Proteins in the blood perform many functions, including transporting nutrients, aiding in blood clotting, and supporting the immune system. When the concentration of these proteins rises above the normal limit—generally considered above 8.3 grams per deciliter (g/dL)—the condition is called hyperproteinemia. Serum protein consists mainly of two types: albumin, which helps regulate fluid balance, and globulins, which are made by the immune system to fight infection. An elevation in total serum protein suggests an imbalance, though hyperproteinemia itself is not a specific disease but rather an indication of an underlying issue that requires further medical investigation.
Recognizing the Physical Signs
Hyperproteinemia often does not produce distinct symptoms on its own and is frequently discovered incidentally during routine blood work. Instead, the physical signs a person experiences are usually a direct result of the underlying condition causing the protein elevation. One of the most common complaints associated with the conditions that lead to high protein is unexplained and persistent fatigue or generalized weakness.
Patients may also notice changes in their body weight, specifically unintentional loss, which can be a sign of a more serious systemic disease. Swelling, also known as edema, can occur, particularly in the extremities like the legs and ankles, sometimes due to the disruption of fluid distribution caused by protein imbalances. Changes in urination, such as a decrease in frequency or the urine appearing highly concentrated, might be observed if the hyperproteinemia is due to dehydration.
If the underlying cause involves the nervous system, a person may experience numbness or tingling sensations, known as neuropathy. Some individuals report an increased frequency of infections, suggesting the elevated proteins may be related to an immune system that is either overactive or compromised. Other signs can include bone pain, which is especially relevant if the protein elevation is linked to certain blood cancers.
Medical Conditions That Elevate Protein
Elevated total protein is grouped into two categories based on the mechanism of increase. The most common cause is relative hyperproteinemia, which happens when the liquid portion of the blood decreases while the amount of protein remains stable. This is seen in cases of severe dehydration caused by insufficient fluid intake, or excessive fluid loss from conditions like vomiting and persistent diarrhea. Because the blood plasma volume is reduced, the proteins become concentrated, leading to an artificially high reading.
The second, more concerning cause is absolute hyperproteinemia, where the body is actively producing an excess amount of protein. This production often involves the globulin fraction of the total protein, particularly immunoglobulins. Chronic inflammatory diseases, such as rheumatoid arthritis or lupus, can stimulate the immune system to produce a high volume of these globulins. Chronic infections like Hepatitis C or HIV can also cause a sustained increase in globulin production as the body attempts to fight the pathogen.
A significant cause of absolute hyperproteinemia involves plasma cell disorders, known as monoclonal gammopathies. The most common of these is Multiple Myeloma, a cancer of the plasma cells in the bone marrow that produces a large, abnormal, single type of protein called a monoclonal protein or M-protein. Related conditions, such as Waldenström macroglobulinemia, also lead to an overproduction of a specific immunoglobulin. Liver diseases, including cirrhosis, can also disrupt the body’s normal protein metabolism, contributing to imbalances and elevated levels.
Diagnosis and Medical Evaluation
When a blood test reveals high total protein levels, the medical evaluation begins with a search for the underlying cause. The initial screening for total protein is often part of a routine comprehensive metabolic panel. If the level is high, a physician will first assess for signs of dehydration, as this is the simplest and most common explanation. Correcting dehydration, if present, should resolve this type of hyperproteinemia quickly.
If dehydration is ruled out or the elevation is significant, the next step is a specialized test called Serum Protein Electrophoresis (SPEP). This procedure separates the different proteins in the serum—albumin and the various globulins—into distinct bands. The SPEP helps identify which specific protein fraction is elevated, providing a crucial clue to the underlying pathology, such as an overproduction of gamma globulins seen in immune disorders or monoclonal gammopathies.
Further investigation requires additional tests to pinpoint the exact condition.
Advanced Diagnostic Tests
- Urine protein electrophoresis checks for abnormal proteins being excreted by the kidneys.
- A serum free light chain assay is highly sensitive for screening certain plasma cell disorders.
- If a blood cancer like Multiple Myeloma is suspected, a bone marrow biopsy may be ordered.
- Specific imaging studies, such as a whole-body, low-dose CT scan, may be necessary to complete the diagnosis.