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Pleural Effusion
Author: Jeffrey Rubins, MD; Chief Editor: Ryland P Byrd, Jr, MD more...

Updated: Jun 30, 2016

Background

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Pleural Effusion: Background, Anatomy, Etiology http://emedicine.medscape.com/article/299959-overview

A pleural effusion is an abnormal collection of fluid in the pleural space resulting

from excess fluid production or decreased absorption or both.[1] It is the most
common manifestation of pleural disease, with etiologies ranging from
cardiopulmonary disorders to symptomatic inflammatory or malignant diseases
requiring urgent evaluation and treatment. Approximately 1.5 million pleural
effusions are diagnosed in the United States each year (see the images below).

Large, malignant, right-sided pleural effusion.

Chest radiograph showing left-sided pleural effusion.

Anatomy
The pleural space is bordered by the parietal and visceral pleurae. The parietal
pleura covers the inner surface of the thoracic cavity, including the mediastinum,
diaphragm, and ribs. The visceral pleura envelops all lung surfaces, including the
interlobar fissures. The right and left pleural spaces are separated by the
mediastinum.

The pleural space plays an important role in respiration by coupling the movement of
the chest wall with that of the lungs in 2 ways. First, a relative vacuum in the space
keeps the visceral and parietal pleurae in close proximity. Second, the small volume
of pleural fluid, which has been calculated at 0.13 mL/kg of body weight under
normal circumstances, serves as a lubricant to facilitate movement of the pleural
surfaces against each other in the course of respirations.[2] This small volume of
fluid is maintained through the balance of hydrostatic and oncotic pressure and
lymphatic drainage, a disturbance of which may lead to pathology.[3]

Etiology
The normal pleural space contains approximately 10 mL of fluid, representing the
balance between (1) hydrostatic and oncotic forces in the visceral and parietal
pleural vessels and (2) extensive lymphatic drainage. Pleural effusions result from
disruption of this balance.

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Pleural effusion is an indicator of an underlying disease process that may be

pulmonary or nonpulmonary in origin and may be acute or chronic.[4, 5] Although the
etiologic spectrum of pleural effusion is extensive, most pleural effusions are caused
by congestive heart failure, pneumonia, malignancy, or pulmonary embolism. The
following mechanisms play a role in the formation of pleural effusion:

Altered permeability of the pleural membranes (eg, inflammation, malignancy,

pulmonary embolus)
Reduction in intravascular oncotic pressure (eg, hypoalbuminemia due to
nephrotic syndrome or cirrhosis)
Increased capillary permeability or vascular disruption (eg, trauma,
malignancy, inflammation, infection, pulmonary infarction, drug
hypersensitivity, uremia, pancreatitis)
Increased capillary hydrostatic pressure in the systemic and/or pulmonary
circulation (eg, congestive heart failure, superior vena cava syndrome)
Reduction of pressure in the pleural space, preventing full lung expansion or
"trapped lung" (eg, extensive atelectasis, mesothelioma)
Decreased lymphatic drainage or complete blockage, including thoracic duct
obstruction or rupture (eg, malignancy, trauma)
Increased peritoneal fluid, with migration across the diaphragm via the
lymphatics or structural defect (eg, cirrhosis, peritoneal dialysis)
Movement of fluid from pulmonary edema across the visceral pleura
Persistent increase in pleural fluid oncotic pressure from an existing pleural
effusion, causing further fluid accumulation

The net result of effusion formation is a flattening or inversion of the diaphragm,

mechanical dissociation of the visceral and parietal pleura, and a restrictive
ventilatory defect as measured by pulmonary function testing.[6]

Pleural effusions are generally classified as transudates or exudates, based on the

mechanism of fluid formation and pleural fluid chemistry. Transudates result from an
imbalance in oncotic and hydrostatic pressures, whereas exudates are the result of
inflammation of the pleura or decreased lymphatic drainage. In some cases, the
pleural fluid may have a combination of transudative and exudative characteristics.

Transudates
Transudates are usually ultrafiltrates of plasma in the pleura due to imbalance in
hydrostatic and oncotic forces in the chest. However, they can also be caused by the
movement of fluid from peritoneal spaces or by iatrogenic infusion into the pleural
space from misplaced or migrated central venous catheters or nasogastric feeding
tubes. Transudates are caused by a small, defined group of etiologies, including the
following:

Congestive heart failure

Cirrhosis (hepatic hydrothorax)
Atelectasis - Which may be due to malignancy or pulmonary embolism
Hypoalbuminemia
Nephrotic syndrome
Peritoneal dialysis
Myxedema
Constrictive pericarditis
Urinothorax - Usually due to obstructive uropathy
Cerebrospinal fluid (CSF) leaks to the pleura - Generally in the setting of
ventriculopleural shunting or of trauma or surgery to the thoracic spine
Duropleural fistula - Rare, but may be a complication of spinal cord surgery
Extravascular migration of central venous catheter [7]
Glycinothorax - A rare complication of bladder irrigation with 1.5% glycine
solution following urologic surgery

Exudates
Exudates are produced by a variety of inflammatory conditions and often require
more extensive evaluation and treatment than transudates. Exudates arise from
pleural or lung inflammation, impaired lymphatic drainage of the pleural space,
transdiaphragmatic movement of inflammatory fluid from the peritoneal space,
altered permeability of pleural membranes, and increased capillary wall permeability
or vascular disruption. Pleural membranes are involved in the pathogenesis of the
fluid formation. The permeability of pleural capillaries to proteins is increased in
disease states resulting in an elevated protein content.

The more common causes of exudates include the following:

Parapneumonic causes [8]

Malignancy (most commonly lung or breast cancer, lymphoma, and leukemia;
less commonly ovarian carcinoma, stomach cancer, sarcomas, melanoma) [9]
Pulmonary embolism
Collagen-vascular conditions (rheumatoid arthritis, systemic lupus
erythematosus [10] )
Tuberculosis (TB)
Pancreatitis
Trauma

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Postcardiac injury syndrome

Esophageal perforation
Radiation pleuritis
Sarcoidosis
Fungal infection
Pancreatic pseudocyst
Intra-abdominal abscess
Status-post coronary artery bypass graft surgery
Pericardial disease
Meigs syndrome (benign pelvic neoplasm with associated ascites and pleural
effusion)
Ovarian hyperstimulation syndrome
Drug-induced pleural disease (see Pneumotox On Line for an extensive list of
drugs that can cause pleural effusion)
Asbestos-related pleural disease
Yellow nail syndrome (yellow nails, lymphedema, pleural effusions)
Uremia
Trapped lung (localized pleural scarring with the formation of a fibrin peel
prevents incomplete lung expansion, at times leading to pleural effusion)
Chylothorax (acute illness with elevated triglycerides in pleural fluid)
Pseudochylothorax (chronic condition with elevated cholesterol in pleural
fluid)
Fistula (ventriculopleural, biliopleural, gastropleural)

Epidemiology
Occurrence in the United States

Because pleural effusion is a manifestation of underlying disease, its precise

incidence is difficult to determine. However, the incidence in the United States is
estimated to be at least 1.5 million cases annually.[11] Congestive heart failure,
bacterial pneumonia, malignancy, and pulmonary embolus are responsible for most
of these cases.

International occurrence

The estimated prevalence of pleural effusion is 320 cases per 100,000 people in
industrialized countries, with a distribution of etiologies related to the prevalence of
underlying diseases.[4]

Sex-related demographics

In general, the incidence of pleural effusion is equal between the sexes. However,
certain causes have a gender predilection. About two thirds of malignant pleural
effusions occur in women, in whom they are associated with breast and gynecologic
malignancies.

Pleural effusion associated with systemic lupus erythematosus is also more

common in women than in men. In the United States, the incidence of pleural
effusion in the setting of malignant mesothelioma is higher in males, probably
because of their higher occupational exposure to asbestos.

Pleural effusions associated with chronic pancreatitis are more common in males,
with the majority of male cases having alcoholism as the etiology. Rheumatoid
effusions also occur more commonly in males than in females.

Race- and age-related demographics

Because pleural effusion is a manifestation of underlying disease, racial differences

will most likely reflect racial variation in incidence of the causative disorder.

Pleural effusions usually occur in adults. However, they appear to be increasing in

children, often in the setting of underlying pneumonia.[12] Fetal pleural effusions
have also been reported and under certain circumstances may be treated prior to
delivery.[13]

Prognosis
The prognosis in pleural effusion varies in accordance with the conditions
underlying etiology. However, patients who seek medical care earlier in the course of
their disease and those who obtain prompt diagnosis and treatment have a
substantially lower rate of complications than do patients who do not.

Morbidity and mortality

Morbidity and mortality of pleural effusions are directly related to cause and stage of
the underlying disease at the time of presentation, and biochemical findings in the
pleural fluid.

Morbidity and mortality rates in patients with pneumonia and pleural effusions are
higher than those in patients with pneumonia alone. Parapneumonic effusions, when

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recognized and treated promptly, typically resolve without significant sequelae.

However, untreated or inappropriately treated parapneumonic effusions may lead to
empyema, constrictive fibrosis, and sepsis.

Development of a malignant pleural effusion is associated with a very poor

prognosis, with median survival of four months and mean survival of less than one
year.[14] . The most common associated malignancy in men is lung cancer. The most
common associated malignancy in women is breast cancer. Median survival ranges
from 3-12 months, depending on the malignancy. Effusions from cancers that are
more responsive to chemotherapy, such as lymphoma or breast cancer, are more
likely to be associated with prolonged survival, compared with those from lung
cancer or mesothelioma.[15, 16]

Cellular and biochemical findings in the fluid may also be indicators of prognosis.
For example, a lower pleural fluid pH is often associated with a higher tumor burden
and a worse prognosis.[17]

Clinical Presentation

Contributor Information and Disclosures

Author
Jeffrey Rubins, MD Professor of Medicine, University of Minnesota Medical School; Director, Palliative Medicine,
Hennepin County Medical Center

Jeffrey Rubins, MD is a member of the following medical societies: American Academy of Hospice and Palliative
Medicine, American College of Chest Physicians

Disclosure: Nothing to disclose.

Chief Editor
Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James
H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians,
American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements
Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of
Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine
Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine
Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake
Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies:
American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American
College of Chest Physicians, American College of Physicians, American Federation for Medical Research,
American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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