Pleural effusion - Etiopathogenesis, Clinical features, Advances in Management - Lights Haeffner Transudate Exudate

1. ETIOPATHOGENESIS
AND DIAGNOSTIC
APPROACH TO
PLEURAL EFFUSION
Chairperson –Dr. Chandrashekar K
Student- Dr. Vinod Kumar L

2. ANATOMY OF THE PLEURA
 The pleura is the serous membrane that covers the lung
parenchyma, the mediastinum, the diaphragm, and the rib
cage.
 This structure is divided into the visceral pleura and the
parietal pleura.
 Visceral and the parietal pleura meet at the lung root.

4. A film of fluid (pleural fluid) is normally present between the
parietal and the visceral pleura.
 This thin layer of fluid acts as a lubricant and allows the
visceral pleura covering the lung to slide.
 The space, or potential space, between the two layers of
pleura is designated as the pleural space. (18-20micron)
 The mediastinum completely separates the right pleural
space from the left in humans.

5. HISTOLOGY OF THE PLEURA
 The parietal pleura is composed of loose, irregular
connective tissue covered by a single layer of mesothelial
cells.
 Blood, lymph vessels and nerves are located in the
connective tissue.
 Visceral pleura is composed of two layers: the mesothelium
and connective tissue. Blood, lymph vessels and nerves are
located in the connective tissue.

6. PARIETAL PLEURA

7. PLEURAL FLUID
Volume
 The total pleural fluid volume in humans is
around 0.26 mL/kg
 Rate of production – 0.01ml/kg/hr
 Maximum rate of absorption – 0.2ml/kg/hr

8. PHYSICOCHEMICAL FACTORS
 Small amount of protein is normally present in the pleural
fluid - 1 to 1.5 g/dL
 Ionic concentrations in pleural fluid differ significantly from
those in serum.
 Bicarbonate concentration is increased by 20% to 25%
relative to that in plasma
 whereas the major cation (Na•) is reduced by 3% to 5%, and
the major anion (Cl-) is reduced by 6% to 9%.
 The concentration of K• and glucose in the pleural fluid and
plasma appears to be nearly identical.

9. BLOOD SUPPLY TO THE PLEURA
 The parietal pleura receives its blood supply from the
systemic capillaries.
 The venous drainage of the parietal pleura is primarily
by the intercostal veins, which empty into the inferior
vena cava or the brachiocephalic trunk.

10.  In general, the blood supply to the visceral pleura originates
from the systemic circulation through the bronchial arteries.
 Bronchial artery supplies most of the visceral pleura and a
small portion is through the pulmonary artery .
 The venous drainage of the visceral pleura is through the
pulmonary veins.

11. PLEURAL LYMPHATICS
 The lymphatic vessels of the costal pleura drain ventrally
toward nodes along the internal thoracic artery and
dorsally toward the internal intercostal lymph nodes near
the heads of the ribs.
 The lymphatic vessels of the mediastinal pleura pass to
the tracheobronchial and mediastinal nodes, whereas the
lymphatic vessels of the diaphragmatic pleura pass to the
parasternal, middle phrenic, and posterior mediastinal
nodes.

12.  The lymphatic vessels in the parietal pleura have many
branches. Some submesothelial branches have dilated
lymphatic spaces called lacunas .Stomas are found only
over the lacunas.
 At the stoma, the mesothelial cells with their microvilli are
in continuity with the endothelial cells of the lymphatic
vessels.
 These stomas with their associated lacunas and lymphatic
vessels are thought to be the main pathway for the
elimination of particulate matter from the pleural space .

13.  No stomas are seen in the visceral pleura, and the lymphatic
vessels of the visceral pleura are separated from the
mesothelial cells by a layer of connective tissue.
 The lack of stomas in the visceral pleura explains that fluid
from the pleural space does not enter the lymphatics in the
visceral pleura in humans.

14. INNERVATION OF THE PLEURA
 Sensory nerve endings are present in the costal and
diaphragmatic parietal pleura.
 The intercostal nerves supply the costal pleura and the
peripheral part of the diaphragmatic pleura.
 When either of these areas is stimulated, pain is perceived
in the adjacent chest wall.

15.  In contrast, the central portion of the diaphragm is
innervated by the phrenic nerve.
 Stimulation of this pleura causes the pain to be
perceived in the ipsilateral shoulder.
 The visceral pleura contains no pain fibers.

16. PHYSIOLOGY OF THE PLEURAL
SPACE
PLEURAL FLUID FORMATION
 Fluid that enters the pleural space can originate in the
pleural capillaries, the interstitial spaces of the lung, the
intrathoracic lymphatics, the intrathoracic blood vessels,
or the peritoneal cavity.

17. Pleural Capillaries
 The movement of fluid between the pleural capillaries and
the pleural space is believed to be governed by Starling's law
of transcapillary exchange

18.  Normally the fluid in pleural space due to capillaries is
governed by starling forces.
 But in disease states more fluid can accumulate from
interstitium.
 With increasing levels of interstitial fluid, it has been
shown that the subpleural interstitial pressure increases.

19.  The barrier to the movement of fluid across the visceral
pleura appears to be weak, even though the visceral
pleura is thick.
 Therefore, once the subpleural interstitial pressure
increases, it follows that fluid will traverse the visceral
pleura to the pleural space.

20. Peritoneal Cavity
 Pleural fluid accumulation can occur if there is free fluid
in the peritoneal cavity and if there are openings in the
diaphragm.
 Under these conditions, the fluid will flow from the
peritoneal space to the pleural space because the pressure
in the pleural cavity is less than the pressure in the
peritoneal cavity.

21. Thoracic Duct or Blood Vessel
Disruption
 If the thoracic duct is disrupted, lymph will accumulate
in the pleural space, producing a chylothorax .
 The rate of fluid accumulation with chylothorax can be
more than 2500 mL/day.
 In a like manner, when a large blood vessel in the thorax
is disrupted owing to trauma or disease, blood can
accumulate rapidly in the pleural space, producing a
hemothorax.

22. PLEURAL FLUID
ABSORPTION
Lymphatic Clearance
 The pleural space is in communication with the
lymphatic vessels in the parietal pleura by means of
stomas in the parietal pleura.
 No such stomas are present in the visceral pleura.
 Proteins, cells, and all other particulate matter are
removed from the pleural space by these lymphatics in
the parietal pleura .

23. Clearance through Capillaries in
Visceral Pleura
Several hundred milliliters of water probably traverse the
pleural membranes each day, but the net movement is of
only a few milliliters because the osmolarity is nearly
identical on each side of the membrane.

24. Transudate vs Exudate
Light's criteria :
 1 . Pleural fluid protein divided by serum protein
greater than 0.5
 2. Pleural fluid LDH divided b y serum LDH greater
than 0.6
 3 . Pleural fluid LDH greater than two thirds of the
upper limit of normal serum LDH

25. DIAGNOSTIC APPROACH

31. Pleural transudates
Increased hydrostatic pressure
 Congestive cardiac failure
 Constrictive pericarditis
 Pericardial effusion
 Constrictive cardiomyopathy
 Massive pulmonary embolism
Decreased capillary oncotic pressure
 Cirrhosis
 Nephrotic syndrome
 Malnutrition
 Protein-losing enteritis
 Small bowel disease

32. Transmission from peritoneum
 Any cause of ascites
 Peritoneal dialysis
 Liver transplantation
Increased capillary permeability
 Small pulmonary emboli
 Myxoedema
 Obstructed lung lymphatics
 Lung transplantation

33. Pleural exudates
Neoplasms
 Mesothelioma, very rarely pleural sarcoma
 Metastases
 Lymphoma
Infections
 Pneumonia, abscess
 Tuberculosis
 AIDS
 Hantavirus syndrome
 Fungal and actinomycotic disease
 Subphrenic abscess
 Hepatic amoebiasis

34. Immune disorders
 Post-myocardial infarct/cardiotomy
syndrome
 Rheumatoid disease
 Systemic lupus erythematosus
 Wegener’s granulomatosis
 Rheumatic fever
Abdominal diseases
 Pancreatitis
 Uraemia
 Other causes of peritoneal exudates

35. Pulmonary embolism and infarction
Other causes
 Sarcoidosis
 Drug reactions
 Radiation therapy
 Asbestos exposure
 Recurrent polyserositis
 Yellow nails syndrome
 Oesophageal rupture

36. Chest film showing left pleural effusion

37. PLEURAL TRANSUDATES
 Most common cause is cardiac failure
 This effusion is often unilateral initially, usually on the
right side
 In severe cases, bilateral
 Mechanism -
increased pulmonary interstitial pressure
increased capillary pressure transudation
of fluid from the lung.

38. Pulmonary embolism
 Transudative, but blood staining occurs in ¼ of cases
 These are often bilateral and small
 Associated with dome shaped or linear pulmonary
shadows

39. Hypoproteinemia
 Cirrhosis
 Nephrotic syndrome
and
 Protein malnutrition
Constrictive pericarditis ( old TB,
Rheumatoid disease, malignant
infiltration of the pericardium) and
constrictive cardiomyopathies are
usualy associated with ascitis
 This fluid tracks up into the right
pleural space through small defects
in the diaphragm producing a large
unilateral effusion.

40. Meigs syndrome
 Benign ovarian fibroma
 Ascitis
 right sided pleural effusion
Myxoedema
 Consequence of ascitis or pericardial effusion
 Rarely direct effect on pleural capillary permeability

41. PLEURAL EXUDATES
Neoplasms
 Mesothelioma
 Mets from bronchial, breast, stomach and ovarian Ca
 Malignant effusions are usually but not always blood
stained

42. Infections
 Bacterial pneumonia is associated with effusion in
40% of cases
 Tuberculosis
 Viral and mycoplasma

43. PARAPNEUMONIC
EFFUSIONS AND EMPYEMA
 Any pleural effusion associated with bacterial
pneumonia, lung abscess, or bronchiectasis is a
parapneumonic effusion .
 An empyema, by definition, is pus ( thick, purulent )in
the pleural space

44.  PATHOPHYSIOLOGIC FEATURES
 divided into three stages
 exudative stage
 fibropurulent stag
 organization stage

45. BACTERIOLOGIC FEATURES
 Aerobic organisms are isolated slightly more frequently
than anaerobic organisms
 S. aureus and S. pneumoniae account for approximately
70% of all aerobic gram-positive isolates.
 When there is a single aerobic gram-positive organism
in the pleural fluid, it almost always is S. aureus, S.
pneumoniae, or Streptococcus pyogenes.

46.  gram-positive aerobic organisms are isolated approximately
twice as frequently as are gram-negative aerobic organisms.
 Escherichia coli is the most commonly isolated gram-
negative aerobic organism,
 Klebsiella sp, Pseudomonas sp, and Hemophilus influenzae
are the next three most commonly isolated aerobic gram-
negative organisms, and these three organisms account for
approximately 75% of all aerobic gram negative empyemas
with a single organism.

47.  Bacteroides sp and Peptostreptococcus are the two most
commonly isolated anaerobic organisms from infected
pleural fluid.
 it is uncommon for a single anaerobic organism to be
isolated from pleural fluid.
 In patients with community-acquired pneumonia, the
organisms most commonly responsible were Streptococcus
intermedius-anginosus-constellatus (milleri) group , S.
pneumoniae, and other streptococcus species , S. aureus (
methicillin resistant Staphylococcus aureus [MRSA]), gram
negatives , and anaerobes

48.  In patients with hospital acquired parapneumonic effusions,
the most common organism was S. aureus ( MRSA ).
Streptococcus intermediusanginosus-constellatus (milleri)
was also the most common organism isolated in culture
positive complicated parapneumonic effusions.
 In the intensive care unit, gram-negative aerobic organisms
are most likely to be responsible, with K.pneumonia being
the most common organism .

49. TUBERCULOUS PLEURAL
EFFUSIONS
 When a tuberculous pleural effusion occurs in the absence
of radiologically apparent TB, it may be the sequel to a
primary infection 6 to 12 weeks previously or it may
represent reactivation TB.
 The tuberculous pleural effusion is thought to result from
rupture of a subpleural caseous focus in the lung into the
pleural space .
DELAYED HYPERSENSITIVITY plays a large
role in the pathogenesis of tuberculous pleural effusion.

50. Extensive right pleural calcification following tuberculosis effusion

51. Fatal left pyopneumothorax due to extensive pulmonary tuberculosis

52. IMMUNE DISORDERS
Rheumaoid arthritis-
 within 5 yrs of start of disease
 Straw colored or turbid
 Low glucose and pH and high LDH
 Rheumatoid factor and immune Complexes may be
found at higher titres than blood
 Thoracoscopy shows highly characteristic granular
appearance

53. Systemic lupus erythematosis
 Bilateral small effusions
 Lupus cell
 High titre of antinuclear antibodiesin the fluid is
diagnostic
 Fluid blood stained with normal glucose and low
LDH

54. ABDOMINAL DISEASES
Acute pancreatitis
 Transmission of inflammation through adjacent
diaphragm and of fluid through diaphragmaic
lymphatics.
 High amylase levels more than serum.

55. YELLOW NAILS SYNDROME
 Hypoplasia of lymphatic vessels
 Lymphedema
 Dystrophic changes in nails
 Intractable pleural effuusion
 Complicated by bronchiectasis, sinusitis or
protein losing enteropathy.

57. DRUGS
 Practolol
 sulphonamides
 Salicylates
 Β blockers
 Para aminosalicylic acid
 Methylsergide
 Nitrofurantoin

58. CLINICAL FEATURES
Symptoms
 Small effusions are often symptomless
 Very large effusions – pleuritic chest pain
 shortness of breath
 recurrent dry cough if fluid has accumulated
quickly

59. Signs
 Since most effusions are on the dependent part of pleural
space, diminished movements, dull note on percussion
and absent breath sounds are found here.
 bronchial breath sounds or aegophony may be heard
immediately above the effusion
 Large effusions displace the mediastinum to the opposite
side

60. Investigations
 Pleural aspiration and biopsy
 Imaging
 Examination of the fluid

61. ABRAM’S NEEDLE

64. Macroscopic appearances
 Transudate- clear and pale straw-coloured
 Exudate –amber-coloured and may be turbid if the cell count is high.
 Uniform blood-staining, of a red or brown colour,
frequently indicates pleural tumour, although infarction,
rheumatoid, leukaemic and tuberculous effusions may be
haemorrhagic.
 Milky fluid is usually due to chyle (see
 Purulent fluid in cases of frank empyema from that due to a high cell
content.
 A fluid with a shimmering sheen may contain high levels of cholesterol

65. Microscopic appearances
 Infective cause in lung or pleura, other than tuberculosis-
polymorphs are predominant.
 Tuberculosis – lymphocytes are predominant
 Pulmonary eosinophilia, polyarteritis nodosa, tropical
eosinophilia, filariasis and Hodgkin’s- eosinophils are
predominant
 Examination of the fluid for malignant cells

66. Biochemical tests
 protein content of pleural fluid 30g/L being taken as the
dividing line between transudateand exudate
 cholesterol content is usually less than 55mg/dL and the
fluid–blood ratio is 0.3 or below in transudates
 Glucose content may be low (<1.7mmol/L or 30 mg/dL) in
infected effusions and rheumatoid disease
 Lactate dehydrogenase is raised in exudates above the serum
level
 Amylase levels may be very high (>1000 u/L) in effusions due
to pancreatitis and oesophageal rupture

67. Further diagnostic tests
 Ultrasound.
 CT scan.
 Thoracoscopy can be carried out using a rigid
thoracoscope or video-assisted techniques with
biopsy of any pleural lesions seen.

68. MANAGEMENT
 The management of pleural effusion depends on the cause.
 Infective effusions should be treated with the appropriate
antibiotics and tube drainage may be necessary.
 Tuberculous effusions require antituberculosis and it is usual to
add corticosteroids (prednisolone 20mg daily or 2–3 weeks,
reducing over a further 2–4 weeks, speeds reabsorption and
prevents pleural fibrosis,
 Corticosteroids- sarcoidosis, systemic lupus erythematosus, the
post-cardiac injury syndrome and rheumatoid disease.

69.  Large malignant pleural effusion-Promote pleurodesis, To
prevent lung compression by instillation of
1. nitrogen mustard
2. radioactive colloidal gold
3. tetracycline SUCCESS RATE 60%
4. doxorubicin
5. quinacrine
 Use of Corynebacterium parvum

70. Pleural manifestations of
asbestosis
 Pleural disease is the most common manifestation of
asbestos exposure
1. pleural plaques
2. diffuse pleural thickening
3. rounded atelectasis
4. Asbestos related pleural effusion

71. Pleural plaques
 Focal round irregular white lesions found on parietal and
rarely visceral pleura
 Asbestos fibers scratch, irritate and injure pleural surface
leading to hemorrhage, inflammation and eventually
fibrosis
 Most cases are asymptomatic but can result in decreased
vital capacities in later stages

72.  Imaging- Chest x-ray and CT
 CT scanning increases plaque detection rates
 Treatment- No specific treatment required
 They are markers of asbestos exposure and they identify

74. Diffuse pleural thickening
Mechanisms –
 Confluence of large pleural plaques
 Extension of subpleural fibrosis to visceral pleura
 Fibrotic resolution of a benign pleural effusion
Clinical features-
 Dyspnea on exertion
 Chronic dry cough
 Chest pain

75. Rounded atelectasis
 Rare complication
 Scarring of visceral and parietal pleuraand the adjacent
lung
 Pleural surfaces fuse to one other and trap the underlying
lung causing atelectasis
 Chest x ray- mass lesion which mimics lung cancer is seen.
 HRCT- diffuse pleural thickening , volume loss, comet tail of
vessels and bronchi sweeping into wedge shaped mass.

77. Other complications
1. Acute benign pleural effusion
2. Malignant mesothelioma
3. Lung cancer- all histologic types can occur but
adenocarcinoma is the most common

78. Post radiation lung injury
Mechanism
 Transient increase in reactive oxygen and nitrogen species
 Macrophage infiltration and proliferation
 Oxidative stress and
 Induction of interstitial fibrosis with regional tissue hypoxia.

79. Acute manifestation
 Erythematous mucosa
with thickened secretions
 Irritative dry cough
 Resolution of symptoms
within several weeks
Chronic manifestations
 Pneumonitic process 6
weeks to 6 months
following radiation
 Fever, cough congestion
 Hemoptysis, dyspnea,
respiratory distress in
severe cases

81. Diagnosis- bronchoscopy and lung biopsy
Treatment-
 Asymptomatic- observation and symptomatic treatment
 Severe cases- antibiotics with glucocorticoids tailored to
severity of symptoms
 To be tapered slowly after patient is stabilized
 Response rate-20 to 100%

82. Complications of Pleural Effusion
Empyema
Pleural Fibrosis
Pleural Thickening

83. REFERENCES
1. CROFTON AND DOUGLAS’S RESPIRATORY DISEASES, 5TH
EDITION
2. HARRISON’S PRINCIPLES OF INTERNAL MEDICINE, 20TH
EDITION.
3. LIGHT’S PLEURAL DISEASES 6TH EDITION

84. THANK YOU