What Does a Total Protein Test Measure?
A total protein test measures the combined concentration of all proteins in the blood, primarily consisting of albumin (approximately 60% of total serum protein) and globulins (the remaining 40%), expressed in grams per liter or grams per deciliter. 1
Components Measured
The total protein test quantifies:
- Albumin: Produced exclusively by the liver, this protein maintains oncotic pressure and binds substances including fatty acids, bilirubin, and drugs 1
- Globulins: The remaining protein fraction, which includes immunoglobulins, complement proteins, and other serum proteins 1
- Combined measurement: The sum of these fractions provides the total protein concentration 2
Clinical Applications
Total protein measurement serves multiple diagnostic purposes:
- Assessment of nutritional status: Low albumin may indicate nutritional deficiency or nephrotic syndrome 3
- Detection of protein-losing conditions: Helps identify kidney disease, liver dysfunction, or gastrointestinal protein loss 3
- Screening for immunodeficiency: High total protein with normal or low albumin suggests increased immunoglobulin production from B-cell hyperplasia in untreated HIV infection 3
- Evaluation of secondary hypogammaglobulinemia: When measured alongside serum albumin, low levels of both suggest secondary causes of immunoglobulin deficiency 3
Interpretation Considerations
Elevated Total Protein
When both total protein and albumin are elevated:
- Dehydration/hemoconcentration is the most common cause, concentrating all blood components 1
- Prolonged standing can cause temporary fluid shifts that increase protein concentration 1
- Discordant results (elevated total protein with normal/low albumin) should prompt investigation for paraproteinemias or monoclonal gammopathies 1, 3
Clinical Context Matters
- Inflammatory states: Most inflammatory conditions decrease albumin while total protein may increase due to elevated globulins—not both proteins simultaneously 1
- HIV infection: High total protein commonly occurs with untreated HIV due to increased immunoglobulin fraction from B-cell hyperplasia 3
- Kidney disease: Proteinuria assessment requires specific testing beyond total protein, including albumin-to-creatinine ratio or protein-to-creatinine ratio 3
Common Pitfalls to Avoid
- Overinterpreting isolated values: Total protein and albumin must be interpreted within the full clinical context, not as standalone findings 1
- Confusing with inflammatory markers: In inflammatory conditions, albumin typically decreases while globulins increase—simultaneous elevation of both suggests dehydration rather than inflammation 1
- Ignoring hydration status: Moderate to severe elevations warrant investigation only after confirming adequate hydration 1
- Missing paraproteinemias: When total protein is elevated but albumin is normal or low, perform serum protein electrophoresis and immunofixation to detect monoclonal proteins 3
Measurement Methods
Laboratory techniques for total protein include:
- Biuret reaction: The standard clinical chemistry method for total protein quantification 4, 5
- Kjeldahl method: Serves as the primary reference procedure for calibrating certified reference materials 6
- Near-infrared spectroscopy: Can measure total protein, albumin, and globulins simultaneously in unmodified serum 2