Dhainaut J F, Marin N, Mignon A, Vinsonneau C
Medical Intensive Care Unit, Cochin Port-Royal University-Hospital, AP-HP, Paris V University, France.
Crit Care Med. 2001 Jul;29(7 Suppl):S42-7. doi: 10.1097/00003246-200107001-00016.
a) To review the hepatic response to sepsis and to establish how this response contributes to coagulation and inflammatory processes; b) to review the physiologic and biochemical mechanisms that suggest hepatic dysfunction may occur during sepsis, enhance procoagulant and proinflammatory activities, and participate in the potential evolution to multiple organ dysfunction syndrome.
A summary of published medical literature from MEDLINE search files and published reviews on liver function in experimental and human sepsis.
In sepsis, the liver plays a major role in host defense mechanisms. Kupffer cells are responsible for bacterial scavenging, bacterial products inactivation, and inflammatory mediators clearance and production. Hepatocytes, via receptors for many proinflammatory cytokines, modify their metabolic pathway toward gluconeogenesis, amino-acid uptake, and increased synthesis of coagulant and complement factors and protease inhibitors. The acute-phase protein (APP) response also contributes to the procoagulant state, especially by enhancing the inhibition of protein C (alpha1-antitrypsin and alpha2-macroglobulin) and by decreasing liver synthesis of protein C and antithrombin (negative APPs). Elevated C-reactive protein levels (positive APPs) promote the expression of tissue factor by mononuclear cells. Increased liver production of thrombin-activatable fibrinolytic inhibitor (positive APPs) enhances fibrinolysis inhibition. Conversely, such hepatic inflammatory and coagulation processes in sepsis may alter the function of this organ. Indeed, the liver can be injured by activated Kupffer cells that release chemokines, attract blood neutrophils into the liver, and activate them. Neutrophils up-regulate their surface adhesion molecules, tissue factor, and Kupffer cells, whereas tissue factor pathway inhibitor and thrombomodulin are almost undetectable in endothelial cells. This may lead to microcirculatory disturbances, fibrin deposition, hepatocyte injury, endotoxin and bacteria spillover, and multiple organ failure.
In sepsis, the liver participates in host defense and tissue repair through hepatic cell cross-talk that controls most of the coagulation and inflammatory processes. When this control is not adequate, a secondary hepatic dysfunction may occur and may sometimes lead to bacterial products spillover, enhanced procoagulant and inflammatory processes, and in turn, multiple organ failure and death.
a）回顾肝脏对脓毒症的反应，并确定这种反应如何促进凝血和炎症过程；b）回顾生理和生化机制，这些机制提示脓毒症期间可能发生肝功能障碍，增强促凝和促炎活性，并参与向多器官功能障碍综合征的潜在演变。
MEDLINE搜索文件中已发表的医学文献摘要以及关于实验性和人类脓毒症中肝功能的已发表综述。
在脓毒症中，肝脏在宿主防御机制中起主要作用。库普弗细胞负责清除细菌、使细菌产物失活以及清除和产生炎症介质。肝细胞通过许多促炎细胞因子的受体，将其代谢途径转向糖异生、氨基酸摄取，并增加凝血因子、补体因子和蛋白酶抑制剂的合成。急性期蛋白（APP）反应也有助于促凝状态，特别是通过增强对蛋白C的抑制作用（α1-抗胰蛋白酶和α2-巨球蛋白）以及减少肝脏中蛋白C和抗凝血酶的合成（负急性期蛋白）。C反应蛋白水平升高（正急性期蛋白）促进单核细胞表达组织因子。肝脏中凝血酶激活的纤溶抑制物产生增加（正急性期蛋白）增强了对纤溶的抑制。相反，脓毒症中这种肝脏炎症和凝血过程可能会改变该器官的功能。实际上，肝脏可能会被激活的库普弗细胞损伤，这些细胞释放趋化因子，将血液中的中性粒细胞吸引到肝脏并激活它们。中性粒细胞上调其表面黏附分子、组织因子以及库普弗细胞，而在内皮细胞中几乎检测不到组织因子途径抑制物和血栓调节蛋白。这可能导致微循环紊乱、纤维蛋白沉积、肝细胞损伤、内毒素和细菌溢出以及多器官衰竭。
在脓毒症中，肝脏通过肝细胞间的相互作用参与宿主防御和组织修复，这种相互作用控制着大多数凝血和炎症过程。当这种控制不足时，可能会发生继发性肝功能障碍，有时可能导致细菌产物溢出、促凝和炎症过程增强，进而导致多器官衰竭和死亡。
