After studying this chapter, you should be able to:
- List the major functions of blood.
- Explain the functions of the major plasma proteins, including albumin, haptoglobin, transferrin, ceruloplasmin, α1-antitrypsin, and α2-macroglobulin.
- Describe how iron homeostasis is maintained and how it is affected in certain disorders.
- Describe the general structures and functions of the five classes of immunoglobulins and the uses of monoclonal antibodies.
- Appreciate that the complement system is involved in a number of important biological processes.
- Indicate the causes of Wilson disease, Menkes disease, the lung and liver diseases associated with α1-antitrypsin deficiency, amyloidosis, multiple myeloma, and agammaglobulinemia.
The fundamental role of blood in the maintenance of homeostasis (see Chapter 51) and the ease with which blood can be obtained have meant that the study of its constituents has been of central importance in the development of biochemistry and clinical biochemistry. The basic properties of a number of plasma proteins, including the immunoglobulins (antibodies), are described in this chapter. Changes in the amounts of various plasma proteins and immunoglobulins occur in many diseases and can be monitored by electrophoresis or other suitable procedures. As indicated in an earlier chapter, alterations of the activities of certain enzymes found in plasma are of diagnostic use in a number of pathologic conditions. Plasma proteins involved in blood coagulation are discussed in Chapter 51.
The functions of blood—except for specific cellular ones such as oxygen transport and cell-mediated immunologic defense—are carried out by plasma and its constituents (Table 50–1).
Table 50–1 Major Functions of Blood
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Table 50–1 Major Functions of Blood
Respiration—transport of oxygen from the lungs to the tissues and of CO2 from the tissues to the lungs
Nutrition—transport of absorbed food materials
Excretion—transport of metabolic waste to the kidneys, lungs, skin, and intestines for removal
Maintenance of the normal acid–base balance in the body
Regulation of water balance through the effects of blood on the exchange of water between the circulating fluid and the tissue fluid
Regulation of body temperature by the distribution of body heat
Defense against infection by the white blood cells and circulating antibodies
Transport of hormones and regulation of metabolism
Transport of metabolites
Plasma consists of water, electrolytes, metabolites, nutrients, proteins, and hormones. The water and electrolyte composition of plasma is practically the same as that of all extracellular fluids. Laboratory determinations of levels of Na+, K+, Ca2+, Mg2+, Cl−, HCO3−, PaCO2, and of blood pH are important in the management of many patients.
The concentration of total protein in human plasma is approximately 7.0–7.5 g/dL and comprises the major part of the solids of the plasma. The proteins of the plasma are actually a complex mixture that includes not only simple proteins but also conjugated proteins such as glycoproteins and various types of lipoproteins. Use of proteomic techniques is allowing the isolation and characterization of previously unknown plasma proteins, some present in very small amounts (eg, detected in hemodialysis fluid and in the plasma of patients with cancer), thus expanding the plasma proteome. Thousands of antibodies are present in human plasma, although the amount of any one antibody is usually quite low under normal circumstances. The relative dimensions and molecular masses of some of the most important plasma proteins are shown in Figure 50–1.
Relative dimensions and approximate molecular masses of protein molecules in the blood (Oncley).
The separation of individual proteins from a complex mixture is frequently accomplished by the use of solvents or electrolytes (or both) to remove different protein fractions in accordance with their solubility characteristics. This is the basis of the so-called salting-out methods, which find some usage in the determination of protein fractions in the clinical laboratory. Thus, one can separate the proteins of the plasma into three major groups—fibrinogen, albumin, and globulins—by the use of varying concentrations of sodium or ammonium sulfate.
The most common method of analyzing plasma proteins is by electrophoresis. There are many types of electrophoresis, each using a different supporting medium. In clinical laboratories, cellulose acetate is widely used as a supporting medium. Its use permits resolution, after staining, of plasma proteins into five bands, designated albumin, α1, α2, β, and γ fractions, respectively (Figure 50–2). The stained strip of cellulose acetate (or other supporting medium) is called an electrophoretogram. The amounts of these five bands can be conveniently quantified by use of densitometric scanning machines. Characteristic changes in the amounts of one or more of these five bands are found in many diseases.
Technique of cellulose acetate zone electrophoresis. (A) A small amount of serum or other fluid is applied to a cellulose acetate strip. (B) Electrophoresis of sample in electrolyte buffer is performed. (C) Separated protein bands are visualized in characteristic positions after being stained. (D) Densitometer scanning from cellulose acetate strip converts bands to characteristic peaks of albumin, α1-globulin, β2-globulin, β-globulin, and γ-globulin. (Reproduced, with permission, from Parslow TG et al (editors): Medical Immunology, 10th ed. McGraw-Hill, 2001.)
The Concentration of Protein in Plasma Is Important in Determining the Distribution of Fluid between Blood & Tissues
In arterioles, the hydrostatic pressure is about 37 mmHg, with an interstitial (tissue) pressure of 1 mmHg opposing it. The osmotic pressure (oncotic pressure) exerted by the plasma proteins is approximately 25 mmHg. Thus, a net outward force of about 11 mmHg drives ...