1. APPROACH TO THE PATIENT OF PLEURAL EFFUSION
Presented by :
Dr. Vidhu Mittal
Junior Resident
Deptt. of Chest and TB

2. PLEURAL SPACE
Introduction The pleural space is a potential space around the lungs, bounded by two membranes, the visceral pleura covering the lung and the parietal pleura covering the chest wall and the diaphragm. Blood Supply of Pleura The parietal pleura is supplied by intercostal arteries. The visceral pleura is exclusively supplied by the bronchial circulation which drains into the pulmonary veins.

3. Lymphatic Drainage The visceral pleura has extensive lymphatics but they do not connect to the pleural space. The parietal pleura lymphatics connect to the pleural space via stomata, holes of 8-10 m in diameter. From stoma liquid drains into Lacunae  Spider like submessothelial collecting lymphatics  infracostal lymphatics Systemic Venous System  Thoracic Duct  Parasternal & Periaortic Nodes

4. In a normal pleural space, fluid enters and exists at a constant, equal rate because of the ongoing filtration of a small amount of low protein liquid in normal microvessels. Near the end of the 19th Century, Starling and Tubby hypothesized that the exchange of microvascular fluid and solutes was governed by the balance between the hydrostatic pressure, osmotic pressure and membrance permeability and they devised the starling equation :
QF = LP x A [(PCAP-PPL ) -  D (piCAP-piPL)]
QF = Fluid movement
LP = Filtration Coefficient
A = Surface area of the pleura
D = Reflection coefficient for protein movement across the pleura (PL)
P = Hydrostatic pressure of the pulm. capillary bed. (CAP).
Pi= Oncotic pressure of pleural space.

5. This equation formed the basis for understanding fluid accumulation in the pleural space, where the hydrostatic forces that filter water out of the vessel are balanced by osmotic forces that reabsorb water back into the vessel. In the pleura, reabsorption is facilitated by the extensive lymphatic system on the diaghram and mediastinal surfaces of the parietal pleura.
Normal Characteristics of Pleural Space/Fluid
Major Consideration are given to :-
Volume of pleural fluid
Thickness of Pleural Space
Cellular Components
Physiochemical Factors

6. Volume :- Normally, the volume of fluid in the right and left pleural spaces is quite similar expressed/kg of bodymass, the total pleural fluid volume in normal non-smoking humans in 0.260.1 ml/kg.
Thickness of space :- The normal pleural space is m in width, although it widens at its most dependent areas.
Cellular components :- In the pleural space WBC count has been reported to be 1700 cells/mm3 and the mean RBC count of 700 cells/mm3 and approx. 75% of the cells are macrophages and 25% are lymphocytes, with mesothelial cells, neutrophils and eosinophils accounting for <2% each.

7. Physiochemical Factors :-
Protein : A small amount of protein is normally present in pleural fluid and is similar to serum fluid except for former contain more of LMW albumin.
HCO3  Bicarbonate conc. is increased by 20-25% relative to that in plasma.
NA+  reduced by 3% to 5%
Cl-  reduced by 6% to 9%
Concentration of K+ and glucose in the pleural fluid & plasma appears to be nearly identical.
Pathophysiology :- For pleural liquid to accumulate to form an effusion it is likely that both the entry rate of liquid must increase and the exit rate must decrease.

8. Increased entry rate Decreased exist of liquid
If only the entry rate increased it would require a sustained rate more than 30 times normal to exceed the reserve lymphatic removal capacity; if the exit rate decreased it would take more than a month at the normal entry rate at 12ml/day to produce an effusion detectable by chest radiograph.
Increased entry rate Decreased exist of liquid
May result from ed filtration May result from interference
across systemic or pulm. capillaries with lymphatic function (e.g.)
Obst. of parietal pleura stomata.
Inhibition of lymphatic contractility
Infiltration of draining parasternal lympha nodes.
Elevation of systemic venous pressure into which the lymph drains.

9. HOW TO APPROACH :
(1) Clinical Signs and Symptoms :- Common symptoms of patients with effusion are pleuritic chest pain, cough and dyspnoea and it appears that the three symptoms are due to different causes.
(a) Pleuritic chest pain :- it is derived from inflammation of the parietal pleura. Some patients with pleural effusions experience a dull aching chest pain rather than pleuritic chest pain which suggests patient has pleural malignancy.

10. (2) Second symptoms for pleural effusion is dry, non-productive
(2) Second symptoms for pleural effusion is dry, non-productive. The exact mechanism for cough is not clear.
(3) Third symptom is dyspnoea. Pleural effusion acts as a space occupying process in the thoracic cavity and therefore reduces all the subdivisions of lung volumes.
Physical Examination :-
Inspection : While inspecting it is important to examine the relative sizes of the hemithoraces and the intercostal spaces.
If the pleural pressure is increased on the side of the effusion, that hemithorax will be larger and usual concavity of ICSs will be blunted or even convex.
Whereas if the pleural pressure on the side of effusion is decreased (as with obstruction of major bronchus or a trapped lung). The ipsilateral hemithorax will be smaller and the normal concavity of ICS will be exaggerated.
In addition with inspiratory efforts, the intercostal spaces retract.

11. Palpation :
Is useful for delineating the extent of effusion in areas where pleural fluid separates the lung from the chest wall, tactile fremetus is absent or accentuated.
With a thin rim of fluid, the percussion note may still be resonant, but the TF is diminished.
Palpation may also reveal that the cardiac point of maximum impulse is shifted to one side or the other.
Percussion :- The percussion not over a pleural effusion is dull or flat. The dullness is maximum at the lung bases where the thickness of the fluid is greatest.

12. Auscultation :-
Auscultation over the pleural fluid characteristically reveals decreased or absent breath sounds.
Near the superior border of the fluid, however, breath sounds may be accentuated and take on a bronchial characteristic.
Auscultation may also reveal a pleural rub. pleural rubs often appear as pleural effusions diminish in size, either spontaneously or as a result of treatment because the pleural fluid is no longer present between the roughened pleural surfaces.
Obviously the chest is not the only structure that should be examined when evaluating a patient with a pleural effusion, clues to the origin of the effusion are often present elsewhere.

13. 1
CHF
Cardiomegaly, neck vein distension or peripheral edema. 2
Rheumatoid or Lupus erythematosis
Signs of joint disease or subcut. nodules. 3
Metastatic Disease
Enlarged nontender nodular liver.
Hypertrophic osteo arthropathy. 4
Subdiaphragmatis Process
Abdominal Tenderness 5
Cirrhosis & hepatothorax
Tense Ascitis 6
Lymphoma, sacrodosis
Lymphadenopathy

14. Separation of Exudates from Transudates
A diagnostic thoracocentesis should be performed on nearly every patient with free pleural fluid that measures >10mm on the decubitus radiograph.
If the patient has obvious CHF, consideration can be given to postponing the thoracentosis until the heart failure is treated.
Thoracacentesis procedure :-
Is a safe procedure and may be much safer when guided by USG but due to cost and inaccessibility USG is accompanied in high risk cases only.
Because of the small bore of the needle required, it can be safely performed in patients with coagulopathies and thrombocytopenia.

15. Descriptions of Technique emphasizes on :
Proper positioning of the patient.
Identification of the area of decreased tactile fremitus.
Adequate local anaesthesia of parietal pleura as well as skin.
The needle should run over the top of the rib to avoid the neurovascular bundle that travels in the middle of the intercostal space from the spine for approx. 5-6 inches before taking its safer position beneath the upper rib. Thus one should avoid thoracocentesis medial to midclavicular line.
Complication from thoracocentesis include :-
Pneumothorax (2-6%)
hemothorax (1%)

16. The risk for pneumothorax is higher in patients.
With prior radiotherapy to the chest.
Multiple prior thoracocentesis
Use of vaccum bottles.
The first question that should be answered with the diagnostic thoracoceatesis is whether the patient has a transudative or an exudative pleural effusion.
Light's Criteria :-
Pleural fluid protein-to-serum protein ratio > 0.5
Pleural fluid LDH - to - serum LDH > 0.6.
Pleural fluid LDH > 2/3 of the upper normal limit for serum.

17. But this criteria may misidentify a transudative effusion as an exudative effusion in as many as 25% of cases. If a patient appears to have a transudative effusion clinically, additional tests can be assessed to verify its transudative etiology.
If the difference between the protein conc. of serum and the pleura exceeds 3.1 gm/dl the patient in all probability has a tranudative effusion.
If pleural concentrations of N-terminal brain natruretic peptide (NT-BNP) are >1300 pg/ml the patient likely has a transudate from a cardiac cause.

18. Differentiating Among Various Exudative Pleural Effusions :-
Once it has been determined that the patient has an exudative pleural effusion attempt is made to find out the cause.
The various tests done that can eb done are :-
Appearance of pleural fluid :-
The gross appearance and the odor of the pleural fluid is to be noted.

19. Fluid Appearance / Odor
Cause
Fluid Appearance / Odor
Pseudochylothorax & Chycothorax
Urinothorax
Anaerobic empyema
Chylothorax
Aspergillus infection
Empyema
Amebic liver abscess
Esophageal rupture
Trauma/pul embolism/ malignancy, benign asbestor related, pneumonia or after MI syndrome.
Milky white
Ammonical urine
Putrid
Bile stained
Black
Turbid
Anchovy Brown
Food particles
Blood stained

20. PLEURAL FLUID IS BLOODY Hematocrit of pleural fluid >50% of peripheral blood 1-50% <1% Hemothorax Malignant Pleural No clinical Disease/Pulm. Significance Chest tube embolus/trauma induced

21. PLEURAL FLUID IS TURBID OR MILKY
Centrifugation
Turbidity clears Turbidity Persists
In due to cells or debris in Chylothorax or
pleural fluid Pseudochylothorax

22. Results of Fluid Analysis
Pseudochylothorax
Chylothorax
TG level
Cholesterol level
Cholesteral crystals
Chylomicrons
<50 mg/dl
>200 mg/dl
Yes, common No
Disease process is usually chronic & pleural surfaces are thickened
> 110 mg/dl
< 200 mg/dl
Yes
Disease process is usually acute 2 pleural surfaces not thickened.

23. Pleural Fluid Protein :- It is generally not useful in the differential diagnosis of exudative pleural effusion as these tends to be elevated to a comparable degree with all exudative pleural effusion. However :- To label it exudative effusion  protein > 2.9 gm/dl If protein is >5g/dl likelihood of tuberculous pleurisy is increased.

24. Pleural Fluid LDH :
Whereas pleural liquid protein and LDH arise from filtration from serum and thus serves as indication of vascular premeability LDH as an intracellular enzyme, may also indicate the degree of cell turnover and/or the degree of inflammation within the pleural space. The pleural fluid LDH level is increased to a comparable degree inpatients with all categories of exudative pleural effusion.
However, pleural fluid LDH level should be measured everytime thoracocentesis is performed.

25. Pleural Fluid Glucose :-
A low glucose concentration probably indicate the co-existence of two abnormalities : a thickened, infilterated pleura leading to an impaired diffusion of glucose into the pleural space plus increased metabolic activity leading to increased glucose utilization within the pleural space.
Demonstration of pleural fluid glucose <60mg/dl narrows the diagnostic possibilities to 7.
Parapneumonic effusion
Malignant Effusion
Tuberculous
Rheumatoid
Paragonimiasis
Churg - Strauss - Syndrome

26. If a patient with parapneumonic effusion has a pleural fluid glucose <40mg/dl tube thoracostomy is considered. Pleural Fluid White Cell Count and Differential :- Pleural liquid that is submitted for white cell count and differential should be sent in a tube with an anticoagulant to prevent the cells from clumping. The differential cell count on the pleural fluid is much more useful than the white cell count itself. The normal pleural space contains predominnalty macrophages (75%) lymphocytes (23%)

27. For pleural fluid differential count, cells are partitioned into :-
Polymorphonuclear leukocytes.
Eosinophils
Small lymphocytes
Mesothelial cells and
Other mononuclear cells.
Pleural effusion due to an acute disease contain predominantly polymorphonuclear leucocytes.
Due to chronic diseae  predominanlty mononuclear cells.

28. Pleural fluid eosinophilia :-
Most commonly due to air or blood in the pleural space.
Can also be due to drugs like nitrofurantoin or dantrolene.
Small lymphocytes when >50% of WBC's in an exudative pleural effusion indicates that patient may either has a malignant or a tuberculous pleural effusion. Hence, the presence of pleural fluid lymphocytosis should alert the physician to consider needle biopsy of pleural for diagnosis.

29. Pleural fluid cytology :-
The first pleural fluid cytologic study is positive for malignant cells in upto 60% and is 3 separate specimens 90% of effusion due to pleural malignancy.
The frequency of positive pleural fluid cytologic tests is depedent on the tumor type. For e.g. <25% of patients with Hodgkins disease have the positive cytology, whereas most patients with adeno carcinoma have positive cytology.

30. Other diagnostic tests for malignancy :-
Cytology may be non diagnostic either because of a problem of specificity or sensitivity.
Fish fluorescent in situ hybridization with chromosome specific probes that can confirm abnormal numbers of specific chromosomes.
Early findings of malignancy including DNA methylation can be detected by methylation specific PCR.
Gene expression patterns can help distinguish mesothelioma and adenocarcinoma.

31. Culture & Bacteriological Stains :-
Pleural fluid should be sent for culture for bacteria, mycobacteria and fungi along with gram's stain.
The newer adjuncts are :-
Detection of bacterial antigens via CIE or latex agglutination or of bacterial DNA by PCR.
Antigen specific assays especially in children against most common pathogens like staphlococcus, streptococcus and H.influenza.
Amplification and sequencing of bacterial 16s ribosomal RNA.

32. Other Diagnostic Tests for Pleural Fluid
Pleural Fluid pH and pCO2
The pleural fluid pH is most useful in determining whether chest tubes should be inserted in patients with parapneumonic effusion as a fall in pH i.e. <7.2 is an indication for ICCT.
In general pleural fluid much a low pH also have a low glucose hence glucose level can be used as an alternative as measuring pH require the similar condition of measurement as measuring arterial pH.

33. Other Diagnostic Tests for Pleural Fluid
Pleural Fluid Amylase:-
Pleural fluid amylase is elevated in patients with effusion secondary to
esophageal perforation.
Pancreatic disease
Malignancy
As first 2 are rare causes of effusion so amylase levels are usually not done.
Malignancy can be differentiated from pancreatic disease with amylase isoezymes because the amylase with malignant effusion is primarily of the salivary type.

34. Tests for collagen vascular disease:
About 5% of patients with rheumatoid arthritis and 50% of patients with SLE have a pleural effusion during the course of the disease or may be the first manifestation of disease.
Measurement of ANA litre is the best screening test for lupus pleuritis although it is now evident that a positive pleural fluid ANA is not specific for the diagnosis.
Rheumatoid Arthiritis :
When a rheumatoid pleural effusion is suspected, the clinical picture usually establishes the diagnosis but patients with rheumatoid pleuritis have a pleural fluid RA factor titre of  1:320 and  serum titre.

35. Adenosine Deaminase
The pleural fluid ADA levels are elevated in almost all patients with tuberculous pleuritis and remains a sensitive marker for tuberculous pleurisy in pateints with HIV also.
As it is a highly sensitive test it can be useful to exclude the diagnosis of tuberculosis when the ADA level is low (<40 U/L).

36. Interferon  - (IFN-)
Pleural fluid IFN- is elevated almost exclusively in tuberculous effusions.
However IFN- release assays had variable results and have not added to the use of ADA or IFN-  measurements for the diagnosis or exclusion of active pleural tuberculosis.

37. Molecular Techniques for diagnosis of mycobacterium tuberculosis
PCR to detect specific mycobacterial DNA sequences in clinical specimens.
Nucleic acid probes to identify the organism in culture.
RFLP to compare strains in epidemologic studies.
Gene based susceptibility studies to screen for known genes associated with drug resistance.

39. USEFUL RADIOGRAPHIC TESTS IN PATIENTS WITH SUSPECTED PLEURAL DISEASE
Chest Radiography:-
Two main factors influence the distribution of free fluid in the pleural space.
Fluid collects in the most dependent part of the thoracic cavity because the lung is less dense than the pleural fluid.
Because of their, elastic recoil the lobes of the lung, if normal, maintain their traditional shape at all stages of collapse.

40. If Fluid is < 75 ml, in upright position fluid first accumulates between inferior surface of the lower lobe and diaphragm without overflowing into the costphrenic sinuses.
The presence of a clinically significant amount of free pleural fluid can be excluded if both posterior costophrenic angles are clear.
When there are larger amounts of pleural fluid the lateral costophrenic angle on the PA radiograph becomes blunted.

41. Lateral decubitus radiographs should be obtained in most instances when free pleural fluid is suspected as, as little as 5ml of pleural fluid can be demonstrated with properly exposed decubitus radiographs.
We can also semiquantitate the amount of pleural fluid by measuring the distance between the inner border of the chest wall and the inner border of the lung as when this distance is <10mm, the amount of pleural fluid is small and a diagnostic thoracocentesis is usually not attempted.

43. Pleural fluid may become encapsulated by adhesions anywhere between the visceral and parietal pleura or interlobar fissures.
When the loculation is situated between the lung and the chest wall, there is a characteristic radiographic 'D-shaped' loculation seen with the base of D against the chest wall and the smooth convexity protruding inward toward the lung.
The absence of air bronchograms helps differentiate between a loculated pleural effusion and a parenchymal infilterate.
A definate diagnosis of loculated pleural effusion is best established by USG or CT.

44. For semiquantitation of pleural fluid Blackmore et al demonstrated that if > 750ml of pleural fluid (is present)
Visible on lateral radiograph as a memories positively.
>200 ml - menesin can be identified in the lateral costophrenic angle of the PA radiograph.
> 500ml - menesive observes the entire hemidiaphragm.

45. Ultrasonography
In context with the pleural effusion USG is useful in following situations:
Determining whether pleural fluid is present.
Marking the site for appropriate thoracocentesis.
Identification of pleural fluid loculation.
Distinction of pleural fluid from pleural thickening.
Semiquantitation of the amount of pleural fluid.

46. Ultrasonography
A 2-5 MHz curvilinear probe allows visualization of the deeper structures and the sector scan field allows a wider field of view through a small acoustic window.
The best distinguishing characteristic of pleural fluid collection on ultrasound is that it changes its shape with respiration.

48. Positioning:- Posterior chest - patient sitting upright
Anterior and lateral chest - lateral decubitus position.
If patients arm is raised above his head the distance between the rib spaces is increased and this facilitates scanning the patient in erect or recumbent position.

49. Apart from the above uses one more use of USG is in ICU.
USG helps to diagnose pleural effusion in supine patients in ICU as many chest radiograph are taken with the patient in the supine position and pleural effusions are often missed.
Identification of pleural effusion in ICU patients in is important for atleast 2 reasons:-
If the patient in on ventilator removal of the fluid may facilitate weaning.
If the patient is febrile, it is important to ascertain whether the patient has infected pleural fluid.

50. Advantages of USG over CT Scan
Ease and speed with which examination can be done.
Availability of portable units hence useful for bedside examination in seriously ill patients.
Lack of ionizing radiation.
Low cost.
USG is also useful to evaluate pleural effusion due to pulmonary embolism.

51. Pleural effusion
S/o pulmonary Colour
embolism doppler of lower Positive Treat for
extremities thrombo embolism
Negative
Proceeds to lung V/Q Scan
or CT angio
Where CT angio is > sensitive and specific and can diagnose alternate diagnosis.

53. Computed Tomography (CT Scan):
1. CT chest has it greatest utility in distinguishing parenchymal and pleural abnormalities as between lung abscess and loculated empyema.
Empyema
Lung Abscess
Cavity walls are of uniform thickness both internally and externally and adjacent lung is usually collapsed.
* Walls of the cavity are not of uniform thickness and the adjacent lung is not compressed.
The angle of contact with the chest mall may be obtuse.
Acute
Most empyemas have lenticular shape and demonstrate the split pleura sign.

55. 2. Distinguish between malignant and benign causes in diffuse pleural disease as features associated with malignancy are:-
Circumferential pleural thickening
Pleural nodules
Parietal thickening >1 cm and
Mediastinal pleural involvement.

56. 3. When free fluid lies in posterior costophrenic recess adjacent to the diaphragm, it may be difficult to differentiate from ascitis. So several CT signs have been described for differentiated pleural effusion from ascitis.
Displaced crus sign:-
Pleural effusion
Ascites
Displacement of diaphragmatic crus away from the spine by the fluid.
Ascites lies anterior and lateral to the crus.

57. Interface Sign:- Diaphragm sign
(c) Bare area sign: restriction of ascitis by the coronary ligaments from the base area of the liver indicates ascitis.
Ascitis
Pleural Effusion
If present a sharp interface between fluid and liver / spleen.
Line much less distinct.
Pleural Effusion
Ascitis
Fluid present outside the diaphragm
Fluid present inside the diaphragm.

58. Magnetic Resonance Imaging
Pleural effusions generally have a long T1 and T2 values. The intensity of pleural effusion is therefore low to extremely low on T1 weighted images. However, at the present time MRI of chest is less satisfactory than USG or CT in identifying the presence of pleural fluid, major limitation being the respiratory and cardiac motion.

59. INVASIVE TESTS IN PATIENTS WITH UNDIAGNOSED EXUDATIVE PLEURAL EFFUSION
Three main factors which necessitates the aggressive approach for the diagnosis in pleural effusion :.

60. Sign and symptom of the patient are not improving with time.
Serial LDH level after thoracocentesis if increases after each aspiration.
Patient himself is anxious to know the cause.
The various invasive tests that can be done
Needle biopsy of pleura.
Image guided pleural biopsy
Bronchoscopy
VATs
Open biopsy of pleura.

62. Needle biopsy of the pleura
Because needle biopsy of the pleura is useful mainly to establish the diagnosis of malignant or tuberculous pleural effusion, this procedure should be considered when one of these diagnosis is suspected.
Needles most commonly used are COPE needle and ABRAMS needle.
Procedure is usually blind or also called closed needle biopsy.

63. In malignant pleural disease the needle biopsy of the pleura will be positive in 40-60% of patients. But it should be considered only if the initial pleural fluid cytology after thoracocentesis is non diagnostic.
It has greater utility for tuberculous pleuritis than malignancy. The initial biopsy is positive for granulomas in 50-80% of patients and the demonstrations of granulomas on pleural biopsy is virtually diagnostic of tuberculous pluritis, caseous nacrosis or acid fast bacilli need not to be demonstrated.
The greatest value of needle biopsy for a patients with tuberculosis is obtaining material for culture for mycobacterium tuberculosis for the determination of drug susceptibility.

64. Complications
Pneumothorax : in about 1% of pleural biopsies.
Hemothorax can result if an intercostal artery or vein is in advertantly biopsied.
IMAGE GUIDED PLEURAL BIOPSY
Situations in which the pleural effusion is small or there is loculation or pleural thickening without an effusion, CT image guided pleural biopsy is an excellent choice.

65. BRONCHOSCOPY
If the patient of undiagnosed pleural effusion has associated parenchymal lesion or hemoptysis, fibreoptic bronchoscopy will provide diagnosis in nearly 75% of patients and in <10% time in patients with no parenchymal lesion. And for confirming the parenchymal lesions CT scan is usually done prior to bronchoscopy.
PLEUROSCOPY OF VIDEO ASSISTED THORACOSCOPIC SURGERY (VATS)
Pleuralscopy can be performed by pulmonologist using local anaesthesia and conscious sedation for direct visualization of pleural services, tissue sampling and pleurodesis;

66. Thoracoscopy performed by thoracic surgeons generally referred to as VATS utilizes general anaesthesia and single lung ventilation by double lumen intubation and allows greater access to the pleura and lung surface.
In patients who are strong suspect for malignancy but pleural fluid cytology or needle biopsy is inconclusive, this can make diagnosis in over 80% of cases of malignancy including mesothelioma.
Also insufflation of talc may be carried out to control the pleural effusion.

67. DISADVANTAGES
Risks of the procedure.
Need for post procedure chest tubes.
Cost
OPEN BIOPSY OF THE PLEURAL
Thoracotomy with direct biopsy of the pleura provides the best visualization of the pleural and the best biopsy specimen.
The main indication for open pleural biopsy is progressive undiagnosed pleural disease that cannot be approached by or has failed to be diagnosed by thoracoscopy.

68. It is important the remember that no diagnosis is established for approximately 20% of all exudative pleural effusions and that many resolve spontaneously, leaving no residua.