Etiology
- Infectious causes: (viral causes are often associated with transudative pleural effusions, and the others often have exudative pleural effusions)
- Viral (e.g., coxsackie, cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus, Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus, influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza): often associated with a transudative pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
- Bacterial (e.g., pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (50% develop pleuritis), tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, Legionnaires disease, rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia)
- Parasitic (e.g., amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Amebiasis)
- Fungal infections
- Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver or splenic abscesses
- Systemic causes: (often with transudative pleural effusions)
- Autoimmune disorders: rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis (5% have pleuritis) or systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus (50% have pleuritis), others
- Inflammatory bowel disease
- Lung cancer, mesothelioma Mesothelioma Malignant mesothelioma (usually referred to as simply "mesothelioma") is the malignant growth of mesothelial cells, most commonly affecting the pleura. The majority of cases are associated with occupational exposure to asbestos that occurred > 20 years before clinical onset, which includes dyspnea, chest pain, coughing, fatigue, and weight loss. Malignant Mesothelioma (from asbestos exposure), other malignancies involving the pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura
- Lymphoma
- Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
- Cardiac problems (ischemia, pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis)
- Pancreatitis
- Traumatic or mechanical causes: (trauma often associated with
hemothorax
Hemothorax
A hemothorax is a collection of blood in the pleural cavity. Hemothorax most commonly occurs due to damage to the intercostal arteries or from a lung laceration following chest trauma. Hemothorax can also occur as a complication of disease, or hemothorax may be spontaneous or iatrogenic.
Hemothorax)
- Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax (90% develop pleuritis)
- Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism (5%–20% associated with pleuritis)
- Chest injuries (blunt or penetrating):
- Rib fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures
- Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a "false lumen." Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection
- Disruption or obstruction of the thoracic duct, leading to accumulation of lymph in the pleural space (chylothorax)
- Medications:
- Amiodarone, bleomycin, bromocriptine, cyclophosphamide, methotrexate, procarbazine, hydralazine, procainamide, quinidine, etc.
Pathogenesis
- Anatomical pathology considerations:
- Pleural space: a potential space lined by a single layer of mesothelial cells supported by connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue
- Inflammation can cause inflammatory mediators to infiltrate the pleural space, causing the production of pleural fluid, which can be transudative or exudative; if frank pus is within the space, then it is called an “empyema,” which is different from an abscess because the neutrophils accumulate in a pre-formed space.
- Blood, air, or chyle can also enter the pleural space.
- Pain receptors
- Present on the parietal pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura
- Peripheral and lateral hemidiaphragm pleural membranes are innervated by intercostal nerves that also have cutaneous distributions.
- Central diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura is innervated by the phrenic nerve and can refer pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain to the ipsilateral neck and shoulder.
- Pain is transmitted by fast-conducting A-delta fibers → sharp and well-localized pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
Clinical Presentation
- Sharp, sudden
chest pain
Chest Pain
Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies.
Chest Pain (i.e. pleuritic
pain
Pain
Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care.
Physiology of Pain) upon inhalation and exhalation
- Worsens with increased intrathoracic pressure (e.g., deep respiration, coughing, sneezing, body trunk movement)
- Other common descriptors: dull, burning, catching, stabbing
- Can be alleviated when the pleural cavity fills with fluid, as in pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
- Dry cough
- Sneezing
- Dyspnea and rapid, shallow breathing
- Fever and/or chills if infectious
- Other signs and symptoms which present will depend on the underlying cause
Diagnosis
- Blood tests
- Test for presence of infection via elevated WBC on CBC with differential
-
Antibodies
Antibodies
Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.
Immunoglobulins can be tested to determine/rule out autoimmune conditions:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- D-dimer elevation can suggest pulmonary embolism.
- Cardiac troponin is suggestive of myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction.
- Physical examination
- Pleural friction rub upon auscultation
- May also reveal other abnormal sounds if concomitant lung disease is present, such as crackles and decreased breath sounds in pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
- Imaging
- Chest X-ray: may show air or fluid in the pleural space, and suggest a cause (e.g., fractured rib, malignancy)
- Consolidation can represent pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia.
- Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax
- A widened mediastinum Mediastinum The mediastinum is the thoracic area between the 2 pleural cavities. The mediastinum contains vital structures of the circulatory, respiratory, digestive, and nervous systems including the heart and esophagus, and major thoracic vessels. Mediastinum and Great Vessels is indicative of aortic dissection.
- Cardiomegaly can represent pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis.
- Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy or cavitation may suggest tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis.
- CT scan: may show signs of pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia or the presence of a causative abscess, tumor, or blood clot within the lung with angiography
- Ultrasound: can be used to confirm pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion at bedside
- Chest X-ray: may show air or fluid in the pleural space, and suggest a cause (e.g., fractured rib, malignancy)
- Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG): used to help diagnose cardiac causes including myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, and pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
- Diagnostic procedures
- Sputum testing: test for infectious causes, especially tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
- Thoracentesis: Fluid is aspirated for laboratory analysis.
- Exudative pleural fluid shows elevated pleural fluid protein, elevated lactate dehydrogenase, or leukocytosis.
- Use Light’s criteria (see table below) to determine etiology.
- Thoracoscopy: direct visualization of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs and pleural cavity to visualize abnormalities and obtain a tissue sample for pathologic examination and possible microbiologic culture
| Transudate | Exudate | |
|---|---|---|
| Protein (pleural/serum) | ≤ 0.5 | > 0.5 |
| LDH (pleural/serum) | ≤ 0.6 | > 0.6 |
| Pleural LDH ≤ two-thirds upper limit of normal serum LDH | Pleural LDH > two-thirds upper limit of normal serum LDH | |
| Common causes |
|
|
Patient undergoing thoracentesis. Note that the person sits upright and leans on a table. Excess fluid from the pleural space is drained into a bag.
Image: “A person undergoing thoracentesis.” by National Heart, Lung and Blood Institute. License: Public Domain
Chest X-ray showing advanced bilateral pulmonary tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis. Notice the presence of bilateral pulmonary infiltrates (white triangles) and cavitary formation (black arrows) in the right apical region.
Image: “An anteroposterior X-ray of a patient diagnosed with advanced bilateral pulmonary tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis” by Centers for Disease Control and Prevention’s Public Health Image Library (PHIL). License: Public Domain
CT pulmonary angiography showing a “saddle embolus” at the bifurcation of the main pulmonary artery and thrombus burden in the lobar arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries on both sides. Can cause pleuritic symptomatology.
Image: “CT pulmonary angiography images confirming the presence of a saddle embolus” by Aung Myat and Arif Ahsan. License: CC BY 2.0
Management
- Relief of symptoms:
- NSAIDs are used to reduce pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
- Opiate analgesics
- Corticosteroids
- Removal of the fluid, air, or blood from the pleural space:
- Thoracentesis can be diagnostic as well as therapeutic
- The insertion of a chest tube may be required in the case of large amounts of fluid accumulation.
- Treatment of the underlying condition
Clinical Relevance
- Pleural effusion: the presence of fluid in the pleural cavity, which can be classified as transudative or exudative depending on the underlying cause.
- Hemothorax: a collection of blood in the pleural cavity. It usually occurs following chest trauma which leads to lung laceration or damage to intercostal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries.
- Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax: a collection of air in the pleural space, which leads to a collapsed lung due to the loss of negative pressure between the visceral and parietal pleural membranes.
- Empyema: constitutes the accumulation of pus within a pre-existing cavity, such as pleural empyema.
- Pneumonia: acute or chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of lung tissue, which can be caused by an infection from bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, viruses, or fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology: Overview. In more rare cases, pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia can also be caused by toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.
