• STUDY OF BLOOD GASES AND BLOOD pH
• Determinations of the blood partial pressure of oxygen (Po2), carbon dioxide (CO2), and pH.

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• 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.

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• The following simple and rapid methods have been developed to make these measurements within minutes, using no more than a few drops of blood.

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1. Determination of Blood pH: Blood pH is measured using a glass pH electrode of the type commonly used in chemical laboratories.

2. Determination of Blood CO2 : A glass electrode pH meter can also be used to determine blood Pco2

• Blood is super fused onto the outer surface of the plastic membrane, allowing CO2 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 using the formula Henderson-Hasselbalch equation
• pH= 6.1 + log HCO3 /CO2

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3. Determination of Blood Po2 : The concentration of O2 in a fluid can be measured by a technique called polarography.

• All these measurements can be made within a minute or so using a single droplet-sized sample of blood. Thus, changes in the blood gas levels and pH can be followed .

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• In many respiratory diseases, particularly in asthma, the resistance to airflow becomes especially great during expiration, sometimes causing difficulty in breathing.
• This condition 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.

• The maximum expiratory flow is much greater when the lungs are filled with a large volume of air than when they are almost empty.

4. MEASUREMENT OF MAXIMUM EXPIRATORY FLOW

• Figure 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 the alveoli and 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 increase the alveolar pressure greatly, but it also increases the degree of bronchiolar collapse and airway resistance by an equal amount.

• Note that the person quickly reaches a maximum expiratory airflow of more than 400 L/min. However, 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 becomes less.

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• Abnormalities of the Maximum Expiratory FlowVolume Curve. Figure shows the normal and 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, 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 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.
• 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 RV. 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.

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• changes of the FVCs are not greatly different, indicating only a moderate difference in basic lung volumes in the two persons

• FORCED EXPIRATORY VITAL CAPACITY AND FORCED EXPIRATORY VOLUME
• A useful clinical pulmonary test, is to record the forced expiratory vital capacity (FVC) on a spirometer.
• Such a recording is shown in Figure A for a person with normal lungs and in Figure B for a person with partial airway obstruction.
• In performing the FVC maneuver, the person first inspires maximally to the TLC 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 .
• There is a major difference in the amounts of air that these persons can expire each second, especially during the first second.

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• PATHOPHYSIOLOGY OF SPECIFIC PULMONARY ABNORMALITIES
• Chronic pulmonary EMPHYSEMA :
• means excess air in the lungs. However, this term is usually used to describe a complex obstructive and destructive process of the lungs caused by many years of smoking.
• It results from the following major pathophysiological changes in the lungs:

1.Chronic infection : caused by inhaling smoke or other substances that irritate the bronchi and bronchioles.

• The chronic infection result in 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, There is also inhibition of the alveolar macrophages, 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 effect, combined with the lung infection, causes marked destruction of as much as 50% to 80% of the alveolar walls.

Therefore, the final picture of the emphysematous lung is that shown in Figures

• The physiological effects of chronic emphysema are variable, depending on the severity of the disease and the relative degrees of bronchiolar obstruction versus lung parenchymal destruction, include the following:

1. The bronchiolar obstruction increases airway resistance and results in greatly increased work of breathing. It is difficult for the person to move air through the bronchioles during expiration .

2. The marked loss of alveolar walls greatly decreases the diffusing capacity of the lung. This reduces the ability of the lungs to oxygenate the blood and remove CO2 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 situation often causes extremely abnormal ventilation perfusion ratios, with a very low . VA/ . Q in some parts (physiological shunt), resulting in poor aeration of the blood, and a very high . VA/ . Q in other parts (physiological dead space), resulting in wasted ventilation, with 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, which in turn overloads the right side of the heart and frequently causes right-sided heart failure.

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• PNEUMONIA—LUNG INFLAMMATION AND FLUID IN ALVEOLI
• 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.
• 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
• 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 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 being reduced while blood flow through the lung continues normally. This condition causes two major pulmonary abnormalities:
• reduction in the total available surface area of the respiratory membrane

(2) a decreased ventilation-perfusion ratio.

Both these effects cause hypoxemia (low blood O2) and hypercapnia (high blood CO2

• The blood passing through the aerated lung becomes 97% saturated with O2, whereas that passing through the unaerated lung is about 60% saturated. Therefore, the average saturation of the blood pumped by the left heart into the aorta is only about 78%, which is far below normal.

• ATELECTASIS—COLLAPSE OF THE ALVEOLI Atelectasis means collapse of the alveoli. It can occur in localized areas or in an entire lung.
• Common causes of atelectasis are :
• total obstruction of the airway by mucous or solid object ( tumor or foreign body)

(2) lack of surfactant in the fluids lining the alveoli.

The air entrapped beyond the block is absorbed within minutes to hours by the blood flowing in the pulmonary capillaries , 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 process almost always is the effect that occurs when an entire lung becomes atelectatic, a condition called massive collapse of the lung

• The effects on overall pulmonary function caused by massive collapse (atelectasis) of an entire lung are shown in Figure
• 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, which compresses and folds the vessels as the volume of the lung decreases.

• In addition, hypoxia in the collapsed alveoli causes additional vasoconstriction.
• 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.
• As a result, the overall ventilation-perfusion ratio is only moderately compromised, so the aortic blood has only mild O2 desaturation, despite total loss of ventilation in an entire lung.

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• Lack of “Surfactant” as a Cause of Lung Collapse.
• 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 by 2- to 10-fold, which normally plays a major role in preventing alveolar collapse. However, in several 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 greater than normal.
• This surfactant deficiency causes a serious tendency for the lungs of these babies to collapse or to become filled with fluid.
• 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.
• The prevalence of asthma has been increasing and affects 7% to 8% of all people in the United States.
• The WHO estimates that over 235 million people worldwide suffer from asthma, although some estimates of asthma prevalence are as high as 339 million people.
• The usual cause of asthma is contractile hypersensitivity of the bronchioles in response to foreign substances in the air.
• In about 70% of patients younger than 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 typical allergic person tends to form abnormally large amounts of immunoglobulin E (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.
• In persons with 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 an 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 the following:
• Histamine

(2) slow-reacting substance of anaphylaxis (which is a mixture of leukotrienes)

(3) eosinophilic chemotactic factor

(4) bradykinin.

• The combined effects of all these factors, especially the slow reacting substance of anaphylaxis, are to produce the following:
• localized edema in the walls of the small bronchioles, as well as secretion of thick mucus

(2) spasm of the bronchiolar smooth muscle. Therefore, the airway resistance increases greatly

• 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
• (2) reduced timed expiratory volume. Also, all this together results in dyspnea, or “air hunger,”.

• The functional residual capacity and residual volume of the lung become especially increased during an acute asthma 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 so-called 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

(2) “walling off” of the lesion by fibrous tissue to form the so called ……………………..tubercle.

• This walling-off process helps 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% of people in whom tuberculosis develops, if the disease is not treated, 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 by reduced total amount of functional lung tissue

• These effects cause the following:
• increased “work” on the part of the respiratory muscles to cause pulmonary ventilation and reduced vital capacity

(2) reduced total respiratory membrane surface area and increased thickness of the respiratory membrane, causing progressively diminished pulmonary diffusing capacity

(3) abnormal ventilation-perfusion ratio in the lungs, further reducing overall pulmonary diffusion of O2 and CO

• HYPOXIA AND OXYGEN THERAPY
• Almost any of the conditions discussed can cause serious cellular hypoxia throughout the body.
• Sometimes O2 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, and then we can discuss the physiological 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 O2 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 increased physiological ..dead space or increased physiological shunt)

c. Diminished respiratory membrane diffusion

3. Venous-to-arterial shunts (right-to-left cardiac shunts)

4. Inadequate O2 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 O2

a. Poisoning of cellular oxidation enzymes

b. Diminished cellular metabolic capacity for using oxygen because of toxicity, vitamin deficiency, or other factors

• Inadequate Tissue Capability to Use Oxygen.
• The classic cause of inability of the tissues to use O2 is cyanide poisoning, in which the action of the enzyme cytochrome oxidase is blocked by cyanide to such an extent that the tissues simply cannot use O2, 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 the formation of CO2 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 mainly causes
• depressed mental activity, sometimes culminating in coma

(2) reduced work capacity of the muscles.

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• OXYGEN THERAPY IN DIFFERENT TYPES OF HYPOXIA

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1. placing the patient’s head in a “tent” that contains air fortified with O2

(2) allowing the patient to breathe pure O2 or high concentrations of O2 from mask

(3) administering O2 through an intranasal tube.

• In atmospheric hypoxia, O2 therapy can completely correct the depressed O2 level in the inspired gases and, therefore, provide 100% effective therapy.
• In hypoventilation hypoxia, a person breathing 100% O2 can move five times as much O2 into the alveoli with each breath as when breathing normal air.
• O2 therapy can be extremely beneficial. However, this O2 therapy provides no benefit for the excess blood CO2
• In hypoxia caused by impaired alveolar membrane diffusion, O2 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.

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• The highly beneficial effect of O2 therapy in diffusion hypoxia is demonstrated in Figure, which shows that the pulmonary blood in this patient with pulmonary edema :

picks up O2 three to four times as rapidly as would occur with no therapy

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• This action raises the O2 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%.

• In hypoxia caused by anemia, abnormal hemoglobin transport of O2, circulatory deficiency, or physiological shunt, O2 therapy is of much less value because normal O2 is already available in the alveoli. ‘
• Because the mechanisms for transporting oxygen from the lungs to the tissues are deficient.
• Even so, a small amount of extra O2, between 7% and 30%, can be transported in the dissolved state in the blood when alveolar O2 is increased to maximum, but amount transported by the hemoglobin is hardly altered.
• This small amount of extra O2 may be the difference between life and death.

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• In the different types of hypoxia caused by inadequate tissue use of O2, there is no abnormality of O2 pickup by the lungs or of transport to the tissues. Instead, the tissue metabolic enzyme system is simply incapable of using the O2 that is delivered,therefore, O2 therapy provides no measurable benefit.

• CYANOSIS
• The term cyanosis means blueness of the skin; 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 ml of blood.
• A person with anemia almost never becomes cyanotic because there is not enough hemoglobin for 5 grams to be deoxygenated in 100 ml of arterial blood.
• Conversely, in a person with excess red blood cells, as 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

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One might suspect, on first thought, that any respiratory condition that causes hypoxia would also cause hypercapnia.

• Hypercapnia usually occurs in association with hypoxia only when the hypoxia is caused by hypoventilation or circulatory deficiency for the following reasons.
• Hypoxia caused by too little O2 in the air, too little hemoglobin, or poisoning of the oxidative enzymes involves only the availability of O2 or use of O2 by the tissues.
• Therefore, hypercapnia is not associated with these types of hypoxia.

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• In hypoxia resulting from poor diffusion through the pulmonary membrane or the tissues, serious hypercapnia usually does not occur at the same time because CO2 diffuses 20 times as rapidly as O2.
• If hypercapnia does begin to occur, this immediately stimulates pulmonary ventilation, which corrects the hypercapnia but not necessarily the hypoxia.

• In hypoxia caused by hypoventilation, CO2 transfer between the alveoli and the atmosphere is affected as much as O2 transfer, so hypercapnia then occurs along with the hypoxia.
• In circulatory deficiency, diminished flow of blood decreases CO2 removal from the tissues, resulting in tissue hypercapnia in addition to tissue hypoxia. However, the transport capacity of the blood for CO2 is more than three times that for O2, and thus the resulting tissue hypercapnia is much less than the tissue hypoxia.
• When the alveolar Pco2 rises above 60 to 75 mm Hg, in a normal person, then breathing 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 semi comatose.
• Anesthesia and death can result when the Pco2 rises to 120 to 150 mm Hg.
• At these higher levels of Pco2, the excess CO2 now begins to depress respiration rather than stimulate it, thus causing a vicious circle: (1) more CO2, (2) further decrease in respiration, (3) then more CO2, and so forth—culminating rapidly in a respiratory death.

• 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:
• 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

(3) state of mind.

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• A person becomes dyspneic from excess buildup of CO2 in the body fluids,

however, the levels of both CO2 and O2 in the body fluids are normal but, to achieve that the person has to breathe forcefully.

In these cases, the forceful activity of the respiratory muscles frequently gives the person a sensation of dyspnea. Most people have the sensation of severe dyspnea after only 1 to 2 minutes of voluntary breath-holding (apnea).

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• However some individuals can train themselves to suppress respiratory urges for more than 10 minutes, despite buildup of CO2 and very low O2 in the body fluids.

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• A person may experience dyspnea because of an abnormal state of mind despite normal CO2 & O2& respiratory functions.

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• This condition is called neurogenic dyspnea or emotional dyspnea. For example, 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 when entering a small or crowded room