Stammler L, Reichen J, Oehler R, Bianchi L, Landmann L
Department of Anatomy, University of Basel, Switzerland.
J Hepatol. 1990 May;10(3):318-26. doi: 10.1016/0168-8278(90)90139-i.
Cholestasis induced by perfusion of the liver with hypocalcemic media has been ascribed to several defects in bile secretion including increased biliary permeability. To investigate this model of cholestasis further, livers perfused with hypo- and normocalcemic media were examined stereologically using thin sections and freeze-fracture replicas. Organization of tight junctions was not altered by hypocalcemia; neither the number of strands nor the junctional depth were significantly affected. By contrast, the volume of hepatocytes decreased by 11% (p less than 0.001), compensated for by an increase in the space of Dissé and of the sinusoids. The canalicular length decreased by 25% (p less than 0.01), while the canalicular membrane surface was not altered. Multiple indicator dilution studies confirmed a decrease in hepatocellular volume, measured as the water space by 14% (p less than 0.03). This was compensated for by an increase in the extravascular sucrose, but not the albumin space. Immediately after switching from normo- to hypocalcemic perfusate a K+ efflux of 62 mumol/g liver was observed corresponding to approx. 8% of the hepatocellular water space. Our results suggest that hypocalcemia-induced cholestasis is due, at least in part, to a disturbance of the osmotic equilibrium, possibly caused by impairment of an ion transport system involved in hepatocellular volume control.
用低钙培养基灌注肝脏所诱导的胆汁淤积被归因于胆汁分泌的多种缺陷，包括胆管通透性增加。为了进一步研究这种胆汁淤积模型，使用薄切片和冷冻断裂复制品对用低钙和正常钙培养基灌注的肝脏进行了体视学检查。低钙血症并未改变紧密连接的组织结构；股数和连接深度均未受到显著影响。相比之下，肝细胞体积减少了11%（p<0.001），狄氏间隙和肝血窦的空间增加起到了补偿作用。胆小管长度减少了25%（p<0.01），而胆小管膜表面积未改变。多项指示剂稀释研究证实，以水空间衡量的肝细胞体积减少了14%（p<0.03）。这通过血管外蔗糖的增加得到了补偿，但白蛋白空间未增加。从正常钙灌注液切换到低钙灌注液后，立即观察到每克肝脏有62μmol的钾离子外流，约占肝细胞水空间的8%。我们的结果表明，低钙血症诱导的胆汁淤积至少部分是由于渗透平衡紊乱所致，可能是由参与肝细胞体积控制的离子转运系统受损引起的。
