In the field of forensic medicine, shock has been identified as a cause of death owing to various kinds of exogenous insults. The etiology and pathogenesis of shock cannot be explained well by the usual gross appearance in medicolegal autopsies, because it is now generally established that the shock is a functional reaction of the vascular system to bodily injury, and that several organs are secondarily impaired during shock. Thus it seemed to forensic pathologists that these morphological changes in several organs after shock did not reveal any significant differences among the causes of death. We approached to the induction mechanism of shock, and we investigated what etiology induced these morphological changes after shock in order to identify shock as the cause of death. It is now generally accepted that the kidney is a target organ of shock, so we mainly investigated the cause of kidney disorder in a case of burn shock and hemorrhagic shock. 1. Consequences of bacterial translocation (BT) in the shock. The concept of BT indicates that the beginning of shock is induced by the loss of gut barrier function and consequent translocation of bacteria. In general, impaired gut barrier function can be caused either during the shock period by decreased intestinal blood flow and reduced oxygen delivery, resulting during reperfusion in a stage of increased intestinal blood flow, or at a later stage again by reduced flow. A variety of physiological stresses, such as trauma, hemorrhage, thermal injury, surgical operation, various kinds of drags and mental stress, have been shown to cause failure of the gut mucosal barrier, with translocation of bacteria/endotoxin from the gastrointestinal into the mesenteric lymph nodes, and translocation into remote organs and systemic circulation. 2. Burn shock. We designed to evaluate the BT in a burn shock rat model (following 20% full-thickness scald injury). The p38 MAPK pathway is an important stress-responsive signal molecule pathway, and it is responsible for the production and signal transduction of cytokines. This pathway is activated by the bacterial LPS or ischemia, so we examined the effects of FR167653, a specific inhibitor of p38 MAPK, on the development of renal failure after the burn-induced intestinal barrier damage. Our study demonstrated that viable bacteria reached the remote organs after burn by quantitative bacterial culture data and FR167653 blocked the burn-induced intestinal barrier damage, and the immunohistochemical data showed that FR167653 prevented the accumulation of polymorphonuclear leukocytes (PMNs) in the glomerular capillaries after burn, and blockaded the burn-induced renal failure by serum UN assay. FR167653 especially decreased the phosphorylation levels of p38 MAPK in the infant kidney after burn, and TNF-alpha and IL-1beta mRNA decreased through the p38 MAPK pathway. The above-mentioned facts do provide additional support for the hypothesis that postburn renal failure is mediated by endotoxin associated with the bacterial translocation, and we identified the pathophysiologic role of p38 MAPK pathway in the development of renal failure after the burn-induced intestinal barrier damage. 3. Hemorrhagic shock. We evaluated the role of endogenous TNF-alpha in the renal failure and gut bacterial translocation induced by mild hemorrhagic shock (16.7% bleeding of total body blood via a common carotid catheter without fluid resuscitation). FR167653, a potent inhibitor of TNF-alpha up regulation through p38 MAPK pathway, significantly inhibited these increases of TNF-alpha. Adding to this, our study demonstrated that FR167653 prevented renal failure, such as the infiltration of inflammatory cells and tubular cell necrosis after hemorrhage, and the intestinal barrier damage was also dramatically improved by FR167653 treatment. These results show that derived endogenous TNF-alpha plays a key role in renal failure through p38 MAPK activation during the early phase of mild hemorrhagic shock, including the possible participation of BT. According to these results, we hypothesized that the invading leukocytes induced these organs failures after hemorrhagic shock, so we examined the appearances of leukocytes by the immunohistochemical myeloperoxidase (MPO) staining (marker staining for PMNs). The incidences of PMNs in these organs after mild hemorrhagic shock increased significantly, and FR157653 prevented the appearance of PMNs. These results showed the possible effective role of the PMNs on the occurrence of organ failure caused by mild hemorrhagic shock. 4. Forensic practice. Six hundred and seven forensic autopsy cases in our department of forensic medicine during the past 11 years between 1992 and 2002 were analyzed with regard to the cause of death. Shock cases accounted for 18% of all forensic autopsy cases, and among them 65% of cases identified hemorrhagic shock as the cause of death. So we investigated what good grounds to clearly identify the cause of death induced by hemorrhagic shock. Our experimental hemorrhagic shock data showed PMNs activation and priming during hemorrhagic shock, and it might be closely related to BT and remote organ failure. Consequently, we used the MPO staining method, and we immunohistochemically investigated several organs of our practical autopsy cases to detect the appearance of PMNs as a marker of shock induction. We compared the hemorrhagic shock with other causes of death, such as blood loss, asphyxia, drawing and head injury (intracranial hemorrhage). In every organ, a significant appearance of PMNs was observed in the hemorrhagic shock compared to the other causes of death. Especially, the appearance of PMNs in the heart was clear than that of the other organs in the hemorrhagic shock cases. Therefore, detecting the appearance of PMNs as a marker of shock induction is a very useful and significant method forjudging the cause of death in forensic practice.