Porth's Essentials of Pathophysiology, 4e

589

Disorders of Ventilation and Gas Exchange

C h a p t e r 2 3

Pathogenesis Athough pulmonary emboli can originate from a num- ber of sources, most arise from deep vein thrombosis (DVT) in the large veins of the lower legs, typically origi- nating in the popliteal vein or larger veins above it (see Chapter 18). The presence of thrombosis in the deep veins of the legs or pelvis often is unsuspected until embolism occurs. Among the physiologic factors that contribute to venous thrombosis are venous stasis, venous endothelial injury, and hypercoagulability states. Venous stasis and venous endothelial injury can result from prolonged bed rest (particularly with immobilization of the legs), severe trauma (including burns and fractures), surgery (particu- larly orthopedic surgery of the knee or hip), childbirth, myocardial infarction and congestive heart failure, and spinal cord injury. Hypercoagulability is related to vari- ous factors. Cancer cells can produce thrombin and syn- thesize procoagulation factors, increasing the risk for thromboembolism. Pregnancy, and hormone replacement therapy are thought to increase the resistance to endog- enous anticoagulants and risk of pulmonary embolism. There is also increased risk for pulmonary embolism among users of oral contraceptives, particularly in women who smoke. The thrombophilias (e.g., antithrombin III deficiency, protein C and S deficiencies, factor V Leiden mutation) are a group of inherited disorders affecting coagulation that make an individual prone to the devel- opment of venous thromboemboli (see Chapter 12). The pathophysiologic effects of thromboembolism depend largely on the size of the embolus and degree of pulmonary blood flow obstruction. Obstruction of pul- monary blood flow causes reflex bronchoconstriction in the affected area of the lung, ventilation without perfu- sion, impaired gas exchange, and loss of alveolar sur- factant. Pulmonary hypertension and right heart strain may develop with large emboli or in those with poor cardiac reserve. Although small areas of infarction may occur, pulmo- nary infarction is uncommon. This is because the lung is perfused not only by the pulmonary arteries but also by the bronchial arteries and air from the alveoli. If the bronchial circulation is normal and adequate ventilation is maintained, a decrease in pulmonary artery perfusion does not usually cause infarction. Manifestations The clinical manifestations of pulmonary embolism depend on the size and location of the obstruction. Small emboli that become lodged in the peripheral branches of the pulmonary artery are clinically silent and may go unrecognized, especially in the elderly and acutely ill. Persons with moderate-sized emboli often present with breathlessness accompanied by pleuritic pain, apprehen- sion, slight fever, andcoughproductiveofblood-streaked sputum. Tachycardia often occurs to compensate for decreased oxygenation, and the breathing pattern is rapid and shallow. Patients with massive emboli usually present with sudden collapse, crushing substernal chest pain, shock, and sometimes loss of consciousness. The pulse is rapid and weak, the blood pressure is low, the

neck veins are distended, and the skin is cyanotic and diaphoretic. Massive pulmonary emboli often are fatal.

Diagnosis andTreatment Diagnosis of pulmonary embolism is based on clinical signs and symptoms, blood gas determinations, D-dimer testing, lung perfusion scans, CT scans of the chest, and, in selected cases, pulmonary angiography. 59–61 Laboratory studies and radiologic films are useful in ruling out other conditions that might give rise to similar symptoms. Because emboli can cause an increase in pulmonary vas- cular resistance, the electrocardiogram (ECG) may be used to detect signs of right heart strain. There has been recent interest in combining several noninvasive methods (lower limb compression ultrasonography, D-dimer mea- surements, and clinical assessment measures) as a means of establishing a diagnosis of pulmonary embolism. Because most pulmonary emboli originate from DVT, venous studies such as lower limb compression ultra- sonography, impedance plethysmography, and contrast venography are often used as initial diagnostic proce- dures. Of these, lower limb compression ultrasonog- raphy has become an important noninvasive means for detecting DVT. D-dimer testing involves the mea- surement of plasma D-dimer, a degradation product of coagulation factors that have been activated as a result of a thromboembolic event. The ventilation–perfusion scan uses radiolabeled albumin, which is injected intra- venously, and a radiolabeled gas, which is inhaled. A scintillation (gamma) camera is used to scan the vari- ous lung segments for blood flow and distribution of the radiolabeled gas. Ventilation–perfusion scans are useful only when their results are either normal or indi- cate a high probability of pulmonary embolism. Helical (spiral) CT angiography requires administration of an intravenous radiocontrast medium. It is sensitive for the detection of emboli in the proximal pulmonary arteries and provides another method of diagnosis. Pulmonary angiography involves the passage of a venous catheter through the right heart and into the pulmonary artery under fluoroscopy. Although it remains the most accu- rate method of diagnosis, it is an invasive procedure; therefore, its use is reserved for selected cases. Treatment goals for pulmonary emboli include pre- venting DVT and the development of thromboemboli, protecting the lungs from exposure to thromboem- boli when they occur, and in the case of large and life-threatening pulmonary emboli, sustaining life and restoring pulmonary blood flow. 60,61 Thrombolytic ther- apy using streptokinase, urokinase, or recombinant tis- sue plasminogen activator may be indicated in persons with life-threatening pulmonary emboli. Thrombolytic therapy is followed by anticoagulant therapy (e.g., heparin and then warfarin) to prevent clot reoccur- rence but carries the risk of bleeding complications and is contraindicated in many post-surgical patients. Anticoagulation with unfractionated or low-molecular weight heparin is frequently employed to prevent addi- tional clot burden when signs of right heart strain are absent. Surgical interruption of the vena cava or