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104. The answer is b. (Braunwald, 15/e, pp 2008-2010.) The clinical picture suggests hypertrophic osteoarthropathy. This process, the pathogene-sis of which is unknown, is characterized by clubbing of digits, periosteal new bone formation, and arthritis. Hypertrophic osteoarthropathy is associated with intrathoracic malignancy, suppurative lung disease, and congenital heart problems. Treatment is directed at the underlying disease process. While x-rays may suggest osteomyelitis, the process is usually bilateral and easily distinguishable from osteomyelitis. The first step in evaluation of this patient is to obtain a chest x-ray looking for lung infection and carcinoma.

105. The answer is b. (Braunwald, 15/e, pp 1444-1445.) The diagnosis in this patient is suggested by the physical exam findings. The findings of poor excursion, flatness of percussion, and decreased fremitus on the right side are all consistent with a right-sided pleural effusion. A large right-sided effusion may shift the trachea to the left. Histoplasmosis would be one possible cause of such an effusion. A pneumothorax should result in hyperresonance of the affected side. Atelectasis on the right side would shift the trachea to the right. A consolidated pneumonia would characteristically result in increased fremitus, flatness to percussion, and bronchial breath sounds, and would not cause tracheal deviation.

106. The answer is b. (Braunwald, 15/e, pp 1460, 1465.) This 60-year-old woman has peripheral eosinophilia in association with pulmonary infiltrates. The differential diagnosis for eosinophilic pneumonia includes allergic bronchopulmonary aspergillosis, parasitic infections, drug reactions, and a category of idiopathic disease. Nitrofurdantoin and sulfonamides are among the drugs most likely to cause eosinophilic pneumonia. Hypersen-sitivity pneumonitis may cause bilateral infiltrates, but does not of itself cause eosinophilia.

107. The answer is d. (Braunwald, 15/e, p 1478.) Of the organisms listed, only anaerobic infection is likely to cause a necrotizing process. Type III

pneumococci have been reported to cause cavitary disease, but this is unusual. The location of the infiltrate suggests aspiration, also making anaerobic infection most likely. The superior segment of the right lower lobe is the one most likely to develop an aspiration pneumonia.

108-112. The answers are 108-b, 109-d, 110-a, 111-c, 112-e.

(Braunwald, 15/e, pp 1513-1515.) The first step in determining the cause of a pleural effusion is to categorize it as either a transudate or exudate. Tran-sudative effusions occur when factors alter the formation or absorption of pleural fluid; exudative effusions occur when local factors produce an inflammatory process. Exudative effusions have one of the following characteristics: pleural fluid protein-to-serum protein ratio greater than 0.5, pleural fluid LDH-to-serum LDH ratio greater than 0.6, or pleural fluid LDH more than two-thirds the normal upper limit for serum. Congestive heart failure usually produces a right-sided pleural effusion. Of all the disease processes listed, it is the only one that usually results in a transudative effusion.

Tuberculosis causes a hypersensitivity reaction to tuberculous protein in the pleural fluid. It produces an exudative effusion with small lymphocytes. The diagnosis is now established by demonstrating high levels of TB markers such as adenosine deaminase or positive PCR for tuberculous DNA.

Empyema may be defined by the very low pH value. It is an exudative effusion with a polymorphonuclear leukocyte predominance. A drainage procedure is usually necessary when the pleural fluid pH is below 7.20, when there is gross pus, or when the fluid shows a positive gram stain or culture.

Rheumatoid effusions are often exudative and may be lymphocytic, but they are best characterized by their very low glucose levels. Pleural fluid glucose levels below 60 mg/dL also occur in malignancy and bacterial infections.

Mesotheliomas are primary tumors that arise from mesothelial cells that line the pleural cavity. They produce a very bloody effusion. Thora-coscopy or open pleural biopsy are often necessary to make a definitive diagnosis.

113-116. The answers are 113-a, 114-b, 115-c, 116-d. (Braunwald, 15/e, pp 1030, 1323, 1477-1478.) The patient with fever, shaking chills, and a Gram stain showing gram-positive cocci in clusters has Staphylococcus aureus pneumonia. Chest x-ray A shows a necrotizing pneumonia characteristic of this infection. Cavities develop in association with lung infection when necrotic lung tissue is discharged into airways. Cavities greater than 2 cm are described as lung abscesses.

The patient with shortness of breath and paroxysmal nocturnal dyspnea might have chest x-ray B, which shows signs of congestive heart failure including cardiomegaly, bilateral infiltrates, and cephalization. When there has been long-standing venous hypertension, upper lobe vessels become more prominent due to redistribution of pulmonary blood flow. When pulmonary edema becomes severe, fluid extends out from the hila in a batwing distribution.

Chest x-ray C is best matched with the patient who has fever and night sweats. This x-ray shows characteristic changes of tuberculosis, including extensive apical and upper lobe scarring. When the lung is involved with tuberculosis, the range of abnormalities is broad. Cavitary infiltrates in the posterior apical segments are very common. Mass lesions, interstitial infiltrates, and noncavitary infiltrates also occur.

The patient with long-standing hypertension shows chest x-ray evidence for left ventricular hypertrophy. The cardiac silhouette is enlarged and takes on a boot-shaped configuration, as seen in chest x-ray D.

117. The answer is c. (Braunwald, 15/e, p 329.) Because the clinical signs of neurologic deterioration and a petechial rash have occurred in the setting of fracture and hypoxia, fat embolism is the most likely diagnosis. This process occurs when neutral fat is introduced into the venous circulation after bone trauma or fracture. The latent period is 12 to 36 hours, usually earlier than a pulmonary embolus would occur after trauma.

118. The answer is c. (Braunwald, 15/e, p 1525.) When stupor and coma supervene in CO2 retention, fatal arrhythmias, seizures, and death are likely to follow. Stopping oxygen is the worst course of action, as it will exacerbate life-threatening hypoxia. Intubation is the only good alternative. Bicarbonate plays no role in this acidosis, which is respiratory and caused by hypoventilation.

119. The answer is c. (Braunwald, 15/e, pp 1969-1974.) Sarcoidosis is a systemic illness of unknown etiology. Many patients have respiratory symptoms, including cough and dyspnea. Hilar and peripheral lymphadenopathy is common, and 20 to 30% of patients have hepatomegaly. The chest x-ray shows symmetrical hilar lymphadenopathy. The diagnostic method of choice is transbronchial biopsy, which will show a mononuclear cell granulomatous inflammatory process. While liver and scalene node biopsies are often positive, noncaseating granulomas are so frequent in these sites that they are not considered acceptable for primary diagnosis. ACE levels are elevated in two-thirds of patients, but false-positive values are common in other granuloma-tous disease processes.

120. The answer is b. (Braunwald, 15/e, p 1513.) Classifying a pleural effusion as either a transudate or an exudate is useful in identifying the underlying disorder. Pleural fluid is exudative if it has any one of the following three properties: a ratio of concentration of total protein in pleural fluid to serum greater than 0.5, an absolute value of LDH greater than 200 IU, or a ratio of LDH concentration in pleural fluid to serum greater than 0.6. Causes of exudative effusions include malignancy, pulmonary embolism, pneumonia, tuberculosis, abdominal disease, collagen vascular diseases, uremia, Dressler syndrome, and chylothorax. Exudative effusions may also be drug-induced. If none of the aforementioned properties are met, the effusion is a transudate. Differential diagnosis includes congestive heart failure, nephrotic syndrome, cirrhosis, Meigs syndrome (benign ovarian neoplasm with effusion), and hydronephrosis.

121. The answer is d. (Braunwald, 15/e, pp 1450-1451.) Carbon monoxide (CO) diffusing capacity provides an estimate of the rate at which oxygen moves by diffusion from alveolar gas to combine with hemoglobin in the red blood cells. It is interpreted as an index of the surface area engaged in alveolar-capillary diffusion. Measurement of diffusing capacity of the lung is done by having the person inspire a low concentration of carbon monoxide. The rate of uptake of the gas by the blood is calculated from the difference between the inspired and expired concentrations. The test can be performed during a single 10-second breath holding or during 1 minute of steady-state breathing. The diffusing capacity is defined as the amount of carbon monoxide transferred per minute per millimeter of mercury of driving pressure and correlates with oxygen transport from the alveolus into the capillaries. Primary parenchymal disorders, anemia, and removal of lung tissue decrease the diffusing capacity. Conversely, polycythemia, congestive heart failure, and intrapulmonary hemorrhage tend to increase the value for diffusing capacity. In this patient, the possibility of Goodpasture syndrome would be considered.

122. The answer is d. (Stobo, 23/e, p 143.) It is extremely important to accurately determine the severity of an exacerbation of asthma, since the major cause of death from asthma is the underestimation of the severity of a particular episode by either the patient or the physician. Silent chest is a particularly ominous finding, because the airway constriction is so great that airflow is insufficient to generate wheezing. Hypercapnia and thoraco-abdominal paradox are almost always indicative of exhaustion and respiratory muscle failure or fatigue and generally need to be aggressively treated with mechanical ventilation. Altered mental status is frequently seen with severe hypoxia or hypercapnia, and ventilatory support is usually required. An increased pulsus paradoxus may also be a sign of severe asthma, as it increases with greater respiratory effort and generation of more negative intrathoracic pressures during inspiration. However, a pulsus paradoxus of up to 8 to 10 mmHg is considered normal; thus, a value of 5 mmHg would not be indicative of a severe episode of asthma.

123. The answer is b. (Braunwald, 15/e, pp 1476-1482.) Pneumonia is a common disorder and is a major cause of death, particularly in hospitalized elderly patients. Before choosing empiric therapy for presumed pneumonia, it is necessary to know the age of the patient, whether the infection is community-acquired or nosocomial, and whether there are any underlying debilitating illnesses. Community-acquired pneumonias in patients over the age of 35 are most likely due to S. pneumoniae, Legionella species (e.g., pneumophila), and Haemophilus influenzae. In the case outlined, the history is strongly consistent with pneumococcal pneumonia, manifested by a short prodrome, shaking chills with rigor, fever, chest pain, sparse sputum production associated with cough, and a consolidated lobar infiltrate on chest x-ray. The most reliable method of diagnosing pneumococcal pneumonia is seeing gram-positive diplococci on an adequate sputum (many white cells, few epithelial cells). Sputum culture is also important in the era of penicillin-resistant pneumococci, but is not helpful in initial diagnosis. Blood cultures are positive in only about 20% of patients, and, when positive, are indicative of a more severe case. Although rigors may suggest pneumococcal bacteremia, the absence of rigors does not rule out the diagnosis. About 25% of pneumococci in the United States are partially or completely resistant to penicillin due to chromosomal mutations resulting in penicillin-binding protein changes. Penicillin is no longer the regimen of choice for pneumococcal pneumonia pending the results of sensitivity testing. The fluoroquinolones or ceftriaxone are widely used as initial therapy for pneumococcal pneumonia.

124. The answer is b. (Braunwald, 15/e, pp 1508-1512.) The clinical situation described is characteristic of pulmonary embolic disease. In greater than 80% of cases, pulmonary emboli arise from thromboses in the deep venous circulation (DVTs) of the lower extremities. DVTs often begin in the calf, where they rarely if ever cause clinically significant pulmonary embolic disease. However, thromboses that begin below the knee frequently "grow," or propagate, above the knee; clots that dislodge from above the knee cause clinically significant pulmonary emboli, which, if untreated, cause mortality exceeding 80%. Interestingly, only about 50% of patients with DVT of the lower extremities have clinical findings of swelling, warmth, erythema, pain, or "cords." As long as the superficial venous system, which has connections with the deep venous system, remains patent, none of the classic clinical findings of DVT will occur, because blood will drain from the unobstructed superficial system. When a clot does dislodge from the deep venous system and travels into the pulmonary vasculature, the most common clinical findings are tachypnea and tachycardia; chest pain is less likely and is more indicative of concomitant pulmonary infarction. The ABG is usually abnormal, and a high percentage of patients exhibit hypoxia, hypocapnia, alkalo-sis, and a widening of the alveolar-arterial gradient. The ECG is frequently abnormal in pulmonary embolic disease. The most common finding is sinus tachycardia, but atrial fibrillation, pseudoinfarction in the inferior leads, and right and left axis deviation are also occasionally seen. Initial treatment for suspected pulmonary embolic disease includes prompt hospitalization and institution of intravenous heparin, provided there are no contraindications to anticoagulation. It is particularly important to make an early diagnosis of pulmonary embolus, as intervention can decrease the mortality rate from 25% to 5%.

125. The answer is b. (Braunwald, 15/e, pp 1509-1511.) Lung scanning is the principal imaging test for the diagnosis of pulmonary embolus. The diagnosis is very unlikely in patients with normal or near normal scans, and is highly likely in patients with high-probability scans. In patients with a high clinical index of suspicion for pulmonary embolus but low-probability scan, the diagnosis becomes more difficult, and pulmonary angiography may be indicated. About two-thirds of patients with pulmonary embolus have evidence of deep venous disease on venous ultrasound. Therefore, pulmonary embolus cannot be excluded by a normal study. The quantitative D-dimer enzyme-linked immunoabsorbent assay is positive in 90% of patients with pulmonary embolus in some studies. It has been used to rule out pulmonary embolus in patients with a low- or intermediate-probability scan.

126. The answer is c. (Braunwald, 15/e, p 1509.) While all of these signs and symptoms can occur in acute pulmonary embolus, tachypnea is by far the most common. Tachypnea occurs in more than 90% of patients with pulmonary embolus. Pleuritic chest pain occurs in about half of patients and is less common in the elderly and those with underlying heart disease. Hemoptysis and wheezing occur in less than half of patients. A right-sided S 3 is associated with large emboli that result in acute pulmonary hypertension.

127. The answer is c. (Braunwald, 15/e, p 1512.) Warfarin is the principal agent recommended for the prophylaxis of acute pulmonary embolus in patients who receive total hip replacement. Warfarin is started preopera-tively, and the daily dose is adjusted to maintain an international normalized ratio (INR) of 2 to 2.5. Low-molecular-weight heparin given twice daily subcutaneously is also a recommended regimen. The value of aspirin in this setting is unclear. Early ambulation and elastic stockings are also important in preventing thromboembolism, but are not adequate in themselves in this high-risk situation.

128. The answer is b. (Braunwald, 15/e, pp 1456-1460.) Asthma is an incompletely understood inflammatory process that involves the lower airways and results in bronchoconstriction and excess production of mucus, which in turn lead to increased airway resistance and occasionally respiratory failure and death. During acute exacerbations of asthma, and in other obstructive lung diseases such as chronic obstructive pulmonary disease, hyperinflation may be present on chest x-ray. Hypoxia is common and usually a result of ventilation-perfusion mismatch. The FEV1/FVC is reduced, and exacerbations are frequently precipitated by upper airway infections. Only in asthma is the airway obstruction reversible.

129-133. The answers are 129-a, 130-e, 131-c, 132-b, 133-d. (Stobo, 23/e, pp 121-125, 155-158, 162-176.) The blood gas values associated with pulmonary embolism may vary tremendously. The most consistent finding is acute respiratory alkalosis. It is important to note that hypoxemia, although frequently found, need not be present. In severe chronic lung disease, the presence of hypercapnia leads to a compensatory increase in serum bicarbonate. Thus, significant hypercapnia may be present with an arterial pH close to normal, but will never be completely corrected. Acute respiratory acidosis may occur secondary to respiratory depression after drug overdose. Hypoventilation is associated with hypoxia; hypercapnia; and severe, uncompensated acidosis. In the presence of long-standing lung disease, respiration may become regulated by hypoxia rather than by altered carbon dioxide tension and arterial pH, as in normal people. Thus, the unmonitored administration of oxygen may lead to respiratory suppression, as in the patient described in the question, that results in acute and chronic respiratory acidosis. Young patients with type 1 diabetes mel-litus may present with rapid onset of diabetic ketoacidosis (DKA), usually secondary to a systemic infection. These patients usually are maximally ventilating, as indicated by a very low arterial Pco2; however, they remain acidotic secondary to the severe metabolic ketoacidosis associated with this process. In general, these patients are not hypoxic unless the underlying infection is pneumonia.

134-138. The answers are 134-b, 135-d, 136-d, 137-c, 138-a.

(Braunwald, 15/e, pp 1456-1459, 1489, 1932, 1969-1973.) Asthma is predominantly an inflammatory lower airway process. Frequent triggers of airway inflammation, and thus asthma, include infection, inhaled allergens, and processes that cool or dry the airways, such as exercise and exposure to cold weather. In addition, certain chemicals, such as aspirin (but not sodium or magnesium salicylate) and tartrazine yellow, have been implicated in the development of bronchospasm in certain patients.

Pleural effusions are not unusual in patients with rheumatoid arthritis. A history of pleurodynia that would suggest an antecedent inflammatory pleuritis is not always obtained, but characteristically, the pleural fluid, which is sterile, will contain a high level of lactic dehydrogenase and a low glucose concentration. Other pulmonary phenomena associated with rheumatoid arthritis include diffuse interstitial fibrosis and the occurrence of individual or clustered nodules in the lung parenchyma.

The fatality rate for patients with cystic fibrosis is lower today than in previous years; the average life span of patients afflicted with this disease has been significantly increasing. Chronic lung infections, however, are almost universal. The most common and difficult to treat of such infections is caused by the mucoid strain of Pseudomonas aeruginosa. Chronic coughing is one of the major and most distressing problems of patients with cystic fibrosis. Liver disease, particularly biliary cirrhosis, may develop in these patients. Common pulmonary complications include bronchiectasis, severe hemoptysis, and allergic bronchopulmonary aspergillosis. The incidence of liver disease associated with a deficiency of ai antitrypsin is very high. Patients with liver disease secondary to ai antitrypsin deficiency usually, but not always, have accompanying panacinar emphysema.

Sarcoidosis is a nonspecific granulomatous disease of unknown etiology. Blacks and Mediterranean peoples appear to be predisposed. The most commonly involved organs—after the lungs—are the liver, eye, spleen, skin, and kidney. The most characteristic presentation is a patient with a nonproductive cough with bilateral hilar adenopathy on chest x-ray. Treatment with prednisone is usually reserved for patients with diminishing pulmonary function, evidenced by reduced diffusing capacity or reduced lung volumes; 70 to 80% of untreated, stable patients will spontaneously remit.

139. The answer is d. (Braunwald, 15/e, pp 1495-1498.) This patient's chronic cough, hyperinflated lung fields, abnormal pulmonary function tests, and smoking history are all consistent with chronic bronchitis. A smoking cessation program can decrease the rate of lung deterioration and is successful in as many as 40% of patients, particularly when the physician gives a strong antismoking message and uses both counseling and nicotine replacement. Continuous low-flow oxygen becomes beneficial when arterial oxygen concentration falls below 55 mmHg. Antibiotics are indicated only for acute exacerbations of chronic lung disease, which might present with fever, change in color of sputum, and increasing shortness of breath. Oral corticosteroids are helpful in some patients, but are reserved for those who have failed inhaled bronchodilator treatments.

140. The answer is b. (Braunwald, 15/e, p 1515.) The most characteristic findings of pneumothorax are hyperresonance and decreased breath sounds. A tension pneumothorax may displace the mediastinum to the unaffected side. Tactile fremitus would be decreased in the patient with a pneumothorax, but would be increased in conditions in which consolidation of the lung has developed.

141. The answer is c. (Braunwald, 15/e, pp 1523-1526.) Sepsis is the most important single cause of adult respiratory distress syndrome. Early in the course of ARDS, patients may appear stable without respiratory symptoms. Tachypnea, hypoxemia, and diffuse infiltrates gradually develop. It may be difficult to distinguish the process from cardiogenic pulmonary edema, especially in patients who have been given large quantities of fluid. This young patient with no evidence of volume overload would be strongly suspected of having ARDS. The pulmonary capillary wedge pressure would be normal or low in ARDS, but elevated in left ventricular failure. ARDS is a complication of sepsis, but blood cultures may or may not be positive. Neither CT of the chest nor ventilation-perfusion scan would be specific enough to help in diagnosis of ARDS.

142. The answer is a. (Braunwald, 15/e, pp 1506-1508.) Although a difficult diagnosis to make, primary pulmonary hypertension is the most likely diagnosis in this young woman who has used appetite suppressants. There has been a recent increase in primary pulmonary hypertension in the United States associated with fenfluramines. The predominant symptom is dyspnea, which is usually not apparent in the previously healthy young woman until the disease has advanced. When signs of pulmonary hypertension are apparent from physical findings, chest x-ray, or echocardiogra-phy, the diagnosis of recurrent pulmonary embolus must be ruled out. In this case, a normal perfusion lung scan makes pulmonary angiography unnecessary. Restrictive lung disease should be ruled out with pulmonary function testing. An echocardiogram will show right ventricular enlargement and a reduction in the left ventricle size consistent with right ventricular pressure overload.

143. The answer is a. (Braunwald, 15/e, pp 1507-1508.) In all patients in whom primary pulmonary hypertension is confirmed, acute drug testing with a pulmonary vasodilator is necessary to assess the extent of pulmonary vascular reactivity. Inhaled nitric oxide, intravenous adenosine, or intravenous prostacyclin have all been used. Patients who have a good response to the short-acting vasodilator are tried on a long-acting calcium channel antagonist under direct hemodynamic monitoring. Prostacyclin has been approved for patients who are functional class III or IV and have not responded to calcium channel antagonists. Lung transplantation is reserved for late stages of the disease when patients are unresponsive to prostacyclin. The disease does not appear to recur after transplantation.

144. The answer is d. (Braunwald, 15/e, pp 1521-1523.) With the history of daytime sleepiness and snoring at night, the patient requires evaluation for obstructive sleep apnea syndrome. Frequent awakenings are actually more suggestive of central sleep apnea. Polysomnography is required to assess which type of sleep apnea syndrome is present. EEG variables are recorded that identify various stages of sleep. Arterial oxygen saturation is monitored by finger or ear oximetry. Heart rate is monitored. The respiratory pattern is monitored to detect apnea and whether it is central or obstructive. Ambulatory sleep monitoring with oxygen saturation studies alone might identify multiple episodes of desaturation, but negative results would not rule out a sleep apnea syndrome. Overnight oximetry alone can be used in some patients when the index of suspicion for obstructive sleep apnea is high.

145. The answer is a. (Braunwald, 15/e, pp 1522-1523.) In this patient with multiple episodes of desaturation, continuous positive airway pressure would be the recommended therapy Weight loss is often helpful and should be recommended as well, but would probably not be sufficient. Uvulopalatopharyngoplasty has also been used in obstructive sleep apnea, but when applied to unselected patients is effective in less than 50%. Tracheostomy is a course of last resort that does provide immediate relief.

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