TRANSUDATES AND MODIFIED TRANSUDATES

Pure transudates are fluids with low protein concentrations of less than 2.5 to 3 g/dl and low nucleated cell counts of less than 500 to 1000/μl. The primary cell types are mononuclear cells, composed of macrophages, lymphocytes, and mesothelial cells. Modified transudates have a slightly higher protein concentration of up to 3.5 g/dl and nucleated cell counts of up to 5000/μl. The primary cell types include neutrophils as well as mononuclear cells.

Transudates and modified transudates form as a result of increased hydrostatic pressure, decreased plasma oncotic pressure, or a lymphatic obstruction. Increased hydrostatic pressure occurs in association with right-sided congestive heart failure or pericardial disease. Physical examination findings such as abnormal jugular pulses, gallop rhythms, arrhythmias, or murmurs support a diagnosis of heart disease. Heart sounds may be muffled in animals with pericardial effusions. Thoracic radiography (after fluid removal), electrocardiography, and echocardiography are indicated for cardiac evaluation (see Chapter 2).

Decreased plasma oncotic pressure is a result of hypoalbuminemia. Effusions secondary to hypoalbuminemia alone are pure transudates, having very low protein concentrations. Subcutaneous edema may be detected in dependent areas of the body. A decreased production of albumin causes hypoalbuminemia in patients with liver disease, and an increased loss of albumin causes it in patients with glomerulopathies or protein-losing enteropathies. The total plasma protein concentration shown by refractometry during the initial evaluation of the dog or cat can provide an early indication of hypoalbuminemia. Serum biochemical analysis provides an exact measurement of the albumin concentration. In general, albumin concentrations must be lower than 1 g/dl before transudation occurs caused only because of hypoalbuminemia.

Lymphatic obstruction can be caused by neoplasia and diaphragmatic hernias. Diaphragmatic hernias should be suspected in any animal with a history of trauma. The trauma may have been recent or may have occurred years ago. Although a modified transudate usually forms as a result of chronic diaphragmatic hernia, an exudative fluid can also be found. Diaphragmatic hernias are identified by radiography or ultrasonography. Occasionally, it is necessary to administer barium orally and perform an upper gastrointestinal series or to intraperitoneally administer water-soluble iodinated contrast media and perform peritoneography to confirm the presence of a diaphragmatic hernia. Normal imaging findings do not entirely rule out the existence of a tear in the diaphragm, however.

Neoplasia must be considered as a differential diagnosis for patients with any type of effusion, although it is rare for a pure transudate to develop. (See the section on effusions caused by neoplasia for further discussion.)

SEPTIC AND NONSEPTIC EXUDATES

Exudates have a high protein concentration (greater than 3 g/dl) compared with that in transudates. Nucleated cell counts are also high (greater than 5000/μl). Cell types in nonseptic exudates include neutrophils, macrophages, eosinophils, and lymphocytes. The macrophages and lymphocytes may be activated, and typically the neutrophils are nonde generative. There is no evidence of organisms. Differential diagnoses in animals with nonseptic exudates include feline infectious peritonitis (FIP), neoplasia, chronic diaphragmatic hernia, lung lobe torsion, and resolving septic exudates. Prior treatment with antibiotics in animals with a septic effusion can alter the characteristics of the neutrophil population in the fluid, making them appear nondegenerative, and decrease the number of organisms present in the fluid to an undetectable level. Therefore pleural fluid analysis should be performed before treatment is initiated so that bacterial infection is not overlooked.

Cats with FIP can present with fever or chorioretinitis in addition to respiratory signs (see Chapter 97). The pleural fluid protein concentration is often very high in such animals, approaching serum concentrations. It is common to see fibrin strands or clots in the fluid. Careful cytologic evaluation of the fluid is essential to differentiate FIP fluid from exudates caused by pyothorax or malignant lymphoma. The evaluation of animals for diaphragmatic hernia was described in the previous section and is described for neoplasia in a following section (i.e., Effusion Caused by Neoplasia).

Spontaneous lung lobe torsions are most common in dogs with deep, narrow thoracic cavities. In addition to causing an effusion, torsions can be seen in dogs and cats secondary to pleural effusion. Underlying pulmonary disease resulting in lobe atelectasis can also contribute to the development of torsion. Torsion should be considered in animals with a preexisting effusion or pulmonary disease if their condition suddenly deteriorates. The effusion is often a nonseptic exudate, but it may be chylous or hemorrhagic. Signs of lung lobe torsion may be identified through thoracic radiography or ultrasonography (see Chapter 20). Bronchoscopy or thoracotomy is required to verify the condition in some animals.

Septic exudates often have extremely high nucleated cell counts (e.g., 50,000 to more than 100,000/μl), and degenerate neutrophils are the predominant cells. Bacteria can often be observed within neutrophils and macrophages as well as extracellularly (see Fig. 25-1). The fluid may have a foul odor. Septic exudates are diagnostic for pyothorax. Pyothorax can occur spontaneously, secondary to wounds that penetrate into the thoracic cavity through the chest wall or esophagus, secondary to migrating grass awns or other foreign bodies, or as an extension of bacterial pneumonia. Sterile technique should be used during thoracocentesis and chest tube placement in all animals with pleural effusion or pneumothorax to prevent iatrogenic infection.

Gram staining and both aerobic and anaerobic bacterial cultures with antibiotic sensitivity testing should be performed on the fluid. Culture and sensitivity testing provide valuable information that can be used for selecting appropriate antibiotics and monitoring therapy. Mixed bacterial infections are common. However, bacteria do not grow from cultures of all septic exudates, and results are not available for several days. Gram staining provides immediate information that can be used to help select antibiotics and is helpful in cases in which bacteria cannot be grown from the fluid.

CHYLOUS EFFUSIONS

Chylous effusion (chylothroax) results from the leakage of fluid from the thoracic duct, which carries lipid-rich lymph from the body. Such leakage can be idiopathic, congenital, or secondary to trauma, neoplasia, cardiac disease, pericardial disease, dirofilariasis, lung lobe torsion, or diaphragmatic hernia. Chyle is usually milky white and turbid (see Fig 23-1, E), largely as a result of chylomicrons that carry fats from the intestines. The fluid is occasionally blood tinged, although this finding may also be an artifact from prior thoracocentesis. It is also possible to obtain clear and colorless fluids, particularly in anorectic animals, but this is uncommon.

Chyle has the cytologic characteristics of a modified transudate or nonseptic exudate with moderate concentrations of protein, usually greater than 2.5 g/dl. The nucleated cell count is low to moderate, ranging from 400 to 10,000/μl. Early in the disease the predominant cell type is the small lymphocyte. A few neutrophils may also be present. With time, nondegenerative neutrophils become more predominant and there are fewer lymphocytes. Macrophages also increase in number with time, and plasma cells may be present.

A diagnosis of chylothorax is confirmed by measuring the concentrations of triglycerides in the pleural fluid and serum. Each specimen should be well mixed by the laboratory before a portion is analyzed because of the tendency for the lipid portion to rise to the surface. The triglyceride content in chyle is high compared with that in serum. Rarely, the test will need to be repeated after a meal in anorectic animals.

Most cases of chylothorax are idiopathic, but this diagnosis can be made only after the other disorders have been ruled out. Treatment is most likely to be successful if an underlying problem is identified and treated directly. (See Chapter 25 for a complete discussion of chylothorax.)

HEMORRHAGIC EFFUSIONS

Hemorrhagic effusions are grossly red as a result of the large red blood cell content. Hemorrhagic effusions have greater than 3 g/dl of protein and more than 1000 nucleated cells/μl, with a distribution similar to that of peripheral blood. Over time the numbers of neutrophils and macrophages increase. Hemorrhagic effusions (except those obtained immediately after bleeding into the thorax) are readily distinguished from the recovery of peripheral blood through traumatic thoracocentesis by several features: hemorrhagic effusions have erythrophagocytosis and an inflammatory response on cytologic evaluation, hemorrhagic effusions do not clot, and the packed cell volume (PCV) of hemorrhagic effusions is lower than that of peripheral blood.

Hypovolemia and anemia may contribute to the clinical signs of patients with hemothorax (see Chapter 26). Hemothorax can result from trauma, systemic bleeding disorders, neoplasia, and lung lobe torsion. Rarely, septic exudates are grossly hemorrhagic (see Fig 23-1, F) and are distinguished cytologically. Respiratory distress caused by hemothorax may be the only clinical sign in animals with some bleeding disorders, including rodenticide intoxication. An activated clotting time and platelet count should be performed early in the evaluation of these animals, followed by more specific clotting tests (i.e., prothrombin time and partial thromboplastin time). Hemangiosarcoma of the heart or lungs is a common neoplastic cause of a hemorrhagic effusion, but malignant cells are rarely identified cytologically. Neoplastic effusions are discussed further in the next section.

EFFUSIONS CAUSED BY NEOPLASIA

Neoplasia within the thoracic cavity can result in most types of effusion (modified transudates, exudates, chylous effusion, or hemorrhagic effusion). Neoplasms may involve any of the intrathoracic structures, including the lungs, mediastinal tissues, pleura, heart, and lymph nodes. In some cases, neoplastic cells exfoliate from the tumor into the effusion, and an early diagnosis can be made through fluid cytology. This is often possible in patients with mediastinal lymphoma. Unfortunately, other than in cases of lymphoma, it can be difficult or impossible to establish a definitive diagnosis of neoplasia on the basis of cytologic findings in the pleural fluid alone. Inflammation can result in considerable hyperplastic changes of mesothelial cells that are easily confused with neoplastic cells. A cytologic diagnosis of neoplasia other than lymphoma should be made with extreme caution.

In the majority of cases, neoplastic cells are not present in the fluid or a cytologic diagnosis cannot be made. Thoracic radiography and ultrasonography should be performed to evaluate the thorax for evidence of neoplasia (see Chapter 24). Ultrasonography can be used to differentiate localized accumulations of fluid from soft tissue masses. If soft tissue masses are detected, aspirates or biopsy specimens are obtained for cytologic or histopathologic evaluation. A definitive diagnosis cannot be made on the basis of the radiograph findings or ultrasound images alone.

Diffuse neoplastic infiltration of the pleura and some masses cannot be seen with these imaging techniques. Repeated thoracic radiography, computed tomography, thoracoscopy, or surgical exploration may be necessary in such cases.