Levitt David G, Levitt Michael D
Department of Integrative Biology and Physiology, University of Minnesota.
Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USA.
Clin Exp Gastroenterol. 2017 Jul 17;10:147-168. doi: 10.2147/CEG.S136803. eCollection 2017.
Protein losing enteropathy (PLE) has been associated with more than 60 different conditions, including nearly all gastrointestinal diseases (Crohn's disease, celiac, Whipple's, intestinal infections, and so on) and a large number of non-gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on). This review presents the first attempt to quantitatively understand the magnitude of the PLE in relation to the associated pathology for three different disease categories: 1) increased lymphatic pressure (e.g., lymphangiectasis); 2) diseases with mucosal erosions (e.g., Crohn's disease); and 3) diseases without mucosal erosions (e.g., celiac disease). The PLE with lymphangiectasis results from rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph into the intestinal lumen with the resultant loss of CD4 T cells, which is 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 (C) and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 times normal to reduce the C by half. The strengths and limitations of the two quantitative measures of PLE (Cr-albumin or α-antitrypsin [αAT] clearance) are reviewed. αAT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in C and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased C and, if so, could the mechanism responsible for PLE play a role in the increased mortality? A large-scale study correlating αAT 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.
蛋白丢失性肠病（PLE）与60多种不同病症相关，包括几乎所有的胃肠道疾病（克罗恩病、乳糜泻、惠普尔病、肠道感染等）以及大量非肠道疾病（心脏病、肝病、狼疮、结节病等）。本综述首次尝试定量了解与三种不同疾病类别相关的PLE的严重程度：1）淋巴压力增加（如淋巴管扩张）；2）伴有黏膜糜烂的疾病（如克罗恩病）；3）无黏膜糜烂的疾病（如乳糜泻）。淋巴管扩张导致的PLE是由于黏膜淋巴管破裂，全身淋巴液逆行引流至肠腔，导致CD4 T细胞丢失，这具有诊断意义。黏膜糜烂性PLE是由于黏膜屏障的宏观破坏，上皮毛细血管成为白蛋白丢失的限速因素。用于描述血清白蛋白降低（C）与PLE之间关系的公式表明，胃肠道白蛋白清除率必须至少增加至正常水平的17倍，才能使C降低一半。本文回顾了PLE的两种定量测量方法（铬白蛋白或α-抗胰蛋白酶[αAT]清除率）的优缺点。αAT提供了一种简单的定量诊断测试，临床上可能未得到充分应用。在看似健康的个体中，C的轻微降低与随后的死亡率之间存在强烈的、无法解释的相关性，这引发了一个问题，即亚临床PLE是否可以解释C的降低，如果是，那么导致PLE的机制是否在死亡率增加中起作用？为了确定PLE在看似健康的受试者血清白蛋白浓度调节中的作用，需要进行一项将αAT清除率与血清白蛋白浓度相关联的大规模研究。
