1. PHYSIOLOGY OF PLEURAL FLUID PRODUCTION AND BENIGN PLEURAL EFFUSION.

2. Pleural Effusion
More than 1 million case of pleural effusion occurred annually in US.
On lateral decubitus chest radiography, the distance between inside of chest wall and out side of lung is greater than 10 mm, diagnostic thoracentesis is indicated.

3. FORMATION AND RESORPTION OF PLEURAL EFFUSION.
Pleural effusion have several origins---
1).Capillary in parietal and visceral pleura.
2).Interstitial space of lung.
3).Peritoneal cavity--- Through small hole
in diaphragm.
Rate entry into the pleural space in normal ml/kg per hour.

4. Fig

5. Pleural Effusion
Capillary origin--- Starling law of transcapillary exchange: Qf=Lp x A【（Pcap-Ppl）-σd（πcap-πpl）】.
Interstitial origin---exudate , increased permeability, pulmonary edema also originate from lung interstitium.
Peritoneal origin--- Cirrhosis and ascites, pancreatic ascites, Meigs’ syndrome, peritoneal dialysis.

6. Pleural Effusion
Lymphatic clearance--- the lack of fluid accumulation in pleural cavity normally.
The pleural space--- communication with lymphatic vessels by stomas located in parietal pleura., removed the protein, cell, particle matter.
Clearance rate ml/kg per hour.
Lymphatic clearance times as high as the normal rate of pleural fluid formation.

7. DIFFERENTIAL DIAGNOSIS Table 57-1

8. DIFFERENTIAL DIAGNOSIS
Transudate--- Increase hydrostatic pressure or decrease oncotic pressure.
Exudates--- Increase permeability.
Three criteria--- The exudates meet at least one, the transudate meet none :
1) pleural fluid protein/ serum protein > 0.5
2) pleural fluid LDH/ serum LDH > 0.6.
3) pleural fluid LDH > 2/3 upper normal limit
for serum LDH.

9. DIFFERENTIAL DIAGNOSIS
The difference between the serum and pleural fluid albumin exceeds Transudate.
Pneumonia, malignancy, pulmonary embolism account the great majority of all exudates.
Undiagnosed exudates : Check glucose level, amylase, LDH, diffrential cell count, microbiological studies, cytoloty, pH, adenosine deaminase（ADA）, interferon-γ, polymerase chain reaction（PCR）for tuberculosis DNA, lipid analysis.
Gross appearance of pleural effusion and odor.
Hematocrit over 50%--- Hemothorax.

10. Pleural fluid--- WBC count and differential
Greater than per μL--- Parapneumonic effusion, pancreatitis, pulmonary embolism, collagen vascular disease, malignancy, tuberculosis.
Polymorphonuclear（PMN） leukocytosis--- Acute disease such as pneumonia, pulmonary embolism, pancreatitis, intra-abdomen abscess, early tuberculosis.
Mononuclear cell--- Malignancy, tuberculosis, resolving acute process.
Eosinophil--- Benign asbestos, drug reaction as nitrofurantoin, bromocriptine, dantrolene, paragonimiasis（low glucose, low pH, high LDH）.
More than 50% WBC in exudates are small lymphocyte--- malignancy or tuberculosis.

11. Pleural fluid--- glucose
Less than 60 mg/dL--- parapneumonic effusion or empyema, malignant effusion, tuberculosis effusion, rheumatoid effusion（usually less than 30）, hemothorax, paragonimiasis effusion, Churg-Strauss syndrome.
Less than 40 mg/dL--- Tube thoracostomy should be performed.

12. Pleural fluid--- amylase
Elevated above the upper normal limit of serum amylase---- Esophageal perforation（from salivary）, pancreatic disease, malignancy（10%）.
Acute pancreatitis accompanying pleural effusion--- 10%.
Chronic pancreatic disease may develop a sinus tract between the pancrease and the pleura space.
The amylase associated with malignancy--- salivary type.

13. Pleural fluid--- lactic acid dehydrogenase
Pleural fluid lactic acid dehydrogenase---good indicator of the degree of inflammation in pleural space.
LDH increase, the inflammation worsening.

14. Pleural fluid--- cytology
Establishing the diagnosis of malignant pleural effusion %.
Depending on--- the tumor type, amount of fluid, skill of cytologist.
Cytology result usually positive if the primary tumor is adnocarcinoma, usually not positive if the primary tumor is squamous cell carcinoma, lymphoma, mesothelioma.
Immunohistochemical test using monoclonal antibody--- differentiate adenocarcnoma, benign mesothelial and malignant methelial cell.

15. Pleural effusion--- bacteriology
Culture and bateriologic stain--- culture both aeobic and anaerobic, mycobacteria, fungi.
Gram’s stain.

16. Pleural fluid--- pH and pCO2
Less than 7--- Complicated parapneumonic effusion and tube thoracostomy should instituted.
Less than systemic acidosis, esophageal rupture, rheumatoid pleuritis, tuberculosis pleuritis, malignant pleural disease, hemothorax, paragonimiasis, Churg-Strauss syndrome.

17. Diagnosis of tuberculous pleuritis
ADA level, interferon-γ, PCR for tuberculosis DNA.
ADA level above 47 U/L, combined with pleural fluid lymphocyte/ neutrophil > 0.75（no commercial ） .
Interferon-γlevel > 3.7 U/ml.

18. Pleural fluid Other diagnostic test on pleural fluid--- cloudy.
Chylothorax---Triglycerides > 110 mg/dl,
Pseudochylothorax--- the level of cholesterol increase.

19. INVASIVE TEST FOR UNDIAGNOSED EXUDATIVE PLEURAL EFFUSIONS
20% exudates--- no diagnosis.
Needle biopsy.
Thoracoscopy.
Bronchoscopy.
Open biopsy of the lung.

20. Needle biopsy of pleura
For diagnosis of Tuberculous pleuritis, malignant pleural disease.
The needle biopsy usually negative when negative cytology result.

21. Thoracoscopy Direct visualized.
Became primary means of diagnosing pleural malignancy who have negative cytology result（95%）.
Insufflate talc at the time of thoracoscopy.
Video-Assisted Thoracoscopic Surgery. (VATS).

22. Bronchoscopy Not all need. Only used at patient with
1) parenchyma abnormality.
2) Hemoptysis.

23. Open biopsy of the lung Provide the best biopsy specimens.
Has been replaced by VATS.

24. TRANSUDATIVE PLEURAL EFFUSIONS.
Hepatic hydrothorax.
Nephritic syndrome.
Congestive heart failure.
Peritoneal dialysis.

25. Congestive heart failure
Bilateral, same size on each side.
Left ventricular or bi-ventricular failure.
Can be observed while the heart failure is treated and usually resolves.
Pleurodesis with sclerosing agent only if persistent pleural effusion despite intensive therapy of heart failure.

26. Hepatic hydrothorax
5%, direct movement of peritoneal fluid through small hole in diaphragm.
Usually right side, large.
Treatment--- reverse the liver disease, liver transplant, implantation of transjugular intrahepatic portal systemic shunt. Peritoneal jugular shunt.
Pleurodesis is contraindicated--- danger of hypovolemia.

27. Hepatic hydrothorax
Spontaneous bacterial empyema--- infection of hepatic hydrothorax.
13%.
Diagnosis criteria---
1). Positive pleural fluid culture.
2). Pleural fluid neutrophil greater than 250
cells/mL.
Treatment--- tube thoracostomy.

28. Nephritic syndrome Decrease plasma oncotic pressure. 20%.
Treatment--- increase level of serum protein.

29. Peritoneal dialysis Diaphragm defect. Treatment---
1). Chemical pleurodesis.
2). Short period of small-volume,
intermittent peritoneal dialysis.

30. EXUDATIVE PLEURAL EFFUSIONS
Pulmonary embolization.
Esophageal perforation.
Acute pancreatitis.
Chronic pancreatic disease.
Intra-abdominal abscess.

31. Pulmonary embolization
S/s--- dyspnea.
Less than 1/3 of hemithorax, bilateral.
Bloody or clear.
Neutrophil mostly, lymphocyte or mononuclear.
Dx--- lung scan, contrast-enhanced spiral CT, pulmonary arteriography.
Tx--- same with pulmonary emboli.

32. Esophageal perforation
Mortality 100% if not diagnosis in 48 hours.
S/s--- Acutely ill with chest pain, dyspnea, mediastinal and pleural effusion, subcutaneous emphysema.
Dx--- Level of amylase of pleural fluid, contrast studies.
Tx--- Exploration of mediastinum and primary repair esophageal tear, drainage, antibiotics, T-tube intubation.

33. Acute pancreatitis 50%, bilateral most.
S/s--- pleural chest pain, dyspnea.
Pancreatic pseudocyst--- high in pleural effusion.
Pleural effusion not resolve in 2 week---pancreatic abscess or pseudocyst is considered.

34. Chronic pancreatic disease.
Sinus tract through diaphragm into mediastinum and pleural cavity.
S/s--- chest pain, dyspnea, cough. Most without abdominal sign.
Left side, recurs rapidly after thoracentasis.
Dx--- high amylase in pleural effusion, ERCP.
Tx--- first 2-3 week conservative treatment, （NG tube, NPO, atropin, repeat thoracentasis, continuous infusion somatostatin）, failure then laparotomy, (ligated and excised sinus tract, partial pancreatectomy, Roux-en-Y loop.)

35. Intra-abdominal abscess
Subphrenic, pancreatic, intrasplenic, intrahepaic.
Dx--- pleural fluid predominantly neutrophil, CT, antibiotics and drainage.

36. PLEURAL EFFUSION AFTER SURGICAL PROCEDURE
After cardiac injury.
After CABG.
After Fontan procedure.
After abdominal surgery.
After endoscopic variceal sclerotherapy.
After liver transplantation.
After lung transplantation.

37. After cardiac injury
Postcardiac injury syndrome（Dressler’s syndrome）--- pericarditis, pleuritis, pneumonitis.
3 week after injury（3 day-1 year）.
Exudates, clear or bloody.
Tx--- anti-inflammatory agents（aspirin,
indomethacin,）.
Corticosteroid for CABG--- prevent
pericarditis and graft occlusion.

38. After CABG Small pleural effusion, high prevalence,（40%.）
Pathogenesis--- unknown, may pericardial inflammation.
Left side, resolve spontaneously.

39. After CABG Some massive pleural effusion, no clear-cut etiology.
Exudative.
Bloody--- Related to blood from surgery. Maximal size in 30 day, peripheral eosinophilia, high fluid LDH, responded with thoracenteses.
Non-bloody--- More than 30 days, more than 50% small lymphocyte, low LDH, more difficult mamage, require pleurodesis,

40. After Fontan procedure
Fontan procedure--- right ventricle is bypassed by an anastomosis between superior vena cava, the right atrium, inferior vena cava and the pulmonary artery.
Usually performed for tricuspid atresia or univentricular heart.
Transudate pleural effusion.
Occurred in all patient, most occurred in patient with significant aortopulmonary collateral vessels preoperatively..
Tx--- inserting pleuroperitoneal shunt, creation of a late fenestration.

41. After abdominal surgery
50%, 2-3 day after operation.
High incidence in upper abdomen surgery, postoperative atelectasis, free abdominal fluid at surgery.
Cause--- diaphragm irritation trans-diaphragm movement of intra-abdomen fluid.
Thoracenteses--- R/O pleural infection.
More than 72 hours post operatively, not related to surgical procedure, may due to pulmonary embolism, intra-abdominal abscess, hypervolemia.

42. After endoscopic variceal sclerotherapy
50%.
Extravasation of sclerosant into esophageal mucosa, intense inflammatory reaction.
Exudative.
Persist hours, accompanied by fever.
Tx--- thoracentesis.

43. After liver transplantation
Right side, within 72 hr.
Large enough for respiratory compromised,
Tube thoracostomy.
Etiology unknown, may irritation the right hemidiaphragm by extent right upper quadrant dissection and retraction.
Prevent by fibrin sealant.

44. After lung transplantation
Fluid leave lung via lymphatics exits into pleural space.
400 ml/day, up to 1000 ml.
Chest tube drainage.

45. Rheumatoid Glucose--- less than 30 mg/dl. High LDH--- 700IU/l.
Low pH--- less than 7.2.
Resolves spontaneously within 3 months.

46. Lupus erythematosus
40%.
Tx--- Prednisolone, 80 mg/day.

47. Asbestos exposure 3%. Need exudates 5-20 years. Always asymptomatic.
Dx: exposure, exclusion other cause.
Follow up at least 2 year.

48. Drug reaction Nitrofurantoin Dantrolene Methysergide Bromocriptine
Tx--- discontnuation the drug.

49. Uremia
3%.
Exudates.
No relationship between degree of uremia and occurrence of pleural effusion.
Disappear within 4-6 week after dialysis.