Protein, Total, Body Fluid
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Pleural fluid: Pleural fluid is normally present within the pleural cavity surrounding the lungs, serving as a lubricant between the lungs and inner chest wall. Pleural effusion develops when the pleural cavity experiences an overproduction of fluid due to increased capillary hydrostatic and osmotic pressure that exceeds the ability of the lymphatic or venous system to return the fluid to circulation. Laboratory-based criteria are often used to classify pleural effusions as either exudative or transudative. Exudative effusions form due to infection or inflammation of the capillary membranes allowing excess fluid into the pleural cavity. Patients with these conditions benefit from further investigation and treatment of the local cause of inflammation. Transudative effusions form due to systemic conditions such as volume overload, end stage renal disease, and heart failure that can lead to excess fluid accumulation in the pleural cavity. Patients with transudative effusions benefit from treatment of the underlying condition.(1)
Dr. Richard Light derived criteria in the 1970s for patients with pleural effusions that are still used today.(2)
The criteria include the measurement of total protein and lactate dehydrogenase (LD) in pleural fluid and serum. Exudates are defined as meeting one of the following criteria:
1) pleural fluid-to-serum protein ratio above 0.5
2) pleural fluid LD above two-thirds the upper limit of normal serum LD
3) pleural fluid-to-serum LD ratio above 0.6
Light’s criteria were designed to be sensitive for detecting exudates at the expense of specificity.(3) Heart failure and recent diuretic use contribute to most misclassifications by Light’s criteria (transudates falsely categorized as exudates). Serum-to-fluid protein gradient (serum protein minus fluid protein) may be calculated in these cases and when more than 3.1 g/dL suggests the patient has a transudative effusion.
Peritoneal fluid: The pathologic accumulation of fluid within the peritoneal cavity is commonly referred to as ascites. The most common cause of ascites is liver cirrhosis. Differentiating cardiac from cirrhotic ascites is a common clinical conundrum as they are common conditions presenting with elevated serum ascites albumin gradient (SAAG).(4) Heart failure leads to the development of high gradient ascites due to hepatic sinusoidal hypertension. Since the sinusoids are normal and have not been damaged from collagen deposition associated with cirrhosis, protein tends to “leak” more readily into ascites and is associated with higher total protein concentrations.
Pleural fluid: Identification of exudative pleural effusions
Peritoneal fluid: Differentiating hepatic from other causes of ascites that have elevated serum ascites albumin gradient (SAAG)
Pleural fluid: Exudative pleural fluid total protein to serum total protein ratio is typically more than 0.5. Transudative pleural effusions misclassified as exudates have serum protein minus pleural fluid protein more than 3.1 g/dL.
Peritoneal fluid: Total protein may be greater than 2.5 g/dL in patients with high albumin gradient ascites caused by heart failure.
Other fluids: = Total protein may be used to differentiate transudative from exudative effusions. The decision limits are not well defined in fluids other than pleural fluid and should be interpreted in conjunction with other clinical findings.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Total protein may be falsely elevated in samples that contain blood due to trauma during collection.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Block DB, Florkowski CM: Body Fluids. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by N Rifai. Sixth edition. Washington DC: AACC Press, 2017
2. Light RW: The Light criteria: the beginning and why they are useful 40 years later. Clin Chest Med 2013 Mar;34(1):21-26
3. Porcel JM: Identifying transudates misclassified by Light's criteria. Curr Opin Pulm Med 2013;19:362-367
4. Block DB, Genzen JR: Diagnostic Body Fluid Testing. In Contemporary Practice in Clinical Chemistry. Edited by W Clarke. Third edition. Washington DC, AACC Press, 2016 p 773-775