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PHYSIOLOGY OF PLEURAL
FLUID PRODUCTION AND
BENIGN PLEURAL EFFUSION.
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.
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-0.01 ml/kg per hour.
Fig. 57-1.
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.
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--- 0.2-0.28 ml/kg per hour.
• Lymphatic clearance--- 28 times as high as the
normal rate of pleural fluid formation.
DIFFERENTIAL DIAGNOSIS Table 57-1
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.
DIFFERENTIAL DIAGNOSIS
• The difference between the serum and pleural fluid
albumin exceeds 1.2--- 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.
Pleural fluid--- WBC count and
differential
• Greater than 10000 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.
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.
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.
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.
Pleural fluid--- cytology
• Establishing the diagnosis of malignant pleural
effusion--- 40-90%.
• 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.
Pleural effusion--- bacteriology
• Culture and bateriologic stain--- culture
both aeobic and anaerobic, mycobacteria,
fungi.
• Gram’s stain.
Pleural fluid--- pH and pCO2
• Less than 7--- Complicated parapneumonic
effusion and tube thoracostomy should
instituted.
• Less than 7.2--- systemic acidosis,
esophageal rupture, rheumatoid pleuritis,
tuberculosis pleuritis, malignant pleural
disease,
hemothorax,
paragonimiasis,
Churg-Strauss syndrome.
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.
Pleural fluid
• Other diagnostic test on pleural fluid--cloudy.
• Chylothorax---Triglycerides > 110 mg/dl,
• Pseudochylothorax--- the level of
cholesterol increase.
INVASIVE TEST FOR UNDIAGNOSED
EXUDATIVE PLEURAL EFFUSIONS
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20% exudates--- no diagnosis.
Needle biopsy.
Thoracoscopy.
Bronchoscopy.
Open biopsy of the lung.
Needle biopsy of pleura
• For diagnosis of Tuberculous pleuritis,
malignant pleural disease.
• The needle biopsy usually negative when
negative cytology result.
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).
Bronchoscopy
• Not all need.
• Only used at patient with
1) parenchyma abnormality.
2) Hemoptysis.
Open biopsy of the lung
• Provide the best biopsy specimens.
• Has been replaced by VATS.
TRANSUDATIVE PLEURAL
EFFUSIONS.
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Hepatic hydrothorax.
Nephritic syndrome.
Congestive heart failure.
Peritoneal dialysis.
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.
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.
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.
Nephritic syndrome
• Decrease plasma oncotic pressure.
• 20%.
• Treatment--- increase level of serum protein.
Peritoneal dialysis
• Diaphragm defect.
• Treatment--1). Chemical pleurodesis.
2). Short period of small-volume,
intermittent peritoneal dialysis.
EXUDATIVE PLEURAL
EFFUSIONS
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Pulmonary embolization.
Esophageal perforation.
Acute pancreatitis.
Chronic pancreatic disease.
Intra-abdominal abscess.
Pulmonary embolization
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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.
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.
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.
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.)
Intra-abdominal abscess
• Subphrenic, pancreatic, intrasplenic,
intrahepaic.
• Dx--- pleural fluid predominantly neutrophil,
CT, antibiotics and drainage.
PLEURAL EFFUSION AFTER
SURGICAL PROCEDURE
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After cardiac injury.
After CABG.
After Fontan procedure.
After abdominal surgery.
After endoscopic variceal sclerotherapy.
After liver transplantation.
After lung transplantation.
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.
After CABG
• Small pleural effusion, high prevalence,
（40%.）
• Pathogenesis--- unknown, may pericardial
inflammation.
• Left side, resolve spontaneously.
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,
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.
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.
After endoscopic variceal
sclerotherapy
• 50%.
• Extravasation of sclerosant into esophageal
mucosa, intense inflammatory reaction.
• Exudative.
• Persist 24-48 hours, accompanied by fever.
• Tx--- thoracentesis.
After liver transplantation
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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.
After lung transplantation
• Fluid leave lung via lymphatics exits into
pleural space.
• 400 ml/day, up to 1000 ml.
• Chest tube drainage.
Rheumatoid
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Glucose--- less than 30 mg/dl.
High LDH--- 700IU/l.
Low pH--- less than 7.2.
Resolves spontaneously within 3 months.
Lupus erythematosus
• 40%.
• Tx--- Prednisolone, 80 mg/day.
Asbestos exposure
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3%.
Need exudates 5-20 years.
Always asymptomatic.
Dx: exposure, exclusion other cause.
Follow up at least 2 year.
Drug reaction
• Nitrofurantoin
Dantrolene
Methysergide
Bromocriptine
• Tx--- discontnuation the drug.
Uremia
• 3%.
• Exudates.
• No relationship between degree of uremia
and occurrence of pleural effusion.
• Disappear within 4-6 week after dialysis.