The Human Body

The diseases and disorders of the respiratory system can affect any part of the respiratory tract and range from trivial to life-threatening. The nasal passages and pharynx, for example, are targets for the viruses that cause colds. These viruses infiltrate and destroy the cells of the nasal passage membranes. The immune system fights back by increasing blood flow to the area, bringing numerous virus-attacking white blood cells to the scene; this causes the membranes to swell, resulting in the stuffy nose associated with colds. Mucous secretions increase in response to the viral attack, creating the runny nose typical of colds. The infection can spread to the sinuses, the membrane-lined cavities in the head, as well as the lower respiratory tract and the middle ear.

The respiratory system is also subject to allergic reactions such as hay fever and asthma, brought about when the immune system is stimulated by pollen, dust, or other irritants. Hay fever is characterized by a runny nose, watery eyes, and sneezing. It usually occurs seasonally in response to abundant pollen in the air. In asthma, a person has difficulty breathing because the bronchi and bronchioles are temporarily constricted and inflamed. An asthma attack is typically mild, but can be severe enough to be life threatening.

Laryngitis, an inflammation of the larynx, is caused by a viral infection, irritants such as cigarette smoke, or by overuse of the voice. Laryngitis may cause hoarseness, or the voice may be reduced to a whisper until the inflammation subsides. Bronchitis is an inflammation of the membranes that line the bronchi or bronchioles. Bronchitis results from viral or bacterial infection or from irritating chemicals. Infections caused by bacteria or viruses can lead to pneumonia, a potentially serious condition of the lungs in which fluid and inflammation builds up in the alveoli, impeding the flow of oxygen and carbon dioxide between the capillaries and the alveoli.

Tuberculosis is the chronic or acute bacterial infection that primarily attacks the lungs, but which may also affect the kidneys, bones, lymph nodes, and brain. The disease is caused by Mycobacterium tuberculosis, a rod-shaped bacterium. Many people harbor the bacteria but have no symptoms of disease. When symptoms develop, they include coughing, chest pain, shortness of breath, loss of appetite, weight loss, fever, chills, and fatigue. Children and people with weakened immune systems are the most susceptible to TB.

A. Primary TB does not produce noticeable symptoms in its early stages, when it is not contagious. Macrophages, immune cells that detect and destroy foreign matter, ingest the TB bacteria and transport them to the lymph nodes where they may be inhibited or destroyed. If the immune cells fail to control the infection, the bacteria can multiply.

If the TB bacteria multiply, active primary tuberculosis develops. Patients with active primary TB experience such symptoms as coughing, night sweats, weight loss, and fever. A chest X ray may show shadows in the lung or fluid collection between the lung and its lining. If the immune system destroys the bacteria, the patient may experience no more than mild symptoms, such as a cough. If the bacteria are inhibited, rather than destroyed, the body’s immune cells and the bacteria form a lump known as a granuloma or tubercle. In effect, the immune cells form a wall around inactive bacteria. As long as the immune system remains strong, the TB bacteria remain walled off and inactive. The tubercles may appear as shadows in a chest X ray. If the immune system later becomes weakened, the tubercle may open, releasing the bacteria, and the infection may develop into secondary TB.

B. Secondary, or post-primary, TB, the formerly dormant bacteria multiply and destroy tissue in the lungs. They also may spread to the rest of the body via the bloodstream. Fluid or air may collect between the lungs and the lining of the lungs, while tubercles continue to develop in the lung, progressively destroying lung tissue. Coughing of blood or phlegm may occur.

Diagnosis of TB

Diagnosis of TB requires two separate methods. Tuberculin skin testing is a method of screening for exposure to TB infection. People infected with the TB bacteria develop a hypersensitivity to the bacteria even if they do not develop the disease. In the test a purified protein derived from the bacteria is injected into the skin. The skin area is inspected 48 to 72 hours later for a bump, or positive reaction. A positive reaction implies that TB infection has occurred. Skin tests are not 100 percent accurate, however, and they do not always indicate the presence of active disease.

A diagnosis of TB disease is established by identifying bacteria in sputum (material coughed up from the lungs) or other body fluids and tissues, along with an abnormal chest X ray and the presence of TB symptoms. Once TB has been diagnosed, further testing is required to determine which drugs would be most appropriate to treat the particular strain of TB bacteria.

Detecting the presence or the strain of the TB bacterium was once a time-consuming process that would often delay therapy. Today, the use of genetic engineering techniques greatly reduces the time required for diagnosis. A new technique is the polymerase chain reaction (PCR), which can rapidly duplicate a tiny amount of bacterial hereditary material from a small sample of infected sputum.

Treatment and prevention of TB

General preventive measures can be taken to reduce the spread of TB in public places. Ventilation systems lessen the chance of infection by dispersing the bacteria. Ultraviolet lighting also reduces, but does not eliminate, the threat of infection by killing TB bacteria in confined spaces. Vaccines, such as the bacillus Calmette-Guerin (BCG) vaccine, prepared from bacteria that have been weakened, are another preventive measure. The BCG vaccine is most effective in preventing childhood cases of TB.

With the advent of effective antibiotics for TB, drug therapy has become the cornerstone of treatment. Single-drug treatment often causes bacterial resistance to drugs. Therefore, all recommended therapies include multiple drugs given for at least 6 months, often for as long as 9 to 12 months. Adjustments to the treatments are made based on susceptibility of the bacterial strain. A combination of antibiotics is usually prescribed. In 1998, scientists successfully decoded the entire gene sequence, or genome, of the tuberculosis bacteria. This advance is likely to lead to the development of new methods for treatment and prevention of TB.

Pneumonia is the inflammation of one or both lungs. In people with pneumonia, air sacs in the lungs fill with fluid, preventing oxygen from reaching blood cells and nourishing the other cells of the body. Sometimes the inflammation occurs in scattered patches in the tissue around the ends of the bronchioles, the smallest air tubes in the lungs. This is known as bronchopneumonia. In other cases the inflammation is widespread and involves an entire lobe of the lung. This condition is called lobar pneumonia. In the United States about 5 million cases of pneumonia are reported each year.

Causes of Pneumonia

About 50% of pneumonia cases are caused by viruses, particularly those viruses that cause upper respiratory infections,such as the virus that cause influenza, adenoviruses, and rhinoviruses. Infection with the Streptococcus pneumoniae bacterium is the most common cause of bacterial pneumonia.Pneumococcus usually causes lobar pneumonia, attacking an entire lobe or portion of a lobe of the lung; in double pneumonia, pneumococcus attacks both lungs. Other type of pneumonia is also caused by mycoplasma. Epidemics of mycoplasma pneumonia occurs in schools and military.The most prominient symptom of mycoplasma pneumonia is a violent dry cough. Some patients experience nausea or vomiting.

Diagnosis and treatment of Pneumonia

A physician can diagnose pneumonia by tapping the chest and listening with a stethescope to the sound produced.Tapping the chest of a healthy person produces a resonant sound because of the air contained in the lungs. In a person with pneumonia, the air spaces of the lungs become filled with fluid, and tapping produces a dull, flat sound. The diagnosis of pneumonia is confirmed by taking an X-ray picture of the chest.To determine the cause of pneumonia, a physician takes a sample of the patient's sputum. Analysis of the sputum in the laboratory may identify the particular kind of microorganism causing the infection. Identification of the cause of pneumonia is important in determining treatment.

Antibiotics can cure bacterial pneumonia and speed recovery from mycoplasma pneumonia and PCP. Antibiotics rarely have an effect on pneumonia caused by viruses. However, patients with viral pneumonia often receive antibiotics to prevent bacterial pneumonia from developing during the course of their illness.Medication may be given to relieve chest pain and violent coughing, and oxygen may be administered if the patient has difficulty breathing. A vaccine is available that confers immunity against pneumococcus.

Asthma

Spasmodic asthma is characterized by contraction of the smooth muscle of the airways and, in severe attacks, by airway obstruction from mucus that has accumulated in the bronchial tree. This results in a greater or lesser degree of difficulty in breathing. One approach to classifying asthma differentiates cases that occur with an identifiable antigen, in which antigens affect tissue cells sensitized by a specific antibody, and cases that occur without an identifiable antigen or specific antibody. The former condition is known as "extrinsic" asthma and the latter as "intrinsic" asthma. Extrinsic asthma commonly manifests in childhood because the subject inherits an "atopic" characteristic: the serum contains specific antigens to pollens, mold spores, animal proteins of different kinds, and proteins from a variety of insects, particularly cockroaches and mites that occur in house dust. Exacerbation of extrinsic asthma is precipitated by contact with any of the proteins to which sensitization has occurred; airway obstruction is often worse in the early hours of the morning, for reasons not yet entirely elucidated. The other form of asthma, intrinsic, may develop at any age, and there may be no evidence of specific antigens. Persons with intrinsic asthma experience attacks of airway obstruction unrelated to seasonal changes, although it seems likely that the airway obstruction may be triggered by infections, which are assumed to be viral in many cases.

Asthma acquired as the result of occupational exposure (a special form of intrinsic asthma) is now recognized to be more common than previously suspected. Exposure to solder resin used in the electronics industry, to toluene diisocyanate (used in many processes as a solvent), to the dust of the western red cedar (in which plicatic acid is the responsible agent), and to many other substances can initiate an asthmatic state, with profound airflow obstruction developing when the subject is challenged by the agent.

It is a characteristic of all types of asthma that those with the condition may exhibit airflow obstruction when given aerosols of histamine or acetylcholine (both normally occurring smooth muscle constrictors) at much lower concentrations than provoke airflow obstruction in normal people; affected individuals may also develop airflow obstruction while breathing cold air or during exercise. These characteristics are used in the laboratory setting to study the airway status of patients. As a result of much recent work, it is thought that the diagnosis of asthma of any kind is difficult to sustain in the absence of a general increase in airway reactivity.

The acute asthmatic attack is alarming both for the sufferer and for the onlooker. There is acute difficulty in breathing, and the chest assumes a more and more inspiratory position. Despite the severe respiratory difficulty, the patient remains fully conscious. The most dangerous form of the condition is known as status asthmaticus. The bronchial spasm worsens over several hours or a day or so, the bronchi become plugged with thick mucus, and airflow is progressively more obstructed. The affected person becomes fatigued; the arterial oxygen tension falls still further, carbon dioxide accumulates in the blood (leading to drowsiness), and the acidity of the arterial blood increases to dangerous levels and may lead to cardiac arrest. Prompt treatment with intravenous corticosteroids and bronchodilators is usually sufficient to relieve the attack, but in occasional cases ventilatory assistance is required. In a few cases, death from asthma is remarkably rapid—too rapid for this complete sequence of events to have occurred, although at autopsy the lungs are overinflated. The exact mechanism of death in these cases is not completely understood.

Although the state of the airway is influenced by psychogenic factors, asthma is not correctly regarded as a disease commonly caused by psychological factors. It may interrupt normal activities and schooling to such an extent that it casts a shadow over the development of the personality. More commonly, it tends to diminish in severity with age, and people who had quite severe asthma in childhood may lead normal lives after the age of 20. It is now known that asthma attacks may be precipitated by food—in small children, possibly by milk; and some adults are extremely sensitive to sulfite compounds in food or wine. A subgroup of asthmatics are so sensitive to aspirin (acetylsalicylic acid) that ingestion of this chemical may lead to a life-threatening attack.

Changes in mortality from asthma in different countries have been closely studied, but the causes are obscure. It is clear, however, that there has been a considerable increase in the rate of hospital admissions for asthma in children and in adults up to the age of 60. Because there is now more effective treatment for asthma than was available previously, it is not clear why this should be occurring. Unless the asthma is complicated by infection (of which that by the fungus Aspergillus is common in damp climates), the chest radiograph remains normal. Asthma does not lead to the destructive lesions of emphysema (described below), although the physical appearance of the patient and the sounds of airflow obstruction in the lung may be similar in the two conditions.

Bronchitis

Acute Bronchitis: Acute bronchitis most commonly occurs as a consequence of viral infection. It may also be precipitated by acute exposure to irritant gases, such as ammonia, chlorine, or sulfur dioxide. In people with chronic bronchitis—a common condition in cigarette smokers—exacerbations of infection are common. The bronchial tree in acute bronchitis is reddened and congested, and minor blood streaking of the sputum may occur. Most cases of acute bronchitis resolve over a few days, and the mucosa repairs itself.

Bronchiolitis refers to inflammation of the small airways. Bronchiolitis probably occurs to some extent in acute viral disorders, particularly in children between the ages of one and two years, and particularly in infections with respiratory syncytial virus. In severe cases the inflammation may be severe enough to threaten life, but it normally clears spontaneously, with complete healing in all but a very small percentage of cases. In adults, acute bronchiolitis of this kind is not a well-recognized clinical syndrome, though there is little doubt that in most patients with chronic bronchitis, acute exacerbations of infection are associated with further damage to small airways. In isolated cases, an acute bronchiolitis is followed by a chronic obliterative condition, or this may develop slowly over time. This pattern of occurrence has only recently been recognized. In addition to patients acutely exposed to gases, in whom such a syndrome may follow the acute exposure, patients with rheumatoid arthritis may develop a slowly progressive obliterative bronchiolitis that may prove fatal. An obliterative bronchiolitis may appear after bone marrow replacement for leukemia and may cause shortness of breath and disability.

Exposure to oxides of nitrogen, which may occur from inhaling gas in silos, when welding in enclosed spaces such as boilers, after blasting underground, or in fires involving plastic materials, is characteristically not followed by acute symptoms. These develop some hours later, when the victim develops a short cough and progressive shortness of breath. A chest radiograph shows patchy inflammatory change, and the lesion is an acute bronchiolitis. Symptomatic recovery may mask incomplete resolution of the inflammation.

An inflammation around the small airways, known as a respiratory bronchiolitis, is believed to be the earliest change that occurs in the lung in cigarette smokers, although it does not lead to symptoms of disease at that stage. The inflammation is probably reversible if smoking is discontinued. It is not known whether those who develop this change (after possibly only a few years of smoking) are or are not at special risk of developing the long-term changes of chronic bronchitis and emphysema.

Chronic Bronchitis: The chronic cough and sputum production of chronic bronchitis were once dismissed as nothing more than "smoker's cough," without serious implications. But the striking increase in mortality from chronic bronchitis and emphysema that occurred after World War II in all Western countries indicated that the long-term consequences of chronic bronchitis could be serious. This common condition is characteristically produced by cigarette smoking. After about 15 years of smoking, a blob of mucus is coughed up in the morning, owing to an increase in size and number of mucous glands lining the large airways. The increase in mucous cells and the development of chronic bronchitis may be enhanced by breathing polluted air (particularly in areas of uncontrolled coal burning) and by a damp climate. The changes are not confined to large airways, though these produce the dominant symptom of chronic sputum production. Changes in smaller bronchioles lead to obliteration and inflammation around their walls. All of these changes together, if severe enough, can lead to disturbances in the distribution of ventilation and perfusion in the lung, causing a fall in arterial oxygen tension and a rise in carbon dioxide tension. By the time this occurs, the ventilatory ability of the patient, as measured by the velocity of a single forced expiration, is severely compromised; in a cigarette smoker, ventilatory ability has usually been declining rapidly for some years. It is not clear what determines the severity of these changes, since many people can smoke for decades without evidence of significant airway changes, while others may experience severe respiratory compromise after 15 years or less of exposure.

Pulmonary emphysema

This irreversible disease consists of destruction of alveolar walls. It occurs in two forms, centrilobular emphysema, in which the destruction begins at the centre of the lobule, and panlobular (or panacinar) emphysema, in which alveolar destruction occurs in all alveoli within the lobule simultaneously. In advanced cases of either type, this distinction can be difficult to make. Centrilobular emphysema is the form most commonly seen in cigarette smokers, and some observers believe it is confined to smokers. It is more common in the upper lobes of the lung (for unknown reasons) and probably causes abnormalities in blood gases out of proportion to the area of the lung involved by it. By the time the disease has developed, some impairment of ventilatory ability has probably occurred. Panacinar emphysema may also occur in smokers, but it is the type of emphysema characteristically found in the lower lobes of patients with a deficiency in the antiproteolytic enzyme known as alpha1-antitrypsin. Like centrilobular emphysema, panacinar emphysema causes ventilatory limitation and eventually blood gas changes. Other types of emphysema, of less importance than the two major varieties, may develop along the dividing walls of the lung (septal emphysema) or in association with scars from other lesions.

A major step forward in understanding the development of emphysema followed the identification, in Sweden, of families with an inherited deficiency of alpha1-antitrypsin, an enzyme essential for lung integrity. Members of affected families commonly developed panacinar emphysema in the lower lobes, unassociated with chronic bronchitis but leading to ventilatory impairment and disability. Intense investigation of this major clue led to the "protease-antiprotease" theory of emphysema. It is postulated that cigarette smoking either increases the concentration of protease enzymes released in the lung (probably from white blood cells), or impairs the lung's defenses against these enzymes, or both. Although many details of the essential biochemical steps at the cellular level remain to be clarified, this represents a major step forward in understanding a disease whose genesis was once ascribed to overinflation of the lung (like overdistending a bicycle tire).

Chronic bronchitis and emphysema are distinct processes. Both may follow cigarette smoking, however, and they commonly occur together, so determination of the extent of each during life is not easy. In general, significant emphysema is more likely if ventilatory impairment is constant, gas transfer in the lung (usually measured with carbon monoxide) is reduced, and the lung volumes are abnormal. The radiological technique of computerized tomography may improve the accuracy of detection of emphysema. Many people with emphysema suffer severe incapacity before the age of 60; thus, emphysema is not a disease of the elderly only. A reasonably accurate diagnosis can be made from pulmonary function tests, careful radiological examination, and a detailed history. The physical examination of the chest reveals evidence of airflow obstruction and overinflation of the lung, but the extent of lung destruction cannot be reliably gauged from these signs, and therefore laboratory tests are required.

The prime symptom of emphysema, which is always accompanied by a loss of elasticity of the lung, is shortness of breath, initially on exercise only, and associated with loss of normal ventilatory ability. The severity of this loss is a predictor of survival in this condition. But once ventilatory ability is reduced to less than half the normal value, what determines outcome is the severity of the changes in blood gases, chiefly the lowering of arterial blood oxygen tension. The chronic hypoxemia (lowered oxygen tension) is believed to lead to the development of increased blood pressure in the pulmonary circulation, which in turn leads to failure of the right ventricle of the heart. The symptom (subjective evidence perceived by the patient) of right ventricular failure is swelling of the ankles; the signs (objective evidence discovered by the examining physician) are engorgement of the neck veins and enlargement of the liver. These are portents of advanced lung disease in this condition. The hypoxemia may also lead to an increase in total hemoglobin content and in the number of circulating red blood cells, as well as to psychological depression, irritability, loss of appetite, and loss of weight. Thus the advanced syndrome of chronic obstructive lung disease may cause not only such shortness of breath that the afflicted person is unable to dress without assistance, but also numerous other symptoms.

The slight fall in ventilation that normally accompanies sleep may exacerbate the failure of lung function in chronic obstructive lung disease, leading to a further fall in arterial oxygen tension and an increase in pulmonary arterial pressure.

Unusual forms of emphysema also occur. In one form the disease appears to be unilateral, involving one lung only and causing few symptoms. Unilateral emphysema is believed to result from a severe bronchiolitis in childhood that prevented normal maturation of the lung on that side. "Congenital lobar emphysema" of infants is usually a misnomer, since there is no alveolar destruction. It is most commonly caused by overinflation of a lung lobe due to developmental malformation of cartilage in the wall of the major bronchus. Such lobes may have to be surgically removed to relieve the condition.

Lung cancer develops in individuals with a genetic predisposition to the disease who are exposed to cancer-causing agents, such as tobacco smoke, asbestos, and uranium. Cancerous tumors may start in the bronchi, bronchioles, or in the alveolar lung tissue. If lung cancer is detected before the cancer has spread to other parts of the body, treatments are more effective, and the prognosis for full recovery is good. Unfortunately, 85 percent of lung cancer cases are diagnosed after the cancer has spread, and for these cases, the prognosis is very poor.

Respiratory Distress Syndrome (RDS) is the name for a cluster of symptoms that indicate severe malfunctioning of the lungs. In infants, RDS is termed Infant Respiratory Distress Syndrome (IRDS). Commonly found in premature infants, IRDS results when the alveoli fail to fully expand during inhalation. Expansion of the alveoli requires a chemical called surfactant, but in many premature infants, the alveoli are not developed enough to produce this vital substance. IRDS is treated by administering air and surfactant through a breathing tube until the alveoli begin producing surfactant on their own. Adult Respiratory Distress Syndrome (ARDS) results when lungs are severely injured, for example, in an automobile accident, by poisonous gases, or as a response to inflammation in the lungs. ARDS is a life-threatening condition with a survival rate of about 50 percent.