HomeworkAssigned on 13 February 2015By: Nadya Zaragita

Pathogenesis and Pathophysiology of Pleural Effusion and Diseases and Conditions that can Cause Pleural Effusion

Pleural effusion is a condition of excess fluid accumulation within the pleural cavity. Under normal circumstances, pleural fluid is maintained within, approximately, 20cc. However, under condition of increase fluid production or decreased pleural fluid absorption or both, abnormal fluid accumulation can occur.

Small pleural effusions may not affect lung function and go undetected. Most will be removed by the lymphatic system once the underlying condition is resolved. Like pneumothorax, larger pleural effusions can cause compression atelectasis and displace mediastinal contents. Unlike pneumothorax, however, pleural effusion does not cause the lung to collapse. Because there is no communication between the pleural space and environmental air, pressure in the pleural space remains negative and atelectasis is caused solely by pressure exerted by the effusion.

The most common symptom associated with pleural effusion is dyspnea. Pleuritic chest pain may be present if the pleura is inflamed. Physical examination usually reveals decreased breath sounds and dullness to percussion on the affected side, and a pleural friction rub may be heard. In large, rapidly developing effusions, compression atelectasis may cause hypoxemia and mediastinal shift. Inability to expand the lungs may impair ventilation, leading to hypercapnia.

There are two types of fluid that can be found when pleural effusion occurs; they are transudate and exudate. Transudative fluid usually indicates that there are systemic factors that alter the fluid production and absorption, while exudative fluid is usually caused by local factors.

Transudative pleural effusion can be caused by:1. Congestive heart

failure2. Cirrhosis3. Pulmonary

embolization4. Nephrotic syndrome

5. Peritoneal dialysis6. Superior vena cava

obstruction7. Myxedema8. Urinothorax

Exudative pleural effusion can be caused by:1. Neoplastic diseases:

metastatic disease, mesothelioma

2. Infectious diseases: bacterial infections, tuberculosis, fungal infections, viral infections, parasitic infections

3. Pulmonary embolization

4. Gastrointestinal disease

5. Collagen vascular disease

6. Post-coronary artery bypass surgery

7. Asbestos exposure8. Sarcoidosis9. Uremia

10. Meig’s syndrome11. Yellow nail

syndrome12. Drug-induced

pleural disease: Nitrofurantioin, Dantrolene

13. Trapped lung14. Radiation therapy15. Post-cardiac

injury syndrome16. Hemothorax17. Iatrogenic injury18. Ovarian

hyperstimulation syndrome

19. Pericardial disease

20. Chylothorax

EFFUSION DUE TO HEART FAILUREThe effusion occurs due to the increased amounts of fluid

in the lung interstitial spaces exit in part across the visceral pleura; this overwhelms the capacity of the lymphatics in the parietal pleura to remove fluid.

HEPATIC HYDROTHORAXThis occurs due to the movement of peritoneal fluid

through small openings in the diaphragm into pleural space. The effusion is usually right sided and frequently is large enough to produce severe dyspnea.

PARAPNEUMONIC EFFUSIONParapneumonic effusions are associated with bacterial

pneumonia, lung abscess, or bronchiectasis. Patients with aerobic bacterial pneumonia and pleural effusion present with an acute febrile illness consisting of chest pain, sputum production, and leukocytosis. Patients with anaerobic infections present with a subacute illness with weight loss, a brisk leukocytosis, mild anemia, and a history of some factor that predisposes them to aspiration.

The presence of free pleural fluid can be confirmed by lateral decubitus radiograph, CT of the chest, or ultrasound. If the free fluid separates the lung from the chest wall by >10mm, a therapeutic thoracentesis should be performed.

EFFUSION SECONDARY TO MALIGNANCYThe three tumors that cause ~75% of all malignant pleural

effusions are lung carcinoma, breast carcinoma, and lymphoma. Most patients complain of dyspnea, which is frequently out of proportion to the size of the effusion. The pleural fluid is an exudate and its glucose level may be reduced if the tumor burden in the pleural space is high. The diagnosis is made via cytology of the pleural fluid.

MESOTHELIOMAMalignant mesotheliomas are primary tumors that arise

from the mesothelial cells that line the pleural cavities; most are related to asbestos exposure. Patients with mesothelioma present with chest pain and shortness of breath.

Fungal pleural effusions

Fungal diseases account for only 1 percent of all pleural effusions. The most common cause is Aspergillus infection (usually A. fumigatus), which invades the pleural cavity via a bronchopleural fistula complicating lung resection or reactivation tuberculosis.

The signs and symptoms mimic chronic bacterial infection of the pleura. In pleural fluid, clumps of hyphae appear as brown suspended particles, and their gross appearance raises a suspicion of aspergillosis. In patients with pleural aspergillosis, precipitating antibodies in the serumand the wheal and flare cutaneous reaction are almost always positive.

Optimal therapy consists of surgical evacuation of the pleural cavity, closure or excision of the bronchopleural fistula,

and administration of amphotericin B systemically. An entirely different expression of Aspergillus infection is localized pleural thickening developing in the vicinity of an Aspergillusmycetoma.

Approximately 20 percent of patients with acute Coccidioides immitis infection show evidence of pleural disease on the chest radiograph, and 70 percent complain of pleuritic chest pain. Free fluid in the pleural cavity is demonstrable in approximately 7 percent of patients. The patients are almost always febrile, and about one-half have either erythema nodosum or erythema multiforme. In about 50 percent of patients, parenchymal infiltrates accompany the pleural effusion.

The effusions are usually unilateral. Examination of the pleural fluid reveals a predominance of lymphocytes on the white cell count, a glucose concentration greater than 60 mg/dl, and, rarely, eosinophilia. Pleural fluid cultures are positive for C. immitis in 20 percent of patients; culture of the pleural biopsy specimen has a much higher yield.

Complement fixation titers higher than 1:16 are common even when the disease is not disseminated. Most patients with primary coccidioidomycosis and pleural effusion do not require systemic antifungal therapy.

Cryptococcosis is another rare cause of pleural effusion. Pleural cryptococcosis appears to result from extension of a primary subpleural cryptococcal infection into the pleural space. More than half of the patients have serious underlying disease, most often leukemia, lymphoma, or the acquired immunodeficiency syndrome (AIDS).

The pleural effusion is usually unilateral; cultures are positive for the organism in approximately 50 percent of patients. Cryptococcal pleural effusions have high titers of cryptococcal antigen. Patients with serious coexisting disease should receive amphotericin B and 5-fluorocytosine. However, immunocompetent patients may recover without specific therapy.

Histoplasmosis rarely produces pleural effusions, i.e., less than 1 percent of patients with histoplasmosis manifest pleural fluid radiographically.Treatment is unnecessary, since the effusion usually resolves spontaneously in several weeks.

Chylothorax

A chylothorax occurs when the thoracic duct is disrupted and chyle accumulates in the pleural space. The most common cause of chylothorax is trauma (most frequently thoracic surgery), but it also may result from tumors in the mediastinum.

Patients with chylothorax present with dyspnea, and a large pleural effusion is present on the chest radiograph.

Thoracentesis reveals milky fluid, and biochemical analysis reveals a triglyceride level that exceeds 1.2 mmol/L (110 mg/dL). Patients with chylothorax and no obvious trauma should have a lymphangiogram and a mediastinal CT scan to assess the mediastinum for lymph nodes.

The treatment of choice for most chylothoraxes is insertion of a chest tube plus the administration of octreotide. If these modalities fail, a pleuroperitoneal shunt should be placed unless the patient has chylous ascites. An alternative treatment is ligation of the thoracic duct. Patients with chylothoraxes should not undergo prolonged tube thoracostomy with chest tube drainage because this will lead to malnutrition and immunologic incompetence.

Open Pneumothorax

Open pneumothorax is a pneumothorax involving an unsealed opening in the chest wall, when the opening is sufficiently large, respiratory mechanics are impaired.

Some patients with traumatic pneumothorax have an unsealed opening in the chest wall. When patients with an open pneumothorax inhale, the negative intrathoracic pressure generated by the inspiration causes air to flow into the lungs through the trachea and simultaneously into the intrapleural space through the chest wall defect. There is little airflow through small chest wall defects and hence few adverse effects. However, when the opening in the chest wall is sufficiently large (about 2/3 of trachea’s diameter or more), more air passes through the chest wall defect than through the trachea into the lung. Larger defects can eliminate ventilation on the affected side. Inability to ventilate the lungs causes respiratory distress and respiratory failure.

In awake patients, the chest wound is painful and patients have respiratory distress and other manifestations of pneumothorax. The air entering the wound typically makes a characteristic sucking sound.

Diagnosis is made clinically and requires inspecting the entire chest wall structure.

Immediate management is to cover the wound with a rectangular sterile occlusive dressing that is closed securely on only 3 sides. Thus, the dressing prevents atmospheric air from entering the chest wall during inspiration but allows any intrapleural air out during expiration. Tube thoracostomy should be done when the patient is stabilized. The wound may require later surgical repair.

Reference:1. Harrison’s Principle of Internal Medicine2. Fishman’s Pulmonary Diseases and Disorders3. Merck’s Manuals4. McCance’s Pathophysiology: The Biologic Basis for Disease in

Adults and Children