Plasma Proteins PDF

Plasma Proteins, Functions and seParation technique ProF. Biliaminu s.a(mB,Bs; FmcPath., cert. in clin. emBryology) dePt. oF chemical Pathology and immunology, FBcs, cohs, university oF ilorin). Outline Functions and characteristics of plasma proteins Measurement of plasma prote...

Plasma Proteins, Functions and seParation technique ProF. Biliaminu s.a(mB,Bs; FmcPath., cert. in clin. emBryology) dePt. oF chemical Pathology and immunology, FBcs, cohs, university oF ilorin). Outline Functions and characteristics of plasma proteins Measurement of plasma proteins and diagnosis of diseases Electrophoretic patterns of plasma proteins Acute phase proteins  Plasma Proteins  Plasma contains >300 different proteins  Many pathological conditions affect level of pps  Mostly synthesized in the liver  Some are produced in other sites  A normal adult contains ~70 g/L of pps  Functions of Plasma Proteins Transport (Albumin, prealbumin, globulins) Maintain plasma oncotic pressure (Albumin) Defense (Immunoglobulins and complement) Clotting and fibrinolysis (Thrombin and plasmin)  Measurement of Plasma Proteins A) Quantitative measurement of a specific protein: Chemical or immunological reactions B) Semiquantitative measurement by electrophoresis:  Proteins are separated by their electrical charge in electrophoresis  Five separate bands of proteins are observed  These bands change in disease Normal Pattern of Plasma Protein Electrophoresis  Types of Plasma Proteins  Prealbumin  Albumin  α1-Globulins:  a1-Antitrypsin, α-fetoprotein  α2-Globulins:  Ceruloplasmin, haptoglobin  β-Globulins:  CRP, transferrin, β2-microglobulin  γ- Globulins  Prealbumin (Transthyretin)  A transport protein for:  Thyroid hormones  Retinol (vitamin A)  Migrates faster than albumin in electrophoresis  Separated by immunoelectrophoresis  Lower levels found in:  liver disease, nephrotic syndrome, acute phase inflammatory response, malnutrition  Short half-life (2 days)  Albumin  Most abundant plasma protein (~40 g/L) in normal adult  Synthesized in the liver as preproalbumin and secreted as albumin  Half-life in plasma: 20 days  Decreases rapidly in injury, infection and surgery  Functions Maintains oncotic pressure: – The osmotic pressure exerted by plasma proteins that pulls water into the circulatory system – Maintains fluid distribution in and outside cells and plasma volume 80% of plasma oncotic pressure is maintained by albumin  Functions A non-specific carrier of – hormones, calcium, free fatty acids, drugs, etc. Tissue cells can take up albumin by pinocytosis where it is hydrolyzed to amino acids Useful in treatment of liver diseases, hemorrhage, shock and burns  Hypoalbuminaemia Causes – Decreased albumin synthesis (liver cirrhosis, malnutrition) – Increased losses of albumin Increased catabolism in infections Excessive excretion by the kidneys (nephrotic syndrome) Excessive loss in bowel Severe burns (plasma loss in the absence of skin barrier)  Hypoalbuminaemia Effects Edema due to low oncotic pressure – Albumin level drops in liver disease causing low oncotic pressure – Fluid moves into the interstitial spaces causing edema Reduced transport of drugs and other substances in plasma Reduced protein-bound calcium – Total plasma calcium level drops – Ionized calcium level may remain normal  Hyperalbuminaemia No clinical conditions are known that cause the liver to produce large amounts of albumin The only cause of hyperalbuminemia is dehydration  a1-Antitrypsin  Synthesized by the liver and macrophages  An acute-phase protein that inhibits proteases  Proteases are produced endogenously and from leukocytes and bacteria  Digestive enzymes (trypsin, chymotrypsin)  Other proteases (elastase, thrombin)  Infection leads to protease release from bacteria and from leukocytes Types of a1-Antitrypsin  Over 30 types are known  The most common is M type  Genetic deficiency of a1-Antitrypsin  Synthesis of the defective a1-Antitrypsin occurs in the liver but it cannot secrete the protein  a1-Antitrypsin accumulates in hepatocytes and is deficient in plasma  Clinical Consequences of a1-Antitrypsin Deficiency  Neonatal jaundice with evidence of cholestasis  Childhood liver cirrhosis  Pulmonary emphysema in young adults Laboratory Diagnosis  Lack of a1-globulin band in protein electrophoresis  Quantitative measurement of a1-Antitrypsin by:  Radial immunodiffusion, isoelectric focusing or nephelometry  a-Fetoprotein (AFP)  Synthesized in the developing embryo and fetus by the parenchymal cells of the liver  AFP levels decrease gradually during intra-uterine life and reach adult levels at birth  Function is unknown but it may protect fetus from immunologic attack by the mother  No known physiological function in adults  a-Fetoprotein (AFP)  Elevated maternal AFP levels are associated with:  Neural tube defect, anencephaly  Decreased maternal AFP levels are associated with:  Increased risk of Down’s syndrome  AFP is a tumor marker for: Hepatoma and testicular cancer  Ceruloplasmin  Synthesized by the liver  Contains >90% of serum copper  An oxidoreductase that inactivates ROS causing tissue damage in acute phase response  Important for iron absorption from the intestine  Wilson’s disease:  Due to low plasma levels of ceruloplasmin  Copper is accumulated in the liver and brain  Haptoglobin  Synthesized by the liver  Binds to free hemoglobin to form complexes that are metabolized in the RES  Limits iron losses by preventing Hb loss from kidneys  Plasma level decreases during hemolysis  Transferrin  A major iron-transport protein in plasma  30% saturated with iron  Plasma level drops in:  Malnutrition, liver disease, inflammation, malignancy  Iron deficiency results in increased hepatic synthesis  A negative acute phase protein  2–Microglobulin  A component of human leukocyte antigen (HLA)  Present on the surface of lymphocytes and most nucleated cells  Filtered by the renal glomeruli due to its small size but most (>99%) is reabsorbed  Elevated serum levels are found in  Impaired kidney function  Overproduction in disease  May be a tumor marker for:  Leukemia, lymphomas, multiple myeloma  C-Reactive Protein (CRP)  An acute-phase protein synthesized by the liver  Important for phagocytosis  High plasma levels are found in many inflammatory conditions such as rheumatoid arthritis  A marker for ischemic heart disease  Hypergammaglobulinaemia  May result from stimulation of  B cells (Polyclonal hypergammaglobulinemia)  Monoclonal proliferation (Paraproteinemia) Polyclonal hypergammaglobulinemia:  Stimulation of many clones of B cells produce a wide range of antibodies  -globulin band appears large in electophoresis  Clinical conditions: acute and chronic infections, autoimmune diseases, chronic liver diseases  Monoclonal Hypergammaglobulinaemia  Proliferation of a single B-cell clone produces a single type of Ig  Appears as a separate dense band (paraprotein or M band) in electrophoresis  Paraproteins are characteristic of malignant B-cell proliferation  Clinical condition: multiple myeloma  Positive Acute Phase Proteins  Plasma protein levels increase in:  Infection, inflammation , malignancy, trauma, surgery  These proteins are called acute phase reactants  Synthesized due to body’s response to injury  Examples: a1-Antitypsin, haptoglobin, ceruloplasmin, fibrinogen, c-reactive protein  Positive Acute Phase Proteins  Mediators cause these proteins to increase after injury  Mediators: Cytokines (IL-1, IL-6), tumor necrosis factors a and  , interferons, platelet activating factor Functions: 1. Bind to polysaccharides in bacterial walls 2. Activate complement system 3. Stimulate phagocytosis  Negative Acute Phase Proteins  These proteins decrease in inflammation  Albumin, prealbumin, transferrin  Mediated by inflammatory response via cytokines and hormones  Synthesis of these proteins decrease to save amino acids for positive acute phase proteins Thanks