Biochemical Analysis of Pleural Fluid and Ascites

Sa Paul Chubb, Robin A Williams, Sa Paul Chubb, Robin A Williams

Abstract

Biochemical testing of peritoneal and pleural fluids is carried out widely, although the range of tests likely to be useful is limited in comparison to the repertoire of tests available in a modern biochemistry laboratory. Fluids accumulate when pathological processes cause an imbalance between hydrostatic pressure gradients, capillary membrane permeability and lymphatic capacity, resulting in protein-poor transudates or inflammatory exudates. In peritoneal fluid, albumin is the most useful test, for the calculation of the serum-ascites albumin gradient; protein and LDH have a role regarding risk and diagnosis of spontaneous bacterial peritonitis and amylase may be useful in diagnosing fluid accumulation due to pancreatitis. Peritoneal fluid pH and glucose are not indicated analyses. For pleural fluid, protein and LDH are important in distinguishing between transudate and exudate using Light's criteria; albumin and the serum-effusion albumin gradient may have a complementary role in patients already on diuretics. Pleural fluid pH is the most useful marker of infection although LDH and glucose are also used. Pleural fluid amylase is often measured but, if raised, is more likely to reflect a malignant process than pancreatic disease as the former is much more prevalent. Tumour markers in both peritoneal and pleural fluids generally have limited diagnostic accuracy for detecting local malignancy. Limited studies validating standard serum test methods for use with pleural and peritoneal fluids have been published but work is progressing in this area both in Australasia and overseas and opportunities exist for contributing to this effort.

Conflict of interest statement

Competing Interests: None declared.

Figures

Figure
Figure
Pathophysiological processes leading to accumulation of peritoneal fluid in chronic liver disease.

References

    1. Clinical and Laboratory Standards Institute. CLSI document C49-A. Wayne, PA, USA: 2007. Analysis of Body Fluids in Clinical Chemistry; Approved Guideline.
    1. Chung C, Iwakiri Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clin Mol Hepatol. 2013;19:99–104.
    1. Miserocchi G. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J. 1997;10:219–25.
    1. Moore KP, Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut. 2006;55(Suppl 6):vi1–12.
    1. Siddall EC, Radhakrishnan J. The pathophysiology of edema formation in the nephrotic syndrome. Kidney Int. 2012;82:635–42.
    1. Zocchi L. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J. 2002;20:1545–58.
    1. Paddock FK. The Diagnostic Significance of Serous Fluids in Disease. N Engl J Med. 1940;223:1010–5.
    1. Carr DT, Power MH. Clinical value of measurements of concentration of protein in pleural fluid. N Engl J Med. 1958;259:926–7.
    1. Light RW, Macgregor MI, Luchsinger PC, Ball WC., Jr Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med. 1972;77:507–13.
    1. Chandrasekhar AJ, Palatao A, Dubin A, Levine H. Pleural fluid lactic acid dehydrogenase activity and protein content. Value in diagnosis. Arch Intern Med. 1969;123:48–50.
    1. Erickson RJ. Lactic dehydrogenase activity of effusion fluids as an aid to differential diagnosis. JAMA. 1961;176:794–6.
    1. Light RW. The Light criteria: the beginning and why they are useful 40 years later. Clin Chest Med. 2013;34:21–6.
    1. Heffner JE, Brown LK, Barbieri CA Primary Study Investigators. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Chest. 1997;111:970–80.
    1. Hooper C, Lee YCG, Maskell N. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65:ii4–17.
    1. Emergency Care Institute - Clinical Resources. Pleural effusion - classification. 2017. [Accessed 26 January 2018]. .
    1. Feller-Kopman D, Light R. Pleural Disease. N Engl J Med. 2018;378:740–51.
    1. Jenkinson F, Murphy MJ. Biochemical analysis of pleural and ascitic fluid: effect of sample timing on interpretation of results. Ann Clin Biochem. 2007;44:471–3.
    1. Wilcox ME, Chong CA, Stanbrook MB, Tricco AC, Wong C, Straus SE. Does this patient have an exudative pleural effusion? The Rational Clinical Examination systematic review. JAMA. 2014;311:2422–31.
    1. Hoefs JC. Serum protein concentration and portal pressure determine the ascitic fluid protein concentration in patients with chronic liver disease. J Lab Clin Med. 1983;102:260–73.
    1. Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med. 1992;117:215–20.
    1. Romero-Candeira S, Fernández C, Martín C, Sánchez-Paya J, Hernández L. Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure. Am J Med. 2001;110:681–6.
    1. Roth BJ, O’Meara TF, Cragun WH. The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest. 1990;98:546–9.
    1. Romero-Candeira S, Hernández L, Romero-Brufao S, Orts D, Fernández C, Martín C. Is it meaningful to use biochemical parameters to discriminate between transudative and exudative pleural effusions? Chest. 2002;122:1524–9.
    1. Block DR, Ouverson LJ, Wittwer CA, Saenger AK, Baumann NA. An approach to analytical validation and testing of body fluid assays for the automated clinical laboratory. Clin Biochem. 2018;58:44–52.
    1. Engel H, Bac DJ, Brouwer R, Blijenberg BG, Lindemans J. Diagnostic analysis of total protein, albumin, white cell count and differential in ascitic fluid. Eur J Clin Chem Clin Biochem. 1995;33:239–42.
    1. Calleja J. AACB Harmonisation Workshop 2016. Inter-lab Body Fluid Sample Analysis Survey – Analyte Performance Reviews. [Accessed 11 March 2018]. .
    1. Thompson S, Ding L. The bromocresol purple method of albumin measurement significantly underestimates the serum ascites albumin gradient. Pathology. 2018;50:S95.
    1. Heffner JE, Brown LK, Barbieri C, DeLeo JM. Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med. 1995;151:1700–8.
    1. Block DR, Algeciras-Schimnich A. Body fluid analysis: clinical utility and applicability of published studies to guide interpretation of today’s laboratory testing in serous fluids. Crit Rev Clin Lab Sci. 2013;50:107–24.
    1. Runyon BA, Hoefs JC. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology. 1984;4:447–50.
    1. Wu SS, Lin OS, Chen YY, Hwang KL, Soon MS, Keeffe EB. Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation. J Hepatol. 2001;34:215–21.
    1. Cheng DS, Rodriguez RM, Rogers J, Wagster M, Starnes DL, Light RW. Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip. Chest. 1998;114:1368–72.
    1. Ng L, Dabscheck E, Hew M. Diagnosis of complicated parapneumonic effusion by pleural pH measurement is jeopardized by inadequate physician knowledge and guideline-discordant laboratory practice. Respir Med. 2017;122:30–2.
    1. Houston MC. Pleural fluid pH: diagnostic, therapeutic, and prognostic value. Am J Surg. 1987;154:333–7.
    1. Runyon BA. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. 2012. [Accessed 25 April 2018]. .
    1. Light RW. Parapneumonic effusions and empyema. Proc Am Thorac Soc. 2006;3:75–80.
    1. Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y. Rheumatoid pleural effusion. Semin Arthritis Rheum. 2006;35:368–78.
    1. Tarn AC, Lapworth R. Biochemical analysis of ascitic (peritoneal) fluid: what should we measure? Ann Clin Biochem. 2010;47:397–407.
    1. Aalami OO, Allen DB, Organ CH., Jr Chylous ascites: a collective review. Surgery. 2000;128:761–78.
    1. Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc. 1980;55:700–4.
    1. Huggins JT. Chylothorax and cholesterol pleural effusion. Semin Respir Crit Care Med. 2010;31:743–50.
    1. Joseph J, Viney S, Beck P, Strange C, Sahn SA, Basran GS. A prospective study of amylase-rich pleural effusions with special reference to amylase isoenzyme analysis. Chest. 1992;102:1455–9.
    1. Kim EJ, Pamer J, Woods C, Memoli JW. A Case of Recurrent Right-Sided Pleural Effusion Due to a Mediastinal Pancreatic Pseudocyst. Chest. 2013;144:952A.
    1. Villena V, Pérez V, Pozo F, López-Encuentra A, Echave-Sustaeta J, Arenas J, et al. Amylase levels in pleural effusions: a consecutive unselected series of 841 patients. Chest. 2002;121:470–4.
    1. Branca P, Rodriguez RM, Rogers JT, Ayo DS, Moyers JP, Light RW. Routine measurement of pleural fluid amylase is not indicated. Arch Intern Med. 2001;161:228–32.
    1. Iglesias JI, Cobb J, Levey J, Rosiello RA. Recurrent left pleural effusion in a 44-year-old woman with a history of alcohol abuse. Chest. 1996;110:547–9.
    1. Runyon BA. Amylase levels in ascitic fluid. J Clin Gastroenterol. 1987;9:172–4.
    1. Sileo AV, Chawla SK, LoPresti PA. Pancreatic ascites: diagnostic importance of ascitic lipase. Am J Dig Dis. 1975;20:1110–4.
    1. Toms C, Stapledon R, Waring J, Douglas P National Tuberculosis Advisory Committee, for the Communicable Diseases Network Australia, and the Australian Mycobacterium Reference Laboratory Network. Tuberculosis notifications in Australia, 2012 and 2013. Commun Dis Intell Q Rep. 2015;39:E217–35.
    1. Oosthuizen HM, Ungerer JP, Bissbort SH. Kinetic determination of serum adenosine deaminase. Clin Chem. 1993;39:2182–5.
    1. Slaats EH, Asberg EG, van Keimpema AR, Kruijswijk H. A continuous method for the estimation of adenosine deaminase catalytic concentration in pleural effusions with a Hitachi 705 discrete analyser. J Clin Chem Clin Biochem. 1985;23:677–82.
    1. Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med. 2008;102:744–54.
    1. Shen YC, Wang T, Chen L, Yang T, Wan C, Hu QJ, et al. Diagnostic accuracy of adenosine deaminase for tuberculous peritonitis: a meta-analysis. Arch Med Sci. 2013;9:601–7.
    1. Skouras VS, Kalomenidis I. Pleural fluid tests to diagnose tuberculous pleuritis. Curr Opin Pulm Med. 2016;22:367–77.
    1. Janda S, Swiston J. Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis. BMC Pulm Med. 2010;10:58.
    1. Yeh JH, Huang CT, Liu CH, Ruan SY, Tsai YJ, Chien YC, et al. HINT Study Group. Cautious application of pleural N-terminal pro-B-type natriuretic peptide in diagnosis of congestive heart failure pleural effusions among critically ill patients. PLoS One. 2014;9:e115301.
    1. Yang Y, Liu YL, Shi HZ. Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis. Respiration. 2017;94:62–9.
    1. Nguyen AH, Miller EJ, Wichman CS, Berim IG, Agrawal DK. Diagnostic value of tumor antigens in malignant pleural effusion: a meta-analysis. Transl Res. 2015;166:432–9.
    1. Ahadi M, Tehranian S, Memar B, Vossoughinia H, Salari M, Eskandari E, et al. Diagnostic value of carcinoembryonic antigen in malignancy-related ascites: systematic review and meta-analysis. Acta Gastroenterol Belg. 2014;77:418–24.
    1. Zuckerman E, Lanir A, Sabo E, Rosenvald-Zuckerman T, Matter I, Yeshurun D, et al. Cancer antigen 125: a sensitive marker of ascites in patients with liver cirrhosis. Am J Gastroenterol. 1999;94:1613–8.
    1. Standards Australia. SA document AS ISO 15189-2013. Sydney, Australia: SA; 2013. Medical laboratories – Requirements for quality and competence.
    1. Therapeutic Goods Administration. Regulatory requirements for in-house IVDs. Canberra, Australia: TGA; 2016.
    1. National Pathology Accreditation Advisory Council. Requirements for the development and use of in-house in vitro diagnostic medical devices (IVDs) 3rd ed. Canberra, Australia: NPAAC; 2014.
    1. National Association of Testing Authorities. General Accreditation Guidance - Validation and verification of quantitative and qualitative test methods. Rhodes, NSW, Australia: NATA; 2018.
    1. Georgewill DA, Graham GA, Schoen I. Applicability of the Ektachem 400 analyzer for assaying analytes in miscellaneous body fluids. Clin Chem. 1988;34:2534–9.
    1. Lin MJ, Hoke C, Dlott R, Lorey TS, Greene DN. Performance specifications of common chemistry analytes on the AU series of chemistry analyzers for miscellaneous body fluids. Clin Chim Acta. 2013;426:121–6.
    1. Owen WE, Thatcher ML, Crabtree KJ, Greer RW, Strathmann FG, Straseski JA, et al. Body fluid matrix evaluation on a Roche cobas 8000 system. Clin Biochem. 2015;48:911–4.
    1. Kaleta EJ, Tolan NV, Ness KA, O’Kane D, Algeciras-Schimnich A. CEA, AFP and CA 19-9 analysis in peritoneal fluid to differentiate causes of ascites formation. Clin Biochem. 2013;46:814–8.
    1. Chung J, Jones GRD. Validation of Biochemical Testing of Fluid Samples by Dilution into a Serum Matrix: a Preliminary Investigation. Clin Biochem Rev. 2015;36:S28–9.
    1. Calleja J, Robinson B, Bittar I, Reidy Y, Doery J, Choy KW, et al. Report on the Findings of the AACB 2014 Body Fluid Survey. Clin Biochem Rev. 2016;37:177–94.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa