveoli were discussed in Chapter 37. It was pointed out that the surfactant is secreted by special alveolar epithelial cells into the fluids that coat the inside surface of the alveoli. The surfactant in turn decreases the surface tension in the alveoli 2- to 10-fold, which normally plays a major role in preventing alveolar collapse. However, in a number of conditions, such as in hyaline membrane disease (also called respiratory distress syndrome), which often occurs in newborn premature babies, the quantity of surfactant secreted by the alveoli is so greatly depressed that the surface tension of the alveolar fluid becomes several times normal. This causes a serious tendency for the lungs of these babies to collapse or to become filled with fluid. As explained in Chapter 37, many of these infants die of suffocation when large portions of the lungs become atelectatic.
Asthma—Spasmodic Contraction of Smooth Muscles in Bronchioles
Asthma is characterized by spastic contraction of the smooth muscle in the bronchioles, which partially obstructs the bronchioles and causes extremely difficult breathing. It occurs in 3 to 5 percent of all people at some time in life.
The usual cause of asthma is contractile hypersensitivity of the bronchioles in response to foreign substances in the air. In about 70 percent of patients younger than age 30 years, the asthma is caused by allergic hypersensitivity, especially sensitivity to plant pollens. In older people, the cause is almost always hypersensitivity to nonallergenic types of irritants in the air, such as irritants in smog.
The allergic reaction that occurs in the allergic type of asthma is believed to occur in the following way: The typical allergic person tends to form abnormally large amounts of IgE antibodies, and these antibodies cause allergic reactions when they react with the specific antigens that have caused them to develop in the first place, as explained in Chapter 34. In asthma, these antibodies are mainly attached to mast cells that are present in the lung interstitium in close association with the bronchioles and small bronchi. When the asthmatic person breathes in pollen to which he or she is sensitive (i.e., to which the person has developed IgE antibodies), the pollen reacts with the mast cell–attached antibodies and causes the mast cells to release several different substances. Among them are (a) histamine, (b) slow-reacting substance of anaphylaxis (which is a mixture of leukotrienes), (c) eosinophilic chemotactic factor, and (d) bradykinin. The combined effects of all these factors, especially the slow-reacting substance of anaphylaxis, are to produce (1) localized edema in the walls of the small bronchioles, as well as secretion of thick mucus into the bronchiolar lumens, and (2) spasm of the bronchiolar smooth muscle. Therefore, the airway resistance increases greatly.
As discussed earlier in this chapter, the bronchiolar diameter becomes more reduced during expiration than during inspiration in asthma, caused by bronchiolar collapse during expiratory effort that compresses the outsides of the bronchioles. Because the bronchioles of the asthmatic lungs are already partially occluded, further occlusion resulting from the external pressure creates especially severe obstruction during expiration. That is, the asthmatic person often can inspire quite adequately but has great difficulty expiring. Clinical measurements show (1) greatly reduced maximum expiratory rate and (2) reduced timed expiratory volume. Also, all of this together results in dyspnea, or “air hunger,” which is discussed later in this chapter.
The functional residual capacity and residual volume of the lung become especially increased during the acute asthmatic attack because of the difficulty in expiring air from the lungs. Also, over a period of years, the chest cage becomes permanently enlarged, causing a “barrel chest,” and both the functional residual capacity and lung residual volume become permanently increased.
Tuberculosis
In tuberculosis, the tubercle bacilli cause a peculiar tissue reaction in the lungs, including (1) invasion of the infected tissue by macrophages and (2) “walling off” of the lesion by fibrous tissue to form the so-called tubercle. This walling-off process helps to limit further transmission of the tubercle bacilli in the lungs and therefore is part of the protective process against extension of the infection. However, in about 3 percent of all people who develop tuberculosis, if untreated, the walling-off process fails and tubercle bacilli spread throughout the lungs, often causing extreme destruction of lung tissue with formation of large abscess cavities.
Thus, tuberculosis in its late stages is characterized by many areas of fibrosis throughout the lungs, as well as reduced total amount of functional lung tissue. These effects cause (1) increased “work” on the part of the respiratory muscles to cause pulmonary ventilation and reduced vital capacity and breathing capacity; (2) reduced total respiratory membrane surface area and increased thickness of the respiratory membrane, causing progressively diminished pulmonary diffusing capacity; and (3) abnormal ventilation-perfusion ratio in the lungs, further reducing overall pulmonary diffusion of oxygen and carbon dioxide.
Hypoxia and Oxygen Therapy
Almost any of the conditions discussed in the past few sections of this chapter can cause serious degrees of cellular hypoxia throughout the body. Sometimes, oxygen therapy is of great value; other times, it is of moderate value; and, at still other times, it is of almost no value. Therefore, it is important to understand the different types of hypoxia; then we can discuss the physiologic principles of oxygen therapy. The following is a descriptive classification of the causes of hypoxia:
1. Inadequate oxygenation of the blood in the lungs because of extrinsic reasons
a. Deficiency of oxygen in the atmosphere
b. Hypoventilation (neuromuscular disorders)
2. Pulmonary disease
a. Hypoventilation caused by increased airway resistance or decreased pulmonary compliance
b. Abnormal alveolar ventilation-perfusion ratio (including either increased physiologic dead space or increased physiologic shunt)
c. Diminished respiratory membrane diffusion
3. Venous-to-arterial shunts (“right-to-left” cardiac shunts)
4. Inadequate oxygen transport to the tissues by the blood
a. Anemia or abnormal hemoglobin
b. General circulatory deficiency
c. Localized circulatory deficiency (peripheral, cerebral, coronary vessels)
d. Tissue edema
5. Inadequate tissue capability of using oxygen
a. Poisoning of cellular oxidation enzymes
b. Diminished cellular metabolic capacity for using oxygen, because of toxicity, vitamin deficiency, or other factors
This classification of the types of hypoxia is mainly self-evident from the discussions earlier in the chapter. Only one type of hypoxia in the classification needs further elaboration: the hypoxia caused by inadequate capability of the body’s tissue cells to use oxygen.
Inadequate Tissue Capability to Use Oxygen
The classic cause of inability of the tissues to use oxygen is cyanide poisoning, in which the action of the enzyme cytochrome oxidase is completely blocked by the cyanide—to such an extent that the tissues simply cannot use oxygen even when plenty is available. Also, deficiencies of some of the tissue cellular oxidative enzymes or of other elements in the tissue oxidative system can lead to this type of hypoxia. A special example occurs in the disease beriberi, in which several important steps in tissue utilization of oxygen and formation of carbon dioxide are compromised because of vitamin B deficiency.
Effects of Hypoxia on the Body
Hypoxia, if severe enough, can cause death of cells throughout the body, but in less severe degrees it causes principally (1) depressed mental activity, sometimes culminating in coma, and (2) reduced work capacity of the muscles. These effects are specifically discussed in Chapter 43 in relation to high-altitude physiology.
Oxygen Therapy in Different Types of Hypoxia
Oxygen can be administered by (1) placing the patient’s head in a “tent” that contains air fortified with oxygen, (2) allowing the patient to breathe either pure oxygen or high concentrations of oxygen from a mask, or (3) administering oxygen through an intranasal tube.
Recalling the basic physiologic principles of the different types of hypoxia, one can readily decide when oxygen therapy will be of value and, if so, how valuable.
In atmospheric hypoxia, oxygen therapy can completely correct the depressed oxygen level in the inspired gases and, therefore, provide 100 percent effective therapy.
In hypoventilation hypoxia, a person breathing 100 percent oxygen can move five times as much oxygen into the alveoli with each breath as when breathing normal air. Therefore, here again oxygen therapy can be extremely beneficial. (However, this provides no benefit for the excess blood carbon dioxide also caused by the hypoventilation.)
In hypoxia caused by impaired alveolar membrane diffusion, essentially the same result occurs as in hypoventilation hypoxia because oxygen therapy can increase the PO2 in the lung alveoli from the normal value of about 100 mm Hg to as high as 600 mm Hg. This raises the oxygen pressure gradient for diffusion of oxygen from the alveoli to the blood from the normal value of 60 mm Hg to as high as 560 mm Hg, an increase of more than 800 percent. This highly beneficial effect of oxygen therapy in diffusion hypoxia is demonstrated in Figure 42-8, which shows that the pulmonary blood in this patient with pulmonary edema picks up oxygen three to four times as rapidly as would occur with no therapy.
Figure 42-8 Absorption of oxygen into the pulmonary capillary blood in pulmonary edema with and without oxygen tent therapy.
In hypoxia caused by anemia, abnormal hemoglobin transport of oxygen, circulatory deficiency, or physiologic shunt, oxygen therapy is of much less value because normal oxygen is already available in the alveoli. The problem instead is that one or more of the mechanisms for transporting oxygen from the lungs to the tissues are deficient. Even so, a small amount of extra oxygen, between 7 and 30 percent, can be transported in the dissolved state in the blood when alveolar oxygen is increased to maximum even though the amount transported by the hemoglobin is hardly altered. This small amount of extra oxygen may be the difference between life and death.
In the different types of hypoxia caused by inadequate tissue use of oxygen, there is abnormality neither of oxygen pickup by the lungs nor of transport to the tissues. Instead, the tissue metabolic enzyme system is simply incapable of using the oxygen that is delivered. Therefore, oxygen therapy provides no measurable benefit.
Cyanosis
The term cyanosis means blueness of the skin, and its cause is excessive amounts of deoxygenated hemoglobin in the skin blood vessels, especially in the capillaries. This deoxygenated hemoglobin has an intense dark blue–purple color that is transmitted through the skin.
In general, definite cyanosis appears whenever the arterial blood contains more than 5 grams of deoxygenated hemoglobin in each 100 milliliters of blood. A person with anemia almost never becomes cyanotic because there is not enough hemoglobin for 5 grams to be deoxygenated in 100 milliliters of arterial blood. Conversely, in a person with excess red blood cells, as occurs in polycythemia vera, the great excess of available hemoglobin that can become deoxygenated leads frequently to cyanosis, even under otherwise normal conditions.
Hypercapnia—Excess Carbon Dioxide in the Body Fluids
One might suspect, on first thought, that any respiratory condition that causes hypoxia would also cause hypercapnia. However, hypercapnia usually occurs in association with hypoxia only when the hypoxia is caused by hypoventilation or circulatory deficiency. The reasons for this are the following.
Hypoxia caused by too little oxygen in the air, too little hemoglobin, or poisoning of the oxidative enzymes has to do only with the availability of oxygen or use of oxygen by the tissues. Therefore, it is readily understandable that hypercapnia is not a concomitant of these types of hypoxia.
In hypoxia resulting from poor diffusion through the pulmonary membrane or through the tissues, serious hypercapnia usually does not occur at the same time because carbon dioxide diffuses 20 times as rapidly as oxygen. If hypercapnia does begin to occur, this immediately stimulates pulmonary ventilation, which corrects the hypercapnia but not necessarily the hypoxia.
Conversely, in hypoxia caused by hypoventilation, carbon dioxide transfer between the alveoli and the atmosphere is affected as much as is oxygen transfer. Hypercapnia then occurs along with the hypoxia. And in circulatory deficiency, diminished flow of blood decreases carbon dioxide removal from the tissues, resulting in tissue hypercapnia in addition to tissue hypoxia. However, the transport capacity of the blood for carbon dioxide is more than three times that for oxygen, so that the resulting tissue hypercapnia is much less than the tissue hypoxia.
When the alveolar PCO2 rises above about 60 to 75 mm Hg, an otherwise normal person by then is breathing about as rapidly and deeply as he or she can, and “air hunger,” also called dyspnea, becomes severe.
If the PCO2 rises to 80 to 100 mm Hg, the person becomes lethargic and sometimes even semicomatose. Anesthesia and death can result when the PCO2 rises to 120 to 150 mm Hg. At these higher levels of PCO2, the excess carbon dioxide now begins to depress respiration rather than stimulate it, thus causing a vicious circle: (1) more carbon dioxide, (2) further decrease in respiration, (3) then more carbon dioxide, and so forth—culminating rapidly in a respiratory death.
Dyspnea
Dyspnea means mental anguish associated with inability to ventilate enough to satisfy the demand for air. A common synonym is air hunger.
At least three factors often enter into the development of the sensation of dyspnea. They are (1) abnormality of respiratory gases in the body fluids, especially hypercapnia and, to a much less extent, hypoxia; (2) the amount of work that must be performed by the respiratory muscles to provide adequate ventilation; and (3) state of mind.
A person becomes very dyspneic, especially from excess buildup of carbon dioxide in the body fluids. At times, however, the levels of both carbon dioxide and oxygen in the body fluids are normal, but to attain this normality of the respiratory gases, the person has to breathe forcefully. In these instances, the forceful activity of the respiratory muscles frequently gives the person a sensation of dyspnea.
Finally, the person’s respiratory functions may be normal and still dyspnea may be experienced because of an abnormal state of mind. This is called neurogenic dyspnea or emotional dyspnea. For instance, almost anyone momentarily thinking about the act of breathing may suddenly start taking breaths a little more deeply than ordinarily because of a feeling of mild dyspnea. This feeling is greatly enhanced in people who have a psychological fear of not being able to receive a sufficient quantity of air, such as on entering small or crowded rooms.
Artificial Respiration
Resuscitator
Many types of respiratory resuscitators are available, and each has its own characteristic principles of operation. The resuscitator shown in Figure 42-9A consists of a tank supply of oxygen or air; a mechanism for applying intermittent positive pressure and, with some machines, negative pressure as well; and a mask that fits over the face of the patient or a connector for joining the equipment to an endotracheal tube. This apparatus forces air through the mask or endotracheal tube into the lungs of the patient during the positive-pressure cycle of the resuscitator and then usually allows the air to flow passively out of the lungs during the remainder of the cycle.
Figure 42-9 A, Resuscitator. B, Tank respirator.
Earlier resuscitators often caused damage to the lungs because of excessive positive pressure. Their usage was at one time greatly decried. However, resuscitators now have adjustable positive-pressure limits that are commonly set at 12 to 15 cm H2O pressure for normal lungs (but sometimes much higher for noncompliant lungs).
Tank Respirator (the “Iron-Lung”)
Figure 42-9B shows the tank respirator with a patient’s body inside the tank and the head protruding through a flexible but airtight collar. At the end of the tank opposite the patient’s head, a motor-driven leather diaphragm moves back and forth with sufficient excursion to raise and lower the pressure inside the tank. As the leather diaphragm moves inward, positive pressure develops around the body and causes expiration; as the diaphragm moves outward, negative pressure causes inspiration. Check valves on the respirator control the positive and negative pressures. Ordinarily these pressures are adjusted so that the negative pressure that causes inspiration falls to −10 to −20 cm H2O and the positive pressure rises to 0 to +5 cm H2O.
Effect of the Resuscitator and the Tank Respirator on Venous Return
When air is forced into the lungs under positive pressure by a resuscitator, or when the pressure around the patient’s body is reduced by the tank respirator, the pressure inside the lungs becomes greater than pressure everywhere else in the body. Flow of blood into the chest and heart from the peripheral veins becomes impeded. As a result, use of excessive pressures with either the resuscitator or the tank respirator can reduce the cardiac output—sometimes to lethal levels. For instance, continuous exposure for more than a few minutes to greater than 30 mm Hg positive pressure in the lungs can cause death because of inadequate venous return to the heart.
Bibliography
Albert R., Spiro S., Jett J. Comprehensive Respiratory Medicine. Philadelphia: Mosby, 2002.
Barnes P.J. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118:3546.
Cardoso W.V. Molecular regulation of lung development. Annu Rev Physiol. 2001;63:471.
Casey K.R., Cantillo K.O., Brown L.K. Sleep-related hypoventilation/hypoxemic syndromes. Chest. 2007;131:1936.
Eder W., Ege M.J., von Mutius E. The asthma epidemic. N Engl J Med. 2006;355:2226.
Herzog E.L., Brody A.R., Colby T.V., et al. Knowns and unknowns of the alveolus. Proc Am Thorac Soc. 2008;5:778.
Knight D.A., Holgate S.T. The airway epithelium: structural and functional properties in health and disease. Respirology. 2003;8:432.
McConnell A.K., Romer L.M. Dyspnoea in health and obstructive pulmonary disease: the role of respiratory muscle function and training. Sports Med. 2004;34:117.
Mühlfeld C., Rothen-Rutishauser B., Blank F., et al. Interactions of nanoparticles with pulmonary structures and cellular responses. Am J Physiol Lung Cell Mol Physiol. 2008;294:L817.
Naureckas E.T., Solway J. Clinical practice. Mild asthma. N Engl J Med. 2001;345:1257.
Ramanathan R. Optimal ventilatory strategies and surfactant to protect the preterm lungs. Neonatology. 2008;93:302.
Sharafkhaneh A., Hanania N.A., Kim V. Pathogenesis of emphysema: from the bench to the bedside. Proc Am Thorac Soc. 2008;5:475.
Sin D.D., McAlister F.A., Man S.F., et al. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA. 2003;290:2301.
Soni N., Williams P. Positive pressure ventilation: what is the real cost? Br J Anaesth. 2008;101:446.
Taraseviciene-Stewart L., Voelkel N.F. Molecular pathogenesis of emphysema. J Clin Invest. 2008;118:394.
Whitsett J.A., Weaver T.E. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002;347:2141.
Wills-Karp M., Ewart S.L. Time to draw breath: asthma-susceptibility genes are identified. Nat Rev Genet. 2004;5:376.
Wright J.L., Cosio M., Churg A. Animal models of chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2008;295:L1.