Harpers

Plasma Proteins & Immunoglobulins 50Robert K. Murray, MD, PhDBIOMEDICAL IMPORTANCEThe fundamental role of blood in the maintenance ofhomeostasis and the ease with which blood can be obtainedhave meant that the study of its constituents hasbeen of central importance in the development of biochemistryand clinical biochemistry. The basic propertiesof a number of plasma proteins, including theimmunoglobulins (antibodies), are described in thischapter. Changes in the amounts of various plasma proteinsand immunoglobulins occur in many diseases andcan be monitored by electrophoresis or other suitableprocedures. As indicated in an earlier chapter, alterationsof the activities of certain enzymes found in plasma areof diagnostic use in a number of pathologic conditions.THE BLOOD HAS MANY FUNCTIONSThe functions of blood—except for specific cellularones such as oxygen transport and cell-mediated immunologicdefense—are carried out by plasma and itsconstituents (Table 50–1).Plasma consists of water, electrolytes, metabolites,nutrients, proteins, and hormones. The water and electrolytecomposition of plasma is practically the same asthat of all extracellular fluids. Laboratory determinationsof levels of Na + , K + , Ca 2+ , Cl − , HCO − 3 , PaCO 2 ,and of blood pH are important in the management ofmany patients.PLASMA CONTAINS A COMPLEXMIXTURE OF PROTEINSThe concentration of total protein in human plasma isapproximately 7.0–7.5 g/dL and comprises the majorpart of the solids of the plasma. The proteins of theplasma are actually a complex mixture that includes notonly simple proteins but also conjugated proteins suchas glycoproteins and various types of lipoproteins.Thousands of antibodies are present in human plasma,though the amount of any one antibody is usually quitelow under normal circumstances. The relative dimensionsand molecular masses of some of the most importantplasma proteins are shown in Figure 50–1.The separation of individual proteins from a complexmixture is frequently accomplished by the use ofsolvents or electrolytes (or both) to remove differentprotein fractions in accordance with their solubilitycharacteristics. This is the basis of the so-called saltingoutmethods, which find some usage in the determinationof protein fractions in the clinical laboratory.Thus, one can separate the proteins of the plasma intothree major groups—fibrinogen, albumin, and globulins—bythe use of varying concentrations of sodiumor ammonium sulfate.The most common method of analyzing plasmaproteins is by electrophoresis. There are many types ofelectrophoresis, each using a different supportingmedium. In clinical laboratories, cellulose acetate iswidely used as a supporting medium. Its use permitsresolution, after staining, of plasma proteins into fivebands, designated albumin, α 1 , α 2 , β, and γ fractions,respectively (Figure 50–2). The stained strip of celluloseacetate (or other supporting medium) is called anelectrophoretogram. The amounts of these five bandscan be conveniently quantified by use of densitometricscanning machines. Characteristic changes in theamounts of one or more of these five bands are foundin many diseases.The Concentration of Protein in Plasma IsImportant in Determining the Distributionof Fluid Between Blood & TissuesIn arterioles, the hydrostatic pressure is about 37 mmHg, with an interstitial (tissue) pressure of 1 mm Hgopposing it. The osmotic pressure (oncotic pressure)exerted by the plasma proteins is approximately 25 mmHg. Thus, a net outward force of about 11 mm Hgdrives fluid out into the interstitial spaces. In venules,the hydrostatic pressure is about 17 mm Hg, with theoncotic and interstitial pressures as described above;thus, a net force of about 9 mm Hg attracts water backinto the circulation. The above pressures are often referredto as the Starling forces. If the concentration ofplasma proteins is markedly diminished (eg, due to severeprotein malnutrition), fluid is not attracted backinto the intravascular compartment and accumulates inthe extravascular tissue spaces, a condition known asedema. Edema has many causes; protein deficiency isone of them.580