DISORDERS AND LABORATORY EVALUATION

12 DISORDERS AND LABORATORY EVALUATION



Ronald D. Tyler, Rick L. Cowell, James H. Meinkoth



1 What is protein dyscrasia?


Protein dyscrasia refers to a protein with an abnormal structure, as in dysfibrinogenemia.



2 What is dysproteinemia?


Dysproteinemia is the presence of either normal plasma proteins at abnormal concentrations or abnormal proteins in the blood, e.g., hyper and hypoalbuminemia, hyper and hypoglobulinemia.



3 What are the two major categories of plasma proteins, and how are their concentrations usually determined?


The two major categories of plasma proteins are albumin and globulin. Their concentrations are determined by measuring total protein (TP) and albumin concentrations, then calculating the globulin concentration by subtracting the albumin concentration from the TP concentration.



4 Where are the major plasma proteins synthesized?


The liver synthesizes albumin and essentially all plasma globulins other than immunoglobulins and von Willebrand’s factor. The lymphoid system synthesizes immunoglobulins, and endothelial cells (and megakaryocytes) synthesize von Willebrand’s factor.



5 List two major functions of albumin.



a. Transport substances with low plasma solubility

b. Provide oncotic pressure


6 What are the general causes of severe hypoalbuminemia?



a. Hemorrhage

b. Glomerular disease (protein-losing nephropathies)

c. Gastrointestinal loss (protein-losing gastroenteropathies)

d. Decreased hepatic production of albumin


7 What are some supportive features of each of the four general causes of severe hypoalbuminemia?



a. Hemorrhage: concurrent anemia (usually a regenerative anemia unless iron deficiency anemia has developed), evidence of hemorrhage

b. Glomerular disease: moderate to marked proteinuria with benign urine sediment

c. Gastrointestinal loss: diarrhea (generally present but not always)

d. Decreased hepatic production of albumin: low blood glucose and urea nitrogen concentrations; elevated concentration of bile acids; hepatic transaminases and biliary enzymes may be elevated. Diarrhea is also present in some cases.


8 How does inflammation influence serum albumin and globulin concentrations?


During inflammation, albumin catabolism increases and albumin synthesis decreases, resulting in lower albumin concentrations. Concurrently, globulins increase due to increased production of inflammatory globulins, such as fibrinogen, alpha-2 macroglobulin, haptoglobin, ceruloplasmin, alpha-1 antitrypsin, and immunoglobulins. As a result, albumin concentration often decreases by about 1 gram per deciliter (g/dl) for each 3 to 4 g/dl increase in globulin concentration.



9 What are the advantages of measuring plasma or serum protein by refractometry?


Refractometry is a rapid, easy, and rather inexpensive method of measuring total protein and can be done at the clinic while the patient is in the examination room, if necessary.



10 Name two colormetric methods of measuring plasma or serum protein.



a. Biuret method

b. Lowry method


11 What is the chemical method most often used to measure plasma or serum protein in clinical laboratories?


Because of its simplicity, accuracy, and precision, the biuret method is the chemical method of choice for measuring TP concentration in serum or plasma in the clinical laboratory.



12 What is the basis of the biuret method of protein measurement?


The biuret method is based on the formation of a blue peptide–copper complex in alkaline solution and is the most widely used colorimetric method for TP concentration assay.



13 How sensitive is the biuret method for protein measurement?


The biuret method is accurate for assay of protein concentrations from 1 to 10 g/dl. Thus it is adequate for measurement of total plasma and serum protein concentrations, but not for the measurement of the very low levels of protein often found in body fluids, such as cerebrospinal fluid (CSF), urine, and transudates.



14 What is the basis of the phenol-Folin-Ciocalteau method for protein measurement?


The phenol-Folin-Ciocalteau method is based on the reaction of the reagent with the phenolic groups of tryptophan and tyrosine in proteins to form a blue color.



15 Which is better for measuring plasma or serum albumin concentration in domestic animals, the bromocresol green method or the 2-(4′-hydroxyazobenzene) benzoic acid method?


The bromocresol green (BCG) method is the dye-binding procedure that is most acceptable for determining serum albumin levels in domestic animals. Many human laboratories use a 2-(4′-hydroxyazobenzene) benzoic acid (HABA) procedure, which produces erratic results in domestic animals.



16 Can serum albumin concentration be measured by electrophoresis?


Serum protein electrophoresis is the most accurate method for measurement of albumin and is used as the reference method for the colorimetric procedures. However, serum protein electrophoresis is not routinely used to determine albumin levels because of its high cost and the time requirement for processing.



17 How is plasma or serum globulin concentration usually determined, and what are factors to consider when using it?


Serum globulin level is generally not measured but instead is determined mathematically by subtracting the albumin level from the TP level, with the difference being the globulin level. Therefore the globulin level represents all the nonalbumin protein measured in the TP level, and errors in measurement of TP or albumin level will erroneously alter the calculated globulin level. The serum globulin level can be measured colorimetrically or by serum protein electrophoresis. However, these procedures are costly and time consuming and therefore are only used in rare instances.



18 What is the diagnostic value of the albumin/globulin ratio?


An increased albumin/globulin (A/G) ratio may occur with any factor that increases albumin or decreases globulin. A decreased A/G ratio may occur with any factor that decreases albumin or increases globulin. For best interpretation of the A/G ratio, absolute TP, albumin, and globulin values must also be considered.



19 Is serum or plasma preferred for protein electrophoresis?


Generally, serum is preferred for protein electrophoresis, and hemolysis should be avoided. Besides obscuring the patterns of other serum proteins, fibrinogen and hemoglobin produce monoclonal spikes and can be misdiagnosed as monoclonal gammopathies.



20 What factors influence protein migration during electrophoresis?


Direction and rate of migration of the different proteins are determined by the type of charge (positive or negative) of the protein, strength of the charge, size of the protein, intensity of the electrical field, and support medium through which the proteins are induced to migrate. To compare results of serum protein electrophoresis, the support medium, pH, buffer, and electric current should be known. Cellulose acetate is the most frequently used support medium.



21 Does serum electrophoresis identify changes in individual proteins?


Serum protein electrophoresis does not separate individual proteins, other than albumin, and therefore does not specifically identify changes in proteins other than albumin. Instead, electrophoresis separates proteins into groups of similarly charged and sized proteins. A change (increase or decrease) in the area of the electrophoretic pattern where a protein migrates indicates a change (increase or decrease) in that protein and/or another protein migrating in the same area. Therefore, serum protein electrophoresis generally provides only an estimate of which similarly charged and sized groups of proteins have increased or decreased. It usually does not indicate a specific diagnosis but instead indicates a general disease process, such as inflammation or immune response. An important exception is monoclonal spikes.



22 How are monoclonal peaks in electrophoretograms recognized?


Because of its homogeneity, albumin is used as a guide for differentiating sharp monoclonal globulin peaks (monoclonal spikes) from polyclonal peaks. Monoclonal peaks should be as sharp or sharper than the albumin peak.



23 What is the most common pathologic cause of monoclonal peaks in serum electrophoretograms?


Plasma cell myeloma is the most common cause of monoclonal spikes.



24 Besides plasma cell myeloma, what diseases may infrequently be associated with a monoclonal peak in serum protein electrophoretograms?


Monoclonal gammopathies resulting in peaks may be associated with the following:


a. Lymphosarcoma (occasionally)

b. Canine ehrlichiosis

c. Canine lieshmaniasis

d. Feline infectious peritonitis

e. Plasmacytic gastroenterocolitis

f. Chronic pyoderma

g. Idiopathic causes


25 What are two nonpathologic causes of monoclonal peaks in electrophoretograms?



a. Hemoglobin (subsequent to intravascular or in vitro hemolysis)

b. Fibrinogen (if plasma is used)


26 Can protein electrophoresis be performed on fluids other than serum and plasma?


Protein electrophoresis can also be performed on urine, CSF, abdominal fluid, and thoracic fluid.



27 How does the globulin fraction separate on electrophoresis?


There are three major globulin fractions: alpha (α) globulins, beta (β) globulins, and gamma (γ) globulins. The α-globulins are the most anodally migrating, and γ-globulins are the least anodally migrating. Depending on the species, one or more of the three major globulins may divide into subfractions during migration. Globulin subfractions are identified by numeric subscripts, such as α1, α2, β1, β2, γ1, γ2, and γ3, with the smaller number representing the most anodal subfraction.

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Aug 26, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on DISORDERS AND LABORATORY EVALUATION

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