Albumin quotient

The albumin quotient is the most precise, routinely used criterion for assessment of the function of the blood-CSF barrier because albumin in cerebrospinal fluid originates exclusively from serum. Its parallel determination during the monitoring of any CSF protein is necessary because this is the only way to differentiate its increased concentration in cerebrospinal fluid due to passive penetration of the respective serum protein from a more specific increase in the concentration of the monitored protein. It is based on its intrathecal synthesis or on a specific transport mechanism for the given protein across the blood-CSF barrier. Unfortunately, some clinicians disregard this recommendation, and this elementary fact is not sufficiently emphasized in publications on cerebrospinal fluid (A22). 

Protein transfer from the brain into CSF, and from blood into CSF, follows the law of diffusion as a function of molecular size. The diffusion-related transfer of proteins into CSF is the cause for molecular size-dependent discrimination (i.e., selectivity) of the barrier function. As a consequence, we have larger CSF/ serum quotients for the smaller molecules QAlb > QIgG > QIgA > QIgM. Again, the smaller albumin molecule equilibrates faster between blood and CSF than do the larger molecules of IgG, IgA, or IgM. 

The simplest method is the calculation using the Delpech-Lichtblau quotient, which is based on parallel determinations of concentrations of IgG and albumin in cerebrospinal fluid and serum. The mathematical structure of the formula is as follows ... 

The CSF/serum ratio of IgG eliminates the individual variation of serum IgG. The quotient of IgG (CSF/serum) to albumin (CSF/serum) eliminates the variation of the IgG quotient by the individual blood-CSF barrier function. Intrathecal IgG is total CSF IgG minus transudative IgG. The first formulas were based on a linear relationship between Q ib and Qigo (Cl, K3, LI, S4). More recent formulas make use of a hyperbolic or exponential function. The application of the latter two formulas reduces the number of false-positive results in the cases of blood-brain barrier disturbances, while sensitivity is maintained. Soeverijn compared Reiber s hyperbolic formula to five other formulas and showed that Reiber s formula produced the best agreement with the lEF gold standard (LI). For the latest modification of the IgG, IgA, and IgM subclasses of immunoglobulins, see Section 3.2.3. 

Blood—CSF barrier A higher quotient of albumin is frequent owing to a higher permeability of blood-CSF barrier in inflammation... 

Determination of acute-phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgA, IgG, IgM), compressive markers (albumin, fibrinogen), markers of tissue destruction (Apo A-I, A-II, Apo B), components of complement (C3, C4), proteinase inhibitors (antithrombin HI, a -antitrypsin). The measurement was performed simultaneously in CSF and in serum (plasma) by a laser nephelometric method. The functional state of the blood-CSF barrier was evaluated numerically with the help of the quotient Q = Albcsp/s and also by the intrathecal synthesis of immunoglobulins according to Reiber s formula and for each class—IgG, IgM, IgA. 

However, because the quotient obtained by dividing 0.015 to 0.045 g/dL for albumiticsF by 4.0 to 5.5 g/dL for albu-minserurn would be a very small decimal value, this ratio is renamed the CSF/serum albumin index and is arbitrarily calculated as follows (effectively multiplying the ratio by 1000)... 

Based upon such data, direct analysis of some fractions is possible when the components can be identified by their mobility alone. However, such an application is very limited in practice, as many subfractions have almost equal mobilities. In order to measure relative mobilities, it is practical to use pure serum albumin as reference. If the mobility of the latter is aib and the mobility of the unknown protein Ux, the quotient x/Waib is independent of the carrier medium if the migration velocity does not change during the run. In Table 3, relative mobilities... 

The first decision to make is whether the analyte in question is actively pumped or whether it diffuses passively. There is always the caveat of any possible rostro-caudal gradients, in which case the volume removed is important and it is always prudent to measure the levels of analyte in blood plasma (or serum). For proteins with passive diffusion one must correct simultaneously for both the serum level and for an independent measure of barrier function. The quotient of CSF analyte/serum analyte divided by CSF albumin/serum albumin can be expressed as an index value, but if there are alterations in any of the barriers there may be a nonlinear relationship that is particularly characteristic of large molecular weight proteins. This relationship is thus best expressed by a nonlinear function. The golden rule must be to compare like with like, and make appropriate corrections for known differences due to inhomogeneous samples. 

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