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) Decreased Levels Hepatic damage Acute-phase inflammatory responses Tissue necrosis Poor nutrition Increased Levels 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 Decreased Levels • Increased Levels Malnutrition/Malabsorption – Inadequate intake of amino acids • Liver disease • GI loss Dehydration Excessive albumin infusion – Loss of fluids • Renal disease – Excreted excessively • Dilution by excess – IV fluids, polydipsia 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 •Acute phase reactant •Redox activity •90% copper found here •Inflammation •Severe infection •Tissue damage •Pregnancy •Others •Wilson’s disease •Malnutrition •Malabsorption •Severe liver disease •Others α2-Macroglobulin •Inhibits proteases •Nephrosis •Diabetes •Liver disease 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 Globulin Function Increased Decreased IgG Antibodies •Liver disease •Infections •Parasitic disease •Others •Immunodeficiency •Others IgA Antibodies in secretions •Liver disease •Infections •Autoimmune disease •Immunodeficiency •Decreased protein synthesis IgM Antibodies: early response •Toxoplasmosis •Others •Hereditary immunodeficiency IgD Antibodies •Infections •Liver disease 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 Do you feel like this? If the answer is “Yes” take a break! 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 D D N Malabsorption, Inadequate diet, nephroticsyndrome D N D Immunodeficiency syndromes I I I Dehydration I N I 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/