A high blood protein level, often discovered during routine blood work, indicates an elevated concentration of proteins circulating in the bloodstream. This measurement, known as Total Protein, is typically included as part of a Comprehensive Metabolic Panel (CMP), which assesses various components in the blood serum. The result reflects the combined amount of all protein types present in the liquid portion of the blood (plasma). This high concentration signals an underlying issue that requires further investigation, ranging from simple fluid imbalance to more complex medical conditions.
Defining Albumin and Globulin
The Total Protein value is comprised mainly of two protein groups: albumin and globulin. Albumin is the most abundant protein in the blood, synthesized primarily by the liver. Its primary role is to maintain osmotic pressure, which prevents fluid from leaking out of blood vessels and into surrounding tissues. Albumin also serves as a transport vehicle, carrying hormones, fatty acids, vitamins, and certain medications throughout the body.
The second major group, globulins, consists of hundreds of different proteins, including enzymes, carrier proteins, and immunoglobulins (antibodies). Globulins are produced by both the liver and immune system cells and are involved in blood clotting and fighting infections. When total protein is high, it is usually due to an increased concentration of one or both of these components. Understanding which protein is elevated is the next step in determining the cause of the high total protein result.
The Role of Dehydration in Elevated Total Protein
The most common reason for an elevated total protein level is dehydration. When the body loses more fluid than it takes in, the total volume of blood plasma decreases. The proteins themselves are too large to leave the bloodstream, so their absolute amount remains the same, but they become more concentrated within the reduced fluid volume.
This phenomenon is called hemoconcentration, which creates an artificially high measurement of total protein on a lab test. If dehydration is the cause, the high protein level is temporary and returns to the normal range once proper hydration is restored.
Pathological Causes of Globulin Elevation
If dehydration is ruled out, a high total protein level almost always points to an actual increase in globulin production, signaling an underlying health issue. This pathological increase, known as hyperglobulinemia, is often a result of the body’s immune system being activated.
Chronic Inflammation and Infection
The most frequent causes are chronic inflammatory conditions or persistent infections, which provoke the immune system to produce high amounts of antibodies (gamma globulins). Conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and chronic hepatitis B or C can lead to this sustained, widespread increase in various globulin types, known as polyclonal gammopathy.
Liver Disease
Liver disease, particularly cirrhosis, can also cause globulin levels to rise. Impaired liver function reduces the clearance of immunoglobulins from the blood, allowing them to accumulate. Liver dysfunction can disrupt the overall balance of blood proteins.
Plasma Cell Disorders
A more concerning cause involves plasma cell disorders, such as Multiple Myeloma. In these conditions, a single clone of plasma cells multiplies uncontrollably, producing an excessive amount of one specific type of antibody, called a monoclonal protein or M-protein. This production creates a distinct, sharp spike of protein on specialized lab tests, a pattern known as monoclonal gammopathy. Monoclonal Gammopathy of Undetermined Significance (MGUS) is a common, non-cancerous condition that also produces an M-protein.
Diagnostic Follow-Up After High Results
When an elevated total protein is found, especially if it is not easily explained by dehydration, further testing is necessary to pinpoint the cause. The immediate next step is usually to determine whether the elevation is due to an increase in albumin or globulin. The key specialized test used for this purpose is Serum Protein Electrophoresis (SPEP).
SPEP separates the various proteins in the blood serum based on their electrical charge and size, creating a visual pattern that helps identify the specific protein fraction that is elevated. This process distinguishes between a polyclonal pattern (suggesting chronic infection or inflammation) and a monoclonal spike (suggesting a plasma cell disorder). Additional laboratory tests are often ordered alongside the SPEP to complete the diagnostic picture. These may include quantitative immunoglobulin levels, a complete blood count, and a urine protein assessment to check for light chains, also known as Bence Jones proteins.