Reduced microcirculatory flow in severe falciparum malaria: pathophysiology and electron-microscopic pathology
Reduced microcirculatory flow in severe falciparum malaria: pathophysiology and electron-microscopic pathology
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DOI：
10.1016/j.actatropica.2003.10.004
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发表时间：
2004-02-01
期刊：
影响因子：
2.7
通讯作者：
White, NJ
中科院分区：
文献类型：
--
作者：
Dondorp, AM;Pongponratn, E;White, NJ
严重恶性疟疾的病理生理学是复杂的，但越来越多的证据表明，其中心特征是机械性微循环阻塞的旧概念。尸检研究，但也在体内的微循环观察，证明变量阻塞的微循环在严重疟疾。其主要原因是含有寄生虫成熟形式的红细胞粘附于血管内皮，导致小血管的隔离和阻塞。此外，被寄生的红细胞变得僵硬，损害了它们通过毛细血管的流动，毛细血管的管腔已经被隔离的红细胞减少。感染红细胞之间的粘附力（自凝集）、感染和未感染红细胞之间的粘附力（玫瑰花结）以及未感染红细胞之间的粘附力（聚集）可进一步减缓微循环流动。最近的一项发现是，在严重的疟疾中，未受感染的红细胞也会变硬。总体红细胞变形能力的降低对致死性结局具有很强的预测价值。僵硬可能是由于红血球破裂时释放的疟疾色素对红细胞膜的氧化损伤引起的。抗氧化剂，如N-乙酰半胱氨酸可以逆转这种作用，并有望作为重症疟疾的预防性治疗。(C)2003 Elsevier B. V.保留所有权利。
The pathophysiology of severe falciparum malaria is complex, but evidence is mounting that its central feature is the old concept of a mechanical microcirculatory obstruction. Autopsy studies, but also in vivo observations of the microcirculation, demonstrate variable obstruction of the microcirculation in severe malaria. The principal cause of this is cytoadherence to the vascular endothelium of erythrocytes containing the mature forms of the parasite, leading to sequestration and obstruction of small vessels. Besides, parasitized red cells become rigid, compromising their flow through capillaries whose lumen has been reduced by sequestered erythrocytes. Adhesive forces between infected red cells (auto-agglutination), between infected and uninfected red cells (rosetting) and between uninfected erythrocytes (aggregation) could further slow down microcirculatory flow. A more recent finding is that uninfected erythrocytes also become rigid in severe malaria. Reduction in the overall red cell deformability has a strong predictive value for a fatal outcome. Rigidity may be caused by oxidative damage to the red blood cell membrane by malaria pigment released at the moment of schizont rupture. Anti-oxidants, such as N-acetylcysteine can reverse this effect and are promising as adjunctive treatment in severe malaria. (C) 2003 Elsevier B.V. All rights reserved.