MLAB 2401: Clinical Chemistry Keri Brophy-Martinez 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 Decreased Levels Increased Levels Hepatic damage Acute-phase inflammatory responses Tissue necrosis Poor nutrition Steroid therapy Alcoholism Chronic renal failure

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 LevelsIncreased Levels 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

Globulins Group consisting of α 1, β, α 2, and gamma fractions Focus will be on globulins most often encountered in the lab

α 1 - Globulins GlobulinFunctionIncreasedDecreased α 1-Antitrypsin Acute phase reactant Inflammatory reactions, pregnancy, contraceptive use Neonatal Emphysema α 1-Fetoprotein Principal fetal protein Spina bifida Anencephaly Fetal Distress

α 2 - Globulins GlobulinFunctionIncreasedDecreased 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 α 2 -Macroglobulin Inhibits proteases Nephrosis Diabetes Liver disease

β - Globulins GlobulinFunctionIncreasedDecreased 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) GlobulinFunctionIncreasedDecreased 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 GlobulinFunctionIncreasedDecreased IgGAntibodies Liver disease Infections Parasitic disease Others Immunodeficiency Others IgAAntibodies in secretions Liver disease Infections Autoimmune disease Immunodeficiency Decreased protein synthesis IgMAntibodies: early response Toxoplasmosis Others Hereditary immunodeficiency IgDAntibodies Infections Liver disease IgEAntibodies: 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 ProteinAlbuminGlobulinDisease N, DDIHepatic damage, Burns, trauma, Infections DDNMalabsorption, Inadequate diet, nephroticsyndrome DNDImmunodeficiency syndromes IIIDehydration INIMultiple 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. -break/