MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Plasma Proteins

Plasma Proteins Two groups Albumin Globulins

Prealbumin Synthesized mainly in the liver Migrates ahead of albumin on electrophoresis Transport protein for thyroid hormones and retinol(Vitamin A)

Prealbumin Increased Levels Decreased Levels Hepatic damage Acute-phase inflammatory responses Tissue necrosis Poor nutrition Steroid therapy Alcoholism Chronic renal failure Prealbumin

Albumin Synthesized in the liver Protein present in the highest concentration in the plasma Functions Maintenance of colloid osmotic pressure Buffers pH Negative acute phase reactant Binds substances in the blood

Albumin Decreased Levels Increased Levels Dehydration Malnutrition/Malabsorption Inadequate intake of amino acids Liver disease GI loss Loss of fluids Renal disease Excreted excessively Dilution by excess IV fluids, polydipsia Dehydration Excessive albumin infusion Albumin

Globulins Group consisting of α1, β, α2, and gamma fractions Focus will be on globulins most often encountered in the lab

α1- Globulins Globulin Function Increased Decreased α1-Antitrypsin Acute phase reactant Inflammatory reactions, pregnancy, contraceptive use Neonatal Emphysema α1-Fetoprotein Principal fetal protein Spina bifida Anencephaly Fetal Distress

α2- Globulins Globulin Function Increased Decreased Haptoglobin Acute phase reactant Binds hemoglobin Inflammatory diseases Rheumatic disease Hemolytic anemia Liver disease Ceruloplasmin Redox activity 90% copper found here Inflammation Severe infection Tissue damage Pregnancy Others Wilson’s disease Malnutrition/Malabsorption Severe liver disease α2-Macroglobulin Inhibits proteases Nephrosis Diabetes

β- Globulins Globulin Function Increased Decreased Transferrin Transports iron Prevents iron loss Negative acute phase reactant IDA Liver disease Nephrotic syndrome Malnutrition Hemopexin Acute phase reactant Binds free heme Inflammation Diabetes melllitus Melanoma Hemolytic anemia Lipoprotein Transports lipids, mainly LDL Atherosclerosis Heart disease Diabetes mellitus Hypothyroidism

ß- Globulins (con’t) Globulin Function Increased Decreased Fibrinogen Precursor of fibrin clot Acute phase of inflammatory processes Pregnancy Oral contraceptives Excessive coagulation Complement Immune response Inflammation Malnutrition Hemolytic anemia CRP Acute phase reactant Tissue necrosis Cardiac disease

γ- Globulins: Immunoglobulins Function Increased Decreased IgG Antibodies Liver disease Infections Parasitic disease Others Immunodeficiency IgA Antibodies in secretions Autoimmune disease Decreased protein synthesis IgM Antibodies: early response Toxoplasmosis Hereditary immunodeficiency IgD IgE Antibodies: allergies Not diagnostic

Other Noteworthy Proteins Myoglobin Troponin Heart marker for MI BNP Distinguishes between MI and CHF Fibronectin Glycoprotein used to predict the short term risk of premature delivery

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Protein Abnormalities Total protein measures all of the proteins in plasma Measurements reflect Nutritional status Kidney disease Liver disease Other

Hypoproteinemia Total protein level <6.4 g/dL Due to a negative nitrogen balance Causes Excessive loss renal disease, blood loss, burns Decreased intake Malnutrition, intestinal malabsorption Decreased synthesis Liver disease, inherited immunodeficiency Acceleration of catabolism of proteins Burns, trauma

Hyperproteinemia Total protein level > 8.3 g/dL Causes Dehydration Excess water loss leads to the increased concentration of proteins Examples: vomiting, diarrhea, diabetic acidosis, hypoaldosteronism Excessive Production of gamma globulins Examples: multiple myeloma, Waldenstrom’s macroglobulinemia

Summary of Protein Levels Total Protein Albumin Globulin Disease N, D D I Hepatic damage, Burns, trauma, Infections N Malabsorption, Inadequate diet, nephroticsyndrome Immunodeficiency syndromes Dehydration Multiple myeloma, monoclonal and polyclonal gammopathies N= normal I=increased D=decreased

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson. http://www.stoelrivesworldofemployment.com/tags/rest -break/