1. Pleural Effusion
Accumulation of fluid within the visceral and parietal layers of the pleura when there is an imbalance between formation and absorption in various disease states.
Normal amount 8.4 ml per hemithorax with a WBC count of 1700 per c.mm 75% of which are macrophages and 23% lymphocytes.Protein concentration is low about 15% of plasma protein concentration.
High reserve for rate of absorption if excess fluid is introduced into the pleura in normal states, fluid is absorbed into the lymphatic spaces of the parietal pleura.thought to be formed also by the parietal pleura.

2. Pleural Effusion
Origin from systemic circulation of the pleura, absorption is into the lymphatic spaces of the parietal pleura.
Rate of formation equals the rate of absorption which is about 0.01 – 0.02 ml/kg per hr.

3. Exudates Vs transudates
Light’s criteria
Pleural fluid protein/serum protein >0.5
Pleural fluid LDH/serum LDH >0.6
Pleural fluid LDH more than two-thirds normal upper limit for serum
Pleural fluid cholesterol >60mg/dl
Serum albumin and pleural fluid albumin </= 1.2 mg/dl

4. Transudative Pleural effusions
Congestive heart failure
Cirrhosis
Pulmonary embolism
Nephrotic syndrome
Peritoneal dialysis
Superior vena cava obstruction
Myxedema
Urinothorax

5. Exudative Pleural Effusions
Neoplastic diseases
Metastatic disease
Mesothelioma
Infectious diseases
Bacterial infections
Tuberculosis
Fungal infections
Viral infections
Parasitic infections

6. Exudative Pleural Effusions
Pulmonary embolization
Gastrointestinal disease
Esophageal perforation
Pancreatic disease
Intraabdominal abscesses
Diaphragmatic hernia
After abdominal surgery
Endoscopic variceal sclerotherapy
After liver transplant

7. Exudative Pleural Effusions
Collagen-vascular diseases
Rheumatoid pleuritis
Systemic lupus erythematosus
Drug-induced lupus
Immunoblastic lymphadenopathy
Sjögren's syndrome
Wegener's granulomatosis
Churg-Strauss syndrome

8. Exudative Pleural Effusions
Post-coronary artery bypass surgery
Asbestos exposure
Sarcoidosis
Uremia
Meigs' syndrome
Yellow nail syndrome

9. Exudative Pleural Effusions
Trapped lung
Radiation therapy
Post-cardiac injury syndrome
Hemothorax
Iatrogenic injury
Ovarian hyperstimulation syndrome
Pericardial disease
Chylothorax

10. Exudative Pleural Effusions
Drug-induced pleural disease
Nitrofurantoin
Dantrolene
Methysergide
Bromocriptine
Procarbazine
Amiodarone

11. Leading causes of pleural effusion in US
In decreasing order of incidence
Congestive heart failure
Pneumonia
Cancer
Pulmonary embolism
Viral disease
CABG
Cirrhosis with ascitis

12. How to Approach
The diagnostic workup of a patient with a pleural effusion will depend on the probable causes of the condition in that patient
History and physical are critical .
History should focus obviously atleast on the most common etiologies along with occupatioal, smoking, drug exposure (prescription, OTC and illicit) Sexual history, FH, their origin, travel history,sick contacts, hospitalisations, transfusions, Health maintenance status, immunizations.

13. How to Approach
Physical Examination with particular attention to respiratory system
Dullness to percussion, absence of fremitus and diminished or absence of breath sounds.

14. Clues in the physical to the common etiologies
Distended neck veins, an S3 gallop, or peripheral edema suggests congestive heart failure.
A right ventricular heave or thrombophlebitis and sinus tachycardia suggests pulmonary embolus.
The presence of lymphadenopathy or hepatosplenomegaly suggests neoplastic disease.
Ascites may suggest a hepatic cause.
Signs of consolidation above the level of the fluid in a febrile patient suggests parapneumonic effusion.

15. Role Of Imaging
Detection and the differential diagnosis are highly dependent upon imaging of the pleural space.
conventional radiographic methods used are frontal, lateral, oblique and decubitus radiographs.
Because of gravity, fluid accumulates in subpulmoniclocation and then spills over into the costophrenic sulcus posteriorly, anteriorly, and laterally and then surrounds the lung forming a cylinder, seen as a meniscoid arc.

16. Location of effusion-amount of fluid
75 mL-subpulmonic space without spillover, can obliterate the posterior costophrenic sulcus,
175 mL is necessary to obscure the lateral costophrenic sulcus on an upright chest radiograph
500 mL will obscure the diaphragmatic contour on an upright chest radiograph;
1000 ml of effusion reaches the level of the fourth anterior rib,
On decubitus radiographs and CT scans, less than 10 mL, and possibly as little as 2 mL, can be identified

17. Quantitation of effusion
Based on the decubitus films
small effusions are thinner than 1.5 cm, moderate effusions are 1.5 to 4.5 cm thick, and large effusions exceed 4.5 cm.
Effusions thicker than one cm are usually large enough for sampling by thoracentesis, since at least 200 mL of liquid are already present

18. Imaging contd., Role of CT scan Role of ultrasonography
Visualization of underlying lung parenchymal processes that are obscured on chest radiographs by large pleural effusions
Role of ultrasonography
free vs loculated pleural effusions, and iloculated effusions vs solid masses.
Thoracentesis of loculated pleural effusions is facilitated by ultrasound marking or guidance.

19. Imaging contd., Role of MRI
can display pleural effusions, pleural tumors, and chest wall invasion.
can characterize the content of pleural effusions.
Can determine the age of the hemorrhage.

20. Diagnostic thoracentesis
Indicated if the effusion is clinically significant with no known cause.

21. Thoracentesis.,
Also indicated in a patient with CHF if any of the following are present.
A unilateral effusion, particularly if it is left-sided,
Bilateral effusions, but are of disparate sizes
There is evidence of pleurisy or fever
The cardiac silhouette appears normal on CXR
If no response to diuresis in hrs.
The alveolar-arterial oxygen gradient is widened out of proportion to the clinical setting

22. Thoracentesis., Contraindications None obsulute. Relative include
Patient on anticoagulation or with bleeding diathesis
Very small volume of fluid.
Patients are mechanical ventilation though not at increased risk for pneumothorax are at high risk for tension pneumothorax or persistent airleak.
Active skin infection at the port of entry.

23. Thoracentesis., Procedure. Post procedure CXR
Indicated only if air is obtained during the procedure or if cough, pain or dyspnea develops.
Complications. pain, bleeding (hematoma, hemothorax, or hemoperitoneum), pneumothorax, empyema, soft tissue infection, spleen or liver puncture, vasovagal events, seeding the needle tract with tumor, and adverse reactions to lidocaine or topical antiseptic solutions,retained intrapleural catheter fragments.

24. Appearance of the fluid.
Bloody- Cancer, PE, Trauma, Pneumonia in that order
Turbid- either due to cells or debris or a high lipid level.
Putrid odour- Anaerobic infection.
Ammonia odour- urinothorax

25. Further work up based on…
The appearance
Bloody – Hematocrit compared to the blood
<1% is nonsignificant
1-20% indicates either cancer, PE or trauma
>50% indicates hemothorax.
Cloudy or Turbid – Centrifugation
Turbid supernatant indicates high lipid levels
Check TG - >110mg/dl – chylothorax
If TG>50mg/dl and cholesterol>250 - pseudochylothorax
Putrid odour – Stain and Culture

26. Further work up based on…
Exudate or transudate.
If transudative, rule out a diagnosis of congestive heart failure, cirrhosis, or pulmonary embolism.
If exudative send for total and differential cell counts, smears and cultures for organisms, measurement of glucose and lactate dehydrogenase levels, cytologic analysis, and testing for a pleural-fluid marker of tuberculosis.

27. Total and Differential Cell Counts
Predominance of neutrophils in the fluid >50% indicates that an acute process is affecting the pleura.
Common causes include
parapneumonic effusions (81 percent),
effusions secondary to pulmonary embolus (80 percent), and
those secondary to pancreatitis(80 percent).

28. Total and Differential Cell Counts
Mononuclear cells like small lymphocytes >50% indicates a chronic process.
cancer or tuberculous pleuritis,
effusions after coronary-artery bypass surgery.
Pleural-fluid eosinophilia >10%
caused in about two thirds of cases by blood or air in the pleural space.
uncommon in cancer or tuberculosis, unless the patient has undergone repeated thoracenteses
Unusual causes include reactions to drugs (dantrolene, bromocriptine, or nitrofurantoin), exposure to asbestos, paragonimiasis, and the Churg–Strauss syndrome.

29. Smears and Cultures
Gram's staining and culture for both aerobic and anaerobic bacteria
Yield is increased if blood-culture bottles are inoculated at the bedside.
If mycobacterial or fungal infection is suspected (>50% lymphs or a chronic febrile illness) -cultures for these organisms are indicated.
Smears may reveal fungi, but smears for mycobacteria are rarely positive unless the patient has a tuberculous empyema or the acquired immunodeficiency syndrome.

30. Glucose Level
low glucose concentration (< 60 mg per dl) indicates a complicated parapneumonic or a malignant effusion.
less common are hemothorax, tuberculosis, rheumatoid pleuritis,
more rarely, Churg–Strauss syndrome, paragonimiasis, and lupus pleuritis.

31. Lactate Dehydrogenase Level
The level correlates with the degree of inflammation and should be measured each time fluid is sampled from an effusion whose cause has not been determined.
If increasing with repeated thoracentesis suggests that the degree of inflammation is increasing, and a diagnosis should be aggressively pursued.
Conversely, if the lactate dehydrogenase decreasing with repeated thoracentesis, a less aggressive diagnostic approach may be considered.

32. Fluid Tests for Cancer
Cytology is a fast, efficient, and minimally invasive
not routinely warranted in young patients with evidence of acute illness.
establishes the diagnosis in more than 70 percent of cases of metastatic adenocarcinoma
less efficient in the diagnosis of a mesothelioma squamous cell carcinoma, lymphoma or a sarcoma.
If cytology is negative – go for thoracoscopy and not a blind needle biopsy ( adds little to cytologic analysis)
If lymphoma is suspected, flow cytometry can establish the diagnosis by demonstrating the presence of a clonal cell population

33. Markers of Tuberculosis
warranted if there is pleural fluid lymphocytosis.
< 40 % have positive cultures, hence alternative means are used.
adenosine deaminase (>40 U/L) (99.6% sensitive and 97.1 % specific)) or
Interferon (>140 pg/ml) comparable to ADA or
the PCR for mycobacterial DNA – definitive for TB.

34. Other Tests indicated in specific situations.
pH (with the use of a blood-gas machine) is warranted if a parapneumonic or malignant effusion is suspected.
pH below 7.20
in a parapneumonic effusion indicates the need for drainage of the fluid.
in a malignant effusion suggests that the patient's life expectancy is only about 30 days and that chemical pleurodesis is likely to be ineffective.

35. Other tests…,
Amylase only if there are clinical symptoms or if the history suggests pancreatic disease or esophageal rupture in which they are high.
Immunologic tests such as antinuclear antibody titers or rheumatoid factor levels, add little diagnostic information, have high false positive rates.
the diagnosis of lupus pleuritis or rheumatoid pleuritis is established by the clinical picture and the antinuclear antibody and rheumatoid factor levels in the serum.

36. Evaluation for Pulmonary Embolism
Always consider if pleuritic chest pain, hemoptysis, or dyspnea out of proportion to the size of theeffusion.
D-dimer in the peripheral blood is the best screening test .
If a sensitive D-dimer test is used and it is negative, the diagnosis of pulmonary embolism is essentially ruled out.
If the D-dimer test is positive, then additional specific diagnostic testing — such as duplex ultrasonography of the legs, spiral CT, perfusion scanning of the lungs, or pulmonary arteriography — is necessary to establish the diagnosis.

37. The undiagnosed effusion.
No known etiology found in a substantial percentage of patients with exudative effusions
If the effusion persists despite conservative treatment, thoracoscopy should be considered, since it has a high yield for cancer or tuberculosis.
If thoracoscopy is unavailable, alternative invasive approaches are needle biopsy and open biopsy of the pleura.
No diagnosis is ever established for approximately 15 percent of patients despite invasive procedures.

38. The undiagnosed effusion…,
Time Course —the time required for resolution varies depending upon the underlying etiology.
Pulmonary embolism — five to seven days without infarction; seven to 14 days with radiographic infarction.
Uncomplicated parapneumonic effusions — one to two weeks.
Benign asbestos pleural effusion, rheumatoid pleurisy, and radiation pleuritis — months.

39. Time Course.., Tuberculous pleurisy — six weeks to four months
Postcardiac injury syndrome — several weeks.
following abdominal surgery and in the post partum period – usually small effusions – few weeks.
Malignant pleural effusions, on the other hand, do not resolve spontaneously.
Pleural effusions that persist for years are caused only by yellow-nail syndrome, trapped lung , and pulmonary lymphangiectasia producing chylothorax as occurs in Noonan's syndrome

40. Areas of Uncertainty
Whether the use of ultrasonography as an aid in performing thoracentesis decreases the likelihood of pneumothorax.
Which is the best approach in diagnosing pulmonary embolus in patients with an effusion.
Whether patients with a lymphocytic effusion should be treated for pleural tuberculosis solely on the basis of an elevated level of adenosine deaminase in the fluid.
Which is the most cost effective approach in working up an undiagnosed effusion.

41. Recap…, If an effusion is present? Is it significant?, if not observe.
If yes, does the patient have CHF?
If not --- thoracentesis.
If yes.. Are they asymmetric? any chest pain? Fever?
If not diurese and observe.. If no response in 3 days – thoracentesis.
If yes—thoracentesis.

42. Recap..,
Thoracentesis
Transudate- treat cardiosis, cirrhosis, nephrosis.
Exudate- cell count, glucose, cytology and culture.
If lymphocytic– markers for TB
If no cause– evaluate for PE( or earlier if clinical situation was suggestive)