Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome.
Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome.
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DOI：
10.1097/pcc.0000000000001052
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Nguyen TC
中科院分区：
文献类型：
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作者：
Carcillo JA;Podd B;Aneja R;Weiss SL;Hall MW;Cornell TT;Shanley TP;Doughty LA;Nguyen TC
目的探讨儿童多器官功能障碍综合征（MODS）的病理生理学特点。文献综述、研究数据和专家意见不适用由来自该领域的经验丰富的专家主持，描述、讨论和辩论了与儿童MODS相关的病理生理过程，重点是确定知识差距和研究优先事项。相关文献支持和补充的发言和讨论摘要。实验模型提示，巨噬细胞持续活化可能是MODS的病理生理基础。患有MODS的儿童具有1）与炎症成反比的细胞色素P450代谢降低，2）来自受损组织的循环损伤相关分子模式分子（DAMPS）增加，3）来自感染或内源性微生物组的循环病原体相关分子模式分子（PAMPS）增加，以及4）细胞因子驱动的上皮、内皮、线粒体和免疫细胞功能障碍。细胞色素P450代谢内源性化合物和外源性物质，其中许多改善炎症，而DAMPS和PAMPS单独和一起放大细胞因子的产生，导致炎性MODS反应。遗传和环境因素可阻碍具有一系列MODS病理生物学表型的儿童的炎症消退。血小板减少相关的MODS患者具有广泛的内皮活化和血栓性微血管病，并伴有抑制性补体和ADAMTS 13的相关寡基因缺陷。序贯性MODS患者具有sfasL-fas介导的肝衰竭，伴随穿孔素和颗粒酶信号传导的相关寡基因缺陷。免疫瘫痪相关的MODS患者解决感染的能力受损，并有相关的淋巴细胞凋亡的环境原因。这些炎症表型可导致巨噬细胞活化综合征。MODS的解决需要消除炎症源。6至18周后，当上皮、内皮、线粒体和免疫细胞再生和重编程完成时，注意到器官功能完全恢复。
To describe the pathophysiology associated with multiple organ dysfunction syndrome (MODS) in children. Literature review, research data, and expert opinion Not applicable Moderated by an experienced expert from the field, pathophysiological processes associated with MODS in children were described, discussed and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Experiment modeling suggests that persistent macrophage activation may be a pathophysiologic basis for MODS. Children with MODS have 1) reduced cytochrome P450 metabolism inversely proportional to inflammation, 2) increased circulating damage associated molecular pattern molecules (DAMPS) from injured tissues, 3) increased circulating pathogen associated molecular pattern molecules (PAMPS) from infection or endogenous microbiome, and 4) cytokine driven epithelial, endothelial, mitochondrial, and immune cell dysfunction. Cytochrome P450s metabolize endogenous compounds and xenobiotics, many of which ameliorate inflammation, whereas DAMPS and PAMPS alone and together amplify the cytokine production leading to the inflammatory MODS response. Genetic and environmental factors can impede inflammation resolution in children with a spectrum of MODS pathobiology phenotypes. Thrombocytopenia associated MODS patients have extensive endothelial activation and thrombotic microangiopathy with associated oligogenic deficiencies in inhibitory complement and ADAMTS13. Sequential MODS patients have sfasL-fas mediated hepatic failure with associated oligogenic deficiencies in perforin and granzyme signaling. Immune paralysis associated MODS patients have impaired ability to resolve infection, and have associated environmental causes of lymphocyte apoptosis. These inflammation phenotypes can lead to macrophage activation syndrome. Resolution of MODS requires elimination of the source of inflammation. Full recovery of organ functions is noted six to eighteen weeks later when epithelial, endothelial, mitochondrial, and immune cell regeneration and reprogramming is completed.