2. Learning objects
1. Definition of Pleural Effusion, normal pleural fluid composition
2. Pathology and Etiology of Pleural Effusion
3. Symptoms and physical findings in patients with pleural effusion
4. Imaging and Investigations in patients with pleural effusion
5. Parapneumonic effusion and empyema:features and management
6. Tuberculous pleural effusion
7. Malignant pleural effusion: features and management
3. 1. Definition of Pleural Effusion, normal
pleural fluid composition
A pleural effusion is an accumulation of abnormal volumes
(>10–20mL) of fluid in the pleural space.
• The normal pleural space contains approximately 1-2 mL of fluid,
representing the balance between
• (1) hydrostatic and oncotic forces in the visceral and parietal pleural
• (2) extensive lymphatic drainage.
• Pleural effusions result from disruption of this balance.
• Pleural effusion is an indicator of an underlying disease process that
may be pulmonary or nonpulmonary in origin and may be acute or
4. Normal pleural fluid has the following
Clear ultrafiltrate of plasma that originates from the parietal pleura
Protein: < 2% (1-2 g/dL)
White blood cells (WBC): < 1000/mm³
RBC count < 5,000 cells/mm³
Glucose: similar to that of plasma
LDH: <50% plasma concentration
Amylase: 30-110 U/L
Triglycerides: <2 mmol/L
Cholesterol: 3.5–6.5 mmol/L
5. 2. Pathophysiology and Etiology of Pleural Effusion
Pathophysiology •↑ Capillary hydrostatic pressure
(increased capillary wedge pressure)
•↓ Capillary oncotic pressure
•↑ Capillary permeability (e.g., due to
Common causes of
pleural effusion •Congestive heart failure
•Chronic kidney disease (Na+
o Pneumonia (parapneumonic effusion)
o Pleural empyema
o Parasitic illness
•Trauma (high vascular permeability)
7. • Depending on the overall protein concentration of the pleural effusion, a distinction is
made between transudate (< 30 g/L) and exudate (> 30 g/L).
• Transudate is a clear fluid containing few cells. It can emerge, e.g., as a consequence of
stasis: due to the increased hydrostatic pressure, the fluid efflux from the capillaries
increases. Or the colloid osmotic pressure in the vessels may be decreased (e.g., in the
event of hypoalbuminemia), causing more fluid to leak.
• Transudative effusion is caused by systemic factors: either increased hydrostatic
pressure (e.g.,CHF) or decreased oncotic pressure (e.g., nephrotic syndrome or cirrhosis).
Because these diseases are systemic, they usually cause bilateral and equal effusion.
• A transudative effusion needs no further evaluation. It resolves by adequate treatment
of the primary disease.
• Exudate, on the other hand, is rich in cells and is mostly a consequence of inflammation
or tumor diseases. Here, the permeability of the capillary walls for tumor cells, plasma
proteins, and other blood components increases (barrier dysfunction). These particles
will then form part of the pleural effusion, which is why exudate has such high content of
cells and proteins.
• Exudative effusion is caused by local processes: pneumonia, cancer, and tuberculosis.
• An exudative effusion will cause unilateral effusions. This type of effusion needs further
• In both cases, an increase in lymph production can also be observed. This increased
production then exceeds the maximum reabsorption capacity of the pleura and, thus,
also contributes to the increased fluid accumulation.
8. Study aid for the differentiating criteria of both forms
of pleural effusion
Transudate < 30 g/L < 200 U/L
Exudate > 30 g/L > 200 U/L
Pleural fluid protein:serum
≤ 0.5 > 0.5
fluid LDH:serum LDH ratio
≤ 0.6 > 0.6
Pleural fluid LDH
< ⅔ the upper
limit of normal
> ⅔ the upper
limit of normal
9. • Pleural fluid LDH
• Levels > 1000 IU/L are suggestive of empyema, malignancy or rheumatoid effusion.
• A low pleural fluid glucose level (<3.4 mmol/l) may be found in empyema,
rheumatoid pleuritis and pleural effusions associated with TB, malignancy and
• A very low pleural glucose concentration (<1.6 mmol/l) is indicative of empyema
and rheumatoid disease.
• Pleural pH
• A pleural fluid pH of < 7.3 is associated with the same pathologies that cause a low
pleural fluid glucose.
• In malignant effusions, a pleural fluid pH of < 7.3 has been associated with more
extensive pleural involvement and shorter life expectancies.
• Pleural fluid amylase levels > 110U/L are indicative of pancreatitis, malignancy or a
10. Special forms of pleural effusion
• Special forms of pleural effusion are the chylothorax and the hematothorax.
• Chylothorax consists primarily of lymphatic fluid; the pleural effusion is milky and
cloudy with a markedly elevated triglyceride content (> 110 mg/dL or 1.24 mmol/L),
cholesterol concentrations 200 mg/dL (5.18 mmol/L).
• Pseudochylothorax is mainly composed of cholesterol and commonly develops
from cell debris present in the pleural fluid for a long period of time. Cholesterol
concentrations >200 mg/dL (5.18 mmol/L), triglyceride concentrations <50 mg/dL
• A hematothorax is basically an accumulation of blood.
• Note: A bloody pleural effusion has to be considered suspicious for a tumor until
11. 3. Symptoms and physical findings in
patients with pleural effusion
• Dyspnea or breathlessness is the cardinal symptom of
• Besides symptoms that are due to accompanying or underlying
diseases, dyspnea is the only direct symptom. This shortness
of breath can be more or less pronounced, depending on the
severity of the effusion.
• Other symptoms include dry cough, pleuritic chest pain (suggesting
pleural inflammation), chest ‘heaviness’, and sometimes pain referred
to the shoulder or abdomen
12. Signs on clinical examination
• Signs on examination include:
• Visually: reduced chest expansion
(an asymmetrical chest expansion)
• Palpation: reduced tactile vocal fremitus
(vibration is being reflected at the line between lung tissue and pleural
effusion (2 matters of different density) and is, thus, not conducted to the
hand of the examiner)
• Auscultation: decreased or inaudible breath sounds over the effusion,
sometimes a patch of bronchial breathing above the fluid level
(because the lung is consolidated, i.e. compressed, here), a friction rub may
be heard with pleural inflammation.
• Percussion: a stony dull sound
(In the case of an effusion > 300 mL) on subscapular line or posterior axial
line. The upper border of this dullness follows a laterally ascending curve
13. 4. Imaging and Investigations in patients
with pleural effusion
• Ultrasonography (US)
• The most sensitive and gentle way to confirm a pleural effusion
diagnosis while the patient is sitting down. This way, effusions
with a volume of 20 mL or more will be depicted as
an anechoic (= dark) area. Sonographic imaging also allows
for the assessment of the pleura (fibrosis? tumor?) and the
organization of the effusion, as well as for identifying a suitable
site for puncture.
15. CXR – chest X ray
• If the torso is erected, the effusion follows gravity and accumulates on
the costophrenic angles of the pleural spaces (costodiaphragmatic
• Sequential blunting of posterior, lateral, and then anterior
costophrenic angles are seen on radiographs as effusions increase in
• PA CXR will usually detect effusion volumes of 200mL or more;
• lateral CXR is more sensitive and may detect as little as 50mL pleural
• In X-ray images, the effusion is depicted as a homogenous shadow,
but on film you will see whiteness – opacity.
17. • free-flowing effusions lying in a subpulmonic location (<75 mL) not
visible on Chest X Ray.
• Pleural effusions >75 mL of volume can be appreciated on lateral
chest radiography as blunting of costophrenic angle
• >175 mL of fluid can be appreciated on anterior-posterior chest
• 500 mL of fluid demonstrate a meniscus sign. Occasionally, the entire
hemithorax may be occupied by an effusion with associated
underlying lung collapse.
19. Lateral decubitus position
the patient is laying either left lateral or right lateral on a trolley on top of a radiolucent
Note: when investigating pneumothorax, the side of interest should be up; when
investigating pleural effusions, the side of interest should be down
20. Thoracic computed tomography (CT)
• will typically be
performed as part of
procedures when the
etiology is unclear. It
allows for the detection
of the smallest amounts
of effusion, which will be
notable as sickle-shaped
the lung and thoracic
Thoracentesis. Thoracentesis is a procedure to remove extra fluid from the pleural cavity
between the lung and the chest wall using a needle. Removal of the fluid may help to relieve
severe symptoms for a short time. A few days after the extra fluid is removed, it is likely it will
begin to come back. The risk of a thoracentesis includes bleeding, infection, collapsed lung,
fluid in the lungs, and a sudden drop in blood pressure.
Indwelling pleural catheter (IPC). An indwelling pleural catheter (IPC) is a small tube that is
inserted and left in place to keep fluid from building up around the lungs. One end of the tube
stays inside the chest and the other passes outside the body to allow fluid to drain. This type
of catheter may be used for long-term care so that a separate procedure won't need to be
done each time draining is needed. Risks of IPCs include infection and blockage of the
Pleurodesis. This is a procedure to close the pleural space so that fluid cannot collect there.
Fluid is first removed by thoracentesis, using a chest tube. A drug that causes the pleural
space to close is then inserted into the space through a chest tube. Drugs such
as bleomycin or talc may be used.
Surgery. Surgery may be done to put in a shunt (tube) to carry the fluid from the pleural
cavity to the abdominal cavity, where the fluid is easier to remove. Pleurectomy is another
type of surgery that may be used. In this procedure, the part of the pleura that lines the chest
cavity is removed.
23. Thoracentesis or Pleural puncture
• This applies in particular to any case of a first or etiologically unclear pleural effusion.
• Purposes: differential diagnosis, obtaining testing material
• For this procedure, the patient is sitting down, a local anesthetic is applied, and the puncture needle is inserted
dorsally into the area of the effusion, but not below the 9th rib (to avoid sub-diaphragmatic injuries).
• In cases of small effusion, encapsulated effusions or atypical localizations, the finding of the puncture site should be
• The material obtained from the puncture should be stored in 4 tubes:
• The first tube is for microbiology. From this material, a bacterial culture is made in order to perform a Gram
stain and, in case of suspected tuberculosis, a Ziehl-Neelsen stain. This tube has to be kept sterile at all times!
• The second tube is for clinical chemistry. With this material, various parameters will be determined: cell count (e.g.,
lymphocytosis for cases of tuberculosis and sarcoidosis), pH level, glucose (diminished glucose levels and an acidic
pH suggest an inflammatory or malignant genesis), triglyceride (elevated in case of a
chylothorax), amylase and lipase (elevated in case of a pancreatic effusion caused by
pancreatitis, pancreas carcinoma, or others), and specific tumor markers in case of a suspected tumor disease.
• The third tube is for pathology. Here, a cytological smear is prepared for the evaluation of malignancy. Indications
for malignancy would include, inter alia, a shift in the nucleus-plasma relation, many mitoses, and multinucleated
• A fourth tube is kept for other, not yet foreseeable examinations
24. Macroscopically, a first assessment of the punctured effusion can be made:
Serous Bright, clear, ‘amber’ fluid: mostly transudate with few cells
Hemorrhagic Reddish: bloody transudate or exudate – trauma or malignoma?
Chylous Milky and cloudy: chylothorax
Purulent Yellowish and dull: exudate in cases of pleural empyema, tuberculosis,
25. • Note:
• Every pleural puncture should be followed by a chest X-ray to
exclude an iatrogenic pneumothorax!
• never extract more than 1.5 L in a single session since there is the
risk of re-expansion edema or great losses of protein. Therefore, for
larger effusions, treatment consists of suction drainage over the
course of several days.
26. Parapneumonic effusion and
empyema: definition and clinical features
• simple parapneumonic effusion occur in up to 57% of patients with
• in some cases, progress to a complicated parapneumonic effusion and
• Pleural infection may also occur in the absence of a preceding
Clear sterile fluid with normal pH, glucose, LDH
Frequently resolves with antibiotics alone
Drainage not usually required
Fibrin deposited and septations occur
Fluid infected but not yet purulent; appears clear or
H <7.20, glucose <2.2 mmol/L (<40 mg/dL) and LDH >1000 IU/L.
Gram stain/culture may be positive
Empyema Pus in pleural space
May be free-owing or multiloculated Gram stain/culture may be positive Drainage required
Eventually, fibroblastes growth may result in development of thick pleural peel (organizing
stage). Treatment at this stage is difficult and decortication may be required
Typical findings: colour depends on pathogen, viscous because of high concentration of WBC
and fibrin. pH <7.2, glucose <2.2mmol/L, and LDH >1,000IU/L. WBC > 10,000/mm3.
28. Parapneumonic effusion and
empyema: Clinical features
• Similar to clinical presentation of pneumonia: fever, sputum production,
chest pain, breathlessness
• cases of ‘slow-to-respond’ pneumonia (e.g. failure of CRP to fall ≥50% in
first 3 days)
• pleural effusion with fever
• or high-risk groups (diabetes, IVDU, and chronic alcohol use) with non-
specific symptoms such as weight loss, atypical chest pain, vomiting, or
• Anaerobic empyema may present less acutely, often with weight loss and
• Empyema may rarely occur following bronchial obstruction from a tumor
or foreign body.
29. Parapneumonic effusion and
• Community-acquired infection (% of cases):
• Streptococcus ‘milleri’ group (30%)
• Anaerobes (15–30%)
• Streptococcus pneumoniae (15%)
• Staphylococcus aureus (10%)
• Other less common organisms include other streptococci,
enterobacteriaceae, H. influenzae, Pseudomonas, TB, and Nocardia
Hospital-acquired infection (% of cases):
• MRSA (25–30%)
• Staphylococcus aureus (10–20%) • Enterobacteriaceae (20%) •
Enterococci (10%) • Others include streptococci, Pseudomonas, and
Pleural infection is frequently polymicrobial.
30. Parapneumonic effusion and
• All patients with parapneumonic pleural infection should be treated with
antibiotics; refer to local hospital prescribing guidelines. Typical choices:
• Community-acquired empyema—β-lactam/β-lactamase inhibitor (e.g.
• co-amoxiclav) or second-generation cephalosporin (e.g. cefuroxime),
• combined with metronidazole for anaerobic cover. Ciprofloxacin and
clindamycin together may be appropriate
• Hospital-acquired empyema—cover Gram-positive and Gram-negative
organisms and anaerobes. MRSA infection is common. Consult with
microbiology team. One option is meropenem and vancomycin.
31. Chest tube drainage
• Indications for chest tube
• Purulent pleural fluid
• Organisms on pleural fluid Gram
stain or culture
• Pleural fluid pH <7.2.
• combination of intrapleural
alteplase (tPA) and dornase alfa
(DNase) significantly improved
CXR appearances for patients
with pleural infection
32. 6. Tuberculous pleural effusion
• develops from a delayed hypersensitivity reaction to mycobacteria released
into the pleural space. It is a common manifestation of TB in regions
with a high prevalence, affecting children and young adults; it may also be
associated with reactivation of TB in older individuals.
• Clinical features
• fever, sweating, weight loss, and dyspnoea, although it may present acutely
with pleuritic chest pain and fever, mimicking pneumonia
• Pleural fluid composition:
• Lymphocytosis, exudative effusion, pH and glucose moderately depressed,
mesothelial cells rare. Pleural fluid cultures are positive in 25% of cases and
take 2–6 weeks
33. 7. Malignant pleural effusion: causes and
• Commonest cause of exudative pleural effusion in patients older than 60y.o.
• Causes: Most malignant effusions are metastatic, with lung and breast the most
• Clinical features: Breathlessness is the main symptom; chest pain, cough, weight
loss, and anorexia may also be present.
• A small proportion of patients are asymptomatic. Effusions may be unilateral or
bilateral and are frequently large volume
• Key investigations in patients suspected to have a malignant effusion are:
• Pleural fluid cytology
• CT chest with pleural contrast
• Pleural biopsy histology
• Serum/pleural fluid tumour markers
34. Malignant pleural effusion: management
• Observation and follow-up if asymptomatic.
• Therapeutic pleural aspiration of 1–1.5L pleural fluid to improve
breathlessness. Can be performed at the bedside as a day-case
procedure, avoiding hospital admission.
• Intercostal chest drainage and pleurodesis
• Insertion of a long-term IPC