Dr.ehab   plasma protein
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Dr.ehab   plasma protein Dr.ehab plasma protein Presentation Transcript

  • Total blood volume is about 4.5 to 5 liters in adult human beingi.The defibrinated plasma is called serum,which lacks coagulation factors includingprothrombin and fibrinogen.ii.Total protein content of normal plasma is 6 to8 g/100 ml.iii.The plasma proteins consist of albumin (3.5to 5 g/dl), globulins (2.5-3.5 g/dl) and fibrinogen(200-400 mg/dl). The albumin:globulin ratio is usually between 1.2:1 to 1.5:1.iv.Almost all plasma proteins, exceptimmunoglobulins are synthesized in liver.
  • ELECTROPHORESISThe term electrophoresis refers to the movement ofcharged particles through an electrolyte whensubjected to an electric field.
  • Serum electrophoretic patterns
  • 1.Chronic infections: The gamma globulins are increased, but theincrease is smooth and widebased.2.Multiple myeloma: In para-proteinemias, a sharp spike is noted andis termed as M-band. This is due to monoclonal origin ofimmunoglobulins in multiple myeloma3.Nephrotic syndrome: All proteins except very big molecules arelost through urine, and so alpha-2 fraction (containing macroglobulin)will be very prominent.
  • ALBUMINThe name is derived from the whiteprecipitate formed when egg is boiled Functions of Albumin1. Colloid Osmotic Pressure of PlasmaProteins cannot easily escape out of blood vessels,and therefore, proteins exert the effective osmoticpressure. It is about 25 mm HgThe maintenance of blood volume is dependent on thiseffective osmotic pressure.
  • Transport FunctionAlbumin is the carrier of various hydrophobicsubstances in the blood.i Bilirubin and nonesterified fatty acids arespecifically transported by albumin.ii. Drugs (sulpha, aspirin, salicylates,dicoumarol, phenytoin).iii. Hormones: Steroid hormones, thyroxine.iv. Metals: Calcium, copper and heavy metalsare nonspecifically carried by albumin.
  • NutritionalFunction All tissue cells can take up albumin by pinocytosis. It is then broken down to amino acid level. Albumin may be considered as the transport form of essential amino acids from liver to other tissues.
  • Blood Brain BarrierAlbumin-fatty acid complex cannot crossblood brain barrier and hence fatty acidscannot be taken up by brain.The bilirubin from albumin may becompetitively replaced by aspirin and suchother drugs.In newborns, bilirubin is already high.There is a probability that free bilirubin isdeposited in brain leading to kernicterusand mental retardation.
  • EdemaHypoalbuminemia will result in tissue edemai. Manutrition, where albumin synthesis is depressed(generalised edema)ii. Nephrotic syndrome, where albumin is lostthrough urine (facial edema). Presence of albumin inurine is called albuminuria.Large quantities (many grams per day) of albumin islost in urine in nephrotic syndrome.Small quantities are lost in urine in acute nephritis,and other inflammatory conditions of urinary tract.Detection of albumin in urine is done by heat andacetic acid test.
  • iii. Cirrhosis of liver (mainly ascites). Albuminsynthesis is decreased.iv. Chronic congestive cardiac failure: Venouscongestion will cause increased hydrostaticpressure and decreased return of water intocapillaries and so pitting edema of feet may result.
  • Albumin-Globulin RatioIn hypoalbuminemia, there will be increasein globulins which are synthesised by thereticuloendothelial system.Albumin-globulin ratio (A/G ratio) is thusaltered or even reversed. This again leadsto edema.
  • TRANSPORT PROTEINSBlood is a watery medium; so lipids and lipidsoluble substances will not easily mix in theblood. Hence, such molecules are carried byspecific carrier proteins Albumin Pre-albumin or Transthyretin Thyroxine binding globulin (TBG) Retinol binding protein (RBP) Transcortin or cortisol binding globulin (CBG) Transferrin
  • ACUTE PHASE PROTEINSThe level of certain proteins in blood mayincrease 50 to 1000 folds in variousinflammatory and neoplastic conditions.Such proteins are acute phase proteins.Important acute phase proteins are describedC-Reactive Protein (CRP)CeruloplasminWilsons Disease
  • STRUCTURE OF IMMUNOGLOBULINS Immunoglobulin is abbreviated as Ig. The termsgamma globulin and immunoglobulin are notsynonymous. Gamma globulin is the termdescribing its mobility in electrical field. Most ofthe immunoglobulins have the gamma mobility;but some may move along with beta or even withalpha globulins. Immunoglobulin is a functionalterm, while gamma globulin is a physical term. In1962, Rodney Porter and Gerald Edelmanindependently proposed the structure forimmunoglobulin molecule, for which both of themwere awarded Nobel prize in 1972.
  • Heavy and Light ChainsThe structure of IgG molecule. It is made up of 2heavy (H) chains and 2 light (L) chains,combined through disulfide bridges. In the caseof IgG, H chains are composed of 440 aminoadds and L chains made up of 214 amino acids.Depending on the heavy chain make up, the
  • immunoglobulins aredifferentiated into 5 major 1. Immunoglobulin G (lgG) is made up of heavy chain g (gamma) 2. IgM has m (mu) heavy chain 3. IgA has a (alpha) heavy chain 4. IgD contains (delta) 5. IgE heavy chain is called e (epsilon).
  • The light chains are either K (kappa) or l (lambda) in all the classes. Forexample, IgG may consist of either g2 k2 g2 l2 Variable and Constant Regions Both the heavy and light chains contain relatively variable (V) and constant (C) regions with regard to their amino acid composition. VL and CL are the general terms for these regions on the light chain; while VH and CH specify variable and constant regions on the heavy chainAt the amino terminal end, about 100 amino acids in light chains and inheavy chains constitute the variable region. Here the amino acid sequencecan vary in Hand L chains, so that the body could synthesise enormousvarieties of different proteins.
  • Different Classes ofImmunoglobulins1. Immunoglobulin G (lgG)a. IgG contains two heavy chains and two light chains; heavy chains beingof gamma. Due to its sedimentation coefficient, it is sometimes referred toas 78 Ig.b. It is the antibody seen in secondary immune response.c. It can pass from vascular compartment to interstitial space. It can crossplacental barrier, and protects the new born child from infections.
  • 2. Immunoglobulin M (lgM)IgM are macroglobulins or 19S immunoglobulins.Five subunits, each having 4 peptide chains (total10 heavy chains and 10 light chains) are joinedtogether by a J-chain polypeptideIt can combine with 5 antigens simultaneously,and so IgM is very effective for agglutinatingbacteria.Being a large molecule, it cannot come out ofvascular space.IgM are the predominant class of antibodies inprimary response.
  • 3. Immunoglobulin A (lgA)a.IgA usually are dimers (total 4 heavychains and 4 light chains). The J chainconnects the dimers.b.They are the secretory antibodies seen inseromucous secretions of gastrointestinaltract, nasopharyngeal tract, urogenital tract,tears, saliva, sweat, etc. The dimers arestabilised against proteolytic enzymes bythe secretory piece.
  • 4. Immunoglobulin E (lgE)They mediate allergy, hypersensitivity andanaphylaxis.They have the property to fix on mast cellsand basophils. When certain antigenssuch as penicillin are injected a few times,IgE class antibodies are produced whichanchor on mast cells.When the same antigen is injected nexttime, the antigen fixes on cell surfaceantibodies, causing mast celldegranulation, and release of histamineand slow reacting substance.
  • PARAPROTEINEMIAS1. Multiple Myeloma (Plasmacytoma)i. When Ig-secreting cells are transformed into malignant cells, oneclone alone is enormously proliferated. Thus, Ig molecules of thevery same type are produced in large quantities.ii. This is seen in electrophoresis as the myeloma band ormonoclonal band or M band with a sharp narrow spike (Fig. 13.1).iii. Multiple myeloma is characterized by paraproteinemia, anemia,lytic bone lesions and proteinuria.iv. Bone marrow examination reveals large number of malignantplasma cells. Bone pain and tenderness are the commonpresenting complaints. Spontaneous pathological fracture of weightbearing bones, rib and vertebrae may occur.
  • 2. Bence Jones Proteinuria Henry BenceJones described it in 1848.i. This disorder is seen in 20% of patients withmultiple myeloma.ii. Monoclonal light chains are excreted inurine.iii. The Bence Jones proteins have the specialproperty of precipitation when heatedbetween 45°C and 60°C; but redissolving athigher than 80°C and lower than 45°C.
  • 3. Hypergammaglobulinemia Thisdisorder can occur in:i. Chronic infections, where antibodyproduction is high. Examples areleprosy, tuberculosis, malaria andsubacute bacterial endocarditisii. Aberrant immune reactions such as rheumatoidarthritis, collagen disorders, glomerulonephritis,and such autoimmu ne disorders wherecryoglobulins may also be present.iii. Paraproteinemias such as in multiple myeloma
  • Ceruloplasmin contains copper; it isdecreased in Wilsons hepato lenticulardegeneration. Blood fibrinogen level is200-400 mg/dl. Hemophilia is due thedeficiency of anti-hemophilic globulin(AHG) or factor VIII. Immunoglobulinsare classified into 5 classes; IgG, M, A,0 and E. IgM is seen in primaryantibody response. IgA is secretoryantibodies. IgE is associated withallergy and anaphylaxis.