Serum protein abnormalities

For acute symptomatic hypocalcemia, 200 to 300 mg of elemental calcium is administered IV and repeated until symptoms are fully controlled. This is achieved by infusing 1 g of calcium chloride or 2 to 3 grams of calcium at a rate no faster than 30 to 60 mg of elemental calcium per minute. More rapid administration is associated with hypotension, bradycardia, or cardiac asystole. Total calcium concentration is commonly monitored in critically ill patients. Under normal circumstances, about half of calcium is loosely bound to serum proteins while the other half is free. Total calcium concentration measures bound and free calcium. Ionized calcium measures free calcium only. Under usual circumstances, a normal calcium level implies a normal free ionized calcium level. Ionized calcium should be obtained in patients with comorbid conditions that would lead to inconsistency between total calcium and free serum calcium (abnormal albumin, protein, or immunoglobulin concentrations). For chronic asymptomatic hypocalcemia, oral calcium supplements are given at doses of 2 to 4 g/day of elemental calcium. Many patients with calcium deficiency have concurrent vitamin D deficiency that must also be corrected in order to restore calcium homeostasis.2,37,38... 

The results obtained with ISEs have been compared several times with those of other methods. When the determination of calcium using the Orion SS-20 analyser was tested, it was found that the results in heparinized whole blood and serum were sufficiently precise and subject to negligible interference from K and Mg ([82]), but that it is necessary to correct for the sodium error, as the ionic strength is adjusted with a sodium salt [82], and that a systematic error appears in the presence of colloids and cells due to complexa-tion and variations in the liquid-junction potential [76]. Determination of sodium and potassium with ISEs is comparable with flame photometric estimation [39, 113, 116] or is even more precise [165], but the values obtained with ISEs in serum are somewhat higher than those from flame photometry and most others methods [3, 25, 27, 113, 116]. This phenomenon is called pseudohyponatremia. It is caused by the fact that the samples are not diluted in ISE measurement, whereas in other methods dilution occurs before and during the measurement. On dilution, part of the water in serum is replaced by lipids and partially soluble serum proteins in samples with abnormally increased level of lipids and/or proteins. 

The significance of this equation lies in the fact that there must be some intimate relation between the abnormal globulins and the serum proteins, as if part of the serum protein peptides find their way into the globulins, although this may not take place at the same site—that is, it may be a related system. 

Petito CK, Cash KS (1992) Blood-hrain barrier abnormalities in the acquired immunodeficiency syndrome Immunohistochemical localization of serum proteins in postmortem brain. Arm Neurol 32 658-666. 

Figure 20-10 Comparison of immunofixation electrophoresis (IFE) and immunoelectrophoresis (lEP) for two patients with monoclonal gammopathies. A, Patient specimen with an IgG (kappa, k) monoclonal protein as identified by IFE.The arrow indicates the position of monoclonal protein.After electrophoresis, each track except SPE is reacted with its respective antiserum, then all tracks are stained to visualize the respective protein bands. (SPE Chemically fixed serum protein electrophoresis IgG, IgA, IgM, k, and A, indicate antiserum used on each track.) B, Same specimen as in A, with proteins identified by lERThe arrow indicates the position of monoclonal protein. Norma control (C) and patient sera (S) are alternated. After electrophoresis, antiserum is added to each trough as indicated by the labels ig (polyvalent Ig antiserum), IgG, IgA, IgM, K, and A The antisera react with separated proteins in the specimens to form precipitates in the shape of arcs.The IgG and k arcs are shorter and thicker than those in the normal control, showing the presence of the IgG (k) monoclonal protein.The concentrations of IgA, IgM, and A,-iight chains are also reduced. C, Patient specimen with an IgA (lambda, A,) monoclonal protein identified by IFE procedure as described in A. D, Same specimen as in C with proteins identified by lEP as described in B.The abnormal IgA and A,-arcs for the patient specimen indicate an elevated concentration of a monoclonal IgA (A.) protein. Ait separations were performed using the Beckman-Coulter Paragon system.

Livrea P, Trojano M, Simone IL, Zimatore GB, Pisicchio L, Logroscino G, et al. Heterogeneous models for blood-cerebrospinal fluid barrier permeability to serum proteins in normal and abnormal... 

The THBR is derived from a version of the T3 or T4 uptake test. Uptake tests are used to estimate the number of unoccupied (unsaturated) thyroid hormone bindhig sites on serum proteins. This information is important because variations in total thyroid hormone concentrations in blood, as discussed previously, have resulted from changes in binding protein concentrations. Values obtained by uptake methods are expressed as a THBR, which is directly proportional to the free hormone fraction (within limits). Measurement of THBR, in conjunction with a total hormone concentration, is a clinically useful indirect method for calculating the FT4 (or FT3) index. The index approach is particularly useful in patients with nonthyroidal illness in whom FT4 immunoassay methodologies are unreliable. Specifically, TT4 measurement is more diagnostically useful in such patients provided that values are interpreted in accord with the severity of illness in the patient that is indirectly reflected by abnormalities in THBR. 

In summary, none of the above investigations have given any evidence of a primary abnormality in the production or utilization of serum proteins, lipoproteins, or glycoproteins. Also the feeding of amino acids (R19) or alterations in the protein level of the diet (Zl) do not change the disease process. 

Figure VI-1 shows normal and some abnormal patterns of serum protein electrophoresis. The electrophoretic patterns obtained are not indicative of any one disease or class of disease. Furthermore, a characteristic pattern may be obscured or not found in a disease entity where normally such a pattern is expected. Serum electrophoretic patterns provide only a general impression of the disorder and require confirmation by other procedures. An alteration (depression or elevation) in a given fraction should be quantitated by more sensitive and specific methods.

This disease is of considerable interest in relation to oxypurine metabolism, although a wide variety of potential metabolic abnormalities have been said to be associated with it. In a review in 1961 Tickner (T4) asserted that there was evidence to support the postulate that psoriasis was associated with alterations in lipid, protein, carbohydrate, and mineral metabolism as well as in serum protein level. Investigators have since supported a myriad of hypotheses. Note has been taken of variations in carbohydrate metabolism (R16), and of changes in the synthesis of hyaluronic acid with resultant alterations in transport mechanisms (CIO). Changes in fatty acid levels and metabolism (C8), alterations of aldolase activity (C6), increased proteolytic activity (S33), and alterations in the composition of proteins in psoriatic scales (L20) have been suggested. Changes in serum copper content in psoriatic patients have been observed (L18). 

An older man with severe emphysema is found to have decreased amounts and abnormal mobility of tti antitrypsin (AAT) protein in his serum when analyzed by serum protein electrophoresis. Liver biopsy discloses mild scarring (cirrhosis) and demonstrates microscopic inclusions due to an engorged endoplasmic reticulum (ER). The most likely explanation for these findings is... 

Cl. Cell, P. G. H., Immunological analysis of abnormalities in the human serum protein by a gel-diffusion method. /. Clin. Pathol. 8, 269 (1955). 

It is obvious that T4 by RIA and T4 by CPBA are unaffected by contaminating iodine. However, it should be stressed that both total T4 and PBI are uniformly affected by abnormalities in the T4-binding serum proteins, namely TBG, TBPA, and albumin as referred to in Section 2.2. In summary, where drugs or any other extrathyroidal factor increases any of the binding proteins (usually TBG) there is a concomitant increase in PBI or total T4 levels in the serum, and a decrease in the T3 resin uptake. Conversely, decreases in TBP are associated with decreases in PBI and in total T4, and increases in T3 resin uptake. 

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