Guyton and Hall Physiology Chapter 43 - Respiratory Insufficiency PDF

CHAPTER 43 UNIT VII Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen T...

CHAPTER 43 UNIT VII Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy Diagnosis and treatment of most respiratory disorders weak solution of sodium bicarbonate is exposed to CO2 depend heavily on understanding the basic physiological gas, the CO2 dissolves in the solution until an equilib- principles of respiration and gas exchange. Some respira- rium state is reached. In this equilibrium state, the pH tory diseases result from inadequate ventilation. Others of the solution is a function of the CO2 and bicarbo- are caused by abnormalities of diffusion through the pul- nate ion (HCO3−) concentrations in accordance with the monary membrane or abnormal blood transport of gases Henderson-Hasselbalch equation explained in Chapter between the lungs and tissues. Therapy is often entirely 31: − different for these diseases, so it is not satisfactory simply HCO3 pH= 6.1 + log to make a diagnosis of “respiratory insufficiency.” CO2 When the glass electrode is used to measure CO2 in USEFUL METHODS FOR STUDYING blood, a miniature glass electrode is surrounded by a RESPIRATORY ABNORMALITIES thin plastic membrane. A solution of sodium bicarbon- In the previous few chapters, we discussed several meth- ate of known concentration is in the space between the ods for studying respiratory abnormalities, including electrode and plastic membrane. Blood is then super- measuring vital capacity, tidal air, functional residual fused onto the outer surface of the plastic membrane, capacity, dead space, physiologic shunt, and physiological allowing CO2 to diffuse from the blood into the bicar- dead space. This array of measurements is only part of the bonate solution. Only a drop or so of blood is required. armamentarium of the clinical pulmonary physiologist. Next, the pH is measured by the glass electrode, and the Some other tools are described here. CO2 is calculated using the formula that was previously provided. STUDY OF BLOOD GASES AND BLOOD pH Determination of Blood Po2. The concentration of Among the most fundamental of all tests of pulmonary O2 in a fluid can be measured by a technique called po- performance are determinations of the blood partial pres- larography. Electric current is made to flow between a sure of oxygen (Po2), carbon dioxide (CO2), and pH. It is small negative electrode and the solution. If the volt- often important to make these measurements rapidly as age of the electrode is more than −0.6 volt different an aid in determining appropriate therapy for acute respi- from the voltage of the solution, O2 will deposit on ratory distress or acute abnormalities of acid–base bal- the electrode. Furthermore, the rate of current flow ance. The following simple and rapid methods have been through the electrode will be directly proportional to developed to make these measurements within minutes, the concentration of O2 (and therefore to PO2 as well). using no more than a few drops of blood. In practice, a negative platinum electrode with a sur- face area of about 1 square millimeter is used, and this Determination of Blood pH. Blood pH is measured us- electrode is separated from the blood by a thin plastic ing a glass pH electrode of the type commonly used in membrane that allows diffusion of O2 but not diffusion chemical laboratories. However, the electrodes used for of proteins or other substances that will “poison” the this purpose are miniaturized. The voltage generated by electrode. the glass electrode is a direct measure of pH and is gener- Often, all three of the measuring devices for pH, CO2, ally read directly from a voltmeter scale, or it is recorded and Po2 are built into the same apparatus, and all these on a chart. measurements can be made within a minute or so using a single droplet-sized sample of blood. Thus, changes in the Determination of Blood CO2. A glass electrode pH me- blood gas levels and pH can be followed almost moment ter can also be used to determine blood CO2. When a by moment at the bedside. 541 UNIT VII Respiration on the maximum expiratory flow. The curve recorded in MEASUREMENT OF MAXIMUM this section shows the maximum expiratory flow at all EXPIRATORY FLOW levels of lung volume after a healthy person first inhales In many respiratory diseases, particularly in asthma, the as much air as possible and then expires with maximum resistance to airflow becomes especially great during expiratory effort until he or she can expire at no greater expiration, sometimes causing tremendous difficulty in rate. Note that the person quickly reaches a maximum breathing. This condition has led to the concept called expiratory airflow of more than 400 L/min. However, maximum expiratory flow, which can be defined as fol- regardless of how much additional expiratory effort the lows. When a person expires with great force, the expi- person exerts, this is still the maximum flow rate that he ratory airflow reaches a maximum flow beyond which or she can achieve. the flow cannot be increased any more, even with greatly Note also that as the lung volume becomes smaller, increased additional force. This is the maximum expira- the maximum expiratory flow rate also becomes less. The tory flow. The maximum expiratory flow is much greater main reason for this phenomenon is that in the enlarged when the lungs are filled with a large volume of air than lung, the bronchi and bronchioles are held open partially when they are almost empty. These principles can be by way of elastic pull on their outsides by lung structural understood by referring to Figure 43-1. elements. However, as the lung becomes smaller, these Figure 43-1A shows the effect of increased pressure structures are relaxed so that the bronchi and bronchioles applied to the outsides of the alveoli and air passageways are collapsed more easily by external chest pressure, thus caused by compressing the chest cage. The arrows indi- progressively reducing the maximum expiratory flow rate cate that the same pressure compresses the outsides of as well. the alveoli and bronchioles. Therefore, not only does this pressure force air from the alveoli toward the bronchioles, Abnormalities of the Maximum Expiratory Flow- but it also tends to collapse the bronchioles at the same Volume Curve. Figure 43-2 shows the normal maximum time, which will oppose movement of air to the exterior. expiratory flow-volume curve, along with two additional Once the bronchioles have almost completely collapsed, flow-volume curves recorded in two types of lung dis- further expiratory force can still increase the alveolar pres- eases: constricted lungs and partial airway obstruction. sure greatly, but it also increases the degree of bronchiolar Note that the constricted lungs have both reduced total collapse and airway resistance by an equal amount, thus lung capacity (TLC) and reduced residual volume (RV). preventing further increase in flow. Therefore, beyond a Furthermore, because the lung cannot expand to a nor- critical degree of expiratory force, a maximum expiratory mal maximum volume, even with the greatest possible ex- flow has been reached. piratory effort, the maximal expiratory flow cannot rise to Figure 43-1B shows the effect of different degrees of equal that of the normal curve. Constricted lung diseases lung collapse (and therefore also of bronchiolar collapse) include fibrotic diseases of the lung, such as tuberculosis and silicosis, and diseases that constrict the chest cage, such as kyphosis, scoliosis, and fibrotic pleurisy. In diseases with airway obstruction, it is usually much A 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. 500 By contrast, the extra negative pleural pressure that occurs during inspiration actually “pulls” the airways open at the Expiratory air flow (L/min) 400 M ax 500 im um Expiratory air flow (L/min) 300 Airway ex 400 obstruction pi ra t or 200 y 300 Normal flo w 100 Total lung Residual 200 capacity Constricted volume lungs 0 100 B 6 5 4 3 2 1 0 TLC RV Lung volume (liters) 0 7 6 5 4 3 2 1 0 Figure 43-1. A, Collapse of the respiratory passageway during maxi- mum expiratory effort, an effect that limits expiratory flow rate. B, Lung volume (liters) Effect of lung volume on the maximum expiratory airflow, showing Figure 43-2. Effect of two respiratory abnormalities—constricted decreasing maximum expiratory airflow as the lung volume becomes lungs and airway obstruction—on the maximum expiratory flow- smaller. volume curve. RV, Residual volume; TLC, total lung capacity. 542  Chapter 43 Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy same time that it expands the alveoli. Therefore, air tends to normal value. In the normal person (see Figure 43-3A), enter the lung easily but then becomes trapped in the lungs. the percentage of the FVC that is expired in the first sec- Over a period of months or years, this effect increases both ond divided by the total FVC (FEV1/FVC%) is 80%. How- the TLC and RV, as shown by the green curve in Figure ever, note in Figure 43-3B that with airway obstruction, 43-2. Also, because of the obstruction of the airways, and this value decreases to only 47%. In persons with serious UNIT VII because they collapse more easily than normal airways, the airway obstruction, as often occurs with acute asthma, maximum expiratory flow rate is greatly reduced. this value can decrease to less than 20%. The classic disease that causes severe airway obstruc- tion is asthma. Serious airway obstruction also occurs in PATHOPHYSIOLOGY OF SPECIFIC some stages of emphysema. PULMONARY ABNORMALITIES FORCED EXPIRATORY VITAL CAPACITY CHRONIC PULMONARY EMPHYSEMA AND FORCED EXPIRATORY VOLUME The term pulmonary emphysema literally means excess Another useful clinical pulmonary test, and one that air in the lungs. However, this term is usually used to is also easy to perform, is to record the forced expiratory describe a complex obstructive and destructive process vital capacity (FVC) on a spirometer. Such a recording is of the lungs caused by many years of smoking. It results shown in Figure 43-3A for a person with normal lungs from the following major pathophysiological changes in and in Figure 43-3B for a person with partial airway the lungs: obstruction. In performing the FVC maneuver, the per- 1. Chronic infection, caused by inhaling smoke or son first inspires maximally to the TLC and then exhales other substances that irritate the bronchi and bron- into the spirometer with maximum expiratory effort as chioles. The chronic infection seriously deranges rapidly and as completely as possible. The total distance of the normal protective mechanisms of the airways, the downslope of the lung volume record represents the including partial paralysis of the cilia of the res- FVC, as shown in the figure. piratory epithelium, an effect caused by nicotine. Now, study the difference between the two records for As a result, mucus cannot be moved easily out of (1) normal lungs and (2) partial airway obstruction. The the passageways. Also, stimulation of excess mu- total volume changes of the FVCs are not greatly differ- cus secretion occurs, which further exacerbates the ent, indicating only a moderate difference in basic lung condition. There is also inhibition of the alveolar volumes in the two persons. There is, however, a major macrophages, so they become less effective in com- difference in the amounts of air that these persons can bating infection. expire each second, especially during the first second. 2. The infection, excess mucus, and inflammatory Therefore, it is customary to compare the recorded forced edema of the bronchiolar epithelium together cause expiratory volume during the first second (FEV1) with the 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 Normal Maximum in the alveoli and overstretching them. This effect, inspiration combined with the lung infection, causes marked 4 FEV1 destruction of as much as 50% to 80% of the alveolar 3 walls. Therefore, the final picture of the emphyse- Lung volume change (liters) 2 FEV1/FVC% FVC matous lung is that shown in Figure 43-4 (top) and 1 = 80% 43-5. 0 The physiological effects of chronic emphysema are A 0 1 2 3 4 5 6 7 variable, depending on the severity of the disease and the relative degrees of bronchiolar obstruction versus lung Airway Obstruction 4 parenchymal destruction. The different abnormalities include the following: 3 FEV1 1. The bronchiolar obstruction increases airway resist- 2 FEV1/FVC% FVC ance and results in greatly increased work of breath- 1 = 47% ing. It is especially difficult for the person to move 0 air through the bronchioles during expiration be- 0 1 2 3 4 5 6 7 B cause the compressive force on the outside of the Seconds lung not only compresses the alveoli but also com- Figure 43-3. Recordings during the forced vital capacity maneuver in presses the bronchioles, which further increases a healthy person (A) and in a person with partial airway obstruction (B). (The “zero” on the volume scale is residual volume.) FEV1, Forced their resistance during expiration. expiratory volume during the first second; FVC, forced expiratory vital 2. The marked loss of alveolar walls greatly decreases capacity. the diffusing capacity of the lung. This reduces the 543 UNIT VII Respiration ability of the lungs to oxygenate the blood and re- ventilation, with both effects occurring in the same move CO2 from the blood. lungs. 3. The obstructive process is frequently much worse in 4. Loss of large portions of the alveolar walls also some parts of the lungs than in other parts, so some decreases the number of pulmonary capillaries portions of the lungs are well ventilated, whereas through which blood can pass. As a result, the pul- other portions are poorly ventilated. This situa- monary vascular resistance often increases marked- tion often causes extremely abnormal. ventilation-. ly, causing pulmonary hypertension, which in turn perfusion ratios, with a very low VA/ Q in some overloads the right side of the heart and frequently parts (physiological shunt), resulting. in poor. aera- causes right-sided heart failure. tion of the blood, and a very high VA/ Q in other Chronic emphysema usually progresses slowly over parts (physiological dead space), resulting in wasted many years. Both hypoxia and hypercapnia develop 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—LUNG INFLAMMATION AND FLUID IN ALVEOLI The term pneumonia includes any inflammatory condi- tion of the lung in which some or all of the alveoli are filled with fluid and blood cells, as shown in Figure 43-5. A common type of pneumonia is bacterial pneu- monia, caused most frequently by pneumococci. This dis- ease 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 persons with pneumonia, the gas exchange func- tions of the lungs decline in different stages of the dis- ease. In early stages, the pneumonia process might well be localized to only one lung, with alveolar ventilation Figure 43-4. Contrast of the emphysematous lung (top) with the being reduced while blood flow through the lung contin- normal lung (bottom) showing extensive alveolar destruction in em- ues normally. This condition causes two major pulmonary physema. (Courtesy Patricia Delaney and the Department of Anato- my, The Medical College of Wisconsin, Milwaukee, WI.) abnormalities: (1) reduction in the total available surface area of the respiratory membrane; and (2) a decreased Fluid and blood cells Confluent alveoli Edema Normal Pneumonia Emphysema Figure 43-5. Lung alveolar changes in pneumonia and emphysema. 544  Chapter 43 Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy ventilation-perfusion ratio. Both these effects cause not only occludes the alveoli but also almost always hypoxemia (low blood O2) and hypercapnia (high blood increases the resistance to blood flow through the pul- CO2). monary vessels of the collapsed lung. This resistance Figure 43-6 shows the effect of the decreased increase occurs partially because of the lung collapse, ventilation-perfusion ratio in pneumonia. The blood which compresses and folds the vessels as the volume UNIT VII passing through the aerated lung becomes 97% saturated of the lung decreases. In addition, hypoxia in the col- with O2, whereas that passing through the unaerated lung lapsed alveoli causes additional vasoconstriction, as is about 60% saturated. Therefore, the average saturation explained in Chapter 39. of the blood pumped by the left heart into the aorta is only Because of the vascular constriction, blood flow about 78%, which is far below normal. through the atelectatic lung is greatly reduced. Fortu- nately, most of the blood is routed through the ven- tilated lung and therefore becomes well aerated. In ATELECTASIS—COLLAPSE OF THE ALVEOLI the situation shown in Figure 43-7, five-sixths of the Atelectasis means collapse of the alveoli. It can occur in blood passes through the aerated lung, and only one- localized areas of a lung or in an entire lung. Common sixth passes through the unaerated lung. As a result, causes of atelectasis are (1) total obstruction of the airway the overall ventilation- perfusion ratio is only moder- and (2) lack of surfactant in the fluids lining the alveoli. ately compromised, so the aortic blood has only mild O2 desaturation, despite total loss of ventilation in an Airway Obstruction Causes Lung Collapse. The airway entire lung. obstruction type of atelectasis usually results from the fol- lowing: (1) blockage of many small bronchi with mucus; Lack of “Surfactant” as a Cause of Lung Collapse. or (2) obstruction of a major bronchus by a large mucous The secretion and function of surfactant in the alveoli were plug or some solid object, such as a tumor. The air en- discussed in Chapter 38. Surfactant is secreted by special trapped beyond the block is absorbed within minutes to alveolar epithelial cells into the fluids that coat the inside hours by the blood flowing in the pulmonary capillaries. surface of the alveoli. The surfactant in turn decreases the If the lung tissue is pliable enough, this will lead simply surface tension in the alveoli by 2- to 10-fold, which nor- to collapse of the alveoli. However, if the lung is rigid be- mally plays a major role in preventing alveolar collapse. cause of fibrotic tissue and cannot collapse, absorption of However, in several conditions, such as in hyaline mem- air from the alveoli creates very negative pressures within brane disease (also called respiratory distress syndrome), the alveoli, which pull fluid out of the pulmonary capil- which often occurs in newborn premature babies, the laries into the alveoli, thus causing the alveoli to fill com- quantity of surfactant secreted by the alveoli is so greatly pletely with edema fluid. This process almost always is the depressed that the surface tension of the alveolar fluid be- effect that occurs when an entire lung becomes atelectat- comes several times greater than normal. This surfactant ic, a condition called massive collapse of the lung. deficiency causes a serious tendency for the lungs of these The effects on overall pulmonary function caused babies to collapse or to become filled with fluid. As ex- by massive collapse (atelectasis) of an entire lung are plained in Chapter 38, many of these infants die of suffoca- shown in Figure 43-7. Collapse of the lung tissue tion when large portions of the lungs become atelectatic. Pulmonary arterial blood 60% saturated with O2 Pulmonary arterial blood 60% saturated with O2 Pneumonia Atelectasis Right Left pulmonary pulmonary Right Left veins 97% veins 60% pulmonary pulmonary saturated saturated veins 97% veins 60% saturated saturated: flow 1/5 Aorta: normal Blood 1/2 = 97% Aorta: 1/2 = 60% Blood 5/6 = 97% Mean saturation 1/6 = 60% = 78% Mean saturation Figure 43-6. Effect of pneumonia on percentage saturation of oxy- = 91% gen (O2) in the pulmonary artery, the right and left pulmonary veins, Figure 43-7. Effect of atelectasis on aortic blood oxygen (O2) satura- and the aorta. tion. 545 UNIT VII Respiration The functional residual capacity and residual volume ASTHMA—SPASMODIC CONTRACTION OF of the lung become especially increased during an acute SMOOTH MUSCLES IN BRONCHIOLES asthma attack because of the difficulty in expiring air from Asthma is characterized by spastic contraction of the the lungs. Also, over a period of years, the chest cage smooth muscle in the bronchioles, which partially becomes permanently enlarged, causing a so-called barrel obstructs the bronchioles and causes extremely difficult chest, and both the functional residual capacity and lung breathing. The prevalence of asthma has been increasing residual volume become permanently increased. and affects 7% to 8% of all people in the United States, with even higher rates in some groups such as non-Hispanic blacks. The World Health Organization estimates that TUBERCULOSIS over 235 million people worldwide suffer from asthma, In tuberculosis, the tubercle bacilli cause a peculiar although some estimates of asthma prevalence are as high tissue reaction in the lungs, including (1) invasion as 339 million people. of the infected tissue by macrophages, and (2) “wall- The usual cause of asthma is contractile hypersensitiv- ing off ” of the lesion by fibrous tissue to form the so- ity of the bronchioles in response to foreign substances in called tubercle. This walling-off process helps limit the air. In about 70% of patients younger than 30 years, the further transmission of the tubercle bacilli in the lungs asthma is caused by allergic hypersensitivity, especially and therefore is part of the protective process against sensitivity to plant pollens. In older people, the cause is extension of the infection. However, in about 3% of almost always hypersensitivity to nonallergenic types of people in whom tuberculosis develops, if the disease irritants in the air, such as irritants in smog. is not treated, the walling-off process fails, and tuber- The typical allergic person tends to form abnormally cle bacilli spread throughout the lungs, often causing large amounts of immunoglobulin E (IgE) antibodies, extreme destruction of lung tissue, with formation of and these antibodies cause allergic reactions when they large abscess cavities. react with the specific antigens that have caused them Thus, tuberculosis in its late stages is characterized by to develop in the first place, as explained in Chapter 35. many areas of fibrosis throughout the lungs, as well as by In persons with asthma, these antibodies are mainly reduced total amount of functional lung tissue. These effects attached to mast cells that are present in the lung intersti- cause the following: (1) increased “work” on the part of the tium in close association with the bronchioles and small respiratory muscles to cause pulmonary ventilation and bronchi. When an asthmatic person breathes in pollen reduced vital capacity and breathing capacity; (2) reduced to which he or she is sensitive (i.e., to which the person total respiratory membrane surface area and increased thick- has developed IgE antibodies), the pollen reacts with the ness of the respiratory membrane, causing progressively mast cell–attached antibodies and causes the mast cells diminished pulmonary diffusing capacity; and (3) abnormal to release several different substances. Among them are ventilation-perfusion ratio in the lungs, further reducing the following: (1) histamine; (2) slow-reacting substance overall pulmonary diffusion of O2 and CO2. of anaphylaxis (which is a mixture of leukotrienes); (3) eosinophilic chemotactic factor; and (4) bradykinin. The combined effects of all these factors, especially the slow- HYPOXIA AND OXYGEN THERAPY reacting substance of anaphylaxis, are to produce the Almost any of the conditions discussed in the past few following: (1) localized edema in the walls of the small sections of this chapter can cause serious cellular hypoxia bronchioles, as well as secretion of thick mucus into the throughout the body. Sometimes O2 therapy is of great bronchiolar lumens; and (2) spasm of the bronchiolar value, other times it is of moderate value, and at still other smooth muscle. Therefore, the airway resistance increases times it is of almost no value. Therefore, it is important greatly. to understand the different types of hypoxia, and then we As discussed earlier in this chapter, the bronchiolar can discuss the physiological principles of oxygen therapy. diameter becomes reduced more during expiration than The following is a descriptive classification of the causes during inspiration in persons with asthma as a result of of hypoxia: bronchiolar collapse during expiratory effort that com- 1. Inadequate oxygenation of the blood in the lungs presses the outsides of the bronchioles. Because the because of extrinsic reasons bronchioles of the asthmatic lungs are already partially a. Deficiency of O2 in the atmosphere occluded, further occlusion resulting from the external b. Hypoventilation (neuromuscular disorders) pressure creates especially severe obstruction during 2. Pulmonary disease expiration. That is, the asthmatic person often can inspire a. Hypoventilation caused by increased airway re- quite adequately but has great difficulty expiring. Clini- sistance or decreased pulmonary compliance cal measurements show (1) greatly reduced maximum b. Abnormal alveolar ventilation-perfusion ratio expiratory rate, and (2) reduced timed expiratory volume. (including increased physiological dead space or Also, all this together results in dyspnea, or “air hunger,” increased physiological shunt) discussed later in this chapter. c. Diminished respiratory membrane diffusion 546  Chapter 43 Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy 3. Venous-to-arterial shunts (right-to-left cardiac shunts) 300 PO2 in alveoli and blood (mm Hg) 4. Inadequate O2 transport to the tissues by the blood a. Anemia or abnormal hemoglobin Alveolar PO2 with tent therapy b. General circulatory deficiency Normal alveolar PO2 200 c. Localized circulatory deficiency (peripheral, cer- Pulmonary edema + O2 therapy UNIT VII ebral, coronary vessels) Pulmonary edema with no therapy d. Tissue edema 5. Inadequate tissue capability of using O2 100 a. Poisoning of cellular oxidation enzymes Capillary blood b. Diminished cellular metabolic capacity for using oxygen because of toxicity, vitamin deficiency, or other factors 0 Arterial end Venous end This classification of the types of hypoxia is mainly self- Blood in pulmonary capillary evident from the discussions earlier in the chapter. Only one type of hypoxia in the classification needs further Figure 43-8. Absorption of oxygen into the pulmonary capillary blood in pulmonary edema, with and without oxygen tent therapy. elaboration—the hypoxia caused by inadequate capability of the body’s tissue cells to use O2. In hypoxia caused by impaired alveolar membrane dif- fusion, essentially the same result occurs as in hypoventi- Inadequate Tissue Capability to Use Oxygen. The lation hypoxia because O2 therapy can increase the Po2 in classic cause of inability of the tissues to use O2 is cyanide the lung alveoli from the normal value of about 100 mm poisoning, in which the action of the enzyme cytochrome Hg to as high as 600 mm Hg. This action raises the O2 oxidase is blocked by cyanide to such an extent that the pressure gradient for diffusion of oxygen from the alveoli tissues simply cannot use O2, even when plenty is avail- to the blood from the normal value of 60 mm Hg to as able. Also, deficiencies of some of the tissue cellular oxi- high as 560 mm Hg, an increase of more than 800%. This dative enzymes or of other elements in the tissue oxidative highly beneficial effect of O2 therapy in diffusion hypoxia system can lead to this type of hypoxia. A special example is demonstrated in Figure 43-8, which shows that the occurs in the disease beriberi, in which several important pulmonary blood in this patient with pulmonary edema steps in tissue utilization of oxygen and the formation of picks up O2 three to four times as rapidly as would occur CO2 are compromised because of vitamin B deficiency. with no therapy. Effects of Hypoxia on the Body. Hypoxia, if severe In hypoxia caused by anemia, abnormal hemoglobin enough, can cause death of cells throughout the body, transport of O2, circulatory deficiency, or physiological but in less severe degrees, it mainly causes (1) depressed shunt, O2 therapy is of much less value because normal mental activity, sometimes culminating in coma, and (2) O2 is already available in the alveoli. Instead, the problem reduced work capacity of the muscles. These effects are is that one or more of the mechanisms for transporting specifically discussed in Chapter 44 in relation to high- oxygen from the lungs to the tissues are deficient. Even so, altitude physiology. a small amount of extra O2, between 7% and 30%, can be transported in the dissolved state in the blood when alveo- lar O2 is increased to maximum, even though the amount OXYGEN THERAPY IN DIFFERENT TYPES transported by the hemoglobin is hardly altered. This OF HYPOXIA small amount of extra O2 may be the difference between O2 can be administered by the following: (1) placing the life and death. patient’s head in a “tent” that contains air fortified with In the different types of hypoxia caused by inadequate O2; (2) allowing the patient to breathe pure O2 or high tissue use of O2, there is no abnormality of O2 pickup by concentrations of O2 from a mask; or (3) administering the lungs or of transport to the tissues. Instead, the tis- O2 through an intranasal tube. sue metabolic enzyme system is simply incapable of using Recalling the basic physiological principles of the dif- the O2 that is delivered. Therefore, O2 therapy provides no ferent types of hypoxia, one can readily decide when O2 measurable benefit. therapy will be of value and, if so, how valuable. In atmospheric hypoxia, O2 therapy can completely CYANOSIS correct the depressed O2 level in the inspired gases and, therefore, provide 100% effective therapy. The term cyanosis means blueness of the skin; its cause In hypoventilation hypoxia, a person breathing 100% is excessive amounts of deoxygenated hemoglobin in the O2 can move five times as much O2 into the alveoli with skin blood vessels, especially in the capillaries. This deox- each breath as when breathing normal air. Therefore, here ygenated hemoglobin has an intense dark blue–purple again, O2 therapy can be extremely beneficial. However, color that is transmitted through the skin. this O2 therapy provides no benefit for the excess blood In general, definite cyanosis appears whenever the arte- CO2 also caused by the hypoventilation. rial blood contains more than 5 grams of deoxygenated 547 UNIT VII Respiration hemoglobin in each 100 ml of blood. A person with ane- At least three factors often enter into the development mia almost never becomes cyanotic because there is not of the sensation of dyspnea: (1) abnormality of respiratory enough hemoglobin for 5 grams to be deoxygenated in gases in the body fluids, especially hypercapnia and, to a 100 ml of arterial blood. Conversely, in a person with much less extent, hypoxia; (2) the amount of work that excess red blood cells, as in polycythemia vera, the great must be performed by the respiratory muscles to provide excess of available hemoglobin that can become deoxy- adequate ventilation; and (3) state of mind. genated leads frequently to cyanosis, even under other- A person becomes especially dyspneic from excess wise normal conditions. buildup of CO2 in the body fluids. At times, however, the levels of both CO2 and O2 in the body fluids are normal but, to attain this normality of the respiratory gases, the HYPERCAPNIA—EXCESS CARBON person has to breathe forcefully. In these cases, the force- DIOXIDE IN THE BODY FLUIDS ful activity of the respiratory muscles frequently gives the One might suspect, on first thought, that any respiratory person a sensation of dyspnea. condition that causes hypoxia would also cause hypercap- Most people have the sensation of severe dyspnea after nia. However, hypercapnia usually occurs in association only 1 to 2 minutes of voluntary breath-holding (apnea). with hypoxia only when the hypoxia is caused by hypoven- However, as discussed in Chapter 42, some individuals tilation or circulatory deficiency for the following reasons. can train themselves to suppress respiratory urges for Hypoxia caused by too little O2 in the air, too little hemo- more than 10 minutes, despite buildup of CO2 and very globin, or poisoning of the oxidative enzymes involves only low O2 in the body fluids. the availability of O2 or use of O2 by the tissues. Therefore, Finally, dyspnea may be experienced because of an it is readily understandable that hypercapnia is not associ- abnormal state of mind, even though the person’s respira- ated with these types of hypoxia. tory functions, as well as CO2 and O2 in the body fluids, In hypoxia resulting from poor diffusion through the may be normal. This condition is called neurogenic dys- pulmonary membrane or the tissues, serious hypercapnia pnea or emotional dyspnea. For example, almost anyone usually does not occur at the same time because CO2 dif- momentarily thinking about the act of breathing may sud- fuses 20 times as rapidly as O2. If hypercapnia does begin denly start taking breaths a little more deeply than ordi- to occur, this immediately stimulates pulmonary ventila- narily because of a feeling of mild dyspnea. This feeling tion, which corrects the hypercapnia but not necessarily is greatly enhanced in people who have a psychological the hypoxia. fear of not being able to receive a sufficient quantity of air, Conversely, in hypoxia caused by hypoventilation, such as when entering a small or crowded room. CO2 transfer between the alveoli and the atmosphere is affected as much as O2 transfer. Hypercapnia then occurs ARTIFICIAL RESPIRATION along with the hypoxia. In circulatory deficiency, dimin- ished flow of blood decreases CO2 removal from the tis- sues, resulting in tissue hypercapnia in addition to tissue Resuscitator. Many types of respiratory resuscitators are hypoxia. However, the transport capacity of the blood for available, and each has its own characteristic principles CO2 is more than three times that for O2, and thus the of operation. The resuscitator shown in Figure 43-9A resulting tissue hypercapnia is much less than the tissue consists of a tank supply of O2 or air, a mechanism for hypoxia. applying intermittent positive pressure and, with some When the alveolar Pco2 rises above about 60 to 75 machines, negative pressure as well, and a mask that fits mm Hg, an otherwise normal person by then is breath- over the face of the patient or a connector for joining the ing about as rapidly and deeply as he or she can, and air equipment to an endotracheal tube. This apparatus forces hunger, also called dyspnea, becomes severe. air through the mask or endotracheal tube into the lungs If the Pco2 rises to 80 to 100 mm Hg, the person of the patient during the positive-pressure cycle of the re- becomes lethargic and sometimes even semicomatose. suscitator and then usually allows the air to flow passively Anesthesia and death can result when the Pco2 rises to out of the lungs during the remainder of the cycle. 120 to 150 mm Hg. At these higher levels of Pco2, the Earlier resuscitators often caused damage to the lungs excess CO2 now begins to depress respiration rather than because of excessive positive pressure. Their usage was stimulate it, thus causing a vicious circle: (1) more CO2, at one time greatly decried. However, resuscitators now (2) further decrease in respiration, (3) then more CO2, have adjustable positive-pressure limits that are com- and so forth—culminating rapidly in a respiratory death. monly set at 12 to 15 cm H2O pressure for normal lungs, but sometimes much higher for noncompliant lungs. DYSPNEA Tank Respirator (the “Iron Lung”). Figure 43-9B shows Dyspnea means mental anguish associated with inability the tank respirator with a patient’s body inside the tank to ventilate enough to satisfy the demand for air. A com- and the head protruding through a flexible but airtight mon synonym is air hunger. collar. At the end of the tank, opposite the patient’s head, 548  Chapter 43 Respiratory Insufficiency—Pathophysiology, Diagnosis, Oxygen Therapy impeded. As a result, use of excessive pressures with the resuscitator or tank respirator can reduce the cardiac out- put, sometimes to lethal levels. For example, continuous Mechanism exposure for more than a few minutes to more than 30- for applying mm Hg positive pressure in the lungs can cause death be- UNIT VII positive and negative cause of inadequate venous return to the heart. pressure A Bibliography Positive Negative Barnes PJ: Targeting cytokines to treat asthma and chronic obstruc- pressure pressure tive pulmonary disease. Nat Rev Immunol 18:454, 2018. valve valve Barnes PJ: Cellular and molecular mechanisms of asthma and COPD. Clin Sci (Lond) 131:1541, 2017. Celli BR: Pharmacological therapy of COPD: reasons for optimism. Chest 154:1404, 2018. Centers for Disease Control and Prevention, Asthma Surveillance Data. (accessed June 22, 2019). https://www.cdc.gov/asthma/ asthmadata.htm. Furin J, Cox H, Pai M: Tuberculosis. Lancet 393:1642, 2019. Hogg JC, Paré PD, Hackett TL: The contribution of small airway ob- struction to the pathogenesis of chronic obstructive pulmonary dis- ease. Physiol Rev 97:529, 2017. B Leather diaphragm Krishnamoorthy N, Abdulnour RE, Walker KH, Engstrom BD, Levy BD: Specialized proresolving mediators in innate and adaptive immune Figure 43-9. A, Resuscitator. B, Tank respirator. responses in airway diseases. Physiol Rev 98:1335, 2018. Marini JJ: Evolving concepts for safer ventilation. Crit Care. 2019 Jun 14;23(Suppl 1):114. https://doi.org/10.1186/s13054-019-2406-9. a motor-driven leather diaphragm moves back and forth Marini JJ: Acute Lobar Atelectasis. Chest 155:1049, 2019. with sufficient excursion to raise and lower the pressure Martinez FD: Early-life origins of chronic obstructive pulmonary dis- inside the tank. As the leather diaphragm moves inward, ease. N Engl J Med 375:871, 2016. positive pressure develops around the body and causes Papi A, Brightling C, Pedersen SE, Reddel HK: Asthma. Lancet 391:783, 2018. expiration; as the diaphragm moves outward, negative Quinton LJ, Walkey AJ, Mizgerd JP: Integrative physiology of pneu- pressure causes inspiration. Check valves on the respira- monia. Physiol Rev 98:1417, 2018. tor control the positive and negative pressures. Ordinar- Pavord ID, Beasley R, Agusti A et al: After asthma: redefining airways ily, these pressures are adjusted so that the negative pres- diseases. Lancet 391:350, 2018. sure that causes inspiration falls to −10 to −20 cm H2O, Rabe KF, Watz H: Chronic obstructive pulmonary disease. Lancet 389:1931, 2017. and the positive pressure rises to 0 to +5 cm H2O. Raju S, Ghosh S, Mehta AC: Chest CT signs in pulmonary disease: a Use of the tank respirator is now largely obsolete in pictorial review. Chest 151:1356, 2017. modern medicine with the development of superior Schraufnagel DE, Balmes JR, Cowl CT, et al: Air pollution and non- mechanical ventilators that push air into the airways with communicable diseases: a review by the Forum of International positive pressure. Respiratory Societies’ Environmental Committee, part 1: The dam- aging effects of air pollution. Chest 155:409, 2019. Sheel AW, Romer LM: Ventilation and respiratory mechanics. Compr Effect of the Resuscitator and the Tank Respirator on Physiol 2:1093, 2012. Venous Return. When air is forced into the lungs under Suki B, Sato S, Parameswaran H, et al: Emphysema and mechani- positive pressure by a resuscitator, or when the pressure cal stress-induced lung remodeling. Physiology (Bethesda) 28:404, around the patient’s body is reduced by the tank respira- 2013. Veasey SC, Rosen IM: Obstructive sleep apnea in adults. N Engl J Med tor, the pressure inside the lungs becomes greater than 380:1442, 2019. pressure everywhere else in the body. Flow of blood into Zumla A, Raviglione M, Hafner R, von Reyn CF: Tuberculosis. N Engl the chest and heart from the peripheral veins becomes J Med 368:745, 2013. 549