[医学]3 外源化学物在体内的生物转运与生物转化.ppt

第三章 外源化学物在体内的生物转运与生物转化 王取南 Toxicokinetics (Exposure fate of chemicals) disposition - Absorption - Distribution - Metabolism - Excretion Summary of the disposition of toxicants as determined by absorption, distribution, and excretion in the body 外源化学物在体内的生物转运 Biomembrane The Fluid Mosaic Model Membrane transport The differences between diffusionand active transport Passive transport Diffusion across a plasma membrane in which the cell expends no energy the diffusion of oxygen and carbon dioxideosmosis of waterfacilitated diffusion Passive Processes Water diffusion: osmotic pressure Facilitated diffusion Facilitated diffusion Active transport Three Types of Proteins for Active Transport Primary active transportsodium–potassium (Na+–K+) pump Secondary active transport Xenobiotic transporters P-gp Xenobiotic transporters divalent metal transporter (DMT)二价金属离子转运蛋白 DMT1previously known as NRAMP2(natural resistance-associated macrophage protein ), was first identified in 1995 in a screening for homologues of NRAMP1, a protein involved in host defense against several types of infection. Subsequently, it was referred to as divalent cation transporter (DCT1) because of its ability to transport cations, such as Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+, Pb2+ and Fe2+ Endocytosis and Exocytosis Receptor-mediated endocytosis 吸 收 吸收（abosorption）是外源化学物从机体的接触部位透过生物膜屏障进入血液的过程。 经胃肠道吸收 胃肠道是外源化学物的主要吸收途径 吸收可在任何部位进行，但主要在小肠 吸收方式：主要是通过简单扩散，还可以通过滤过、胞饮或吞噬和主动转运系统 经胃肠道吸收 经胃肠道吸收 Intestinal processing and absorption of dietary components 经胃肠道吸收 经胃肠道吸收的外源化学物通过门静脉系统首先达到肝脏，进行生物转化后，再进入体循环，这种现象称为首过消除（first pass elimination） 气态毒物的浓度即毒物在吸入空气中的分压（或称张力） 气态毒物在血液中的溶解度血/气分配系数（blood/gas partition coefficient） 肺泡的通气量和血流量肺泡通气量与血流量的比值称为通气 /血流比值 穿透阶段：外源化学物透过皮肤表皮，即角质层的过程 吸收阶段：由角质层进入乳头层和真皮， 并被吸收入血 吸收方式：简单扩散 皮肤组织学结构示意图（1） 皮肤组织学结构示意图（2） 环境污染物的皮肤吸收 理化性质：脂/水分配系数接近于1，易被 吸收进入血液 皮肤血流速度和出汗状况 皮肤完整性：如皮肤破损，破坏表皮角 质层屏障作用，外源化学物可以直接进 入吸收相 人体不同部位表皮的厚度不同、角质层 厚度不同，所以外源化学物的穿透速度 有别 汞等一些金属及化合物，可以经过毛囊、