Pb中毒的机理（与元素化学相关方面）？

铅和其化合物对人体各组织均有毒性，中毒途径可由呼吸道吸入其蒸气或粉尘，然后呼吸道中吞噬细胞将其迅速带至血液；或经消化道吸收，进入血循环而发生中毒。中毒者一般有铅及铅化物接触史。口服2－3克可致中毒，50克可致死。临床铅中毒很少见。 婴儿中毒常因舔食母亲面部含有铅质的粉类、吮吸涂拭于母亲乳头的含铅软膏，以及患铅中毒母亲的乳汁所致。当小儿乳牙萌出时常喜啮物，可因啃食床架玩具等含铅的漆层而致中毒。有异嗜癖的儿童可因吞食大量油漆地板或墙壁等的脱落物引起铅中毒。食入含铅器皿（锡器劣质陶器的釉质或珐琅中均含铅质）内煮放的酸性食物或饮食被铅污染的水和食物等亦可发生铅中毒。将剩余的罐头食物留在马口铁罐头中贮存于冰箱内也是引致铅中毒的一个原因。
误食过量含铅药物如：羊痫风丸铅丹黑锡丹密陀僧等，可致急性中毒。铅毒亦可由呼吸道吸收如含铅的爽身粉（可被婴儿吸入）燃烧电池筒等所产生的含有铅化物的烟尘，均可导致婴幼儿吸入中毒。小儿生活在周围有铅尘的环境中可经常吸入一定量的铅质铅业工人的工作服长期带回家中污染尘埃，可使他们的孩子经常吸入含有铅毒的尘埃而发生有症状的铅中毒。
铅入人体后被吸收到血液循环中主要以二盐基磷酸铅的甘油磷酸盐蛋白复合物和铅离子等形态而循环。最初分布于全身随后约有95％以三盐基磷酸铅的形式贮积在骨组织中，少量存留于肝肾脾肺心脑肌肉骨髓及血液血液中的铅约有95％左右，分布在红细胞内血液和软组织中的铅浓度过高时可产生毒性，作用铅储存于骨骼时不发生中毒症状，由于感染创伤劳累饮用含酒类的饮料或服酸性药物等而破坏体内酸碱平衡时骨内不溶解的三盐基磷酸铅转化为可溶的二盐基磷酸铅移至血液；由于血液中铅浓度大量增加可发生铅中毒症状。
铅毒主要抑制细胞内含巯基的酶，而使人体的生化和生理功能发生障碍，引起小动脉痉挛损伤毛细血管内皮细胞，影响能量代谢导致卟啉代谢紊乱阻碍高铁血红蛋白的合成，改变红细胞及其膜的正常性能，阻抑肌肉内磷酸肌酸的再合成等从而出现一系列病理变化。其中以神经系统肾脏造血系统和血管等方面的改变更为显著。

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Pathophysiology

Exposure occurs through inhalation, ingestion or occasionally skin contact. Lead may be taken in through direct contact with mouth, nose, and eyes (mucous membranes), and through breaks in the skin. Tetra-ethyl lead, which was a gasoline additive and is still used in fuels such as aviation fuel, passes through the skin; however inorganic lead found in paint, food, and most lead-containing consumer products is only minimally absorbed through the skin. The main sources of absorption of inorganic lead are from ingestion and inhalation. In adults, about 35–40% of inhaled lead dust is deposited in the lungs, and about 95% of that goes into the bloodstream. Of ingested inorganic lead, about 15% is absorbed, but this percentage is higher in children, pregnant women, and people with deficiencies of calcium, zinc, or iron.Children and infants may absorb about 50% of ingested lead, but little is known about absorption rates in children.

The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.Lead in the bones, teeth, hair and nails is bound tightly and not available to other tissues, and is generally thought not to be harmful. In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health impacts on children. The estimated half-life of lead in bone is 20–30 years, and bone can introduce lead into the bloodstream long after the initial exposure is gone.The half-life of lead in the blood in men is about 40 days, but it may be longer in children and pregnant women, whose bones are undergoing remodeling, which allows the lead to be continuously re-introduced into the bloodstream. Also, if lead exposure takes place over years, clearance is much slower, partly due to the re-release of lead from bone.Many other tissues store lead, but those with the highest concentrations (other than blood, bone, and teeth) are the brain, spleen, kidneys, liver, and lungs.It is removed from the body very slowly, mainly through urine.Smaller amounts of lead are also eliminated through the feces, and very small amounts in hair, nails, and sweat.

Lead has no known physiologically relevant role in the body, and its harmful effects are myriad. Lead and other heavy metals create reactive radicals which damage cell structures including DNA and cell membranes.Lead also interferes with DNA transcription, enzymes that help in the synthesis of vitamin D, and enzymes that maintain the integrity of the cell membrane.Anemia may result when the cell membranes of red blood cells become more fragile as the result of damage to their membranes. Lead interferes with metabolism of bones and teeth and alters the permeability of blood vessels and collagen synthesis. Lead may also be harmful to the developing immune system, causing production of excessive inflammatory proteins; this mechanism may mean that lead exposure is a risk factor for asthma in children.Lead exposure has also been associated with a decrease in activity of immune cells such as polymorphonuclear leukocytes.Lead also interferes with the normal metabolism of calcium in cells and causes it to build up within them.

Enzymes
The primary cause of lead's toxicity is its interference with a variety of enzymes due to the fact that it binds to sulfhydryl groups found on many enzymes.Part of lead's toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act.Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme's ability to catalyze its normal reaction or reactions. Among the essential metals with which lead interacts are calcium, iron, and zinc.

One of the main causes for the pathology of lead is that it interferes with the activity an essential enzyme called delta-aminolevulinic acid dehydratase, or ALAD, which is important in the biosynthesis of heme, the cofactor found in hemoglobin.Lead also inhibits the enzyme ferrochelatase, another enzyme involved in the formation of heme.Ferrochelatase catalyzes the joining of protoporphyrin and Fe2+ to form heme. Lead's interference with heme synthesis produces anemia. Another effect of lead's interference with heme synthesis is the buildup of heme precursors, such as aminolevulinic acid, which may be directly or indirectly harmful to neurons.

Neurons

Lead exposure damages cells in the hippocampus, a part of the brain involved in memory. Hippocampi of lead-exposed rats (bottom) show structural damage such as irregular nuclei (IN) and denaturation of myelin (DNS) compared to controls (top).Lead interferes with the release of neurotransmitters, chemicals used by neurons to send signals to other cells. It interferes with the release of glutamate, a neurotransmitter important in many functions including learning, by blocking NMDA receptors. The targeting of NMDA receptors is thought to be one of the main causes for lead's toxicity to neurons.A Johns Hopkins report found that in addition to inhibiting the NMDA receptor, lead exposure decreased the amount of the gene for the receptor in part of the brain.[67] In addition, lead has been found in animal studies to cause programmed cell death in brain cells.

Pb是重金属，使蛋白质永久变性