This document provides an overview of diseases of the pleura, including pleurisy, pleural effusion, empyema, pneumothorax, and mesothelioma. It discusses the anatomy and physiology of the pleura, causes and characteristics of pleural diseases, and how they are investigated and managed. Key points include that pleurisy is inflammation of the pleura causing chest pain, pleural effusion is abnormal fluid accumulation in the pleural space, and the fluid can be transudative or exudative depending on the underlying cause such as heart failure or infection/malignancy respectively.

1. Diseases of the pleura
Pratap Sagar Tiwari, MD, Internal Medicine
Note: This is lecture class slides for MBBS Students

2. Topics
• Pleurisy
• Pleural effusion
• Empyema
• Pneumothorax
• Mesothelioma

3. Pleura
• A pleural cavity is the thin fluid-filled
space between the two pleurae (visceral
and parietal) of each lung.
• The pleural cavity contains pleural fluid,
which allows the pleurae to slide
effortlessly against each other during
ventilation.(Normal amount:0.13 ml/kg).1
• Most fluid is produced by the parietal
circulation (intercostal arteries) and
reabsorbed by the lymphatic system.
• 1. Noppen M. Normal volume and cellular contents of pleural fluid. Curr Opin Pulm Med. 2001 Jul.
7(4):180-2.
Anatomy & Physiology, Connexions Web site.
http://cnx.org/content/col11496/1.6/

4. Pleurisy
• Pleurisy is not a diagnosis but a term used to describe pleuritic pain
resulting from any one of a number of disease processes involving the
pleura.
• There are many possible causes of pleurisy but viral infections
spreading from the lungs to pleural cavity are the most common.
• The inflamed pleural layers rub against each other every time the
lungs expand to breathe in air. This can cause sharp pain when
breathing, also called pleuritic chest pain.
• Pleurisy is a common feature of pulmonary infection and infarction; it
may also occur in malignancy.

5. Clinical features
• Sharp pain that is aggravated by deep breathing or coughing is
characteristic.
• On examination, rib movement is restricted and a pleural rub (rough ,
scratchy, grating leathery sound as inflamed pleura rub against each
other) may be present.
Pleural rub:
More often heard on inspiration than expiration, the pleural friction rub is easy to confuse with a pericardial
friction rub.
To determine whether the sound is a pleural friction rub or a pericardial friction rub, ask the patient to hold
his breath briefly. If the rubbing sound continues, its a pericardial friction rub because the inflamed pericardial
layers continue rubbing together with each heart beat - a pleural rub stops when breathing stops.

6. Extra notes : Pain
• Causes of Chest Pain
• Cardiac pain
• Angina vs Oesophageal pain
• Angina vs Myocardial infarction
• Characteristics of pericarditic pain
• Pain caused by dissection of the thoracic aorta
Reference: Mcleods clinical examination 11th edition

7. Chest Pain Causes: Central vs Non-central
Central
Tracheal Infection
Cardiac Acute myocardial infarction/ischaemia
Oesophageal Oesophagitis/ Rupture
Great vessels Aortic dissection
Non-central
Pleural •Infection: pneumonia ,bronchiectasis ,Tb
•Malignancy: lung cancer ,mesothelioma
Pneumothorax
Pulmonary infarction
Chest wall •Malignancy: lung cancer ,mesothelioma
Persistent cough
Muscle sprains
Bornholm's disease (Coxsackie B infection)
Tietze's syndrome (costochondritis)
Heartburn is a hot, burning retrosternal discomfort
which radiates upwards.
When heartburn is the principal symptom, gastro-
oesophageal reflux disease is the most likely diagnosis.
It is often accompanied by acid reflux due to
regurgitation of acid producing a sour taste in the
mouth.
The burning quality and upward radiation of heartburn,
and its occurrence on lying flat or bending forward help
to differentiate it from retrosternal chest pain originating
from the heart.

8. Extra notes: Types of cardiac pain
Type Cause Characteristics
Angina Coronary stenosis Precipitated by exertion, eased by rest and/or glyceryl trinitrate
Characteristic distribution
Myocardial infarction Coronary occlusion Similar sites to angina, more severe, persists at rest
Pericarditis pain Pericarditis Sharp, raw or stabbing Varies with movement or breathing
Aortic Pain Aortic dissection Severe, sudden onset, radiates to the back
Reference: Mcleods clinical examination 11th edition

9. Angina vs Oesophageal pain
Angina Oesophageal pain
Usually precipitated by exertion Can be worsened by exertion, but often present at other times
Rapidly relieved by rest Not rapidly relieved by rest
Retrosternal and radiates to arm and jaw Retrosternal or epigastric, sometimes radiates to arm or back
Seldom wakes patient from sleep Often wakes patient from sleep
No relation to heartburn Sometimes related to heartburn
Rapidly relieved by nitrates Often relieved by nitrates
Typical duration 2-10 minutes Variable duration

10. Angina vs Myocardial infarction
Angina Myocardial infarction
Site: retrosternal, radiates to arm, pigastrium, neck As for angina
Precipitated by exercise or emotion Often no obvious precipitant
Relieved by rest, nitrates Not relieved by rest, nitrates
Mild/moderate severity Usually severe (may be 'silent')
No increased sympathetic activity Increased sympathetic activity
No nausea or vomiting Nausea and vomiting are common

11. Characteristics of pericarditic pain
Site Retrosternal, may radiate to left shoulder or back
Prodrome May be preceded by a viral illness
Onset No obvious initial precipitating factor; tends to fluctuate in intensity
Nature May be stabbing or 'raw' - 'like sandpaper'. Often described as sharp, rarely as
tight or heavy
Made worse by Changes in posture, respiration
Helped by Analgesics, especially non-steroidal anti-inflammatory drugs
Accompanied by Pericardial rub

12. Characteristics of pain caused by dissection of
the thoracic aorta
Site Often first felt between shoulder blades, and/or behind the sternum
Onset Usually sudden
Nature Very severe pain, often described as 'tearing'
Relieved by No, tends to persist. Patients often restless with pain
Accompanied by Hypertension, asymmetric pulses, unexpected bradycardia, early diastolic murmur,
syncope, focal neurological symptoms and signs

13. End of extra notes

14. Investigation: Pleurisy
• Every patient should have a chest X-ray, but if normal, this does not
exclude a pulmonary cause of pleurisy.
• A preceding history of cough, purulent sputum and pyrexia is
presumptive evidence of a pulmonary infection which may not have
been severe enough to produce a radiographic abnormality, or which
may have resolved before the chest X-ray was taken.

15. Management: Pleurisy
• The primary cause of pleurisy must be treated.
• NSAIDs

16. Pleural effusion: Case summary
• 30 years old male c/o SOB of 2 weeks duration.
• SOB: insidious, progressive.
• A/w dry cough, Low grade evening rise fever.
• H/o Loss of weight, decrease appetite and night sweats.

17. Pleural effusion
Source: wikipedia
A pleural effusion is an abnormal collection of
fluid in the pleural space resulting from excess
fluid production or decreased absorption or
both.1
Ref:
1. Diaz-Guzman E, Dweik RA. Diagnosis and management of pleural effusions: a practical approach. Compr Ther. 2007 Winter. 33(4):237-46.

18. Mechanisms of Fluid accumulation
1. increased drainage of fluid into the space
2. increased production of fluid by cells in the space
3. decreased drainage of fluid from the space

19. Development of Pleural effusion
The normal pleural space contains approximately 0.1 mL/kg 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.
• Altered permeability of pleural membranes (eg, inflammation, malignancy, pul embolus)
• Reduction in IV oncotic pressure (eg, hypoalbuminemia due to nephrotic syn or cirrhosis)
• Increased capillary hydrostatic pressure in systemic /pulmonary circulation (eg, CHF)
• 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)

20. Types
• Pleural effusion have been classically divided into transudative and exudative effusions.
Other types are empyema, Hemorrhagic pleural effusion and Chylous or chyliform
effusion.
• A transudative pleural effusion occurs when alterations in the systemic
factors that influence pleural fluid movement result in a pleural effusion.
Examples are elevated pleural capillary pressure with heart failure, and
decreased serum oncotic pressure with the nephrotic syndrome, hepatic
cirrhosis.
• In contrast, exudative pleural effusions occur when the pleural surfaces
themselves are altered. Inflammation of the pleura, leading to increased
protein in the pleural space, is the most common cause of exudative
pleural effusions.

21. Causes of Pleural effusion
EXUDATIVE (usually unilateral)
Parapneumonic effusion
Tuberculosis
Connective tissue disorders
Malignancy
Subphrenic abscess
Infections /Pancreatitis
Pulmonary embolism (E+T)
TRANSUDATIVE (usually bilateral )
Congestive heart failure
Cirrhosis
Nephrotic syndrome
Constrictive pericarditis (*)
Peritoneal dialysis (hypervolemia)
Hypothyroid pleural effusion(*)(pleural capillary leak)
Atelectasis
CHYLOTHORAX(*)
Congenital chylothorax
Post-traumatic
HEMOTHORAX
Blunt trauma
Malignancy
*=mostly exudative
URINOTHORAX
Due to obstructive uropathy
• Meigs syndrome (benign pelvic neoplasm with associated ascites and pleural effusion)
• Yellow nail syndrome (yellow nails, lymphedema, pleural effusions)
• Chylothorax (acute illness with elevated triglycerides in pleural fluid)
• Pseudochylothorax (chronic condition with elevated cholesterol in pleural fluid)

22. Drugs causing Pleural effusion
• Minoxidil
• Amiodarone
• Beta blockers
• Calcium channel blockers
• Chemo (methotrexate, bleomycin, cyclophosphamide)
• Ramipril
• Procainamide
• Hydralazine

23. History
• A detailed medical history should be obtained from all patients presenting
with a pleural effusion, as this may help to establish the etiology.
• For eg, a H/O chronic hepatitis or alcoholism with cirrhosis suggests
hepatic hydrothorax or alcohol-induced pancreatitis with effusion.
• The patient should be asked about a history of cancer, even remote, as
malignant pleural effusions can develop many years after initial diagnosis.
• An occupational history should also be obtained, including potential
asbestos exposure, which could predispose the patient to mesothelioma or
benign asbestos-related pleural effusion.
• The patient should also be asked about medications they are taking.

24. • The clinical manifestations of pleural effusion are variable and often
are related to the underlying disease process.
• The most commonly associated symptoms are progressive dyspnea,
cough, and pleuritic chest pain.
• Pain may be mild or severe.
• It is typically described as sharp or stabbing and is exacerbated with deep inspiration.
• Pain may be localized to the chest wall or referred to the ipsilateral shoulder or upper abdomen because of
diaphragmatic irritation.
• Pain may diminish in intensity as the pleural effusion increases in size and the inflamed pleural surfaces are no
longer in contact with each other.

25. Additional points
• Other symptoms in association with PE may suggest the underlying
disease process.
• Increasing lower extremity edema, orthopnea, and PND may all occur
with CCF.
• Night sweats, fever, hemoptysis, and weight loss should suggest TB.
• Hemoptysis also raises the possibility of malignancy, other
endotracheal or endobronchial pathology, or pulmonary infarction.
• An acute febrile episode, purulent sputum production, and pleuritic
chest pain may occur in patients with an effusion associated with
pneumonia.

26. Physical examination
• Physical findings in pleural effusion are variable & depend on the vol of the effusion. Generally, there
are no physical findings for effusions <300 mL. With effusions >300 mL, findings may include the
following:
• Asymmetrical chest expansion, with diminished expansion on the side .
• Mediastinal shift away from the effusion. (> 1000 mL)
• Dullness to percussion, decreased tactile fremitus.
• Diminished or inaudible breath sounds
• Egophony at the most superior aspect of the pleural effusion
• Pleural friction rub
Note:Displacement of the trachea and mediastinum toward the side of the effusion is an important clue to
obstruction of a lobar bronchus by an endobronchial lesion, which can be due to malignancy .

27. DIAGNOSIS
Chest radiograph (x-ray)
-able to distinguish >200ml of fluid (blunted costophrenic angles)
-Chest radiographs acquired in the lateral decubitus position are more sensitive
and can pick up as little as 50 ml of fluid.
Pleural fluid analysis
Chest ultrasound
-locates small amounts or isolated loculated pockets of fluid
-able to give precise position of accumulation
Computed Tomography (CT) scan
-Differentiates between fluid collection, lung abscess, or tumor

28. A posteroanterior and lateral chest radiograph of pleural effusion
blunting of the posterior costophrenic angle
28Dr. Canmao xie

29. Workup
• Thoracocentesis
• Distinguish Transudate or Exudate
Normal pleural fluid has the following characteristics:
• Clear
• A pH of 7.60-7.64
• Protein content of less than 2% (1-2 g/dL)
• Fewer than 1000 (WBCs) per cubic ml
• Glucose content similar to that of plasma
• Lactate dehydrogenase less than 50% of plasma

30. Extra note
• Frankly purulent fluid =empyema
• A putrid odor suggests = anaerobic empyema
• A milky, opalescent fluid = chylothorax (dt lymphatic obstruction by
malignancy or thoracic duct injury by trauma or surgical procedure)
• Grossly bloody fluid = trauma, malignancy, postpericardiotomy syndrome,
or asbestos-related effusion.( A pleural fluid hematocrit level of >50% of
the peripheral hematocrit level defines a hemothorax, which often requires
tube thoracostomy)
• Black pleural fluid =infection with Aspergillus or Rizopus, malignant
melanoma, non-small cell lung cancer or ruptured pancreatic pseudocyst.

31. Distinguishing Transudates From Exudates :
Light’s criteria
The fluid is considered an exudate if any of the following are found:
1. Ratio of pleural fluid to serum protein >0.5
2. Ratio of pleural fluid to serum LDH >0.6
3. Pleural fluid LDH > 2/3rd of the upper limits of normal serum LDH
The fluid is considered a transudate if all of the above are absent.

32. TREATMENT
Therapy should be aimed at the underlying disease.
Therapeutic drainage for relief of symptoms.
Transudative effusion by fluid overload as in cardiac or renal failure: diuretics & fluid
management
Nephrotic syndrome and cirrhosis of liver: Albumin infusion
Tubercular pleural effusion: Anti-tubercular drugs
Note: Pleural biopsy should be considered, only if TB or malignancy is suggested.
Effusions that are chronic or recurrent and causing symptoms can be treated with pleurodesis
or by intermittent drainage with an indwelling catheter.
Pleurodesis is done by instilling a sclerosing agent into the pleural space to fuse the visceral and
parietal pleura and eliminate the space. The most effective and commonly used sclerosing
agents are talc, doxycycline, and bleomycin delivered via chest tube or thoracoscopy.
The effusion is empyema if bacteria are present on Gram staining, the pH is <7.20, glucose<40 mg/dl
and LDH>1000 IU/L and there are >100,000 neutrophils/µL. ========= Chest tube drainage

33. End of Slides
Next lecture:
Pneumothorax and Mesothelioma
References :
• http://emedicine.medscape.com/article/299959-overview
• Uptodate 20.3
• Davidson
• Mcleods’ Examination