I. Overview
In normal people, there is 3 to 15 ml of fluid in the chest cavity, which acts as a lubricant during respiratory movements, but the amount of fluid accumulation in the pleural cavity is not fixed. Even in a normal person, 500 to 1000ml of fluid is formed and absorbed every 24 hours. The pleural cavity is reabsorbed from the venous end of the capillaries, and the rest of the fluid is recycled to the blood by the lymphatic system, so that filtration and absorption are in a dynamic balance. If this dynamic balance is disrupted by systemic or local lesions, resulting in too rapid formation or too slow absorption of fluid in the pleural cavity, a clinical pleural effusion (Pleural effusion for short) will result.
II. Etiology
Laboratory tests.
1. Increased hydrostatic pressure in the pleural capillaries
such as congestive heart failure, constrictive pericarditis, increased blood volume, and obstruction of the superior vena cava or the odd vein, producing pleural effusion.
2.Increased permeability of pleural capillaries
Such as pleural inflammation (tuberculosis, pneumonia) connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis), pleural tumors (malignant metastases, mesothelioma), pulmonary infarction, subphrenic inflammation (subphrenic abscess, liver abscess, acute pancreatitis), etc., producing pleural exudate.
3.Decreased colloid osmotic pressure in pleural capillaries
such as hypoproteinemia, liver cirrhosis, nephrotic syndrome, acute glomerulonephritis, mucinous edema, etc., producing pleural leakage fluid.
4.Mural pleural lymphatic drainage obstruction
Cancer lymphatic duct obstruction, developmental lymphatic duct drainage abnormalities, etc., producing thoracic exudate.
5.Intra-thoracic hemorrhage due to injury
Aortic aneurysm rupture, esophageal rupture, thoracic duct rupture, etc., producing hemothorax, pus thorax, celiac thorax.
Pleural effusion is most common with exudative pleurisy; tuberculosis is especially common in young and middle-aged patients. Pleural effusion (especially hemothorax) in middle-aged and elderly patients should be carefully considered malignant lesions with malignant tumors (such as lung cancer, breast cancer, lymphoma, etc.) metastasizing to the pleura or mediastinal lymph nodes, which can cause pleural effusion. Tumor involving the pleura, which increases its surface permeability, or obstruction of lymphatic drainage, or accompanied by obstructive pneumonia involving the pleura, can cause exudative pleural effusion.
Occasionally, the thoracic duct is obstructed, resulting in celiac disease. When the pericardium is involved and produces pericardial effusion, or when the superior vena cava is obstructed and the intravascular hydrostatic pressure is increased, or when malnutrition and hypoproteinemia are caused by malignant tumors, the pleural effusion may be a leaky fluid.
III. Pathogenesis
Mechanism of pleural effusion and absorption
In healthy people, the pleural cavity is at negative pressure (-5cmH2O on average when breathing, 1cmH2O=98Pa), and the pleural fluid contains protein and has colloidal osmotic pressure (8cmH2O). The accumulation and dissipation of pleural fluid is also closely related to the osmotic pressure and hydrostatic pressure in the pleural capillaries. The wall pleura is supplied by the body circulation and has a high capillary hydrostatic pressure (30 cmH2O); the dirty pleura is supplied by the pulmonary circulation and has a low venous pressure (11 cmH2O). The blood membranes of the body circulation and the pulmonary circulation are absorbed at equal rates.
According to animal experiments, the human pleural cavity can have 0.5 to 1L of fluid passing through it every day. The proteins in the pleural fluid enter the thoracic duct mainly via the lymphatics.
Pleural inflammation can increase the permeability of the duct wall, and more proteins enter the pleural cavity, increasing the osmotic pressure of the pleural fluid. Tumors can compress and block lymphatic drainage, resulting in protein accumulation in the pleural fluid, leading to pleural effusion. Portal cirrhosis often has hypoproteinemia and reduced plasma glial osmotic pressure, which can produce leakage of fluid, and when there is ascites, it can in turn cause pleural effusion through congenital defects in the diaphragm or via lymphatic vessels. Pleural effusion may be produced by allergic reactive diseases, autoimmune diseases, cardiovascular diseases or thoracic trauma.
IV. Clinical manifestations
Age, medical history, symptoms and signs are of reference value for diagnosis. Tuberculous pleurisy is mostly seen in young people, often with fever; middle-aged or older patients should be alert to pleural metastases caused by lung cancer. Inflammatory effusions are mostly exudative and are often accompanied by chest pain and fever. Pleural effusion due to heart failure is leaking fluid. The right pleural effusion associated with liver abscess may be reactive pleurisy or abscess chest.
If the amount of fluid is less than 0.3L, the symptoms are not obvious; if it exceeds 0.5L, the patient will feel chest tightness gradually. The local percussion is turbid and the breath sounds are reduced. When the amount of fluid accumulation increases, the two layers of pleura are separated and no longer rub with breathing, chest pain is gradually relieved, but dyspnea is also gradually increased; when a large amount of fluid accumulates, the mediastinal organs are compressed, and palpitation and dyspnea are more obvious.
V. Auxiliary examination
1.Appearance
The leaking fluid is clear and bright, does not coagulate at rest, specific gravity <1.016~1.018, while the exudate is slightly turbid and straw yellow, specific gravity >1.018. purulent pleural fluid often has a foul odor if it is infected with E. coli or anaerobic bacteria. The hemorrhagic pleural fluid is in varying degrees of washed flesh water-like or venous blood-like; milky pleural fluid is celiac disease; if the pleural fluid is chocolate colored, the possibility of amoebic liver abscess breaking into the pleural cavity should be considered; black pleural fluid may be varicella infection.
2.Cells
There are a small number of mesothelial cells or lymphocytes in normal pleural fluid, and various inflammatory cells and proliferating and degenerating mesothelial cells can be seen in pleural fluid when pleural inflammation is present. The cell count of leakage fluid is often less than 100×106/L, with lymphocytes and mesothelial cells as the main cells. The leukocytes in exudate often exceed 500×106/L. The leukocytes in septic chest can be more than 1000×106/L. Neutrophil increase suggests acute inflammation; lymphocyte predominance is more likely to be tuberculosis or malignant; eosinophils often increase in parasitic infection or connective tissue disease.
When the red blood cells in the pleural fluid exceed 5×109/L, it can be light red, mostly caused by malignant tumor or tuberculosis. Thoracic puncture injury to blood vessels may also cause hemorrhagic pleural fluid, which should be carefully differentiated. Trauma, tumor or pulmonary infarction should be considered when erythrocytes exceed 100×109/L. Malignant tumor cells can be detected in about 60% of malignant pleural fluid, and repeated examinations can improve the detection rate. Malignant tumor cells in pleural fluid often have enlarged nuclei of different sizes, nuclear aberrations, deep nuclear staining, abnormal nuclear to plasma ratio and abnormal mitotic division, etc., which should be distinguished. The mesothelial cells in pleural fluid are often deformed and easily misdiagnosed as tumor cells. Intermediate cells in non-tuberculous pleural fluid exceed 5%, and often less than 1% in tuberculous pleural fluid. When SLE is complicated by pleural effusion, the antinuclear antibody titer in the pleural fluid can reach more than 1:160, and lupus cells can be easily found.
3.pH
The pH of tuberculous pleural fluid is often <7.30; those with pH <7.00 are only seen in abscess chest and pleural effusion due to esophageal rupture. The pH of pleural fluid due to acute pancreatitis is <7.30; if the pH is <7.40, malignant pleural fluid should be considered.
4.Pathogens
Pleural fluid smear to find bacteria and culture can help pathogenic diagnosis. Tuberculous pleurisy pleural fluid sedimentation for TB culture, the positive rate is only 20%, chocolate colored pus should be microscopic examination of amoebic trophozoites.
5.Protein
The protein content of exudate, pleural fluid/serum ratio is greater than 0.5. When the protein content is 30g/L, the specific gravity of pleural fluid is about 1.018 (for every 1g of protein added or subtracted, the weight increases or decreases by 0.003). The protein content of the leaking fluid was low (<30g/L), mainly albumin, and the mucin test (Rivalta test) was negative.
Carcinoembryonic antigen (CEA): elevated CEA levels in malignant pleural fluid appear earlier and more significantly than in serum. A pleural fluid CEA value >15-15 μg/L or pleural fluid/serum CEA >1 is often indicative of malignant pleural fluid. Increased ferritin levels in malignant pleural fluid can be accompanied as a reference for differential diagnosis. Combined detection of multiple markers can improve the positive detection rate.
6.Lipid-like
In celiac disease, the neutral fat and triglyceride content in the pleural fluid is high (>4.52 mmol/L), and it is milky and cloudy, stained red with Sudan III, but the cholesterol content is not high, which can be seen when the thoracic duct is ruptured. “Celiac” or cholesterol pleural fluid (cholesterol >2.59 mmol/L), associated with cholesterol accumulation in old effusions, can be seen in old tuberculous pleurisy, malignant pleural fluid or liver cirrhosis, rheumatoid arthritis, etc. Cholesterol pleural fluid contains high amount of cholesterol, but triglycerides are normal, light yellow or dark brown, containing cholesterol crystals, fat particles and a large number of degenerated cells (lymphocytes, red blood cells).
7.Glucose
The glucose content in normal human pleural fluid is similar to the blood glucose content and changes with the rise and fall of blood glucose. Determination of pleural fluid glucose content can help identify the etiology of pleural effusion. The glucose content of leaking fluid and most exudate is normal; while the glucose content in tuberculous, malignant, rheumatoid arthritic and septic pleural effusion can be <3.35 mmol/L. If the pleural lesion is extensive, making it difficult for glucose and acidic metabolites to pass through the pleura, the glucose content can be low, suggesting extensive tumor infiltration and a high rate of finding malignant tumor cells in their pleural fluid.
8.Enzyme
Increased pleural fluid lactate dehydrogenase (LDH) content, greater than 200 U/L, and pleural fluid LDH/serum LDH ratio greater than 0.6, suggesting exudate, pleural fluid LDH activity can reflect the degree of pleural inflammation, the higher the value, the more obvious the inflammation. LDH>500 U/L often suggests malignant tumor or pleural fluid has been complicated by bacterial infection.
Elevated pleural fluid amylase can be seen in acute pancreatitis, malignant tumors, etc. When acute pancreatitis is accompanied by pleural effusion, amylase leakage results in higher levels of the enzyme in the pleural fluid than in the serum. Some patients with severe chest pain and dyspnea may mask their abdominal symptoms, when the pleural fluid amylase is already elevated, and the clinical diagnosis should be noted.
Adenosine deaminase (ADA) is found in higher levels in lymphocytes. In tuberculous pleurisy, ADA in pleural fluid may be higher than 100 U/L (usually not more than 45 U/L) because cellular immunity is stimulated and lymphocytes are significantly increased. Its sensitivity for diagnosing tuberculous pleurisy is higher.
9.Immunological examination
With the progress of cell biology and molecular biology, immunological examination of pleural fluid has received attention and plays a role in identifying benign and malignant pleural fluid, studying the pathogenesis of pleural effusion and carrying out biological treatment of pleural effusion in the future.
In tuberculous and malignant pleural effusions, T lymphocytes are increased, especially in tuberculous pleurisy up to 90%, and T4 (CD+4) is predominant. The T-cell function in malignant pleural effusion was suppressed, and their killing activity against autologous tumor cells was significantly lower than that of peripheral blood lymphocytes, suggesting that the local immune function of the thoracic layer in patients with malignant pleural effusion was suppressed. The complement C3 and C4 components in pleural effusions caused by SLE and rheumatoid arthritis were reduced, and the content of immune complexes was increased.
10.Pleural biopsy
Percutaneous pleural biopsy is helpful in identifying the presence or absence of tumors and determining pleural granulomatous lesions. When tuberculosis is to be diagnosed, the biopsy specimen can be cultured for tuberculosis in addition to pathological examination. Pleural biopsy is not recommended in cases of abscess chest or bleeding tendency. If necessary, biopsy can be performed by thoracoscopy.
11.Ultrasound examination
It can identify pleural effusion, pleural thickening, liquid pneumothorax, etc. It can provide more accurate localization diagnosis for encapsulated effusion and help thoracentesis to extract fluid.
VI. Diagnosis
Diagnostic imaging
When the amount of pleural effusion is 0.3-0.5L, the X-ray only shows blunting of the rib diaphragm angle; more effusions show an effusion shadow to the lateral, upward arc of the upper edge. The effusion spreads out when lying down, making the whole lung field less translucent. In pneumothorax, the effusion has a fluid plane. The entire affected side is shaded and the mediastinum is pushed to the healthy side when a large amount of fluid is accumulated. In the case of fluid accumulation, the edges are often smooth and full, confined to the interlobular area or between the lung and the diaphragm, and ultrasonography is useful for diagnosis.
CT examinations can indicate exudate, blood or pus depending on the density of the pleural fluid, and can also show mediastinum, paratracheal lymph nodes, intrapulmonary masses, pleural mesothelioma and intrathoracic metastatic tumors. It is easy to detect the small amount of effusion that is difficult to show on X-ray plain film.
Differential diagnosis
Pleural fluid examination is large enough to determine effusion holding. The differential diagnosis should pay attention to the urgency of onset, fever, weakness, chest pain and other systemic or local symptoms of lung and pleura; dyspnea, whether one can lie down, whether there is lower limb edema; whether there is ascites or abdominal mass, superficial lymph node enlargement, joint or skin lesions, etc., and combine with the corresponding blood picture, X-ray chest film, ultrasound, pleural fluid, tuberculosis. B ultrasound, pleural fluid, tuberculin test, etc., and pleural biopsy if necessary, should be used for comprehensive analysis.
In the diagnosis of pleural effusion, we should first distinguish exudative fluid from leaking fluid. The most common cause of exudative pleural fluid is tuberculous pleurisy, mostly in young patients, with positive tuberculin test and no important findings on physical examination except for pleural effusion signs, straw yellow pleural fluid, lymphocytes predominant, and no special changes on pleural biopsy. Without effective anti-tuberculosis treatment, about 1/3 may develop intrapulmonary or extrapulmonary tuberculosis lesions after 5 years of follow-up. Leaky pleural fluid may be associated with left heart failure, hypoproteinemia, etc. Medical all online website www.med126.com
Tuberculous and malignant pleural fluid often need to be carefully differentiated. Both are more common in clinical practice, but the treatment and prognosis are very different. Malignant tumors invade the pleura causing pleural effusion called malignant pleural fluid, which is mostly bloody, massive, rapidly growing, pH <7.4, CEA over 10-15 μg/L and LDH >500 U/L, often caused by lung cancer and breast cancer metastasizing to the pleura.
Tuberculous pleurisy mostly has fever, pH is mostly below 7.3, ADA activity is significantly higher than other causes of pleural effusion, and CEA and ferritin are usually not increased. If clinical differentiation is difficult, anti-tuberculosis treatment can be given and the disease can be monitored and followed up with chemotherapy. Elderly patients with tuberculous pleurisy may not have fever and often have a negative tuberculin test, which should be noted.
The accuracy of CT scan in the diagnosis of pleural effusion lies in its ability to correctly identify pleural invasion or extensive metastasis of bronchial lung cancer, which is essential for the diagnosis of the cause of malignant pleural effusion, lung cancer staging and selection of the protocol. MRI can complement CT scan in the diagnosis of pleural effusion, especially in the diagnosis of malignant pleural effusion, and its characteristics are obviously better than CT. pleural needle biopsy has the advantages of being simple, easy to perform and less damaging, with a positive diagnostic rate of 40% to 75%. Thoracoscopy has the highest diagnostic rate for the etiology of malignant pleural effusion, which can reach 70% to 100%, providing evidence for the formulation of treatment plans.
Through thoracoscopy, the pleural cavity can be examined comprehensively to observe the morphological characteristics of the lesion, its distribution and the involvement of adjacent organs, and multiple biopsies can be performed under direct vision, so the diagnosis rate is higher and the clinical staging of the tumor is more accurate. There are a few clinical cases of pleural effusion whose etiology is still difficult to be determined by the above mentioned examinations.
Treatment measures
Pleural effusion is part of systemic diseases of the chest, and etiologic treatment is particularly important. Leaky fluid can often be absorbed after correcting the etiology. The common causes of exudative pleurisy are tuberculosis, malignancy and pneumonia.
1. Tuberculous pleurisy
Most patients are satisfied with anti-tuberculosis drug therapy, and a small amount of pleural fluid is usually not necessary for aspiration or only for diagnostic puncture. Thoracentesis not only helps to diagnose, but also can relieve pulmonary and cardiac and vascular compression, improve respiration, prevent fibrin deposition and pleural thickening, and save lung function from damage. After fluid extraction, the toxicity symptoms can be reduced and the body temperature can be decreased, which helps to make the compressed lung reopen rapidly. Large amounts of pleural fluid are pumped 2 to 3 times a week until the pleural fluid is completely absorbed. The amount of fluid pumped should not exceed 1000 ml each time. Too fast and too much fluid pumping can cause a sudden drop in chest pressure and pulmonary edema or circulatory disorders.
This kind of pulmonary edema after pulmonary resuscitation, which is rapidly produced by pumping pleural fluid, is manifested by severe cough, shortness of breath, coughing a lot of foamy sputum, both lungs are full of cloudy wet stalls PaO2 drop, and X-ray shows pulmonary edema signs. Oxygen should be administered immediately, glucocorticoids and diuretics should be applied as appropriate, water intake should be controlled, and the condition and acid-base balance should be monitored closely. If “pleural reaction” occurs during fluid extraction, which is characterized by dizziness, cold sweat, palpitation, pallor, thin pulse and cold extremities, fluid extraction should be stopped immediately, the patient should be made to lie down, and if necessary, 0.1% epinephrine 0.5ml should be injected subcutaneously, and the condition should be closely observed to pay attention to blood pressure and prevent shock.
In general, after pumping chest fluid, there is no need to inject drugs into the chest cavity.
Glucocorticoids can reduce the metabolic and inflammatory reactions of the body, improve the toxic symptoms, accelerate the absorption of pleural fluid, and reduce the sequelae such as pleural adhesions or pleural thickening. However, there are certain adverse effects or lead to the spread of tuberculosis, so the indications should be carefully controlled. For acute tuberculous exudative pleurisy with severe systemic toxicity symptoms and more pleural fluid, glucocorticoids can be added along with anti-tuberculosis drug therapy, usually prednisone or prednisolone 25-30mg/d, divided into 3 oral doses. When the body temperature is normal, the systemic toxicity symptoms are reduced and subside, and the pleural fluid is obviously reduced, then the dosage should be gradually shut down or even discontinued. The speed of discontinuation should not be too fast, otherwise it is easy to rebound phenomenon, and the general course of treatment is about 4-6 weeks.
2.Pustothorax
Pustothorax is an infectious inflammation of the pleural cavity caused by various pathogenic microorganisms, accompanied by cloudy appearance and pus-like characteristics of the pleural exudate. Bacteria are the most common pathogens of pustothorax. Most bacterial abscess thorax is associated with failure to effectively control bacterial pleurisy. A small number of pustular pleural effusions can be caused by tuberculosis or fungi, actinomycetes, and nocardia. The most common pathogens in infected pleural effusions are currently gram-negative bacilli, followed by Staphylococcus aureus and pneumococcus.
Among the gram-negative bacilli, Pseudomonas aeruginosa and other pseudomonads and Escherichia coli are more common. Anaerobic bacteria have also been widely confirmed as common pathogens of pneumothorax. Pneumonia complicated by pneumothorax is often a monobacterium infection. In the case of lung abscess or bronchiectasis complicated by pneumothorax, it is more often a mixed bacterial infection. Fungal and gram-negative bacillary infections are common in patients on immunosuppressive drugs.
Acute abscess chest often presents with high fever, wasting state, chest distension and pain. The principles of treatment are to control the infection, drain the pleural effusion and promote lung reopening to restore lung function. Effective antibacterial drugs are applied as early as possible against the pathogenic bacteria of pustulothorax, and systemic and intrathoracic drugs are administered. Drainage is the most basic treatment for abscess chest, repeatedly pumping pus or closed drainage. The thoracic cavity can be repeatedly flushed with 2% sodium bicarbonate or saline, and then the appropriate amount of antibiotics and streptokinase can be injected to make the pus dilute and facilitate drainage. A small number of abscess chests can be closed drainage with intercostal open water sealed bottles. For those who have bronchopleural fistula, it is not advisable to flush the chest cavity, so as not to cause the spread of bacteria.
For chronic abscess chest with pleural thickening, thoracic collapse, chronic consumption, pestle finger (toe), etc., surgical pleurodesis and other treatments should be considered. In addition, general supportive treatment is also quite important, high energy, high protein and vitamin-containing food should be given. Correct the water-electrolyte disorder and maintain acid-base balance, and give small amount of blood transfusion if necessary.
3.Malignant pleural effusion
Malignant pleural effusion is mostly caused by the progression of malignant tumor and is a common complication of advanced malignant tumor, such as lung cancer with pleural effusion is already in advanced stage. Imaging examination can help to understand the extent of lesions in the lung and mediastinal lymph nodes. In view of the rapid growth and persistence of pleural fluid, the compression of large amount of fluid often causes severe respiratory distress and even death, so repeated thoracentesis and aspiration are required, but repeated aspiration can cause too much protein loss (1L of pleural fluid contains 40g of protein), so the treatment is very difficult and the effect is not ideal.
For this reason, correct diagnosis of malignant tumor and tissue type and timely reasonable and effective treatment are important to relieve symptoms, reduce pain, improve survival quality and prolong life.
Systemic chemotherapy has certain efficacy for pleural effusion caused by some small cell lung cancers. Local radiation therapy is feasible for those with metastasis in mediastinal lymph nodes. After aspiration of pleural fluid, intrathoracic injection of antitumor drugs including adriamycin, cisplatin, fluorouracil, mitomycin, nitrocarbamazine, bleomycin, etc. is a common treatment method, which helps to kill tumor cells, slow down the production of pleural fluid, and can cause pleural adhesions.
Intrathoracic injection of biological immunomodulators is a more successful method to explore the treatment of malignant pleural effusion in recent years, such as short rods vaccine (CP), IL-2, interferon β, interferon γ, lymphokine-activated killer cells (LAK cells), tumor-infiltrating lymphocytes (TIL), etc., which can inhibit malignant tumor cells, enhance local infiltration and activity of lymphocytes, and cause pleural adhesions.
In order to occlude the pleural cavity, a pleural cannula can be used to inject pleural adhesives, such as tetracycline, erythromycin and talcum powder, after the drainage of pleural fluid, to make the two layers of pleura adhere to avoid the re-formation of pleural fluid. If a small amount of lidocaine and dexamethasone is injected at the same time, it can reduce pain and fever and other adverse reactions. The prognosis of malignant pleural effusion is poor despite the above-mentioned multiple treatments.