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As discussed above, there is very little size selectivity in PLE, with albumin and IgG having similar leak rates

As discussed above, there is very little size selectivity in PLE, with albumin and IgG having similar leak rates. with the resultant loss of CD4 T cells, which is usually diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal barrier, with the epithelial capillaries becoming the rate-limiting factor in albumin loss. The equation derived to describe the relationship between the reduction in serum albumin (CP) and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 occasions normal to reduce the CP by half. The strengths and limitations of the two quantitative steps of Acetaminophen PLE (51Cr-albumin or 1-antitrypsin [AT] clearance) are examined. AT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for PLE play a role in the increased mortality? A large-scale study correlating AT clearance with serum albumin concentrations will be required in order to determine the role of PLE in the regulation of the serum albumin concentration of seemingly healthy subjects. from that for any PLE subject and assuming that ClUr is usually unchanged in PLE: is usually obtained if one assumes that both Synthesis and ClCat remain normal Acetaminophen in the subject with PLE in Equation 4: equal to the normal total albumin clearance and, adding the baseline GI clearance (Equation 4) required to maintain the serum albumin at a given level. Measurements of the rates of synthesis in patients with severe PLE (serum albumin about half normal) and normal Acetaminophen hepatic function showed ratios of SynthesisPLE/SynthesisN varying from 1.24 to 2.61.4C6 In a study of the response of a normal subject to a decrease in CP produced by plasmapheresis, lowering the CP by 20% increased the synthesis by 25%.2,7 In addition, there is a not commonly acknowledged reduction in ClCat as CP falls due to the competitive binding of albumin to the Fc IgG receptor (FcRn).8C10 FcRn was originally shown to bind IgG at acidic pH, diverting it from lysosomal degradation and prolonging the lifespan of IgG. Recently, it has been shown that this receptor also binds albumin, protecting it from lysosomal degradation. Since the amount of FcRn is usually insufficient to bind all albumin, only a portion is usually guarded by this mechanism. As CP falls, the portion of albumin rescued increases and the ClCat decreases, with the rate of ClCat falling to near zero in subjects with very low serum albumin levels (congenital analbuminemia).2,8 As a rough approximation, we have assumed that this change in Synthesis and ClCat as CP falls is explained by: are 240, 215, and 15 mL/day, respectively). By using this more likely relationship between ClGI and CP, the normally normal subject with a CP of half of the normal would have to have a GI of 523 mL/day. Open in a separate window Physique 2 The predicted relationship between the increase in GI albumin clearance and the producing steady-state serum albumin (serum albumin/normal albumin) in a PLE subject with normal renal and hepatic functions. Abbreviations: GI, gastrointestinal; PLE, protein losing enteropathy. Qualitative and quantitative measurements of PLE Because most serum proteins lost into the intestine are rapidly hydrolyzed and the amino acids reabsorbed, analysis of intestinal or fecal contents cannot be used to diagnose PLE. In 1960, Steinfeld et al11 explained the first attempt to quantitate PLE by measuring the percentage of an intravenous (IV) dose of 131I-polyvinylpyrrolidone (PVP) excreted in a 4-day stool collection. In a series of patients with regional enteritis or ulcerative colitis with low serum albumin, the percentage of the injected PVP excreted ranged from 2.3% to 7.4% (mean=4.1%), about 10 hSNFS occasions the control value (range 0.16%C0.63%).11 Unfortunately, 131I-PVP measurements are only qualitative because PVP has a very heterogeneous size distribution (mean molecular excess weight of about 40 kDa), and the gut clearance may not be representative of albumin (molecular excess weight of 68 kDa).11,12 In 1961, Waldmann13 introduced what is considered to be Acetaminophen the gold standard1 for quantitating PLE: measurement of the.