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Elevated Total Protein

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Last Updated: 02 July 2021

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General | Latest Info

A healthy 54 year - old man without a past medical history presents for routine physical exam for his insurance company. His blood work reveals total protein of 9. 4 G / dl and Albumin of 3. 0 G / dl. What should be included in these patients ' diagnostic workup? Elevate TP: Albumin ratio often necessitates finding protein responsible for such elevation. Plasma proteins largely consist of albumin and globulins such as immunoglobulins, carrier proteins, and acute phase reactants. Elevate globulin levels are concerning. An important question to ask oneself in workup of elevated proteins is whether there is an increase in multiple immunoglobulins or in one specific clone. Monoclonal proteins are made by proliferation of single clone of plasma cells. In order to assess for presence of Monoclonal Protein, SPEP should be order. In this test, patients ' serum is placed into agarose medium that separates proteins based on size and charge. A Typical Gamma M Spike means that we have large amount of very specific protein. For further characterization of M - Spike, immunofixation study should be order. If uses Monoclonal antibody probes to determine the isotype of Monoclonal Protein. If is often used when presence of M - Protein cannot be ascertained using SPEP, but clinical suspicion is high. The newer test known as Serum free light chains is even more sensitive, and has rendered true non - secretory myeloma into a rare entity. Look for Monoclonal Protein in urine, UPEP and urine IF can also be useful. Lastly, hematologist may be needed for bone marrow biopsy as well. Note discreet bands in IgG lane and Kappa lane - clearly identifying Kappa restrict IgG Protein. Once above diagnostic studies are obtain, physicians can often use clinical signs and symptoms along with biopsy results and M Spike characteristics to help define the clinical disease state. For example: one should be mindful of patients who present with elevated proteins plus nephrotic syndrome, carpal tunnel syndrome, autonomic neuropathy and / or cardiomyopathy. Amyloidosis should be high in differential as plasma cells produce amyloid proteins that deposit in variable organs. Fat pad biopsy can help to cinch diagnosis. Patients with significant Protein abnormalities should be referred to a hematologist for evaluation and treatment as a variety of options exist and many Protein disorders carry serious risks and progression to more serious entities. Treatment options for MM, while largely incurable, include conventional agents like melphalan, steroids, or auto - transplant as well as newer agents like thalidomide, lenalidomide or Bortezomib. The risk of progression to MM from MGUS is 1 - 2% per year and patients need to be assessed yearly for signs of CRAB. For SMM, risk is higher, and follow - up is warranted every 3 to 4 months. Abnormal Serum free light chain ratio is also predictive of progression to frank multiple myeloma. This progression is independent of size and type of Serum Monoclonal Protein.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What do the results mean?

Results of the total protein test are usually considered along with those from other tests of CMP and will give healthcare practitioners information on a person's general health status with regard to nutrition and / or conditions involving major organs, such as the kidney and liver. However, if results are abnormal, further testing is usually required to help diagnose disease affecting protein levels in blood. A low total protein level can suggest liver disorder, kidney disorder, or disorder in which protein is not digested or absorbed properly. Low levels may be seen in severe malnutrition and with conditions that cause malabsorption, such as celiac disease or inflammatory bowel disease. High total protein levels may be seen with chronic inflammation or infections such as viral hepatitis or HIV. It also may be associated with bone marrow disorders such as multiple myeloma. Low / G ratio may reflect overproduction of globulins, such as seen in multiple myeloma or autoimmune diseases, or underproduction of albumin, such as may occur with cirrhosis, or selective loss of albumin from circulation, as may occur with kidney disease. High / G ratio suggests underproduction of immunoglobulins as may be seen in some genetic deficiencies and in some leukemias. With low total protein that is due to plasma expansion, G ratio will typically be normal because both albumin and globulin will be diluted to the same extent. Following abnormal total protein result and depending on suspect cause, more specific tests are typically performed to make an accurate diagnosis. Some examples include liver enzyme tests, renal panel, serum protein electrophoresis, or tests for celiac disease or IBD.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What causes high blood protein?

Blood tests provide information on high blood protein. Protein levels are often included as part of comprehensive metabolic panel, blood test ordered by doctors as part of overall examination. A health provider collects blood samples through a small needle inserted into a vein in your arm. The laboratory analyzes blood samples to measure the amount of total protein in your body, among other items. Blood test results often include total protein levels, albumin level and ratio of albumin to globulins. Abnormal levels of blood proteins may require further follow - up testing like protein electrophoresis and quantitative immunoglobulins.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What Is It?

The normal range for total protein is between 6 and 8. 3 grams per deciliter. This range may vary slightly among laboratories. These ranges are also due to other factors such as: age gender population test method If total protein is abnormal, additional tests must be performed to identify which specific protein is low or high before diagnosis can be make. Inflammation or infections, such as viral hepatitis B or C, or HIV bone marrow disorders, such as multiple myeloma or Waldenstroms disease, bleeding liver disorder, kidney disorder, such as nephrotic disorder or glomerulonephritis malnutrition, malabsorption conditions, such as celiac disease or inflammatory bowel disease, extensive burns agammaglobulinemia, which is inherited condition in which your blood doesnt have enough of type of globulin, affecting strength of your immune system inflammatory conditions delay post - surgery recovery low albumin is consider albumin below 3. 4 G / dL. It is associated with decreased effectiveness of medications used for ulcerative colitis. Low albumin levels may result in complications during or after surgery. Normally, / G ratio is slightly higher than 1. If the ratio is too low or too high, additional testing must be done to determine cause and diagnosis. If the ratio is low, it can suggest: autoimmune disease multiple myeloma cirrhosis kidney disease high / G ratio can indicate genetic deficiencies or leukemia. Make sure to discuss your results with your doctor. They may want to do follow - up testing.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Interpretation

Mild hyperproteinemia may be caused by increase in concentration of specific proteins normally present in relatively low concentration, eg, increases in acute phase reactants and polyclonalimmunoglobulins produce inflammatory states, late - stage liver disease, and infections. Moderate - to - mark hyperproteinemia may also be due to multiple myeloma and other malignant paraproteinemias, although normal total protein levels do not rule out these disorders. Serum protein electrophoresis should be performed to evaluate the cause of elevated serum total protein. Hypoproteinemia may be due to decreased production or increased protein loss. Serum protein electrophoresis should be performed to evaluate the cause of the decrease in serum total protein. If a nephrotic pattern is identify, urine protein electrophoresis should also be perform.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Definition

Hundreds of proteins dissolve in plasma. By measuring concentration of these proteins, clinicians can obtain information regarding disease states in different organ systems. Measurement of protein is done on serum, which is fluid that remains after plasma has clot, thus removing fibrinogen and most of the clotting factors. Total Protein content provides some information regarding patient's general status; more clinically useful data is obtained from fractionating total protein. The normal serum protein level is 6 to 8 G / dL. Albumin make up 3. 5 to 5. 0 G / dL, and the remainder is total globulins. These values may vary according to individual laboratory.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Technique

Proteins are large polymers of amino acids linked by peptide bonds. Amino acid subunits of proteins are organic molecules that include carboxylic acid link through carbon atom to primary amine with chemical formula H 2 N - CHR - COOH, in which R is side group that largely determines chemical properties of amino acid. The simplest amino acid is glycine, H 2 N - CH 2 - COOH, in which the R side group is hydrogen atom. Although this chemical template can be modified into an infinite array of molecules based on variations in the R group, only approximately 20 amino acids occur in proteins. R groups confer acidic, alkaline, polar, or non - polar properties to various amino acids. Peptide bond is formed when primary amine reacts with carboxylic acid. Because molecule of H 2 O is lost in reaction, reaction constitutes dehydration synthesis, which can be reversed by hydrolytic cleavage. However, reverse reaction is very slow; as a result, peptide bonds are stable at physiological temperatures and pH. Digestion and metabolism of proteins are catalyzed by protease enzymes. Biuret and peptide bonds that react with cupric ion to form blue adduct that absorb at a wavelength of 540 nm. Reaction only occurs under alkaline conditions. The Biuret reagent also includes sodium potassium tartrate to stabilize cupric ions that would otherwise be susceptible to reduction in cuprous ion. Biuret reaction is the most common technique for measuring total protein using automated chemistry analyzers. Modifications of Biuret method include Lowry and Folin - Ciocalteu techniques, which greatly enhance sensitivity. These modifications are not necessary for measuring total protein in the serum but are useful in detecting minute amounts of protein that are present after isolation or separation procedures. Michaelis - Menton curve that demonstrates the relationship between reaction rate; substrate concentration; maximal reaction rate; and K M, Michaelis constant. K M is a thermodynamic quantity that expresses equilibrium constant between substrate, enzyme, and substrate - enzyme complex. Maximal rate, V Max, is the rate at which reaction proceeds when the enzyme is fully saturated with substrate. Lineweaver - Burk derivation of Michaelis - Menton equation produces a linear plot of 1 / vs 1 / V with slope of K M / V Max and y - intercept of 1 / K M. Measurement of creatine kinase activity by linking transfer of phosphate group from phosphocreatine to adenosine diphosphate to produce adenosine triphosphate with hexokinase reaction that transfers phosphate group from ATP to glucose. This produces glucose - 6phosphate, which in turn is oxidized by glucose - 6phosphate dehydrogenase to form 6 - phosphogluconate. Reaction is monitored by change in absorbance at 340 nm when G - 6PDH cofactor of oxidized form of nicotinamide adenine dinucleotide phosphate is converted to a reduced form of nicotinamide adenine dinucleotide phosphate. Some CK methods measure reverse reaction, from creatine to phosphocreatine, linking ADP produce to pyruvate kinase reaction.


Measurement of Proteins

Immunoassays are available for a variety of protein and nonprotein - analytes. Proteins express a rich array of epitopes and heterogeneous 2 - site immunoassays for Proteins can be highly specific. For detection and quantitation of specific proteins, immunoassay is currently the most common analytical technique. Many clinically important proteins are commonly measured in the serum using immunochemical methods: albumin, immunoglobulins, transferrin, peptide hormones, ceruloplasmin, tumor markers, cardiac markers, coagulation factors, ferritin, myoglobin, haptoglobin, hormone - binding Proteins, fibrinogen, and C - reactive protein are examples. Immunoassays can be classified in several ways based on general approach to using antibodies to detect and measure antigens. Heterogeneous immunoassays require physical isolation of antibody - bound antigen fraction, whereas in homogeneous methods, bound antigen can be chemically distinguished from free antigen so separation is not require. Most homogeneous immunoassays involve small antigens because detection of bound fraction in the presence of unbound antigens requires that the chemical property of antigen is changed when it bind to a comparatively large antibody molecule. Rotational frequency influenced by mass of antibody, enzyme activity influenced by antibody obscuring active site on enzyme, ability of enzyme subunits to spontaneously associate, and cross - linking of antigen - label microparticles that produce turbidity all have been used in homogeneous immunoassays. Virtually all immunoassays for proteins are heterogeneous. Immunoassays can be classified as competitive or noncompetitive. In competitive immunoassays, antigens are in excess and labelled antigens compete with endogenous antigens for binding sites on limited number of antibodies. 10 in noncompetitive immunoassays, antibodies are in excess and therefore capture all target antigens present. Although both competitive and noncompetitive methods exist for measuring proteins, noncompetitive methods are more common and have the advantage of greater sensitivity because all target antigens are captured and available for measurement. Another distinction exists between 1 - site and 2 - site immunoassays. In former, single antibody preparation is used to recognize and bind with epitopes on target antigen. In latter, two antibody preparations are used that recognize 2 different epitopes on target antigen; 2 - site methods are often called sandwich immunoassays because antigen is sandwiched between 2 antibodies. Although exceptions exist, competitive immunoassays are almost always of 1 - site type, whereas noncompetitive assays are of 2 - site type and involve label second antibody that reveal antigens adsorb by capturing antibodies. The prototype for 2 - site noncompetitive immunoassays is an enzyme - link immunosorbent assay. A key element in many immunoassays, competitive and noncompetitive, is the label used to detect competing antigen in single - site competitive methods, or secondary antibody in 2 - site noncompetitive methods. Immunoassays at least partially derive their names from the type of label used. Radioimmunoassay uses radioactive isotopes as label, enzyme immunoassays uses enzyme,ss and fluorescent immunoassay uses fluorophore.S Many contemporary immunoassays use chemiluminescent label that create a burst of light when reactant is add. Chemiluminescent labels have advantages over enzymes used for labels.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Basic Science

Albumin makes up more than half of the total protein present in the serum. Approximately 30 to 40% of the body's total albumin pool is found in the intravascular compartment. The remainder is extravascular and is located in interstitial spaces, mainly of muscles and skin. Albumin is also found in small amounts in a variety of body tissue fluids such as sweat, tears, gastric juice, and bile. Albumin does not diffuse freely through intact vascular endothelium. Hence, it is a major protein providing critical colloid osmotic or oncotic pressure that regulates passage of water and diffusable solutes through capillaries. Albumin accounts for 70% of colloid osmotic pressure. It exerts greater osmotic force than can be accounted for solely on the basis of the number of molecules that dissolve in plasma, and for this reason, it cannot be completely replaced by inert substances such as dextran. The reason is that albumin has negative charge at normal blood pH and attracts and retains cations, especially Na + in the vascular compartment. This is called the Gibbs - Donnan effect. Albumin also bind small number of Cl ions that increases its negative charge and ability to retain Na + ions inside capillaries. This enhanced osmotic force causes colloid osmotic pressure to be 50% greater than it would be by protein concentration alone. Albumin serves in transport of bilirubin, hormones, metals, vitamins, and drugs. It has an important role in fat metabolism by binding fatty acids and keeping them in soluble form in plasma. This is one reason why hyperlipemia occurs in clinical situations of hypoalbuminemia. Binding of hormones by albumin regulates the amount of free hormones available at any time. Because of its negative charge, albumin is also able to furnish some of the anions needed to balance cations of plasma. Albumin is synthesize in the liver. The rate of synthesis is constant in normal individuals at 150 to 250 mg / kg / day, resulting in production of 10 to 18 g of albumin daily in a 70 - kg man. Liver produces albumins at less than half of its capacity. Primary factors affecting albumin synthesis include protein and amino acid nutrition, colloidal osmotic pressure, action of certain hormones, and disease states. Fasting or protein - deficient diets cause decrease in albumin synthesis as long as deficiency state is maintain. In normal individual, liver increases albumin synthesis in response to increased availability of amino acids provided by portal blood following each protein - containing meal. A decrease in extravascular colloidal pressure serves as stimulus for albumin synthesis and is thought to act within the liver. Thyroid hormone, corticosteroids, growth hormone, and insulin can all increase albumin synthesis. The main site of the albumin degradation is not know. Albumin appears to be catabolize in locations that are capable of rapid equilibration with bloodstream. It is degraded into amino acids that are used for energy requirements of cells or secreted into pool of extracellular amino acids.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Clinical Significance

The only clinical situation that causes elevation in serum albumin is acute dehydration. A variety of clinical entities result in decreased albumin level, either from depressed synthesis or increased losses. The decrease in albumin synthesis is caused by end - stage liver disease, intestinal malabsorption syndromes, and protein - calorie malnutrition. Examples of albumin loss are nephrotic syndrome and severe burns because skin is the most important extra storage pool for albumin. The consequence of the decrease in serum albumin is the shift of fluid from intravascular to interstitial space, resulting in intravascular volume depletion and edema formation. Any increase or decrease in globulin fraction should be evaluated by serum electrophoresis. Patterns should be visually inspected for abnormalities in particular regions. 1 fraction consists mainly of 1 antitrypsin. Significant decreases in this fraction are seen in patients with congenital 1 antitrypsin deficiency; increase is seen in acute inflammatory disorders because 1 antitrypsin is an acute phase reactant. Major proteins migrating in 2 regions include 2 macroglobulin and haptoglobin. There is an increase in 2 macroglobulin in nephrotic syndrome when lower molecular weight proteins are lost in urine. Haptoglobin rises in response to stress, infection, acute inflammation, or tissue necrosis, probably by stimulation of synthesis. Haptoglobin levels decrease after hemolytic reaction because haptoglobin complexes with free hemoglobin and is clear from circulation. The major globulin is transferrin. Elevations occur in severe iron deficiency. Complement components C3, C4, and C5 also migrate in region. Most frequent abnormalities in the region are broad - base polyclonal increase or narrow monoclonal spike. Polyclonal increases are seen in chronic infections, connective tissue diseases, and liver disease. Monoclonal spikes suggest multiple myeloma, Waldenstrom's macro - globulinemia, primary amyloidosis, lymphoma, or monoclonal gammopathy. Any abnormality in the region suggesting monoclonal spike should be further evaluated by immunoelectrophoresis. Hypogammaglobulinemia is characterized by a decrease in component.S It is seen in congenital immune deficiency syndromes or in association with diseases such as nephrotic syndrome, chronic lymphocytic leukemia, and corticosteroid treatment.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Total Protein and A/G Ratio

You may need this test to find out whether you have liver disease, such as cirrhosis. Symptoms of cirrhosis include: Fluid buildup in the belly, which causes pain and swelling, Fluid buildup in feet, ankles, or legs, Fatigue, Itching, Nausea and vomiting, Lack of appetite, weight loss, Spiderlike blood vessels on skin, yellowing of skin and eyes. This test can also help healthcare providers diagnose nephrotic syndrome, condition that affects your kidneys. In adults, this problem may be caused by diabetes or lupus. Nephrotic syndrome causes puffiness around your eyes and in your arms and legs. With this condition, you lose too much protein in your urine. Protein testing may also show abnormal results if you have problem that cause you to lose protein from your digestive tract.


What is this test?

Many things may affect your lab test results. These include the method each lab uses to do the test. Even if your test results are different from normal value, you may not have a problem. To learn what results mean for you, talk with your healthcare provider. Certain diseases tend to lower your level of albumin and raise your level of one or more types of globulins. The normal range of albumin is 39 to 51 grams per liter of blood. The normal range for globulins varies by specific type. The normal range for total globulins is 23 to 35 g / L.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

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