Hyperproteinemia : Causes, Symptoms, Diagnosis & Treatment

• Classification
• Causes Of False Hyperproteinemia
• Causes Of True Hyperproteinemia
• Infections
• Inflammatory Diseases
• Monoclonal Gammopathy (Paraproteinemia)
• Rare Causes
• Diagnostics
• Correction
• Forecast

Hyperproteinemia is an increase in the concentration of total protein in the blood plasma of more than 84 g / l. This condition can develop due to a wide range of reasons - from excessive sweating and pregnancy to various inflammatory diseases and malignant neoplasms. In itself, a high protein content has no clinical signs, with the exception of monoclonal gammopathy, in which hyperproteinemia is a key pathogenetic link in the hyperviscosity syndrome (GBS). The protein level is examined in plasma on an empty stomach. To correct this disorder, therapy of the underlying disease is necessary.

Classification

A high concentration of protein can also be observed in absolutely healthy people (physiological hyperproteinemia). This happens during pregnancy, taking blood for analysis 3 minutes after a long stay in a horizontal position. According to etiopathogenesis, 2 types of hyperproteinemia are distinguished:

• Hemoconcentration (false). This type develops as a result of thickening of the blood due to a decrease in its liquid part. It occurs with diarrhea, extensive burns, profuse sweating.
• Hypersynthetic (true). The increase in protein levels is due to increased protein production. It is typical for infectious and non-infectious, acute and chronic inflammatory diseases, storage diseases, monoclonal gammopathy.

Hyperproteinemia can occur due to an increase in any protein fraction. Allocate:

• Hyperalbuminemia. Increase in albumin fraction. It occurs mainly with dehydration of the body.
• Hyperglobulinemia. Increased blood levels of alpha-beta-gammaglobulins, immunoglobulins. It is observed in infections, various autoimmune, chronic inflammatory diseases.
• Paraproteinemia. It is characterized by the production of structurally abnormal proteins - macroglobulins, Bence-Jones protein. These proteins appear in Waldenström's macroglobulinemia, multiple myeloma.

Causes of false hyperproteinemia

The development of this type of hyperproteinemia is associated with an increase in the relative protein content due to a significant decrease in the amount of fluid in the blood. At the same time, there is no protein overproduction. Typical for:

• acute intestinal infections (salmonellosis, dysentery), accompanied by indomitable vomiting and profuse diarrhea;
• extensive burns;
• prolonged hectic fever with profuse sweating.

The degree of hyperproteinemia is almost always moderate and quickly regresses after correction of water deficit.

Hyperproteinemia

Causes of true hyperproteinemia

infections

One of the most common causes of this condition. When an infectious agent (bacteria, viruses, parasites) enters the human body, they are phagocytosed. In the process of phagocytosis of microorganisms, leukocytes begin to produce peptide factors and pro-inflammatory cytokines (interleukins, interferon, tumor necrosis factor).

These substances, together with the activation of the sympathetic-adrenal system, stimulate the formation of acute phase proteins (C-reactive protein, complement system proteins, seromucoids) and immunoglobulins (antibodies) in B-lymphocytes in the liver. An increase in protein concentration is observed approximately 5-6 hours after the onset of an acute or exacerbation of a chronic infectious disease and reaches a maximum after 48-72 hours.

The level of hyperproteinemia correlates with the activity of the pathological process, but rarely reaches high values ​​(the degree is mostly moderate). Protein levels are higher in bacterial (pneumonia, pyelonephritis) and parasitic (malaria, trypanosomiasis) infections, as well as in generalized infections of any etiology (sepsis). The protein concentration normalizes quite quickly after inflammation subsides under the influence of specific therapy.

Inflammatory diseases

This group mainly includes pathologies of an autoimmune nature - rheumatoid arthritis, systemic connective tissue diseases (SLE, systemic scleroderma), inflammatory bowel diseases (Crohn's disease, ulcerative colitis). The exact pathogenetic mechanism of hyperproteinemia in chronic inflammatory autoimmune diseases is still unknown.

It is assumed that under the influence of an unknown etiological factor, there is an increased production of inflammatory proteins (mainly CRP) and globulins (autoantibodies) as part of immune autoaggression. Hyperproteinemia appears only during an exacerbation of the disease, almost always minor or moderate. After the onset of relapse, hyperproteinemia may persist for some time (from several days to several weeks).

Monoclonal gammopathy (paraproteinemia)

This group of diseases should be suspected with high and long-lasting hyperproteinemia. These include multiple myeloma (Rustitzky-Kaller myeloma), Waldenström macroglobulinemia, light chain disease. The pathogenesis is based on hyperproduction by tumor plasma cells of paraprotein proteins that are abnormal in molecular structure and immunological properties: macroglobulins, monoclonal immunoglobulins, kappa or lambda light chains.

A distinctive feature of this type of hyperproteinemia is that it serves not only as a diagnostic marker, but also directly determines the severity of the disease. Due to the peculiarities of the physical properties of paraproteins, they increase blood viscosity several times, which significantly disrupts blood circulation in all organs and tissues, especially in the brain.

Hyperproteinemia in these diseases can lead to a coma (paraproteinemic coma). Protein concentration increases slowly, over several years, in parallel with tumor progression. The level of total protein increases by about 15-20%. Its decrease occurs only after the removal of excess paraproteins from the systemic circulation using extracorporeal methods of blood purification (plasmapheresis).

Rare Causes

• Various forms of amyloidosis.
• Familial Mediterranean fever (periodic illness).
• cryoglobulinemia.

Diagnostics

By itself, hyperproteinemia is a rather rare phenomenon, so its detection requires special attention and differential diagnosis. When receiving a biochemical blood test with a high protein content, you must first consult a general practitioner. Anamnestic data are important: the age of the patient, previously diagnosed chronic diseases.

It is clarified what preceded the appearance of a high level of protein - profuse sweating, prolonged diarrhea, etc. Also, during a physical examination of the patient, the presence of certain symptoms is revealed, which can help in establishing the cause of deviations in the analyzes, for example, fever with infections, joint pain with autoimmune rheumatological pathology, bone pain and recurrent nosebleeds with paraproteinemias. To identify the cause of this laboratory phenomenon, the following examination is prescribed:

• Blood tests. In the general blood test, markers of inflammation are noted - an increase in CRP and an erythrocyte sedimentation rate. These figures are especially high in severe exacerbation of rheumatic diseases and paraproteinemia. Leukocytosis, anemia may be detected. With hyperproteinemia, the content of individual fractions is necessarily determined - albumin, alpha and gamma globulins.
• Urinalysis. Urinalysis often shows proteinuria. In multiple myeloma, Bence-Jones protein is found in the urine.
• Protein electrophoresis. This study is carried out to obtain more accurate and complete information about the content of various protein fractions. Monoclonal gammopathy is characterized by a high concentration of M-protein.
• Identification of the infectious agent. To identify an infectious agent, microbiological, virological studies are performed: bacterial culture of sputum, urine, blood on nutrient media; ELISA and PCR methods check the presence of DNA of microorganisms or antibodies to them.
• Examination for autoimmune disease. The titer of autoantibodies will be determined - rheumatic factor, antibodies to cyclic citrullinated peptide, to DNA, etc. If inflammatory bowel disease is suspected, an analysis for fecal calprotectin is informative.
• X-ray. With autoimmune arthropathies, a narrowing of the joint space, periarticular osteoporosis is visualized on the x-ray. Multiple foci of osteolysis and osteodestruction are characteristic of multiple myeloma, which are especially clearly visible in the skull area (“punch symptom”)
• Histological studies. Obtaining a bone marrow aspirate by trepanobiopsy or sternal puncture is prescribed only if the malignant nature of hyperproteinemia is suspected. The following changes can be detected - this is lympho- or plasma cell infiltration, stromal fibrosis.

Hyperproteinemia is diagnosed by the results of a biochemical blood test.

Correction

To combat hyperproteinemia, it is necessary to treat the underlying disease against which it developed. Physiological hyperproteinemia does not require any intervention, as it is not a sign of a disease or pathological condition. To correct hemoconcentration hyperproteinemia, it is enough to eliminate the fluid deficiency orally or by intravenous administration of crystalloid solutions. In other cases, the following activities are carried out:

• Anti-infective therapy. To eliminate the infectious agent, antibacterial (amoxicillin, levofloxacin), antiparasitic (hydroxychloroquine, mefloquine) are prescribed. For generalized bacterial infections (sepsis, endocarditis), a combination of at least 2 antibiotics from different groups is recommended.
• Anti-inflammatory therapy. In order to stop the inflammatory process and achieve remission of autoimmune diseases, glucocorticosteroids (prednisolone), immunosuppressants (cyclophosphamide, azathioprine), 5-aminosalicylic acid derivatives (sulfasalazine) are used. In severe cases, they resort to genetically engineered biological drugs (monoclonal antibodies), such as rituximab.
• Chemotherapy. If monoconal gammopathy is confirmed, to slow down the proliferation of tumor cells, combinations of chemotherapeutic agents are used - nucleoside analogues (fludarabine), alkylating drugs (horambucil), tumor necrosis factor inhibitors.
• Bone marrow transplantation. A certain group of patients with oncohematological diseases, together with courses of chemotherapy, is indicated for transplantation of hematopoietic cells.
• Plasmapheresis. Plasmapheresis is the only way to directly lower serum protein levels. Removal of excess protein from the patient's body is prescribed only for multiple myeloma and Waldenström's macroglobulinemia, accompanied by extremely high hyperproteinemia, causing a pronounced picture of GBS.

Forecast

Hyperproteinemia in the vast majority of cases does not have any adverse consequences for the patient. The prognosis is determined by the disease that caused the development of this laboratory phenomenon. An exception is high levels of protein in monoclonal gammopathy, when hyperproteinemia can cause coma, trophic ulcers and gangrene of the extremities, and chronic renal failure. Therefore, any excess of reference protein values, especially high and persistent, requires a visit to a doctor.