Clinical Applications: Diagnostic Assays on Pleural Fluid Online Training

Welcome to the Diagnostic Assays on Pleural Fluid Online Training course.  This course will provide an overview of the pleural cavity, its fluid, and laboratory tests used in the diagnosis of abnormal build up. Select Next to continue. This course was developed by: Dr. Farogh Nazari, PhD, MBA, MLS (ASCP)CM Senior Manager, Global Continuing Education Siemens Healthcare Diagnostics   Upon successful completion of this course you will be able to: Describe the pleural cavity and its fluid   Discuss the causes of Pleural Effusion   Describe laboratory tests which assist in the diagnosis and treatment of patients with Pleural Effusions   Select Next to continue. Fluid between the Visceral and Parietal pleura Serves as a lubricant Coordinated action for respiration Volume based on body weight Source: http://emedicine.medscape.com/article/299959-overview#aw2aab6b2b2 http://www.youtube.com/watch?v=x-625AkBwDc Pleural Fluid is a clear ultra filtrate   Pleural Fluid vs. Serum Concentrations Protein level 1 to 2 g/dL pH 7.60 to 7.64 WBC < 1000 cells/mm2 Glucose about equal LDH about ½ bicarbonate slightly increased Also contains ⇒ sodium and chloride Macrophages, Lymphocytes and Mesothelial: Normally < 1700 cell/cubic cm Source: http://emedicine.medscape.com/article/299959-workup http://www.youtube.com/watch?v=x-625AkBwDc Pleural Effusion Excessive amount of fluid Many mechanisms for build-up Associated with many conditions Exudative vs. Transudative Thoracentesis used to drain To find the cause To ease breathing http://emedicine.medscape.com/article/299959 Pleural effusion  Too much pleural fluid Common types of Pleural Effusions Serous fluid – hydrothorax Blood – hemothorax Chyle – chylothorax Pus – pyothorax or empyema http://emedicine.medscape.com/article/299959-workup   Altered permeability of the pleural membranes -- inflammation, malignancy, pulmonary embolus Reduction in intravascular oncotic pressure Increased capillary permeability or vascular disruption Increased capillary hydrostatic pressure Reduction of pressure in the pleural cavity Decreased lymphatic drainage --  malignancy, trauma http://emedicine.medscape.com/article/299959-overview#aw2aab6b2b3   Clinical Presentation Disease Associated with: Transudative effusion Malignant pleural effusion Parapneumonic effusion Hemoptysis (cough up blood) Ascites Unilateral leg swelling Bilateral leg swelling Shortness of breath Fever Weight loss Cardiac, renal or liver disease Cancer Pneumonia Malignant neoplasm, Pulmonary embolism or severe TB Cirrhosis, Ovarian cancer, Meig syndrome Strong sign of Pulmonary embolism Chronic heart, Liver failure Heart failure, Constrictive pericarditis Pneumonia, Empyema, TB Cancer, TB, Anaerobic bacterial pneumonia McGraft EE & Anderson PB. Journal of Critical Care. 2011;20:119-128. Porcel JM, Light RW. Am Fam Physician. 2006(73):1211-1120.  Malignant pleural effusion Ascites Porcel JM, Light RW. Am Fam Physician. 2006(73):1211-1120. http://emedicine.medscape.com/article/299959-overview Unilateral leg swelling Bilateral leg swelling Shortness of breath Fever Weight loss Strong sign of Pulmonary embolism Chronic heart, Liver failure Heart failure, Constrictive pericarditis Pneumonia, Empyema, TB Cancer, TB, Anaerobic bacterial pneumonia   These presentations along with a confirming medical history and the chest x-ray may be enough evidence to avoid performing thoracentesis. McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. http://www.nhlbi.nih.gov/health/health-topics/topics/thor/printall-index.html http://emedicine.medscape.com/article/299959-workup#aw2aab6b5b9 Small volume of pleural fluid Tendency to bleed Systemic anticoagulation Mechanical ventilation Cutaneous disease over propose site Jones PW. et al. CHEST 2003;123:418-423. http://emedicine.medscape.com/article/299959-workup#aw2aab6b5b9 Pain Bleeding Infection Pneumothorax Shortness of breath Liver or spleen puncture (rarely) Jones PW. et al. CHEST 2003;123:418-423. Test Room Temp (21ºC) Refrigerated (4ºC) Frozen (-21ºC) Glucose* 2 days 7 days 7 days LDH 4 days 1 day < 1 day Albumin 7 days 7 days 7 days Total Protein 7 days 7 days 7 days Cholesterol 4 days 14 days 14 days Triglycerides 4 days 4 days 4 days * With or without anticoagulant Adapted from: Antonangelo L. et al. Clinica Chimica Acta. 2010;411:1275–1278. Mishra, EK. Rahman, NM. Curr Opin Pulm Med. 2009;15:353–357.   Local anesthetic Exchange of syringe Use ultrasound for guidance Perform Laboratory testing as quickly as possible Store 2 aliquots if testing is not performed quickly Adapted from: Antonangelo L. et al. Clinica Chimica Acta. 2010;411:1275–1278.   McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Scholz et al. Journal of Medical Case Reports 2011 5:492. 1st step – Transudate or Exudate Order both Pleural Fluid & Serum Total protein and LDH  to use Light’s criteria to distinguish which type of effusion McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Light’s criteria: Identifies nearly all exudates Misclassifies ~ 20% of transudates A different set of criteria using only pleural fluid analysis, LDH   > 0.45 times upper limit of normal serum levels Cholesterol  > 45 mg/dL Total Protein  > 2.9 g/dL Fluid is an exudate, if one or more of the criteria are met. http://emedicine.medscape.com/article/299959-workup   Transudate or Exudate Light’s Criteria:  Serum protein & LDH and  Pleural Fluid protein & LDH Alternate Criteria: Pleural Fluid LDH, cholesterol, and protein Very high Pleural Fluid LDH ( > 1000 IU/L) suggests empyema, or a malignant or rheumatoid effusion. Pneumocystis jiroveci pneumonia is indicated by: Pleural fluid/serum  LDH ratio being > 1 Pleural fluid/serum protein < 0.5 http://emedicine.medscape.com/article/299959-workup#aw2aab6b5b3 Serous Transudate Pleural Effusion Pneumocystis cysts in the lung of a patient with AIDS Hemothorax: Presence of blood in the pleural fluid Reddish in color Pleural fluid hemocrit > 50% of the serum hematocrit Cause is most often chest trauma Other causes -- thoracic or heart surgery, pulmonary infarction, lung or pleural cancer, TB McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Common Causes Left Ventricular failure Liver Cirrhosis Hypoalbuminemia Peritoneal dialysis Less Common Causes Hypothyroidism Nephritic syndrome Mitral stenosis Pulmonary embolism Rare Causes Constrictive pericarditis Urinothorax Superior vena cava obstruction Ovarian hyper stimulation Meigs’ syndrome Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17. McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Common Causes Malignancy Pneumonia Tuberculosis* Less Common Causes Pulmonary infarction Rheumatoid Arthritis Autoimmune disease Benign asbestos effusion Pancreatitis Post-myocardial infarction syndrome Rare Causes Yellow nail syndrome Drugs (see below) Fungal infections Drugs that cause Exudates Amiodarone Nitrofurantoin Phenytoin Methotrexate Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17. McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Khan FY et al. Eastern Mediterrean Health Journal. 2011;17(7):611-618. http://www.who.int/tb/publications/factsheet_global.pdf Normal PH of about 7.6 pH should be performed on all non-purulent effusions, if infection is suspected In an infected effusion a pH of <7.2 indicates an urgent need for tube drainage Other Causes of Low pH in Exudates vascular diseases (commonly rheumatoid arthritis) esophageal rupture malignancy Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17. Glucose Level Associated Disease 30 to 50 mg/dL Malignancy, tuberculosis, esophageal rupture, lupus > 30 mg/dL Rheumatoid arthritis, empyema Glucose levels are lowest in rheumatoid effusions and empyema. 5% of Rheumatoid Arthritis patients have Pleural Effusion Rheumatoid Arthritis unlikely if Glucose > 30 mg/dL Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17.   > 85% lymphocytes suggests TB, lymphoma, sarcoidosis, chronic rheumatoid pleurisy, chylothorax, or yellow nail syndrome >10% eosinophils in pleural fluid suggestive of Hemorrhaging pulmonary embolism or benign asbestos pleural effusion Less likely to progress to TB pleurisy or parapneumonic effusion Mesothelial cells are in most effusions If > 5% TB unlikely & suggests pulmonary embolism, especially if bloody effusion Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17. Tuberculosis principal cause of exudative pleural effusions. TB Global Facts (2011) 8.7 million cases 1.1 million cases in HIV patient Death 1.4 million cases with TB 430,000 cases with HIV patient TB mortality down 41% since 1990 http://www.who.int/tb/publications/factsheet_global.pdf Mycobacterium tuberculosis   Porcel JM. Curr Opin Pulm Med. 2005:11:329-333.   In Heart Failure, effusion is found to be transudate Light’s criteria incorrect in 15 - 25% cardiac related effusions 1/3 of pleural effusions in US due to Heart Failure Can NT-proBNP be a differentiator? Yorgancioglu A. et al. Tuberkuloz ve Toraks Dergisi 2011; 59(11):1-7 Left-sided effusion caused by Heart Failure Porcel JM. Curr Opin Pulm Med. 2005:11:329-333. Porcel JM, et al. Am J Med 2004;116:417-420. Urinothorax is urine in pleural effusion Rare and is typically the result of either obstructive uropathy or injury to the kidney or urinary tract. Clinical presentation Pleural fluid is straw colored and a transudate Confirmed by pleural fluid/serum creatinine ≥ 1 Mechanism Leakage of urine into the retroperitoneal space Urine passes through the diaphragmatic lymphatics or diaphragm into the pleural space Treatment Resolves after the obstruction is removed http://pgblazer.com/2010/11/urinothorax-etiology-clinical-features-and-management.html Malignant effusions can be diagnosed by pleural fluid cytology alone in only 60% of cases. If the first pleural cytology specimen is negative, it should be repeated a second time. Both cell blocks and fluid smears should be prepared for examination and, if the fluid has clotted, it needs to be fixed and sectioned as a histological section. Maskell NA, Butland RJA. Thorax 2003:58 (Suppl II) ii8 – ii17.     Sensitivity Specificity CEA > 50 ng/mL 29% 100% CA 125 > 2,800 U/mL 17% 100% CA 15–3 > 75 U/mL 30% 100% CYFRA 21–1 > 175 ng/mL 22% 100% All 4 combined 54% 100% All 4 + cytology 72% 100% Porcel JM. CHEST 2004;126:1757–1763. “At present, pleural fluid tumor markers are not used so often for diagnosis of malignancy but it certainly may help in certain situations like pleural fluid cytology negative cases and where facilities of invasive procedures are not available. But in future, with advancement in Medicine, tumor markers which have a high sensitivity may be found and may be of greater importance in early screening and diagnosing of malignancy.” Banka A,Gayathri AR, Narasimhan R. Pulmon 2009; 11(1):8- 11. McGrath EE, Anderson PE. Am J Crit Care 2011(20):119-127. Describe the pleural cavity and its fluid Pleural fluid is located between visceral and parietal membranes Describe the causes of Pleural Effusion Most pleural effusions are caused by congestive heart failure, pneumonia, malignancy or pulmonary embolism They may be exudative (inflammatory) or transudative (non-inflammatory) in nature Describe laboratory tests which assist in the diagnosis and treatment of patients with Pleural Effusions Thoracentesis is a procedure that may be used to determine the cause of a pleural effusion Light’s Criteria depends on total protein and LDH results from both serum and pleural fluid to determine exudate or transudate; alternately total protein, LDH and cholesterol results from pleural fluid only may be used