An educational overview of common pleural diseases.

1. DISEASES OF THE PLEURA AND
PLEURAL SPACE
MOHAMMAD VAZIRI
THORACIC SURGEON
Iran University of Medical Sciences
Member of the
International Association for the Study of Lung Cancer
European Society of Medical Oncology
New York Academy of Sciences

2. ◼ Pleural Effusion
Pleural effusion refers to any significant collection of fluid within the
pleural space.
Normally, there is an ongoing balance between the lubricating fluid
flowing into the pleural space and its continuous absorption.
Between 5 and 10 L of fluid normally enters the
pleural space daily by filtration through microvessels supplying the
parietal pleura (located mainly in the less dependent regions of the
cavity).

3. Pleural Effusion
The net balance of pressures leads to fluid flow from the
parietal pleural surface into the pleural space, and
the net balance of forces in the pulmonary circulation
leads to absorption through the visceral pleura.
Normally, 15 to 20 mL of pleural fluid is present at any
given time.
.

4. ◼ Differential Diagnosis of Pleural Effusions
I. Transudative pleural effusions
A. Congestive heart failure
B. Cirrhosis
C. Nephrotic syndrome
D. Superior vena caval obstruction
E. Fontan procedure
F. Urinothorax
G. Peritoneal dialysis
H. Glomerulonephritis
I. Myxedema
J. Cerebrospinal fluid leaks to pleura
K. Hypoalbuminemia
L. Pulmonary emboli
M. Sarcoidosis

5. II. Exudative pleural effusions
A. Neoplastic diseases
I. Metastatic disease
2. Mesothelioma
3. Body cavity lymphoma
4. Pyothorax-associated lymphoma
B. Infectious diseases
I. Bacterial infections
2. Tuberculosis
3. Fungal infections
4. Parasitic infections
5. Viral infections
C. Pulmonary embolization

6. . Exudative pleural effusions
D. Gastrointestinal disease
I. Pancreatic disease
2. Subphrenic abscess
3. Intrahepatic abscess
4. Intrasplenic abscess
5. Esophageal perforation
6. Postabdominal surgery
7. Diaphragmatic hernia
8. Endoscopic variceal sclerosis
9. Post-liver transplant
E. Heart diseases
I. Post-coronary artery bypass graft surgery
2. Post-cardiac injury (Dressler's) syndrome
3. Pericardial disease

7. F. Obstetric and gynecologic disease
I. Ovarian hyperstimulation syndrome
2. Fetal pleural effusion
3. Postpartum pleural effusion
4. Meigs‘ syndrome
5. Endometriosis
G. Collagen-vascular disease
I. Rheumatoid pleuritis
2. Systemic lupus erythematosus
3. Drug-induced lupus
4. Immunoblastic lymphadenopathy
5. Sjogren's syndrome
6. Familial Mediterranean fever
7. Churg-Strauss syndrome
8. Wegener's granulomatosis

8. Exudative pleural effusions
H. Drug-induced pleural disease
I. Nitrofurantoin
2. Dantrolene
3. Methysergide
4. Ergot alkaloids
5. Amiodarone
6. Interleukin-2
7. Procarbazine
8. Methotrexate
9. Clozapine

9. Exudative pleural effusions
I. Miscellaneous diseases and conditions
I. Asbestos exposure
2. Post-lung transplant
3. Post-bone marrow transplant
4. Yellow nail syndrome
5. Sarcoidosis
6. Uremia
7. Trapped lung
8. Therapeutic radiation exposure
9. Drowning

10. Exudative pleural effusions
I. Miscellaneous diseases and conditions
10. Amyloidosis
II. Milk of calcium pleural effusion
12. Electrical burns
13. Extramedullary hematopoiesis
14. Rupture of mediastinal cyst
I5. Acute respiratory distress syndrome
16. Whipple's disease
17. Iatrogenic pleural effusions
J. Hemothorax
K. Chylothorax

11. ◼ Diagnostic Work-Up
The initial diagnostic work-up for pleural effusion is
guided in large part by the patient's history and physical
examination.
Bilateral pleural effusions are due to congestive heart
failure in over 80% of patients >>a trial of
diuresis may be indicated (rather than thoracentesis).
Up to 75% of effusions resolve within 48 hours
with diuresis alone.

12. A patient presenting with cough, fever, leukocytosis, and unilateral
infiltrate and effusion is likely to have a parapneumonic process.
If the effusion is small and the patient responds to antibiotics, a
diagnostic thoracentesis may be unnecessary.
A patient who has an obvious pneumonia and a large pleural effusion
that is purulent has an empyema.
Aggressive drainage with chest tubes is required.
Most patients with pleural effusions of unknown cause should
undergo thoracentesis.

13. ◼ Diagnostic Work-Up
A general classification of pleural fluid collections into
transudates and exudates is helpful
Transudates are protein-poor ultrafiltrates of plasma that
occur because of alterations in the systemic hydrostatic
pressures or colloid osmotic pressures
On gross visual inspection, a transudative effusion is
generally clear or straw-colored.

14. Exudates are protein-rich pleural fluid collections that
generally occur because of inflammation or invasion of
the pleura by tumors.
Grossly, they are often turbid, bloody, or purulent.
Grossly bloody effusions in the absence of trauma are
frequently malignant, but may also occur in the setting of
a pulmonary embolism or pneumonia.

15. Criteria used to differentiate transudates from exudates:
An effusion is considered exudative if the pleural fluid to
serum ratio of protein is greater than 0.5 and the LDH
ratio is greater than 0.6 or
The absolute pleural LDH level is greater than two-thirds
of the normal upper limit for serum.

16. If an exudative effusion is suggested, further diagnostic
studies is helpful.
If total and differential cell counts reveal a predominance
of neutrophils (>50% of cells), the effusion is likely to
be associated with an acute inflammatory process :
parapneumonic effusion or empyema, pulmonary embolus,
or pancreatitis

17. Exudative effusion
A predominance of mononuclear cells suggests a more
chronic inflammatory process (such as cancer or
tuberculosis).
Gram's stains and cultures should be obtained, if possible
with inoculation into culture bottles at the bedside.
Pleural fluid glucose levels are frequently decreased (<60
mg/dL) with complex parapneumonic effusions or
malignant effusions.

18. Cytologic testing should be done on exudative effusions to rule out
an associated malignancy.
Cytologic diagnosis is accurate in diagnosing over 70% of malignant
effusions associated with adenocarcinomas, but is less sensitive
for mesotheliomas(<10%), squamous cell carcinomas (20%), or
lymphomas (25 to 50%).
If the diagnosis remains uncertain after drainage and fluid analysis,
thoracoscopy and direct biopsies are indicated.
Tuberculous effusions can now be diagnosed accurately by increased
levels of pleural fluid adenosine deaminase (above 40 U per L).

19. Pulmonary embolism should be suspected in a patient with a pleural
effusion occurring in association with pleuritic chest pain,
hemoptysis, or dyspnea out of proportion to the size of the
effusion.
These effusions may be transudative, but if an associated infarct near
the pleural surface occurs, an exudate may be seen.
If a pulmonary embolism is suspected in a postoperative patient,
obtain a spiral CT scan. Alternatively, duplex ultrasonography of
the lower extremities may yield a diagnosis of deep vein
Thrombosis

26. ◼ Malignant Pleural Effusion
Occur in association with a number of different
malignancies, most commonly lung cancer, breast
cancer, and lymphomas.
Malignant effusions are exudative and often tinged with
blood.
An effusion in the setting of a malignancy means a more
advanced stage; it generally indicates an unresectable
tumor, with a mean survival 3 to 11 months.

29. ◼ Malignant Pleural Effusion
Symptomatic, moderate to large effusions should be
drained by chest tube, or VATS, followed by instillation
of a sclerosing agent. >>PLEURODESIS
Before sclerosing the pleural cavity, the lung should be
nearly fully expanded.
The choice of sclerosant includes talc, bleomycin, or
doxycycline. Success rates of controlling the effusion
range from 60 to 90%

30. Empyema
Thoracic empyema is defined by a purulent pleural
effusion.
The most common causes are parapneumonic, postsurgical
and posttraumatic
In the early stage, small to moderate turbid pleural
effusions in the setting of a pneumonic process may
require further pleural fluid analysis.
A deteriorating clinical course or a pleural pH of less than
7.20 and a glucose level of less than 40 mg/dL indicates
the need to drain the fluid.

31. ◼ Pathogenesis of Empyema
Contamination from a source contiguous to the pleural space (50--
60%)
Lung
Mediastinum
Deep cervical
Chest wall and spine
Subphrenic
Direct inoculation of the pleural space (30--40%)
Minor thoracic interventions
Postoperative infections
Penetrating chest injuries
Hematogenous infection of the pleural space from a distant site

32. Patients of all ages can develop empyema, but the frequency
is increased in older or debilitated patients.
The mortality of empyema frequently depends on the degree
of severity of the comorbidity
It may range from as low as 1% to over 40% in
immunocompromised patients.

33. ◼ Pathophysiology
Multiple organisms may be found in up to 50% of patients,
but cultures may be sterile if antibiotics were initiated
before the culture or if the culture process was not
efficient.
Common gram-negative organisms include
Escherichia coli, Klebsiella, Pseudomonas, and
Enterobacteriaceae.

34. ◼ Management of Empyema
If there is a residual space, persistent pleural infection is
likely to occur.
A persistent pleural space may be secondary to contracted,
but intact, underlying lung; or it may be secondary to
surgical lung resection.

35. Management of Empyema
Larger spaces may require open thoracotomy and
decortication in an attempt to reexpand the lung to fill
this residual space
Most chronic pleural space problems can be avoided by
early specialized thoracic surgical consultation and
complete drainage of empyemas, allowing space
obliteration by the reinflated lung.

38. ◼ Chylothorax
Chylothorax develops most commonly after surgical trauma
to the thoracic duct or a major branch.
It is generally unilateral. it may occur on the right after
esophagectomy
If the mediastinal pleura is disrupted on both sides, bilateral
chylothoraces may occur.
Left-sided chylothoraces may develop after a left-sided
neck dissection, especially in the region of the confluence
of the subclavian and internal jugular veins.

40. ◼ Etiology of Chylothorax
I-Congenital
Atresia of thoracic duct
Thoracic duct-pleural space fistula
Birth trauma

41. ◼ Etiology of Chylothorax
II-Traumatic and/or Iatrogenic
Blunt
Penetrating
Surgery
Cervical: excision of lymph nodes; radical neck dissection
Thoracic
Patent ductus arteriosus
Coarctation of the aorta
Vascular procedure reinvolving the origin of left subclavian artery
Esophagectomy
Sympathectomy
Resection of thoracic aneurysm
Resection of mediastinal tumors
Left pneumonectomy
Abdominal: sympathectomy; radical lymph node dissection
Diagnostic procedures
Translumbar arteriography
Subclavian vein catheterization
Left-sided heart catheterization

42. ◼ Etiology of Chylothorax
III-Neoplasms
IV-Infections
Tuberculous lymphadenitis
Nonspecific mediastinitis
Ascending lymphangitis
Filariasis
V-Miscellaneous
Venous thrombosis
Left subclavian-jugular vein
Superior vena cava
Pulmonary lymphangiomatosis

43. ◼ Pathophysiology of the Chylothorax
The main function of the duct is to transport fat absorbed
from the digestive system. The composition of normal
chyle is fat, with variable amounts of protein and
lymphatic material
Given the high volumes of chyle that flow through the
thoracic duct, significant injuries can cause leaks in
excess of 2 L per day
If left untreated, protein, volume, and lymphocyte depletion
can lead to serious metabolic effects and death.

45. The diagnosis generally requires thoracentesis, often the
pleural fluid is milky and nonpurulent.
If the patient is nil per os (NPO, nothing by mouth), the
pleural fluid may not be grossly abnormal.
Laboratory analysis of the pleural fluid shows a high
lymphocyte count and high triglyceride levels.
If the triglyceride level is greater than 110 mg/l 00 mL, a
chylothorax is almost certainly present (a 99% accuracy
rate).

46. ◼ Management of Chylothorax
Depends on its cause, the amount of drainage, and
the clinical status of the patient.
In general, most patients are treated with a short
period of chest tube drainage, NPO orders, total
parenteral nutrition (TPN), and observation.
Somatostatin has been advocated by some authors,
with variable results.

47. ◼ Management of Chylothorax
If significant chyle drainage (>500 mL per day in an adult,
> 100 mL in an infant) continues despite TPN and good
lung expansion, early surgical ligation of the duct is
recommended.
Ligation can be approached best by right thoracotomy, and
in some experienced centers, by right VATS.
Chylothoraces due to malignant conditions often respond
to radiation and/or chemotherapy.

50. ◼ Access and Drainage of Pleural Fluid Collections
◼ Approaches and Techniques
Once the decision is made to invasively access a pleural
effusion, the next step is to determine if a sample of the
fluid is required or if complete drainage of the pleural
space is desired.
This step is influenced by the clinical history, the type and
amount of fluid present, the nature of the collection
(such as free-flowing or loculated), the cause, and the
likelihood of recurrence.

51. ◼ Access and Drainage of Pleural Fluid Collections
For small, free-flowing effusions, an outpatient
thoracentesis with a relatively small-bore needle
or catheter (14- to l6-gauge) can be performed.
Fluid should be grossly examined as it is drained:
clear straw-colored fluid is often transudative;
turbid or bloody fluid is often exudative.

52. If the effusion is more complex with loculations, a CT scan
or ultrasound-guided approach may be indicated.
If complete drainage is the goal and the fluid is nonbloody
and nonviscous, a small-bore (14- to 16-gauge) pigtail
catheter is inserted and connected to a Pleurovac or
similar device for drainage.
If the fluid is bloody or turbid, a larger-diameter drainage
tube (such as a 28F chest tube) may be required.

54. ◼ Complications of Pleural Drainage
The most common complication is inadvertent access to
another cavity or organ.
Examples include puncture of the underlying lung, with air
leakage and pneumothorax.
Subdiaphragmatic entry, with damage to the liver, spleen.
Bleeding secondary to intercostal vessel injury, or larger
vessel injury and even cardiac puncture.

55. Other technical complications include loss of a catheter,
guidewire, or fragment in the pleural space, and
infections.
Occasionally, rapid drainage of a large effusion can be
followed by shortness of breath and clinical instability,
a phenomenon referred to as post-expansion pulmonary
edema.
For this reason, it is recommended to drain only up to I L

56. ◼ Tumors of the Pleura
◼ Malignant Mesothelioma
The most common type of tumor of the pleura
In 20% of malignant mesotheliomas, the tumor arises from
the peritoneum.
Exposure to asbestos is the only known risk factor.
Frequently associated with industries using asbestos in the
manufacturing process, such as shipbuilding.
The risk extends beyond the worker directly exposed to the
asbestos; family members exposed to the dust of the
clothing or the work environment are also at risk.

57. Malignant Mesothelioma
Other risk factor >>> exposure to radiation.
Cigarette smoking does not appear to increase the risk of
malignant mesothelioma, even though asbestos exposure
and smoking synergistically increases the risk for lung
cancer.
Malignant mesotheliomas have a male predominance of 2:
1, and are most common after the age of 40.

58. The latency period between asbestos exposure and the development
of mesothelioma is at least 20 years.
The tumor generally is multicentric, with multiple
pleural-based nodules coalescing to form sheets of tumor.
This process initially involves the parietal pleura, generally with early
spread to the visceral surfaces and with a variable degree of
invasion of surrounding structures.
Most patients have distant metastases, but the natural history of the
disease culminates in death due to local
extension.

59. Malignant Mesothelioma - Clinical Presentation.
Most patients present with dyspnea and chest pain. Over 90% have a
pleural effusion.
Thoracentesis is diagnostic in less than 10% of patients.
Frequently, a thoracoscopy or open pleural biopsy with special stains
is required to differentiate mesotheliomas from adenocarcinomas.
Cell types >> epithelial, sarcomatoid, mixed
Epithelial tumors are associated with more favorable prognosis.

60. ◼ Management.
The treatment of malignant mesotheliomas remains
controversial.
While prognosis does depend on the stage of the disease,
the problem is that many patients present with advanced
local or distant disease beyond curative potential.
Treatment options include supportive care only, surgical
resection, and multimodality approaches (using a
combination of surgery, chemotherapy, and radiation
therapy).

61. Malignant Mesothelioma
Surgical options include :
1-palliative approaches such as pleurectomy or talc
pleurodesis.
2-More radical surgical approaches (such as extrapleural
pneumonectomy followed by adjuvant chemotherapy and
radiation) have an increased morbidity rate; moreover,
the mortality rate exceeds 10%.

62. ◼ Current approach to malignant mesotheliomas is based
on tumor stage and pulmonary performance status.
For patients with early-stage mesotheliomas and good
pulmonary function, extrapleural pneumonectomy is
recommended and patients are referred for clinical trials
of multi modality therapy.
For more advanced disease, or if patients have less-than-
optimal pulmonary function or performance
status, talc pleurodesis is recommended.

66. ◼ Fibrous Tumors of the Pleura
Are unrelated to asbestos exposure or malignant
mesotheliomas.
They generally occur as a single pedunculated mass arising
from the visceral pleura.
Frequently, they are discovered incidentally on routine chest
x-rays, without an associated pleural effusion and may be
benign or malignant.

67. Fibrous Tumors of the Pleura
Symptoms such as cough, chest pain, and dyspnea occur in 30 to 40%
of patients.
Less common are fever, hypertrophic pulmonary osteoarthropathy,
hemoptysis, and hypoglycemia (4% of patients and resolves with
surgical resection)
Given the localized, pedunculated nature of both benign and
malignant tumors, most are cured by complete surgical resection.
Incompletely resected malignant tumors may recur locally or
metastasize