PLEURiSy

by: Dr. zerihun a. (internist)

 Introduction
• The pleural space lies between the lung and the chest wall and
normally contains a very thin layer of fluid, which serves as a
coupling system.
• A pleural effusion is present when there is an excess quantity
of fluid in the pleural space.
 Etiology

• Pleural fluid accumulates when pleural fluid formation exceeds pleural fluid
absorption.
• Normally, fluid enters the pleural space from the capillaries in the parietal pleura
and is removed via the lymphatics in the parietal pleura.
• Fluid also can enter the pleural space from the interstitial spaces of the lung via
the visceral pleura or from the peritoneal cavity via small holes in the diaphragm.
• The lymphatics have the capacity to absorb 20 times more fluid than is formed
normally.
• Diagnostic approach:
– Clinical presentation
– Imaging
– Diagnostic thoracentesis.
– Pleural biopsy
• Clinical presentation:
– Ranges for asymptomatic to very symptomatic.
– Dyspnea, cough and pleuritic chest pain.
– Dullness to percussion, decreased air entry and decreased tactile fremitus
over the area of the effusion.
Chest x ray:
 PA film:
 175ml results obliteration of lateral CPA
 500ml results obliteration of diaphragmatic contour.
 1000ml results opacification to the level of 4th rib
 Decubitus film
 Can detect as little as 5-10 ml of fluid
 Supine film:
 considerable quantities must be present
Loculated effusion
 Pleural fluid may become
encapsulated by adhesion
 It occurs in intense pleural
inflammation
 Produce a characteristic D
shape.
b) Ultrasound
 Permits easy identification of free or loculated pleural effusions
 Highly sensitive & specific, can detect as low as 5ml

c) Computed tomography
 Detects small pleural effusions ( 2-10ml)
 Assess thickness of parietal & visceral pleura
 Contrast enhancement of the pleura
 Diagnostic- Thoracocentesis

 Indication : if the thickness of the fluid on the decubitus

chest radiograph is greater than 10 mm
 Caution in cases of
 Bleeding diathesis
 Mechanical ventilation: risk of pneumothorax
Active skin lesion at the site of pleural tap
 Classification of pleural effusion
 Light’s criteria is used
 Light's criteria identify approximately 25% of transudative
effusions as exudates
 How can these mislabeled transudates be identified?
 Transudative Effusions

I. Heart Failure
 Commonest cause of transudative effusion
 Seen in 50- 90% of admitted HF patients
 How does effusion occur?

 Due to increased interstitial fluid which overwhelms the capacity of the

parietal pleura to remove fluid
 In Corpulmonale by increasing systemic venous pressure
 Characteristic of the effusion

 Bilateral ( 60-85%)
 If unilateral, right side predominate (2:1)
 Analysis is not indicated unless other ddx are entertained
 In 25-30% of pts the analysis may be suggestive of exudative effusion

 Due to diuretic use

 Due to RBCs
 Pleural fluid assay of: NT-proBNP >1500 pg/ml and BNP>400 pg/ml are highly
suggestive.
 Treatment- treat the underlying condition.
II. Hepatic Hydrothorax
 Transudative effusion in cirrhotic pts with PHTN in the absence of other
explanation
 Among cirrhotic pts : 6% have clinical apparent hepatic hydrothorax
: 15% have evidence of effusion on U/S or CT
 How does effusion occur?
Ascites pass thru stomas that are found in the diaphragm
 Characteristic of the effusion
 Right side ( 80%), left (18%), bilateral(2%)
 In 10% analysis could be falsely exudative
 Spontaneous bacterial pleuritis is found in 15% of patient with hepatic
hydrothorax
 ANC > 250 cells/μL plus positive culture
ANC > or = 500 plus culture negative
 Treated with antibiotics like SBP
 Chest tube is contraindicated.
 Non- Malignant Exudative Effusions
INFECTIOUS
A. Parapneumonic effusion & Empyema
 PPE is effusion cause by Pneumonia, lung abscess or bronchiectasis
 Empyema, is pus in the pleural space
 20- 57% of hospitalized CAP patients develop PPE
 Common risk factors : DM, Alcoholism , Other immunodeficiency conditions
 PPE is associated with high mortality compared with pneumonia without PPE

» 3.5X more if patient has unilateral PPE

» 7x more if patient has bilateral PPE

 How does effusion occur?
 Inflammatory mediators from adjacent lung parenchyma enters the
pleura space
 Mediators result increase permeability of partial pleura capillaries
resulting in influx of inflammatory mediators & protein

 Empyema has three stages: Exudative

: Fibropurulent
: Organizing
 Etiologic agents

 Gram positive aerobes are the commonest cause in PPE followed by

gram negative aerobes
 Anaerobes are important in empyema

 Clinical presentation tend to be acute in aerobes and subacute in

anaerobes
 TREATMENT

 Depends on the classification

 Uncomplicated PPE : Antibiotics only
 Complicated PPE: Antibiotic plus Drainage
a
 Drainage
 We have different options
 Chest tube

 Easy and less expensive

 Fibrinolytic plus mucolytic agents
• tPA 10mg and DNAse 5mg administered twice daily for three days is appropriate
• For patients with ongoing signs of infection(fever, leukocytosis, anorexia) with
incompletely drained empyema due to loculation
 VATS

 Indications: If pleural fluid is incompletely drained after 10 days

 Other option

 Open thoracotomy and decortication

 Tuberculous Pleurisy

 The 2nd most common extra pulmonary TB

 Occur in 30% of patients with pulmonary TB
 It is the cause 30- 80% of exudative pleural effusion in developing
countries
 Patients tend to be younger & immunocompetent when it occurs alone
 How does effusion occur?
 Due to delayed hypersensitivity when tuberculin protein gain access to
pleural space
 Direct invasion of MTB
 CLINICAL PRESENTATION

 Could present as acute or subacute presentation

 Patient may have cough, pleuritic chest pain, fever, other TB symptom
complex
 Usually its unilateral, mild to moderate effusion, resolves in 4-16 weeks
 In some patients it may result in empyema
 DIAGNOSIS
 Definitive diagnosis requires microbiology or pathology evidence
 Imaging : 20% of pts CXR and 80% of pts CT have concomitant pulmonary TB

Analysis : Cell count ( lymphocyte predominate )

: Protein ( > 5g/dl)
: Glucose & PH usually normal
: AFB….20-30% positive ( in empyema its >90%)
: GeneXpert …. 40-45% positive ( in empyema its around 98%)
: Culture ….30% in solid media/ 50% in liquid media ( higher in RVI
pts )
: Pleural biopsy …. Caseating granuloma (98%)
Adenosine deaminase (ADA) Interferon-Gamma

 Produced by T-lymphocyte  Produced by T-lymphocyte

 Lymphocyte/Neutrophil ration >0.75  Level > 3.7 IU/ml is suggestive of TB

& ADA > 40U/L is important to dx pleurisy
TB pleurisy.
 Sensitivity/ specificity > 98%
 Sensitivity/ specificity > 97%
 Malignant Exudative Effusions

 Is the 2nd commonest cause of exudative pleural effusion worldwide

 Cause : Primary or Metastasis
Pleural fluid analysis Pleural fluid Cytology
 Positive yield ranges from 40-87%
 Appearance : Mostly hemorrhagic
 Yield depends on
 Cell count : WBC (1000-10,000)
– Amount of fluid sent for cytology
with lymphocyte predominance
– Type of malignancy
 Protein : Usually normal
 LDH : Usually elevated
 Glucose: Normal or Low
 PH: Normal or Low
 Amylase : Elevated in 10% of cases
 Lung cancer
• The term lung cancer, or bronchogenic carcinoma, refers to malignancies that
originate in the airways or pulmonary parenchyma.
• ~95% of all lung cancers are classified as either SCLC or NSCLC.
• This distinction is essential for staging, treatment, and prognosis.

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 Epidemiology
• Lung cancer is uncommon below age 40,
– rates increasing until age 80, after which the rate tapers off.
• The projected lifetime probability is ∼8% among males and ∼6% among females.
• Lung cancer remained the leading cause of cancer death, with an estimated 1.8
million deaths (18%), followed by colorectal, liver, stomach , and female breast
cancers.

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 RISK FACTORS
• Smoking tobacco(cigarettes) is the most important risk factor for the development of
lung cancer.
• Secondhand smoke is also a significant cause of lung cancer.
• Cigarette smokers have a 10-fold or greater increased risk of developing lung cancer
compared to those who have never smoked.
• One genetic mutation is induced for every 15 cigarettes smoked.
• There is a dose-response relationship between intensity of exposure and relative risk
of lung cancer.

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The risk for development of lung cancer correlates with:
• The number of cigarettes smoked per day
• Lifetime duration of smoking,

• Age at onset of smoking,

• Tar and nicotine content of the cigarettes
• Degree of inhalation,

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• Smoking cessation decreases the risk of lung cancer.
• Stopping tobacco use before middle age avoids more than 90% of the lung
cancer risk attributable to tobacco.
• Smoking cessation can even be beneficial in individuals
with an established diagnosis of lung cancer, as it is associated with
 Improved survival,
 Fewer side effects from therapy, and
 An overall improvement in quality of life.
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Chemical compounds in cigarette smoke

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• The International Agency for Research on Cancer (IARC) has identified at least 50
carcinogens in tobacco smoke.
• N-nitrosamines has been shown to induce adenocarcinoma in animal models.
Environmental and occupational exposures
– Asbestos
– Radon
Other Environmental Toxins
 Chromium, formaldehyde, ionizing radiation, nickel, polycyclic aromatic
hydrocarbons, and vinyl chloride

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• Prior lung diseases such as COPD, and tuberculosis have been linked to increased
risks of lung cancer as well.
OTHER FACTORS
 Radiation therapy
 HIV infection
 Pulmonary fibrosis
 Genetic factors
 Dietary factors
 Beta-carotene supplementation
 Viral infections(HPV, EBV, SEMIAN VIRUS 40)

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• Lung ca in never smokers
– Comprises ~15 – 20% of cases in men and over 50% in women

– Adenocarcinoma is more common

– It has been postulated that lung cancer occurs at a younger age

– The causative factors are not well understood.
– The risk factors that are considered to be most important among never-smokers are
 Secondhand smoke- 15 – 35%
 Radon
 Environmental exposures
– Asbestos, chromium, and arsenic
 Lung disease
 Oncogenic viruses
 Genetic factors

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 Histopathology of lung ca

• A tissue diagnosis is necessary

– to determine whether a lung cancer is a NSCLC or an SCLC

– to rule out a nonmalignant process or lung metastasis

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• The WHO classification system divides epithelial lung cancers into four major cell
types:
• Small-cell lung cancer (SCLC), (20-25% )
• Adenocarcinoma,
• Squamous cell carcinoma, and collectively known as NSCLC(~80%)
• Large-cell carcinoma;.
• SCLC may be distinguished from NSCLC by the presence of neuroendocrine
markers including CD56, neural cell adhesion molecule (NCAM), synaptophysin,
and chromogranin

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• The exact cell of origin for lung cancers is not clearly defined.
• Whether one cell of origin leads to all histologic forms of lung cancer
is unclear.
– Adenocarcinoma, evidence suggests that type II epithelial cells (or alveolar epithelial cells) have
the capacity to give rise to tumors.
– SCLC- neuroendocrine origin

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 Squamous cell carcinoma
• Slow growing
• Makes up 20-30% of all lung cancers
• more common in males
• most occur centrally in the large bronchi
• Uncommon metastasis that is slow, affects the liver, adrenal glands and lymph
nodes.
• Associated with smoking
• Not easily visualized on x-ray (may delay dx)

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 Adenocarcinoma
• Most common type of Lung cancer(~40% of all lung cancers)
• Common in non smokers
• Clearly defined peripheral lesions
• Easily seen on a CXR
• Highly metastatic in nature
- brain, liver, adrenal or bone metastasis

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 Large cell carcinomas

• Makes up <15% of all lung cancers

• Poorly differentiated cells
• Tends to occur in the outer part (periphery) of lung, invading sub-segmental
bronchi or larger airways.
• Metastasis is slow but early metastasis occurs to the kidney, liver organs as
well as the adrenal glands.

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 Small Cell Lung Cancer

• Most aggressive form of lung cancer

• Accounts ~20% of lung cancer
• Because of aggressive nature, at the time of diagnosis these tumors have often
metastasize to other parts of the body (brain, liver, and bone marrow.

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 CLINICAL MANIFESTATIONS

• Symptoms are nonspecific and variable, thereby delaying

• Over half of all patients diagnosed with locally advanced or metastatic
disease
• The findings are attributed to the primary lesion, local tumor growth,
invasion or obstruction of adjacent structures, growth at distant metastatic
sites, or a paraneoplastic syndrome.

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• Dyspnea is frequently a complaint of patients who present with bronchogenic
carcinoma.
• Hemoptysis in a smoker should raise suspicion of lung cancer.
• Clinicians should not be misled, because up to 5% of patients with hemoptysis
and a smoking history and a normal radiograph can harbor lung cancer.
• Because of the vascular nature of lung cancer, patients can also present with
massive hemoptysis.

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 Paraneoplastic syndromes
• Are common in patients with lung cancer, especially those with SCLC
1. hypercalcemia- from PTH related peptide production
2. SIADH - Hyponatremia
3. Cushings syndrome- ectopic secretion of ACTH
4. Neurologic –immune mediated
5. Hematologic- anemia, leukocytosis, thrombocytosis, hypercoagulable disorders
6. Hypertrophic osteoarthropathy

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 Screening for lung cancer

 The ACS recommends annual screening for lung cancer with LDCT in adults who
are ;
 55 to 80 years old
 Are current smokers or have quit smoking within the last 15 years
 Have at least a 30 pack-year smoking history

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 Investigation modalities
• CXR
• CT scanning
• PET
• MRI
• Sputum cytology
• TTFNAC
• Fiberoptic bronchoscopy
• EUS/EBUS
• Mediastinoscopy
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CXR

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 Diagnosis

• Tissue sampling is required to confirm a diagnosis

• Tumor tissue may be obtained via minimally invasive techniques such as
bronchial or transbronchial biopsy during fiberoptic bronchoscopy, by FNA or
percutaneous biopsy using image guidance, or via endobronchial ultrasound
(EBUS)-guided biopsy.

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 Staging
• The TNM staging system is used for treatment planning and prognostic
purposes in patients with NSCLC.
• Staging of SCLC usually uses the Veterans Administration Lung Study Group
designations of
 Limited (confined to one hemithorax) or extensive (beyond one
hemithorax) disease.

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Staging…NSCLC

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 Staging…..SCLC
• A two-stage system (VALSG), has been utilized instead of the TNM.
Limited-stage(LS) disease
 Disease confined to one hemithorax.
 Tumors with local extension and ipsilateral supraclavicular nodes.
 Able to be encompassed in the same radiation portal as the primarytumor.
Extensive stage (ES) disease
 Malignant pleural or pericardial effusions
 The presence of contralateral hilar or supraclavicular lymph nodes
 Extrathoracic disease

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 Management
• Multidisciplinary teams, including
– Oncologists(clinical and radiation)
– Thoracic surgeons
– Pulmonologist
– Trained nurses.
• Treatment is dependent on the type and stage of tumor.

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• In general, for NSCLC,
 Early lung cancer (stage I) is treated with surgery alone,
 Stage II lung ca is treated with surgery ff by adjuvant chemotherapy,
 Locally advanced lung cancer (stage IIIA and B) is treated with a
combination of chemotherapy and radiotherapy, and
 Metastatic disease (stage IV) is treated with chemotherapy alone.
• For small cell lung cancer,
 Localized disease is treated by chemoradiotherapy.
 Extensive disease is treated with chemotherapy alone.

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 Prognosis
• Stage of disease
 The TNM stage in patients with NSCLC is the factor that has the greatest
impact on prognosis.
The most important prognostic factor in patients with SCLC is the extent of
disease at presentation.
Limited stage disease, median survivals range from 15 to 20 months,
and the reported five-year survival rate is 10 - 13%.
Extensive-stage disease, the median survival is 8 to 13 months, and the
five-year survival rate is 1 to 2 percent
• Clinical parameters
– performance status
• Histopathology
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 Prevention
• Smoking cessation decreases the incidence of lung cancer (primary prevention) and
improves overall survival for those diagnosed with lung cancer (tertiary prevention).
• Increasing physical activity and decreasing exposure to radon, nickel, arsenic,
chromium, nitrogen mustard, and asbestos, which have also been linked to an
increased risk of lung cancer.

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 References
• Harrison’s textbook of internal medicine 21 st edition.
• Up-to-date 2022
• American cancer society

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Thank you
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