Lead

Lead Poisoning Xiaoyu Chen

Professor

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Lead

has a wide spectrum of

applications

The pollution of the lead is a global problem.

The lead pollution is a major public health problem in the world.

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The lead output is about 340 000 tons in the world every year.  Lead has a wide spectrum of applications that result in environmental dissemination and human exposure. It is estimated that about 160 000 tons lead get into the environment every year. The maximum of the air pollution is about 1000 tons a day.

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It has been reported that the total lead burden of the mankind is 500—1000times than that of period of Columbus (new continent, America)

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Property of the Lead:

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1.Lead is a bluish-grey (blue-grey), soft , malleable heavy metal ,with specific gravity of 11.3(it is large than that of many other metals ,high density ). So it can be used for making hydrometer ,bullet ,pellet ,and shot( 铅球，运 动员 athlete). It dissolved well in acidity solution.

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2. The melting point for lead is 327℃ (degrees centigrade). So: ① Hazardous evaporation results when the temperature exceeds about 500℃.this fact is important where lead is melted or modeled in factories and workshops. The hazardous evaporation can be inhaled by workers and pollute the atmosphere.

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② With lower melting point and softness lead usually is used to manufacture alloys. Lead alloys are harder than lead and with lower melting point (than lead,327 ℃). They are very convenient for use:

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Fuse( a kind of lead alloy).

Tin-lead

alloys (soldering tin ,tin solder)are used in solder for electrical application. Tin solder(used in family) is a alloy with melting point 183℃. It is harder than lead.(lead 38%,tin 62%).Lead alloys are made chiefly with antimony( 锑 Sb) and tin(Sn).

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3. Corrosion resistance  

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With the properties above ,lead has a wide spectrum applications in industry and human life.

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Occurrence ＆ uses

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Lead occurs in many ores in concentrations of 1%~11% . The ores of commercial interest include the sulfide ( galena ,Pbs),which is usually found associated with sulfides of silver, copper, arsenic(As 砷 ), antimony(Sb 锑 ), bismuth( 铋 ),and tin. Other common lead ores are carbonate (cerussite,pbco3) , and sulfate(anglesite,pbso4). 15

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Use : Lead is used with 40% lead, 35% lead compounds, 25% lead alloys:

1.The primary use of lead is in the manufacture of storage batteries.

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2. With property of corrosion resistance , lead is used in pipes and sheathing( 保 护套， ),shielding electrical cables, where they impart （给予） resistance to acid and moisture. Tin –lead alloys are used in solder （焊料） for electrical applications , and sealing joints. It is also used to coating metals exposed to the water especially to sea water ( bridge ,ship ). 19

lead pipes

鉛管大便器用 20

used in solder （焊料） for electrical applications 21

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3. Lead compounds are used in paints and plastics as pigments and stabilizors.

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Antirust paint

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4.  Lead is used in construction for attenuation （稀释，减弱） of sound and vibrations and for the shielding ( 盾牌 ) of radioactivity.

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5.  Lead glazes( 使光滑，釉 光 )impart brilliance and hardness to ceramics ( 陶器 ) 。

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搪瓷 Porcelain ； enamel

陶瓷 pottery

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6. Other uses include ammunition 军火 (lead shot),bronze( 青铜 ) and brass( 黄 铜 ),cosmetics( 化妆品 )and jewelry ,additives to glass.pigment. 7.(by the way) Tetraethyl( 四乙基 ) lead and tetranethyl （四甲基） lead are used as antiknock agents in gasoline ,though this use has declined significantly.

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2.5PbCrO4·PbSO4+xAl(OH)3+yAl PO

PbCrO4+xAl(OH)3

25PbCrO4·4PbM oO4·PbSO4 PbCrO4+xAl(OH)3

PbO

Pb3O4

pigmen t

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Occupational exposure 

Occupational lead exposure occurs in particular in the following processes:

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1. Production of lead from lead ores , during the processes of mining and smelting ,will generate high levels of lead dust and lead fume in the working environment.

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2.Secondary lead production from used automobile batteries and scrap metal. In the United states (and other), over one-third of the lead produced is recovered from secondary sources of lead scrap. 38

3. Production of batteries; 4.  Production of ,and spray with, paints containing lead pigments and desiccant( 干燥剂 ).

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5.Welding and flame cutting of leadcontaining alloys; molding of leadcontaining alloys in foundries ;soldering with lead solder if the temperature is too high; shipdisassembly( 拆卸，分解 ) facilities and scrap metal handing. Touch burning to remove lead-based paints generates significant quantities of lead fume. Welder （电焊工） and brazers （ coppersmith 铜匠） may be exposed to lead alloys ,fluxes( 熔 融 )and coatings.

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6. Workers in munitions 军需品 plants and rifle ranges 射击 ,may have exposure to lead dust ,particularly indoor.( instructors from indoor shooting ranges). 7.Glass-makers , artists ,and pottery workers may unknowingly be exposed to high levels of lead in pigments and glazes. 41

So many………

Exposures may be considerable in small workshops with few employees and poor hygiene

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Mechanism of action (absorption ,metabolism ,excretion)

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1. Absorption: Inhalation and ingestion （ alimentary tract ） are the primary routes of absorption of lead and its compounds. Absorption through the skin is importance only in case of organic compounds (for example lead 44

Approximately 40% of inhaled lead oxide fumes is absorbed though the respiratory tract. Absorption of particulate lead dust depends on particle size and solubility . More readily dissolved in water ,more readily absorbed.

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smaller particles can be retained in the lungs ,whereas larger particles are deposited in the upper respiration tract ,from where they are transported by the mucociliary movement to the pasopharynx from where ,they can be excreted.

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2.Distribution: The absorbed lead is transported by the blood to other organs. In the blood stream , the majority of the absorbed lead is bound to erythrocytes(red blood cells),about 95%. The free diffusible plasm fraction is distributed to brain ,kidney ,liver, skin, skeletal muscle and other soft tissues. Where it is readily exchangeable. 47

The concentrations in these tissues are highest with acute , high-dose exposure ,lead crosses the placenta , and fetal levels correlate with maternal levels. It is thought that only lead in soft tissues is directly toxic.

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After several weeks , absorbed lead(have distributed to soft tissues) will have a redistribution . Bone constitutes the major site of deposition of absorbed lead , where it is incorporated into the bony matrix similar to calcium. Absorbed lead also deposit in hair , nails and teeth.

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The half-life of lead is long , estimated to be from 5 to 10 years. This varies with the intensity and duration of exposure and the ultimate body burden accumulated. The biological half-life of lead is difficult to establish. Bone diseases (osteoporosis 骨质疏 松 ,fracture ) pregnancy and hyperthyroidism （甲亢） may lead to increased release of stored lead and elevated blood lead levels.

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Intracellularly ,lead binds to sulfhydryl groups(--SH) and interferes with numerous cellular enzymes ,including those involved in heme synthesis. Lead also binds to mitochondrial membranes and interferes with protein and nucleic acid synthesis. Lead inhibits the Na-K-ATPase in the cell membranes of the erythrocytes ,making them less stable and thereby shortening their lifespan. Anemia is a typical symptom in classic lead poisoning. 51

Mentioned above ,lead is an important enzyme inhibitor. It interferes with hemoglobin synthesis ,several steps of the heme formation being inhibited by lead. Most sensitive is the enzyme aminolevulinic acid dehydratase(ALAD).

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Lead and heme synthesis   Glycine + succinyl coerzyme A ↓ ALAS (aminolevulimic acid synthetase) ALA (aminolevulimic acid) →blood,urine ↓ALAD (aminolevulinic acid dehydratase) ←Pb prophobilinogen ↓ uroporphyrinogenⅢ ↓ coproporphyrinogenⅢ→urocoproporphyrin(urin e) ↓ 53

protoporphyrinogen ↓ ZPP← FEP← protoporphyrinogenⅨ ↓Fe++

ferro chelatase←Pb

heme

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ALAD is inhibited even at lead serum concentrations as low as 5μg /dl . the ALAD activity correlates closely with the lead content in the blood . ALAD is useful for the examination of persons with relatively low lead exposure ,but the analysis must take place within a few hours of sampling the blood. In severe occupational lead exposure the activity of this enzyme in the erythrocytes is extremely low. 55

Another step inhibited by lead is the incorporation of ferrous ion into protoporphyrin Ⅸ to form heme. When this reaction is inhibited ,zinc substitutes for iron ,and the resulting zinc protophyrin(ZPP) binds to (instead of heme) the hemoglobin molecule, thereby rendering( 致使 )the hemoglobin unable to carry oxygen.

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3.Excretion : excretion is slow over time , primarily through the kidney. Urine lead concentration is useful for diagnosis. Fecal excretion ,sweat ， milk are other routes of excretion. 57

Clinical findings 

Symptoms and signs

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Laboratory findings

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A. Symptoms and signs 

Lead may exert toxic effects on the gastrointestinal , haematopoietic , nervous ( peripheral and central),and renal systems.

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1.symptoms from the gastrointestinal tract include anorexia( 厌食，食欲减退 ) ， constipation ( 便 秘 ),and in some cases diarrhea. These symptoms can be a result of chronic exposures as well as of acute intoxication. Vague ( 含糊，不明确的） gastrointestinal symptoms are early signs of chronic lead intoxication. In sever poisoning , colicky pains occur. After acute or subacute exposure to lead through ingestion or inhalation, the presenting symptoms are usually gastrointestinal . 60

Colicky abdominal pain with constipation are often present early. Colic may continue for a few days ,sometimes is mistaken for an acute abdominal emergency, and have been subjected to surgery for a suspected a appendicitis or ulcer. Sometimes for addiction （ strong interest narcotics ）

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The colic is due to cramps in the smooth muscles of intestines. The same mechanism may contribute to the occasional findings of hypertension and to typical lead pallor( 铅性面容 face pale ,due to cramps of small artery).

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Under chronic exposure conditions and bad oral hygiene the accumulation of lead sulfide can cause a formation of a bluegray at the gingival edge, the so-called lead seam. This sign is rare now.

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2.Nervous system: lead affects both the central and the peripheral nervous system. In the occupational setting, chronic lead intoxication is a slow, insidious disease with protean （变化无常） manifestation. Fatigue ,apathy( 淡漠 ) ， irritability , arthralgias ( 关节痛 ), myalgia ( 肌痛 ), are early signs of chronic lead intoxication.

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As exposure continues ,central nervous system symptoms progress ,with insomnia 失眠 , confusion 精 神混乱 ,impaired concentration 注意力 and memory problems. Clinical examination and neuropsychologial testing frequently show that attention concentration ， memory ， and abstraction are affected. Toxic encephalopathy （中毒性脑病） occur in relation to severe lead exposure in certain occupational ,but such cases now are rare (but can be seen in some time). Lead encephalopathy include headache , confusion, stupor 昏迷 ,coma 昏迷 ,and seizures 发作 .

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Neurological manifestations are common in children .(more sensitive). Cerebral involvement may vary with the age of the patient , the intensity of exposure , and additional exposure to toxic substances ( e.g, alcohol). These effects of lead may not be completely reversible and the risk of permanent complication increases with repeated exposure.

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The adult patient with acute lead poisoning has a week handshake and decreased function of the extensor muscles(distal extensor muscles) of the forearm(“lead palsy ”,Teleky’s sign). Although such obvious effects are now seen rarely ,a decreased nerve conduction velocity has been documented in several studies ,and electrromyography 肌电图 has show fibrillation and decreased number of motor units at maximal motor. Related subjective symptoms may include muscle weakness , fatigue ,pains in the extremities 末端 ,and sometimes even tremor. Children may be somewhat more sensitive to peripheral nervous system effects.

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lead palsy Teleky’s sign

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(Some patients may have abnormal 异常 sense ,feeling ant creeping in the skin .Socks feeling gloves feeling .)

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3. Acute lead exposure may also impair kidney function ,but this effect appears to be reversible.

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4.Anemia is a typical symptom in classic lead poisoning . (frequent manifestations in children) As mentioned above ,lead interfere with hemoglobin synthesis , several steps of the heme formation being inhibited by lead. Most sensitive is the ALAD

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5.Other presenting symptoms include loss of libido ,inhibiting spermatogenesis and infertility in men ,menstrual disturbances and spontaneous abortion in women. Lead crossed the placenta, and maternal exposure prior to and during pregnancy can result in fetal exposure and toxicity. 74

B. Laboratory Findings: 

1. B-Lead (blood lead): Blood levels are an indication of recent exposure(days or weeks). In USA, whole blood lead levels in nonexposed individuals range from 5-15μg /dl. It varies in different countries , and depent on background levels in the district.(if high pollution ,if there is a high level in the local ore ,individuals will have a higher level. But usually lead levels should be maintained below 40μg /dl.

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2.U-lead: As blood levels, the urine lead levels are an indication of recent exposure. But it is very convenient especially for children ,no thrust(no injection, no pain). It varies in different countries ,different district as above. In China it is below 8μg /dl.

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3.EEP, ZPP Because of inhibited heme synthesis,(inhibited heme synthetase), evidenced by an increase in protoporphyrin—measured as FEP(free erythrocyte protoporphyrin) and ZPP (zinc protiporphyrin) , their levels can be increased. Chine: FEP or ZPP≥2.34μmol∕L or 2.07μmol∕L

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Because of inhibited ALAD ,the ALA level will be increased in blood or urine. Chine: ALA≥23.8μmol∕L

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Prevention 

1.Workplace hygiene is critical in the prevention of excessive lead exposure. Clean areas of eating should be provided. Showering and cleaning of work garment are mandatory and should be provided at the plant to prevent exposure to children in the home. Respiratory protection (e.g respirator) should be provided ,to prevent the inhalation of airborne dusts and fumes of lead. 79

2.Medical surveillance is required as above the action level of 30μg∕m3 for more than 30 days a year.(OSHA lead standard . Occupational Safety and Health Administration) Blood lead examination must be carried out at least every 6 months ,and every 2months if the blood lead level exceeds 40μg∕dl. The removel protection provision means that workers with a blood lead levels above 50μg∕dl,or if otherwise indicated by the medical surveillance, should be removed (without losing pay or benefits) until the level has returned to 40μg∕dl or below.

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3. If the lead level cannot be kept below 50μg∕m3,engineering control measures must be initiated. Regular air monitoring is required if levels exceed the action limit of 30μg∕m3.

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Treatment

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1.Removel from exposure.( removel from the workplace.). In all cases of suspected lead intoxication in adults , the first step in management is removel from exposure . Generally, symptoms related to lead will gradually improve after removel from exposure and reduction in blood lead levels. Symptoms that persist or worsen following removel from exposure should not be assumed to be due to lead. 2.Chelation therapy (CaNa2EDTA)

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In adults ,the use of chelation therapy should be reserved for patients with significant symptoms or signs of toxicity. The patient should be hospitalized and treatment overseen by a physician who has experience with chelation therapy. The protocol is for adult patients, not for children. If the BUN and urinalysis are normal, 2 g of CaNa2EDTA in 1000 ml of 5% dextrose (glucose) in water is infused introvenously over 24 hours. This is repeated daily for 5 days.( This 5 days is a period of treatment, whether another period should be reserved , depends on the patient). Urinalysis ,BUN, and serum creatinine ( 肌酐 ) should be monitored daily; If proteinuria , hematuria, or renal dysfunction is observed, CaNa2EDTA treatment should be discontinued. If acute renal failure ensues, institute hemodialysis 血透 . 84

3.Suit the treatment to manifestations as department of internal medicine does.

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End Thanks 86