| IntroductionAcute organophosphorus pesticide poisoning is one of the common diseases in Emergency Department, and now, how to take effective measures and cut down case fatality have been an important topic in the Emergency field .Recently, for the development of Emergency and several means of life support, the achievement ratio of rescuing the AOPP-induced complications such as respiratory failure,cardiac injury,renal injury and shock, has increased ,but there are few studies on hepatic injury by AOPP. Organophosphorus pesticides always lead to hepatic injury through several mechanisms. With the improvement and development of emergency medicine, blood purification has been used in the field of acute poisoning. Among of these techniques, peritoneal dialysis has been an important mean to treat acute poisoning for its superiority. Although there have been many literatures reporting the effects of PD on AOPP, these are all clinical observation, without reports about whether PD removes intoxicants and pathologic data on the influence of PD to organs. So to assess the effect of PD on AOPP, we should explore scientific demonstration.Objective To prove the clear-up effect of PD on organophosphorus pesticides, explore the mechanism of hepatic injury by AOPP and the protective effect of PD, and offer scientific proofs for applying PD for AOPP.Methods Model of rabbits with acute organophosphorus pesticide poisoning was made, by intragastric administration of 25 mg/kg(0.5LD50)40% folimat. Rabbits of control group were given Pralidoxime Chloride and Atropine for intramuscular injection. Besides of these, animals of PD group were inserted in by peritoneal dialysis tube and given peritoneal dialysis for ten times. Blood plasma and liquid of peritoneal dialysis was remained and tested for qualitation of intoxicants. Biochemical indicators of hepatic function in serum and pathological changes under light microscope of livers of both groups were observed dynamicly.Results We detected folimat in the liquid of peritoneal dialysis and blood plasma with obvious difference six hour after intoxication in the detection ratio; After intoxication, serum cholinesterase of both group declined obviously, biochemical indicators of hepatic function had changed also, and when comparing, these changes of PD group was superior to control group. Under light microscope, there were changes of hepatic injury which we called toxic hepatitis, and these of PD group was lighter than control group.DiscussionWhen absorbed, organophosphorus pesticides will distribute in every organs, and although they are not hepatotropic poisons have highest concentration in liver, in which they were transformed biochemically by the system of oxidation enzymes in hepatic microsomal and lead to injury and necrosis of hepatic cells, causing toxic hepatitis. The mechanism maybe the follows:Because that cholinesterase is inhibited by OPs, excess cetylcholine have effects on cholinergic receptors in liver, which lead to hepatic injury through microcirculation disturbance,ischemia,anoxaemia,insufficient energy supply,retention of intracellular Ca2+ and increased permeability of cellular membrane; Ops can lead to hepatic injury directly, because that liver is the first organ for transforming these intoxications biochemically ,and in this metabolic process ,a great quantity of oxygen free radical is produced and cause different degree injury of liver; When AOPP occurs, generous intoxicants induce organism to produce bulk of cytokines, which lead to systemic inflammatory response syndrome and multiply organ dysfunction syndrome, including hepatic injury; Sweats,saliva,vomit and alimentary tract hemorrhage induced by Ops may lead to oligaemia,decreasing of blood pressure and shock, which induce ischemia-reperfusion injury of liver; Ops can destroy red blood cells, leading to acute intravascular hemolysis, which result in generous hemoglobin and other cell contents releasing into blood, and when metabolized in liver, they induce hepatic injury; Medication,solvent and assistant in pesticides can also lead to hepatic injury to certain extent.The results of this experiment displayed:â‘ The levels of ALT and AST in serum of both groups were significantly higher than normal value, which indicated that hepatic cells were injured to certain extent. They reached the peak at 12 or 24 hours later after intoxication, and then fall off.â‘¡After intoxication, the step-up of AST was more obvious and earlier than ALT, because of that severe injury of liver resulted in damage of mitochondria membrane and releasing generous AST from hepatic mitochondrium or considerable AST come from cardiac muscle that was affluent of AST and heavy injured.The fall of albumin occurred also in this study. The mechanism may be that stress and limit of food resulted in decrease of hepatic glycogen and insulin secretion, which led to increasing breakdown of protein. Secondly, hepatic and renal injury by intoxicant and its metabolic products also led to decrease of protein synthesis and increase of excretion .Besides of the above ,liver is the only place of synthesizing albumin, the disorder of synthesis,intracellular transport and release led to decrease of Alb after hepatic injury by AOPP.We found that the level of total bilirubin,direct bilirubin and indirect bilirubin increased after AOPP, and when compared with pre-intoxication, these of control group had significant difference at 24 hours after intoxication, and the increase of IBIL was main. The mechanism of these may be the following:â‘ the disorder to take in,combine and excrete bilirubin induced by hepatic injury for AOPP, led to considerable bilirubin remained in blood ,and hepatic injury resulted in that direct bilirubin was not excluded to small bile duct, which led to its increase.â‘¡For the decrease of the clearance of bilirubin or increased refreshment, starvation and limit of food led to increase of IBIL.â‘¢Large application of hypotensive atropine led to hypotension of blood that result in erythrocatalysis and the increase of IBIL along with the direct effect of OPs.â‘£Hepatic cellular edema induced by intoxication could oppress the biliary system, which led to cholestasis.Through pathology inspection , we found bad-arranged liver cell cords, cellular swelling , loosened endochylema that was ratitas and transparent, and fatty degeneration, under light microscope; In some specimens, there were a great quantity of inflammatory cell infiltration in header region and hepatic lobules; In other ones ,we also found condense of moisture content ,strengthened acidophilia dyeing, vanish of endochylema granularity, condense and vanish of nucleuses, and apoptosis. Peritoneal dialysis is a therapeutic approach ,which utilizes peritoneum as dislysis-membrane, waters prepared dialysate into abdominal cavity, exchanges uninterruptly and achieve the purpose to remove metabolic wastes,poisons and regulate the disturbance of water-electrolyte and acid-base balance through diffusion and ultrafiltration.This experiment proved that peritoneal dialysis could get rid of internal folimat for we detected poison in both serum and peritoneal liquid, and we could only detect poison in two of nine specimens in PD group, while seven of nine in control group at six hours ,which illustrated that PD could make the concentration of folimat reduce, and is effective in toxicokinetics;In toxicodynamics, the decrease of ChE of control group was more obvious than PD group at twelve hours(P<0.01),and although decreasing at 24 hours , this difference increased at 48 hours ,which may be because of that intoxicant took into blood again through liver- intestine circulation, and could be avoided for that PD coule remove intoxicant continuously and prevent relapse .When injured ,liver can not metabolize toxic substances effectively resulting in poison accumulation. PD can be used for hepatic failure because of that it can remove blood ammonia,bilirubin,free fatty acid and other toxic products.When comparing the changes of hepatic pathology ,both group had fatty degeneration and inflammatory infiltration, but these of PD group was lighter, and we could not find apoptosis in PD group other than control group.When comparing the biochemistry changes of hepatic funtion ,we proved that the level of ALT and AST was lower in PD group than in control group, the indexes reflecting cholestais T-BIL and D-BIL were better ,and IBIL was lower .But the level of Alb decreased more obviously than control group for PD can remove Alb.On the whole ,hepatic injury is an common complication in AOPP, and PD can remove Ops, is good at the recovery of ChE, and have hepatic protection .Conclusion Organophosphorus pesticides can lead to hepatic injury in earlier period of poisoning by many mechanisms; Peritoneal dialysis can clean up omethoate slowly and continually and lessen the degree of poisoning ; Peritoneal dialysis has energetic protective effects on livers injured by AOPP; Peritoneal dialysis is favourable to the recovery of choline esterase through its clearance of intoxicants and protective effect on livers; Peritoneal dialysis can result in loss of albumin and make it decrease, so in clinical we should monitor the level of albumin when peritoneal dialysis is carried out and supply in time; Peritoneal dialysis is an effective treatment of blood purification to treat AOPP. |
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