TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 16 page

VI-41. The answer is C. (Chap. 261) In many cases of interstitial lung disease, bronchoscopy can offer some clues to the cause of the disease. Diffuse alveolar hemorrhage (DAH) is a pathologic process that can occur in many diseases including vasculitis, Goodpasture’s syndrome, systemic lupus erythematosus, crack cocaine use, mitral stenosis, and idiopathic pulmonary hemosiderosis, among many others. On bronchoscopy, one would expect to see a progressively increasing bloody return on sequential aliquots of lavage fluid. Microscopic examination would show hemosiderin-laden macrophages and red blood cells. Atypical hyperplastic type II pneumocytes are seen in diffuse alveolar damage or cases of drug toxicity. Ferruginous bodies and dust particles are found in asbestos-related pulmonary disease. Lymphocytosis is common to hypersensitivity pneumonitis and sarcoidosis. Hypersensitivity pneumonitis has a low CD4:CD8 ratio, whereas sarcoidosis has an elevated CD4:CD8 ratio. The bronchoalveolar lavage fluid in pulmonary alveolar proteinosis has a milky appearance with foamy macrophages.

VI-42 and VI-43. The answers are E and E, respectively. (Chap. 261) Pulmonary alveolar proteinosis (PAP) is a rare disorder with an incidence of approximately one per million. The disease usually presents in those between the ages of 30 and 50 and is slightly more common in men. Three distinct subtypes have been described: congenital, acquired, and secondary (most frequently caused by acute silicosis or hematologic malignancies). Interestingly, the pathogenesis of the disease has been associated with antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in most cases of acquired disease in adults. The pathobiology of the disease is failure of clearance of pulmonary surfactant. These patients typically present with subacute dyspnea on exertion with fatigue and low-grade fevers. Associated laboratory abnormalities include polycythemia, hypergammaglobulinemia, and increased LDH levels. Classically, the CT appearance is described as “crazy pavement” with ground-glass alveolar infiltrates in a perihilar distribution and intervening areas of normal lung. Bronchoalveolar lavage is diagnostic, with large amounts of amorphous proteinaceous material seen. Macrophages filled with periodic acid–Schiff (PAS)-positive material are also frequently seen. The treatment of choice is whole-lung lavage through a double-lumen endotracheal tube. Survival at 5 years is higher than 95%, although some patients will need a repeat whole-lung lavage. Secondary infection, especially with Nocardia, is common, and these patients should be followed closely.

VI-44. The answer is E. (Chap. 261) This patient’s clinical presentation and CT imaging are consistent with the diagnosis of idiopathic pulmonary fibrosis (IPF), which is manifested histologically as usual interstitial pneumonitis (UIP). On microscopic examination, UIP is characterized by a heterogeneous appearance on low magnification with normal-appearing alveoli adjacent to severely fibrotic alveoli. There is lymphocytic infiltrate and scattered foci of fibroblasts within the alveolar septae. End-stage fibrosis results in honeycombing with loss of all alveolar structure. The typical clinical presentation of IPF/UIP is slowly progressive exertional dyspnea with a nonproductive cough. Clinical examination reveals dry crackles and digital clubbing. Patients with IPF are usually older than 50 years, and more than two-thirds have a history of current or former tobacco use. In the typical clinical situation of an older individual, a high-resolution CT scan of the chest can be diagnostic and shows subpleural pulmonary fibrosis that is greatest at the lung bases. As disease progresses, traction bronchiectasis and honeycombing are characteristic on CT scan. The cause of UIP is unknown, and no therapies have been shown to improve survival in this disease, with the exception of lung transplantation. The presence of a dense, amorphous material in alveolar spaces that is periodic acid–Schiff positive is characteristic of pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is an interstitial lung disease that presents with progressive dyspnea, and CT imaging shows characteristic “crazy paving” with ground-glass infiltrates and thickened alveolar septae. Fibrosis is not present. Alveolar destruction with emphysematous changes would be seen in chronic obstructive pulmonary disease (COPD). The presence of crackles without wheezing or hyperinflation on examination does not suggest COPD. Furthermore, clubbing is not typically seen in COPD. Diffuse alveolar damage is seen in acute interstitial pneumonitis and acute respiratory distress syndrome (ARDS). These disorders present with a rapid, acute course that is not present in this case. The formation of non-caseating granulomas is typical of sarcoidosis, a systemic disease that usually presents in younger individuals. It is more common in those of African-American race. A typical CT in sarcoidosis would show interstitial infiltrates and hilar lymphadenopathy. End-stage disease may result in pulmonary fibrosis, but it is greatest in the upper lobes. Poorly formed granulomas may be seen in hypersensitivity pneumonitis.

VI-45. The answer is A. (Chap. 261) Pulmonary complications are common in patients with systemic lupus erythematosus (SLE). The most common manifestation is pleuritis with or without effusion. Other possible manifestations include pulmonary hemorrhage, diaphragmatic dysfunction with loss of lung volumes (the so-called shrinking lung syndrome), pulmonary vascular disease, acute interstitial pneumonitis, and bronchiolitis obliterans organizing pneumonia. Other systemic complications of SLE also cause pulmonary complications, including uremic pulmonary edema and infectious complications. Chronic progressive pulmonary fibrosis is not a complication of SLE. Cavitary lung nodules are typical of Wegener’s granulomatosis but may also be seen in a variety of necrotizing lung infections.

VI-46. The answer is E. (Chap. 261) This patient with rheumatoid arthritis (RA) is presenting with pulmonary symptoms, and the biopsy shows a pattern of cryptogenic organizing pneumonia (COP), a known pulmonary manifestation of rheumatoid arthritis. COP (formerly bronchiolitis obliterans organizing pneumonia, BOOP) usually presents in the fifth or sixth decade with a flulike illness. Symptoms include fever, malaise, weight loss, cough, and dyspnea. Inspiratory crackles are common, and late inspiratory squeaks may also be heard. Pulmonary function testing reveals restrictive lung disease. The typical pattern on high-resolution chest CT is patchy areas of airspace consolidation, nodular opacities, and ground-glass opacities that occur more frequently in the lower lung zones. Pathology shows the presence of granulation tissue plugging airways, alveolar ducts, and alveoli. There

is frequently chronic inflammation in the alveolar interstitium. Treatment with high-dose steroids is effective in two-thirds of individuals, with most individuals being able to be tapered to lower doses over the first year. Azathioprine is an immunosuppressive therapy that is commonly used in interstitial lung disease due to usual interstitial pneumonitis. While it may be considered in COP that is unresponsive to glucocorticoids, it would not be a first-line agent used without concomitant steroid therapy. RA has multiple pulmonary complications. However, therapy with infliximab or methotrexate, which is useful for severe RA, is not used in the treatment of COP. Methotrexate also has pulmonary side effects and may cause pulmonary fibrosis. Hydroxychloroquine is frequently useful for joint symptoms in autoimmune disorders. Its major side effect is retinal toxicity, and it is not known to cause COP.

VI-47. The answer is B. (Chap. 262) The D-dimer measured by enzyme-linked immunosorbent assay (ELISA) is elevated in the setting of breakdown of fibrin by plasmin, and the presence of a positive D-dimer can prompt the need for additional imaging for deep venous thrombosis and/or pulmonary embolus in specific clinical situations where the patient would be considered to have an elevation in D-dimer. However, one must be cautious about placing value on an elevated D-dimer in other situations where there can be an alternative explanation for the elevated level. Of the scenarios listed in the question, the only patient who would be expected to have a negative D-dimer would be the patient with calf pain and recent air travel. The presence of a normal alveolar-arterial oxygen gradient cannot reliably differentiate between those with and without pulmonary embolism. In all the other scenarios, elevations in D-dimer could be related to other medical conditions and provide no diagnostic information to inform the clinician regarding the need for further evaluation. Some common clinical situations in which the D-dimer is elevated include sepsis, myocardial infarction, cancer, pneumonia, the postoperative state, and the second and third trimesters of pregnancy.

VI-48. The answer is B. (Chap. 262) Clinically, individuals with massive pulmonary embolus present with hypotension, syncope, or cyanosis. The hypotension and syncope occur due to acute right ventricular overload, and elevated troponin or NT-pro-brain natriuretic peptide can result from this right ventricular strain. Both elevated troponin and NT-pro-brain natriuretic peptide predict worse outcomes in pulmonary embolism. Further prognostic signs of massive pulmonary embolism include the presence of right ventricular enlargement on CT of the chest or right ventricular hypokinesis on echo-cardiogram. The presence of hemoptysis, pleuritic chest pain, or cough in association with pulmonary embolism most commonly indicates a small peripheral lesion.

VI-49. The answer is B. (Chap. 262) For many years, ventilation-perfusion imaging (V-Q) was the standard for the diagnosis of pulmonary embolism (PE). Determination of abnormal V- Q imaging can be difficult. To call a V- Q scan a high-probability scan, one needs to see two or more segmental perfusion defects in the setting of normal ventilation. In patients with underlying lung disease, however, ventilation is frequently abnormal, and most patients with PE do not actually have high-probability V- Q scans. When there is a high-probability V- Q scan, the likelihood of PE is 90% or greater. Alternatively, patients with normal perfusion imaging have a very low likelihood of PE. Most patients fall into either the low or intermediate probability of having a PE by V- Q imaging. In this setting, 40% of patients with a high clinical suspicion of PE are determined by pulmonary angiography to indeed have a PE despite having a low-probability V- Q scan. At the present time, V- Q scanning is largely supplanted by multidetector-row spiral CT angiography of the chest. When compared to conventional CT scanning

with intravenous contrast, the multidetector spiral CT can provide evaluation of the pulmonary arteries to the sixth-order branches, a level of resolution that is as good as or exceeds that of conventional invasive pulmonary angiography. In addition, the CT allows evaluation of the right and left ventricles as well as the lung parenchyma to provide additional information regarding prognosis in acute PE or alternative diagnosis in the patient with dyspnea. Magnetic resonance angiography is a rarely used alternative to the above modalities in patients with contrast dye allergy. This technique provides the ability to detect large proximal PEs, but lacks reliability for segmental and subsegmental PE.

VI-50. The answer is E. (Chap. 262) This patient is presenting with massive pulmonary embolus with ongoing hypotension, right ventricular dysfunction, and profound hypoxemia requiring 100% oxygen. In this setting, continuing with anticoagulation alone is inadequate, and the patient should receive circulatory support with fibrinolysis if there are no contraindications to therapy. The major contraindications to fibrinolysis include hypertension greater than 180/110 mmHg, known intracranial disease or prior hemorrhagic stroke, recent surgery, or trauma. The recommended fibrinolytic regimen is recombinant tissue plasminogen activator (rTPA), 100 mg IV over 2 hours. Heparin should be continued with the fibrinolytic to prevent a rebound hypercoagulable state with dissolution of the clot. There is a 10% risk of major bleeding with fibrinolytic therapy, with a 1–3% risk of intracranial hemorrhage. The only indication approved by the U.S. Food and Drug Administration for fibrinolysis in pulmonary embolus (PE) is for massive PE presenting with life-threatening hypotension, right ventricular dysfunction, and refractory hypoxemia. In submassive PE presenting with preserved blood pressure and evidence of right ventricular dysfunction on echocardiogram, the decision to pursue fibrinolysis is made on a case-by-case basis. In addition to fibrinolysis, the patient should also receive circulatory support with vasopressors. Dopamine and dobutamine are the vasopressors of choice for the treatment of shock in PE. Caution should be taken with ongoing high-volume fluid administration, as a poorly functioning right ventricle may be poorly tolerant of additional fluids. Ongoing fluids may worsen right ventricular ischemia and further dilate the right ventricle, displacing the interventricular septum to the left to worsen cardiac output and hypotension. If the patient had contraindications to fibrinolysis and was unable to be stabilized with vasopressor support, referral for surgical embolectomy should be considered. Referral for inferior vena cava filter placement is not indicated at this time. The patient should be stabilized hemodynamically as a first priority. The indications for inferior vena cava filter placement are active bleeding, precluding anticoagulation, and recurrent deep venous thrombosis on adequate anticoagulation.

VI-51. The answer is E. (Chap. 262) Warfarin should not be used alone as initial therapy for the treatment of venous thromboembolic disease (VTE) for two reasons. First, warfarin does not achieve full anticoagulation for at least 5 days, as its mechanism of action is to decrease the production of vitamin K–dependent coagulation factors in the liver. Second, a paradoxical reaction that promotes coagulation may also occur upon initiation of warfarin as it also decreases the production of the vitamin K–dependent anticoagulants protein C and protein S, which have shorter half-lives than the procoagulant factors. For many years, unfractionated heparin delivered IV was the treatment of choice for VTE. However, it requires frequent monitoring of activated partial thromboplastin time (aPTT) levels and hospitalization until therapeutic international normalized ratio (INR) is achieved with warfarin. There are now several safe and effective alternatives to unfractionated heparin that can be delivered SC. Low-molecular-weight heparins (enoxaparin, tinzaparin) are fragments of unfractionated heparin with a lower molecular weight. These compounds have a greater bioavailability, longer half-

life, and more predictable onset of action. Their use in renal insufficiency should be considered with caution because low-molecular-weight heparins are renally cleared. Fondaparinux is a direct factor Xa inhibitor that, like low-molecular-weight heparins, requires no monitoring of anticoagulant effects and has been demonstrated to be safe and effective in treating both deep venous thrombosis and pulmonary embolism.

VI-52. The answer is E. (Chap. 263) Parapneumonic effusions are one of the most common causes of the exudative pleural effusion. When an effusion is identified in association with pneumonia, it is prudent to perform a thoracentesis if the fluid can be safely accessed. One way to know if there is enough fluid for thoracentesis is to perform a lateral decubitus film and observe if there is 10 mm of free flowing fluid along the chest wall-pleural interface. However, if the fluid does not layer, this may indicate that it is a complex loculated fluid. A loculated effusion often indicates an infected effusion and may require chest tube drainage or surgical intervention. Other factors that are associated with the need for more invasive procedures include pleural fluid pH less than 7.20, pleural fluid glucose less than 60 mg/dL (<3.3 mmol/L), positive Gram stain or culture of the pleural fluid, and presence of gross pus in the pleural space (empyema). Fluid recurrence following initial thoracentesis does indicate a complicated pleural effusion, but a repeat thoracentesis should be performed to ensure that no concerning features have developed.

VI-53. The answer is A. (Chap. 263) The characteristics of the pleural fluid in this patient are consistent with an exudate by Light’s criteria. These criteria are as follows: pleural fluid protein/serum protein greater than 0.5, pleural fluid LDH/serum LDH greater than 0.6, and pleural fluid LDH more than two-thirds of the upper limit of normal serum values. If one of the criteria is met, then the effusion would be classified as an exudate. This patient clearly meets the criteria for an exudate. Exudative pleural effusions occur when there are alterations in the local environment that change the formation and absorption of pleural fluid. The most common causes of exudative pleural effusion are infection and malignancy. Other less common causes include pulmonary embolism, chylothorax, autoimmune diseases, asbestos exposure, drug reactions, hemothorax, and postoperative cardiac surgery or other cardiac injury, among others. Unfortunately, 25% of transudative effusions can be incorrectly identified as exudates by these criteria. Most often this occurs when the effusion has an increased number of cells to cause an elevation in the LDH or has been treated with diuretics to cause an increase in pleural fluid protein. Transudative effusions are most often caused by heart failure, but can also be seen in cirrhosis, nephrotic syndrome, and myxedema.

VI-54. The answer is A. (Chap. 263) The pleural fluid characteristics are typical of a chylothorax, which occurs when there has been an injury to the thoracic duct leading to accumulation of chyle in the pleural space. The most common cause of chylothorax is traumatic disruption of the thoracic duct, especially following surgeries. The surgeries that have been associated most often with chylothorax are esophagectomy and correction of congenital heart disease. The patient often presents with rapidly progressive shortness of breath within a few weeks of the surgery and has large pleural effusions. The appearance of a milky fluid on thoracentesis should alert one to the possibility of chylothorax and prompt measurement of triglyceride levels of the pleural fluid. A triglyceride level of more than 110 mg/dL (1.2 mmol/L) is characteristic of chylothorax. The treatment of chylothorax is placement of a chest tube with administration of octreotide, a somatostatin analogue. While it is not entirely clear why this is effective, the hypothesis is that octreotide decreases splanchnic blood flow and thereby

decreases triglyceride production and thoracic duct flow. Patients are often also asked to stop all oral intake to further decrease chyle production. If conservative measures fail, the thoracic duct ligation can be performed. Prolonged chest tube drainage is contraindicated, however, as the high protein content in the drained fluid can lead to malnutrition and increased infection risk.

VI-55. The answer is B.(Chap. 263) A primary spontaneous pneumothorax occurs in the absence of trauma to the thorax. Most individuals who present with a primary spontaneous pneumothorax are young, and primary spontaneous pneumothorax occurs almost exclusively in cigarette smokers, with cigarette smoking being the primary risk factor. Primary spontaneous pneumothorax is also more common in men and has been associated with a tall, thin body habitus. The primary cause is the rupture of small apical pleural blebs or cysts, and the CT scan of the chest is often normal. About half of individuals will experience more than one primary spontaneous pneumothorax. The initial treatment is simple needle aspiration, which is most commonly done with ultrasound or CT guidance. Oxygen is given simultaneously to speed resorption of the residual air in the pleural space. If conservative treatment fails, tube thoracostomy can be performed. Pneumothoraces that fail to resolve or are recurrent often require thoracoscopy with stapling of blebs and pleural abrasion, a treatment that is effective in almost 100% of cases.

VI-56. The answer is B.(Chap. 263) The most common cause of pleural effusion is left ventricular failure. Pleural effusions occur in heart failure when there are increased hydrostatic forces increasing the pulmonary interstitial fluid and the lymphatic drainage is inadequate to remove the fluid. Right-sided effusions are more common than left-sided effusions in heart failure. Thoracentesis would show a transudative fluid. Pneumonia can be associated with a parapneumonic effusion or empyema. Parapneumonic effusions are the most common cause of exudative pleural effusions and are second only to heart failure as a cause of pleural effusions. Empyema refers to a grossly purulent pleural effusion. Malignancy is the second most common cause of exudative pleural effusion. Breast and lung cancers and lymphoma cause 75% of all malignant pleural effusions. On thoracentesis, the effusion is exudative. Cirrhosis and pulmonary embolus are far less common causes of pleural effusions.

VI-57. The answer is E(Chap. 264) Patients with amyotrophic lateral sclerosis (ALS) often develop hypoventilation due to involvement of their respiratory pump muscles, e.g., diaphragm, intercostal muscles, and sternocleidomastoids. Noninvasive positive pressure ventilation (NIPPV) has been used successfully in the therapy of patients with hypoventilation such as ALS. Nocturnal NIPPV can improve daytime hypercapnea, prolong survival, and improve health-related quality of life. Current ALS guidelines are to institute NIPPV if symptoms of hypoventilation exist and PaC0₂ is 45 mmHg or

greater, nocturnal desaturation to less than 89% is documented for 5 consecutive minutes, maximal inspiratory pressure is less than 60 cmH₂0, or FVC is less than 50% predicted. Symptoms of

hypoventilation are not particular to ALS and may include the following: dyspnea during activities of daily living, orthopnea in diseases that affect diaphragm function, poor quality sleep, daytime hypersomnolence, early morning headaches, anxiety, and impaired cough in neuromuscular disease.

VI-58. The answer is C.(Chap. 264) The patient has muscular dystrophy and is at risk for the development of hypoventilation. Many patients with hypoventilation are relatively asymptomatic or only endorse symptoms after pointed questions about sleep quality, morning headache, or orthopnea due to diaphragmatic weakness if present. The patient described here has asymptomatic hypoxemia and a

normal chest radiograph aside from low lung volumes. Ventilation-perfusion mismatch and shunt are unlikely to be present without infiltrates, thus atelectasis, mucous plug, and pneumonia are not the correct answers. The patient has no risk factors described for methemoglobinemia. The most likely explanation is the presence of hypoventilation with alveolar hypoxia due to elevated PaC0₂ through the

alveolar gas equation. An arterial blood gas measurement would confirm this with elevation in PaC0₂,

depressed Pa0₂, and a normal A-a gradient.

VI-59. The answer is B.(Chap. 264) The physiologic effects of hypoventilation are typically magnified during sleep because of a further reduction in central respiratory drive. Hyper-capnia causes cerebral vasodilation, which manifests as headache upon wakening. The headache typically resolves soon after awakening as cerebral vascular tone returns to normal with increased ventilation. Patients with frequent nocturnal arousals from sleep and patients with nocturnal hypoventilation commonly complain of daytime somnolence and may also exhibit confusion and fatigue. Hypoventilation causes an increase in PC0₂ and an obligatory fall in P0₂. The hypoxemia can stimulate erythropoiesis and result in

polycythemia. With central hypoventilation disorders, patients may also have impaired cranial nerve reflexes or muscular function, causing aspiration.

VI-60. The answer is D.(Chap. 266) Common indications for lung transplantation include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, suppurative lung disease such as cystic fibrosis, and pulmonary arterial hypertension. Five-year survival is similar for all indications for lung transplantation at approximately 50%. For most indications, double-lung transplantation is the preferred procedure, and it is mandatory for patients with suppurative lung disease like cystic fibrosis. In general, in patients with idiopathic pulmonary arterial hypertension, double-lung transplantation is preferred because of concern of overcirculation in the low-resistance vascular bed of the transplanted lung when a native lung is present with markedly elevated pulmonary vascular resistance. It is very rare for the primary disease to recur after transplantation, and this has not been described in idiopathic pulmonary arterial hypertension. The right ventricle is highly plastic and will generally recover function after elevated pulmonary vascular resistance is removed by lung transplantation. Subsequently, it is rare to perform heart-lung transplantation in pulmonary arterial hypertension patients unless there is concomitant complex congenital heart disease that cannot be repaired at the time of lung transplantation.

VI-61. The answer is A.(Chap. 266) The long-term complications of lung transplantation are multisystem and range from the diseases that affect the lung and are complications of a foreign body in the chest to distant organ disease, either due to infections or complications of immunosuppressive therapy. Although osteoporosis, post-transplant lymphoproliferative disorders, and chronic kidney disease are important complications of steroids, calcineurin inhibitors, and other agents used for immunosuppression, the major complications post-transplant are in the lung. Primary graft dysfunction is a form of acute lung injury immediately after lung transplantation and is relatively rare, with severe disease occurring in only 10-20% of cases. Airway complications such as anastomotic dehiscence or stenosis have similar occurrence rates, but can usually be managed bronchoscopically with good survival. Rejection of transplanted organ is very common and is the main limitation to better medium-and long-term outcomes. Rejection occurs as acute cellular rejection often presenting with cough, low-grade fever, dyspnea, infiltrates on radiographs, and declining lung function. In contrast, chronic rejection typically presents with advancing obstruction on pulmonary function testing, no infiltrates, and worsening dyspnea on exertion. This constellation in post-transplant patients is termed bronchiolitis

obliterans syndrome. Fifty percent of lung transplant patients have some degree of bronchiolitis obliterans syndrome, and it is the main impediment to better long-term survival. Therapy is often with augmented immunosuppression, although there is no consensus of how to do this or the duration of this augmentation.

VI-62. The answer is В(Chap. 266) Chronic kidney disease is a common finding in patients after lung transplantation and is associated with poorer outcomes. While rarely patients may have hemolytic-uremic syndrome underlying the kidney disease, it is usually acute, and the most common etiology of gradually progressive decline in renal function is calcineurin inhibitor neuropathy. Cyclosporine and tacrolimus are calcineurin inhibitors commonly used in immunosuppressive regimens after lung transplantation. The exact mechanism of this toxicity is unclear but may include a direct toxicity of inhibition of the calcineurin-NFAT system within the kidney, alteration in glomerular blood flow, and host/environment interactions within the kidney with calcineurin inhibitors. Prednisone, albuterol, and mycophenolate mofetil are not known to be nephrotoxic.

VI-63. The answer is B.(Chap. 266) The optimal timing for lung transplantation is critical to improve survival and add quality-adjusted life years. Individuals with cystic fibrosis should be considered for lung transplantation when the FEVj is less than 30% predicted or is rapidly falling. Other indications

for lung transplantation in cystic fibrosis include oxygen-dependent respiratory failure, hypercapnia, and pulmonary hypertension.

SECTION VII

Disorders of the Kidney and Urinary Tract

QUESTION

DIRECTIONS: Choose the one best response to each question.

VII-1. Which of the following is a potential etiology for ischemic acute renal failure?

Date: 2016-04-22; view: 854