‫به نام خدا‬
‫دكتر محمد امامي‬
‫فوق تخصص ريه ومراقبتهاي ويژه‬
‫هيات علمي دانشكده پزشكي‬
Clinical Manifestations
And Diagnostic
Approache Of Pleural
Effusion
Clinical Manifestations
Asymptomatic
 Pleurtic chest pain
 Cough
 Dyspnea
 dullness to percussion
 decreased breath sounds
 egophony at the upper level of the
effusion
 decreased tactile fremitus

APPROACH TO PATIENTS
WITH PLEURAL EFFUSION

A diagnostic thoracentesis should be
performed on nearly every patient
with free pleural fluid that measures
more than 10 mm on the decubitus
radiograph

Thoracentesis is a safe procedure
when performed by an experienced
operator
it can be safely performed in :
 patients with coagulopathies
 thrombocytopenia
 in patients on positive mechanical
ventilation
ultrasound guidance for thoracentesis
 on small or multiloculated effusions
 in patients with poor lung function
 Bulous lung disease

The first question that should be
answered with the diagnostic
thoracentesis is whether the patient
has a transudative or an exudative
pleural effusion
Exudative pleural effusions
meet at least one of the following
criteria, whereas transudative
pleural effusions meet none
 (1) pleural fluid protein–to–serum
protein greater than 0.50
 (2) pleural fluid LDH–to–serum
LDH greater than 0.60
 (3) pleural fluid LDH greater than
two thirds of the upper normal limit
for serum.

transudative pleural effusion

If none of these criteria is met,



The previously discussed criteria may
misidentify a transudative effusion as
an exudative effusion in as many as
25% of cases.
If a patient appears to have a
transudative effusion clinically,
additional tests can be assessed to
verify its transudative etiology.
If the difference between the protein
concentration of serum and the pleura
exceeds 3.1 gm/dL, the patient in all
probability has a transudative effusion.
TRANSUDATIVE PLEURAL EFFUSIONS
Congestive heart failure
Pericardial disease
Hepatic hydrothorax
Nephrotic syndrome
Peritoneal dialysis
Urinothorax
Myxedema
Fontan procedure
Central venous occlusion
Subarachnoid-pleural fistula
Veno-occlusive disease
Bone marrow transplantation
Iatrogenic
 CHF
and cirrhosis are
responsible for almost all
transudative pleural
effusions.
EXUDATIVE PLEURAL EFFUSIONS

Neoplastic diseases :
Metastatic disease
Mesothelioma
Primary effusion lymphoma
Pyothorax-associated lymphoma

Infectious diseases :
Pyogenic bacterial infections
Tuberculosis
Actinomycosis and nocardiosis
Fungal infections
Viral infections
Parasitic infections
Pulmonary embolism
Gastrointestinal disease :
 Esophageal perforation
Pancreatic disease
Intra-abdominal abscesses
Diaphragmatic hernia
Postabdominal surgery

Collagen vascular diseases
Rheumatoid pleuritis
 Systemic lupus erythematosu
 Drug-induced lupus
 Immunoblastic lymphadenopathy
 Sjýgren's syndrome
 Churg-Strauss syndrome
 Wegener's granulomatosis

Postcardiac injury syndrome
 Post–coronary artery bypass
surgery
 Asbestos exposure
 Sarcoidosis
 Uremia
 Meigs’ syndrome
 Ovarian hyperstimulation
syndrome
 Yellow nail syndrome

Drug-induced pleural disease
Nitrofurantoin
 Dantrolene
 Methysergide
 Bromocriptine
 Procarbazine
 Amiodarone
 Dasatinib

Radiation therapy
 Electric burns
 Iatrogenic injury
 Hemothorax
 Chylothorax


Pneumonia, malignant pleural
disease, pulmonary embolism, and
gastrointestinal disease account for
at least 90% of all exudative pleural
effusions
Appearance of Pleural Fluid

The gross appearance of the pleural
fluid should always be described and
its odor noted
If the pleural fluid smells putrid, the
patient has a bacterial infection
(probably anaerobic) of the pleural
space.
 If the fluid smells like urine, the
patient probably has a urinothorax.





If the pleural fluid is bloody, a pleural
fluid hematocrit should be obtained.
If the pleural fluid hematocrit is
greater than 50% that of the peripheral
blood, the patient has a hemothorax
and the physician should strongly
consider inserting chest tubes.
If the pleural fluid hematocrit is less
than 1%, the blood in the pleural fluid
has no clinical significance.
If the pleural fluid hematocrit is
between 1% and 50%, the patient most
likely has malignant pleural disease, a
pulmonary embolus, or a traumatically
induced pleural effusion.
The supernatant of the pleural fluid
should be examined if the pleural
fluid is turbid, milky, or bloody.
 If the pleural fluid is turbid when
originally obtained, but the turbidity
clears with centrifugation, the
turbidity is due to cells or debris in
the pleural fluid.
 If the turbidity persists after
centrifugation, the patient probably
has a chylothorax or a
pseudochylothorax.

Pleural Fluid Protein

The pleural fluid protein level tends
to be elevated to a comparable
degree with all exudative pleural
effusions and is, therefore, not
generally useful in the differential
diagnosis of an exudative pleural
effusion.
if the protein level is above 5.0 g/dL,
the likelihood of the diagnosis of
tuberculous pleurisy is increased.
 If the pleural fluid protein level is very
low (<0.5 g/dL), the patient probably
has:
 a urinothorax
 an effusion secondary to peritoneal
dialysis,
 a leak of CSF into the pleural space,
 an effusion secondary to the
misplacement of a central
intravascular line.


When pleural fluid protein concentrations
are in the 7.0 to 8.0 g/dL (70 to 80 g/L)
range, Waldenström’s macroglobulinemia
and multiple myeloma should be
considered
Pleural Fluid Lactate Dehydrogenase
LDH, as an intracellular enzyme
 degree of cell turnover and/or the
degree of inflammation within the
pleural space
 no utility in the differential diagnosis
of exudative pleural effusion
 level of LDH in the pleural fluid
reflects the degree of inflammation
in the pleural space

Pleural fluid LDH levels above 1000
IU/L
empyema
 rheumatoid pleurisy
 paragonimiasis
 malignancy.

Cholesterol

Pleural cholesterol is thought to be
derived from degenerating cells and
vascular leakage from increased
permeability
Pleural Fluid Glucose
A low glucose concentration
probably indicates the coexistence
of two abnormalities:
 a thickened, infiltrated pleura
leading to an impaired diffusion of
glucose into the pleural space plus
increased metabolic activity leading
to increased glucose utilization
within the pleural space

reduced pleural fluid glucose
level (<60 mg/dL, 3.33 mmol/L)
Parapneumonic effusion
 malignant effusion
 tuberculous effusion
 rheumatoid effusion
 hemothorax
 paragonimiasis
 Churg-Strauss syndrome


The lowest glucose concentrations are
found in rheumatoid pleurisy and
empyema, with glucose being
undetectable in some cases
Pleural Fluid White Cell Count and
Differential
In the normal pleural space, the cell
count has been reported to be 1700
cells/mm3.
 In effusions, the cell count has
limited diagnostic value.
 A pleural fluid white blood cell
count of 1000/mm3 roughly
separates transudative from
exudative pleural effusion

a pleural fluid white blood cell
count above 10,000/mm3
empyemas
parapneumonic effusions
pancreatitis
pulmonary embolism
collagen vascular diseases
malignancy
tuberculosis

The differential cell count on the
pleural fluid is much more useful
than the white cell count itself
Pleural effusions due to an acute
disease process such as pneumonia,
pulmonary embolization,
pancreatitis, intra-abdominal
abscess, or early tuberculosis
contain predominantly
polymorphonuclear leukocytes.
 Pleural effusions due to a chronic
disease process contain
predominantly mononuclear cells.

Lymphocytosis(>%80)
tuberculous pleurisy
 lymphoma
 Sarcoidosis
 chronic rheumatoid pleurisy
 yellow nail syndrome
 chylothorax

Pleural fluid eosinophilia (≥10%
eosinophils by differential count)
air or blood in the pleural space
 traumatic hemothorax
 pulmonary embolism
 Pneumothorax
 idiopathic
 malignancy
 parapneumonic
 tuberculosis
 Benign asbestos pleural effusions

drug reactions
 Paragonimiasis
 Churg-Strauss syndrome
 Pulmonary infarction
 Fungal infection (coccidioidomycosis,
cryptococcosis, histoplasmosis)


Small lymphocytes, when
accounting for more than 50% of the
white blood cells in an exudative
pleural effusion, indicate that the
patient probably has a malignant or
a tuberculous pleural effusion
Pleural Fluid Cytology



A pleural fluid specimen from every
patient with an undiagnosed exudative
pleural effusion should be sent for
cytopathologic studies
The first pleural fluid cytologic study is
positive for malignant cells in up to
60% of the effusions caused by pleural
malignancy.
If three separate specimens are
submitted, up to 90% of effusions due
to pleural malignancy have positive
cytopathology.
The frequency of positive pleural
fluid cytologic tests is dependent on
the tumor type. For example, less
than 25% of patients with Hodgkin's
disease have positive cytology
 whereas most patients with
adenocarcinomas have positive
cytology.
 The percentage of positive
diagnoses is obviously dependent on
the skill of the cytologist

Tumor markers

No single pleural fluid tumor marker is
accurate enough for routine use in the
diagnostic evaluation of pleural effusion
Culture and Bacteriologic Stains

Pleural fluid from patients with
undiagnosed exudative pleural
effusions should be cultured for
bacteria (both aerobically and
anerobically), mycobacteria, and
fungi
Pleural Fluid pH and PCO2











The pleural fluid pH can be reduced to less
than 7.20 with 10 different conditions:
(1) complicated parapneumonic effusion
(2) esophageal rupture
(3) rheumatoid pleuritis
(4) tuberculous pleuritis
(5) malignant pleural disease
(6) hemothorax
(7) systemic acidosis
(8) paragonimiasis
(9) lupus pleuritis
(10) urinothorax
The decreased pleural fluid pH
appears to result from lactic acid
and carbon dioxide accumulation in
the pleural fluid.
 The routine measurement of pleural
fluid pH is recommended only in
patients with parapneumonic
effusions

In general, pleural fluids with a low pH
also have a low glucose
 pleural fluid glucose can be used as an
alternative to the pH measurement.
 When the pleural fluid pH is used as a
diagnostic test, it must be measured
with the same care as arterial pH.
 The fluid should be collected
anaerobically in a heparinized syringe
and placed on ice.
 If the sample is left open to air, a
spuriously high pH value can be
obtained because of the rapid loss of
carbon dioxide.


Transudates generally have a pleural fluid
pH in the 7.40 to 7.55 range, while the
majority of exudates range from 7.30 to
7.45
Pleural Fluid Amylase
esophageal perforation
 pancreatic disease
 malignant disease
 routine measurement of pleural
fluid amylase is not indicated

Other rare causes of an amylase-rich
pleural effusion include :
 pneumonia
 ruptured ectopic pregnancy
 hydronephrosis
 cirrhosis

Tests for Collagen Vascular Diseases
About 5% of patients with rheumatoid
arthritis and 50% of patients with SLE
have a pleural effusion sometime
during the course of their disease.
 At times, the effusions may be the first
manifestation of the disease; therefore,
these diagnostic possibilities should be
considered in patients with
undiagnosed exudative pleural effusion






Measurement of the ANA titer is the best
screening test for lupus pleuritis, although it is
now evident that a positive pleural fluid ANA is
not specific for the diagnosis.
Although all patients with lupus pleuritis have
a positive pleural liquid ANA (>1 : 40), the
finding of a positive ANA has been found in
between 11% and 27% of other effusions.
Neither the titer of ANA, the ratio of pleurato-plasma ANA, or the pattern of staining has
been found to increase the specificity for SLE.
In fact, a positive pleural fluid ANA in patients
without SLE may be associated with
malignancy.
In patients with SLE, the lack of ANA in
pleural liquid may have a high negative
predictive value
When a rheumatoid pleural effusion
is suspected, the clinical picture
usually establishes the diagnosis.
 If any question exists, the level of
rheumatoid factor in the pleural
fluid should be measured.
 Only patients with rheumatoid
pleuritis have a pleural fluid
rheumatoid factor titer equal to or
greater than 1 : 320 and equal to or
greater than the serum titer

Adenosine Deaminase
a product of activated lymphocytes
 catalyzes the conversion of
adenosine to inosine
 is important for normal immune
function
 The pleural fluid ADA levels are
elevated in almost all patients with
tuberculous pleuritis

An occasional patient with
empyema, lymphoma, or leukemia
may have elevated pleural fluid ADA
levels
 Because it is a highly sensitive test,
the ADA can be a useful test to
exclude the diagnosis of tuberculosis
when the ADA level is low (<40 U/L).
