Clinical diagnostic biochemistry - 5 Dr. Maha Al-Sedik 2015 CLS 334

Albumin  Albumin is a small globular protein with a molecular mass of 66.3 kDa.  It is the most abundant protein found in plasma, accounting for approximately one half the plasma protein mass.  Because of its high plasma concentration and relatively small size, albumin is also the major protein component of most extravascular body fluids, including CSF, interstitial fluid, urine, and amniotic fluid.

Synthesis:  Albumin is synthesized primarily by the hepatic parenchymal cells.  The synthetic rate of albumin is controlled primarily by colloidal osmotic pressure (COP) and secondarily by protein intake.  In the nephrotic syndrome, the synthetic rate may be 300% or more of its normal rate. Exclusive in liver

Functions:  Maintenance of COP in both the vascular and extravascular spaces.  Albumin also binds and transports a large number of compounds, including free fatty acids, phospholipids, metallic ions, amino acids, drugs, hormones, and bilirubin.

Clinical Significance: A.Increased concentrations of albumin are present only in acute dehydration and have no clinical significance. B.Decreased concentration of albumin: I.Decreased synthesis: Malnutrition. Malabsorption. Liver disease II.Increased volume of distribution: Overhydration. Increased capillary permeability for albumin. III. Increased excreation or degradation: Nephrotic syndrome. Protein losing entropathy. Burns IV. Congenetal

Alpha 1 globulin  Alpha 1 Acid Glycoprotein.  Alpha 1 Antitrypsin.  Alpha 1 fetoprotein.

Alpha 2 globulin  Alpha 2 macroglobulin.  Alpha 2 lipoprotein.  Haptoglobulin.  Ceruloplasmin.  Erythropiotein.

Beta globulin  Beta lipoprotein.  Complement.  Beta 2 glycoprotein.  Coagulation factors.  Transferrin.

Gamma globulin  IgG  IgA  IgM  IgE  IgD

Antibody Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies.

BASIC STRUCTURE OF IMMUNOGLOBULINS: A. Fab: Antigen binding - These fragments were called the Fab fragments because they contained the antigen binding sites of the antibody. B. Fc: This fragment was called Fc because it was easily crystallized.

The immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains: IgG, IgA, IgM, IgE and IgD.

immunoglobulins IgGIgAIgMIgEIgD

A. IgG: All IgG's are monomers.  IgG is the major Ig in serum.  75% of serum Ig is IgG.  Placental transfer: IgG is the only class of Ig that crosses the placenta.  Fixes complement.  Binding to cells: Macrophages, monocytes, PMNs and some lymphocytes.  Anti Rh system are of that type.

B.IgM: IgM normally exists as a pentamer.  IgM is the third most common serum Ig.  IgM is also a good agglutinating Ig.  Can not pass the placenta.  Binding to cells - Macrophages, monocytes, PMNs and some lymphocytes.  Fixes complement.  Anti ABO system of that type.

C. IgA: Serum IgA is a monomer but IgA found in secretions is a dimer.  IgA is the 2nd most common serum Ig.  Normally IgA does not fix complement.  IgA can bind to some cells - PMN's and some lymphocytes.  Since it is found in secretions secretory IgA is important in local (mucosal) immunity.

Types of immunoglobulin

D. IgE:  IgE exists as a monomer.  Involved in allergic reactions.  IgE also plays a role in parasitic helminth diseases.  Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections.  IgE does not fix complement.

E. IgD:  IgD exists only as a monomer.  IgD is found in low levels in serum.  IgD is primarily found on B cell surfaces where it functions as a receptor for antigen.  Can not fix complement.

Urinary Proteins Definition: the presence of excessive proteins in the urine, as is seen: (1) In many types of renal disease (2) After strenuous exercise (3) With dehydration. Proteinuria Normal value of protein in urine: (less than 100 mg/day) or ( 1 to 14 mg/dL), and most of it is albumin. The concentration may reach 300 mg/dL in urine of healthy subjects after exercise.

The glomerular basement membrane (GBM) of the kidney acts as an filter for plasma proteins. The degree to which individual proteins pass through the membrane is a function of: (1)Molecular size. (2) Net ionic charge. (3) Plasma concentration of the proteins.

proteinuria occurs with 1.Increased glomerular permeability (glomerular proteinuria), in which the urinary protein is mainly albumin. 2. Defective tubular reabsorption (tubular proteinuria), in which the urinary proteins are mainly low molecular weight proteins. 3. Increased concentration in the plasma of an abnormal Low molecular weight protein, such as immunoglobulin light chains (overload proteinuria). Clinical Significance:

Laboratory Considerations: Qualitative detection of excess protein in urine: is most commonly performed using dipstick tests, many of which are dye based methods. Like all dye-binding techniques ( Bromocresol green BCG ), the dipstick methods are more sensitive to albumin than to other plasma proteins. They are therefore excellent screening tests for glomerular proteinuria, but unsatisfactory for detection of tubular proteinuria or overload proteinuria of the Bence Jones type.

Quantitative assay for total protein: In most cases, a 24-hour collection is chosen, both for quantitative total or specific protein assay and for electrophoretic separation.

Reference: Burtis and Ashwood Saunders, Teitz fundamentals of Clinical Chemistry, 4th edition, 2000.