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Liver Function

Total Protein

A measure of all proteins circulating in the blood — total protein reflects liver synthetic function and helps identify protein deficiency, liver disease, and immune conditions.

SampleBlood (serum) FastingNot required Results1–2 days
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Summary

Total serum protein measures the combined concentration of albumin and globulins in the blood. Together, they reflect liver synthetic function, nutritional status, and immune activity. A low total protein indicates malnutrition or impaired liver function; an elevated total protein may signal chronic infection, inflammation, or blood disorders such as myeloma.

Total protein is divided into albumin (produced by the liver) and globulins (a heterogeneous group including immunoglobulins produced by plasma cells, and other proteins from the liver). The albumin-to-globulin (A:G) ratio — normally > 1 — provides additional diagnostic information: low A:G suggests immune upregulation (chronic infection, autoimmune disease, cirrhosis); high A:G with low albumin confirms liver synthetic failure.

Serum protein electrophoresis (SPEP) can further characterise abnormal globulin patterns and is performed when myeloma or other paraproteinaemias are suspected based on elevated total protein or globulin.

What It Is

Total serum protein is typically measured by the biuret method in routine biochemistry laboratories. It encompasses albumin (normally ~60% of total protein, 35–50 g/L) and globulins (~40%, 18–36 g/L).

Globulins include: (1) alpha-1 and alpha-2 globulins (acute phase proteins: alpha-1-antitrypsin, alpha-2-macroglobulin, haptoglobin); (2) beta globulins (transferrin, complement, LDL); and (3) gamma globulins (immunoglobulins IgG, IgA, IgM).

Reference range: 60–83 g/L. Total protein is interpreted alongside albumin to calculate globulin (total protein − albumin) and the albumin:globulin ratio.

Positioning: a total protein between 60–83 g/L is normal; 83 g/L prompts investigation for hyperglobulinaemia, including myeloma.

Total protein alone has limited clinical value — always interpret alongside albumin, globulin, and A:G ratio. Elevated globulin (high total protein with normal albumin) warrants serum protein electrophoresis.

Functions

Liver synthetic function

Albumin contributes to total protein and is a key marker of hepatic protein synthesis — low total protein with low albumin signals liver impairment.

Immune activity indicator

Elevated globulin (high total protein with normal albumin) reflects immune system activity — seen in chronic infections, autoimmune disease, and myeloma.

Nutritional status marker

Low total protein reflects inadequate dietary protein intake or significant protein loss — an important marker in malnutrition assessment.

Disease screening tool

Abnormal total protein or A:G ratio triggers further investigation — electrophoresis for myeloma, serology for autoimmune conditions.

Reference Ranges

Total Serum Protein

Measured in g/L
Low < 60
Normal 60–83
Elevated > 83
Status Range (g/L) Range (g/dL) What it means
Low < 60 < 6.0 Hypoproteinaemia — investigate for malnutrition, liver disease, or protein loss.
Normal 60–83 6.0–8.3 Normal total protein — adequate liver synthetic function and protein status.
Elevated > 83 > 8.3 Elevated — investigate for hyperglobulinaemia: myeloma, chronic infection, autoimmune disease.

Posture affects total protein (standing raises it by 10% due to haemoconcentration). Dehydration raises, overhydration lowers total protein. Interpret alongside albumin, globulin, and A:G ratio.

Symptoms of Imbalance

Symptoms of total protein abnormalities reflect the underlying cause rather than the protein level itself.

Low — Deficiency
  • Oedema from low oncotic pressure
  • Muscle wasting and fatigue
  • Poor wound healing
  • Increased susceptibility to infection
  • Symptoms of liver disease if that is the cause
High — Excess
  • Bone pain (in myeloma)
  • Fatigue and anaemia
  • Recurrent infections
  • Kidney impairment (myeloma cast nephropathy)
  • Hyperviscosity symptoms — headache, visual changes, confusion

Causes of Imbalance

Causes of Low
  • Malnutrition and protein-energy deficiency
  • Liver failure (reduced albumin synthesis)
  • Nephrotic syndrome (protein loss in urine)
  • Protein-losing enteropathy
  • Overhydration (dilutional)
  • Burns
Causes of High
  • Myeloma or other plasma cell disorders
  • Chronic infections (HIV, hepatitis B/C, tuberculosis)
  • Autoimmune disease (SLE, rheumatoid arthritis, Sjögren's)
  • Cirrhosis (elevated globulins from portal hypertension)
  • Dehydration

FAQs

Globulin is calculated as: total protein − albumin. Normal range: 18–36 g/L. Globulins include immunoglobulins (antibodies) and acute phase proteins. Low globulin may indicate immune deficiency; high globulin (> 40 g/L) suggests excess immunoglobulin production from chronic infection, autoimmune disease, cirrhosis, or myeloma. Serum protein electrophoresis differentiates polyclonal (diffuse) from monoclonal (sharp band — myeloma) elevation.

The A:G ratio is calculated as albumin ÷ globulin. Normal: > 1. A reversed A:G ratio (< 1) means globulin exceeds albumin — seen in cirrhosis, chronic infections, autoimmune disease, and myeloma. An A:G ratio < 1 in an otherwise well person warrants further investigation including immunoglobulin quantification.

Yes significantly. Standing position and dehydration both concentrate the blood, raising total protein by up to 10%. Conversely, lying down or being over-hydrated lowers it. For most routine purposes this does not cause misinterpretation, but if a result is borderline, repeating in a standardised position (sitting for at least 20 minutes before sampling) improves reproducibility.

NICE recommends urgent investigation for myeloma in adults over 60 with unexplained back pain, elevated protein or globulin, hypercalcaemia, anaemia, or bone pain. Investigations include serum immunoglobulins, serum free light chains, urine Bence-Jones protein, and bone marrow biopsy. Myeloma is diagnosed by the presence of a monoclonal protein band on electrophoresis.

No. Dietary protein intake does not significantly raise serum total protein. The body tightly regulates protein catabolism and synthesis. High total protein in a blood test almost always reflects increased globulin production — from immune stimulation, chronic infection, or plasma cell disease — not dietary excess.

References

  1. Harvey RA, et al. Total serum protein and globulin: clinical interpretation. J Clin Pathol. 2019;72(1):1–8. View source
  2. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351(18):1860–1873. View source
  3. Jelkmann W. Physiology and pharmacology of erythropoietin. Transfus Med Hemother. 2013;40(5):302–309. View source

Last medically reviewed: June 2026 · Reviewed by the Trupoint Health Clinical Team.

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