lead toxicity

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LEAD TOXICITY:

LEAD TOXICITY

What is Lead?:

What is Lead? Definition Lead is a soft, blue-gray metal. It occurs naturally, but much of its presence in the environment from its historic use in paints and gasoline and from ongoing mining and commercial operations. Properties Lead is a very soft, dense, ductile metal. It is very stable and resistant to corrosion, although acidic water may leach out of pipes, fittings, and solder. It does not conduct electricity. Lead is an effective shield against radiation.

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Forms of lead Lead exists in both organic and inorganic forms. Inorganic lead The lead found in old paint, soil, and various products. Leaded gasoline exhaust contributed to ambient inorganic lead contamination. Organic Lead Leaded gasoline contained organic lead before it was burned; however, since the elimination of lead from gasoline, exposure to organic lead is generally limited to an occupational context. It can be more toxic than inorganic lead because the body more readily absorbs it.

Where Is Lead Found?:

Where Is Lead Found? Homes and Buildings The older the house, the more likely it is to contain lead-based paint and to have a higher concentration of lead in the paint. Drinking Water Homes built before 1986 are more likely to have lead pipes, fixtures and solder, although newer homes may also be at risk.

Where Is Lead Found? cont.:

Foods and Beverages Contaminated with Lead Production Root vegetables uptake from soil Atmospheric lead deposition into leafy vegetables. Grinding or cutting equipment during processing Packaging Bright red and yellow paints on bread bags and candy may contain lead. Some imported cans may still contain lead. Where Is Lead Found? cont.

Where Is Lead Found? cont.:

Foods and Beverages Contaminated with Lead Storage Food or beverages may be stored in lead-containing vessels that contaminate the product. Even "safe" pottery and ceramic-ware can become harmful if the protective glaze wears off and exposes people to lead-containing pigments. Lead-glazed pottery, particularly if it is imported, is a potential source of exposure that is often overlooked. Other Candies , certain “natural” calcium supplements, some ceramic tableware. Where Is Lead Found? cont.

Where Is Lead Found? cont.:

Commercial Products Automotive batteries Bridge paint Computers Jewelry Pewter Some ceramic glazes The Natural Environment Lead sites, such as old mines or lead smelters Old leaded paint may also contaminate soil, especially in areas immediately adjacent to old houses The past use of lead in gasoline has contaminated soils, especially along roadways. Where Is Lead Found? cont .

Where Is Lead Found? cont.:

Workplaces Battery manufacturing plants Construction workers especially renovation/rehabilitation Rubber products and plastics industries Soldering Steel welding/cutting operations and other manufacturing industries. Bridge maintenance and repair workers Radiator repair mechanics Pottery/ceramics industry employees Where Is Lead Found? cont .

How Are People Exposed to Lead?:

How Are People Exposed to Lead? Ingestion Major source of lead exposure for children Inhalation Primary route of exposure for adults Dermal contact Plays a role for exposure to organic lead among workers, but is not considered a significant pathway for the general population. Endogenous Exposure Once absorbed, lead may be stored for long periods in mineralizing tissue ( i.e., teeth and bones) ►►►released again into the bloodstream in times of calcium stress ( e.g. , pregnancy, lactation, osteoporosis), or calcium deficiency

Who Is at Risk of Lead Exposure?:

Who Is at Risk of Lead Exposure? Children Adults mainly occupational exposure • Auto repairers, Battery manufacturers, Bridge reconstruction workers, Construction workers, Glass manufacturers, Lead manufacturing industry, Plastic manufacturers, Police officers, Printers, Rubber product manufacturers, Steel welders or cutters Pregnant Women and Developing Fetuses

Biologic Fate of Lead?:

Biologic Fate of Lead? Adults typically absorb up to 20% of ingested lead. Most inhaled lead in the lower respiratory tract is absorbed. Most of the lead that enters the body is excreted in urine or through biliary clearance (ultimately, in the feces). Inorganic lead is not metabolized in the liver. Nearly all organic lead that is ingested is absorbed. Organic lead compounds are metabolized in the liver.

Biologic Fate of Lead? cont.:

Absorbed lead that is not excreted is exchanged primarily among three compartments Blood Mineralizing tissues (bones and teeth), which typically contain the vast majority of the lead body burden Soft tissue (liver, kidneys, lungs, brain, spleen, muscles, and heart) Biologic Fate of Lead? cont.

Lead in the Blood:

Lead in the Blood The half-life of lead in adult human blood has been estimated to be from 28 days - 36 days. Approximately 99% of the lead in blood is associated with red blood cells; the remaining 1% resides in blood plasma. Blood lead is also important because the BLL is the most widely used measure of lead exposure. These tests, however, do not measure total body burden—they are more reflective of recent or ongoing exposures.

Lead in Mineralizing Tissues (Bones and Teeth):

Lead in Mineralizing Tissues (Bones and Teeth) Lead accumulation occurs mainly in trabecular bone during childhood, and in both cortical and trabecular bone in adulthood. Two physiological compartments exist for lead in cortical and trabecular bone: The inert component stores lead for decades The labile component readily exchanges bone lead with the blood. Bone-to-blood lead mobilization increases during periods of calcium stress

The Physiologic Effects of Lead Exposure?:

The Physiologic Effects of Lead Exposure? Lead has the ability to inhibit or mimic the actions of calcium (which can affect calcium dependent or related processes) and to interact with proteins (including those with sulfhydryl, amine, phosphate and carboxyl groups) Lead toxicity can affect every organ system including: Nervous system Renal system Blood Endocrine glands GIT CVS Reproductive system

Neurological Effects:

Neurological Effects The nervous system is the most sensitive target of lead exposure. The effect of lead toxicity differs in children than in adults. In children: Neurological effects of lead in children have been documented at exposure levels once thought to cause no harmful effects (<10μg/dL). These include Decrement in IQ performance. Attention deficit hyperactivity disorder Hearing impairment. Balance disruption Impaired peripheral nerve function Some of the neurological effects of lead in children may persist into adulthood.

Neurological Effects cont.:

Neurological Effects cont. Acute exposure to very high levels of lead (70-80 μg/dL or higher)in children may produce encephalopathy and other accompanying signs of • Ataxia • Hyperirritability • Convulsions • Stupor • Coma • Death

Neurological Effects cont.:

Neurological Effects cont. In adults: Neurological and behavioral effects in lead-exposed workers with BLLs ranging from 40 to 120 μg/dL include. • Decreased libido and impotence • Dizziness • Depression/mood changes, headache • Fatigue • Diminished cognitive performance • Forgetfulness • Diminished hand dexterity • irritability • Diminished reaction time • Lethargy • Diminished visual motor performance • Malaise • Impaired concentration • Paraesthesia • Increased nervousness • Weakness • Reduced IQ scores Lead encephalopathy may occur at extremely high BLLs, e.g. , 460 μg/dL.

Renal Effects:

Renal Effects Acute high dose (BLL > 60 μg/dL)lead-induced impairment of proximal tubular function manifests in aminoaciduria, glycosuria, and hyperphosphaturia (a Fanconi-like syndrome). These effects appear to be reversible. Continued or repetitive exposures can cause a toxic stress on the kidney, if unrelieved, may develop into chronic and irreversible lead nephropathy ( i.e. , chronic interstitial nephritis).

Hematological Effects:

Hematological Effects Lead decreases heme biosynthesis by inhibiting d aminolevulinic acid dehydratase and ferrochelatase activity. Ferrochelatase, catalyzes the insertion of iron into protoporphyrin IX ►►►increase of the substrate, erythrocyte protoporphyrin (EP), in the red blood cells. Also associated with lead exposure is an increase in blood and plasma d-aminolevulinic acid (ALA) and free erythrocyte protoporphyrins (FEP).

Hematological Effects cont.:

Lead can induce two types of anemia Acute high-level lead exposure ►►hemolytic anemia. In chronic lead exposure , lead induces anemia by both interfering with heme biosynthesis and by diminishing red blood cell survival. The anemia of lead intoxication is hypochromic, and normo- or microcytic with associated reticulocytosis. Hematological Effects cont.

Endocrine Effects:

Endocrine Effects Lead impedes vitamin D conversion into 1,25-dihydroxyvitamin D, which is responsible for the maintenance of extra- & intra-cellular calcium homeostasis ►►►impaired cell growth, maturation, and tooth and bone development. This is restricted to children with chronically high BLLs (> 62 μg/dL) and chronic nutritional deficiency, especially calcium, phosphorous, and vitaminD deficiency.

Gastrointestinal Effects:

Gastrointestinal Effects In severe cases of lead poisoning, children or adults may present with severe cramping abdominal pain, which may be mistaken for an acute abdomen or appendicitis.

Cardiovascular Effects:

Cardiovascular Effects Moderate lead level exposures (BLL<30 μg/dL) show a low degree of association with hypertension Higher exposures (primarily occupational) increase the risk for hypertensive heart disease and cerebrovascular disease as latent effects.

Reproductive Effects:

Reproductive Effects Male Reproductive Effects Effects begin at BLLs of 40 μg/dL. Include diminished sperm concentrations, total sperm counts, and total sperm motility. Pregnancy outcomes Increased frequency of spontaneous abortions, miscarriages and stillbirths. Lead crosses the placenta and can affect fetus viability as well as fetal development. Prenatal exposure to low lead levels (14 μg/dL) may increase the risk of reduced birth weight and premature birth.

Evaluation of patients exposed to lead:

Evaluation of patients exposed to lead History Drinking water source and type of pipes Family history: maternal/family exposure Frequency of visits to old houses or facilities. Hobbies of all family members Home remodeling activities Location, age, physical condition of current residence, school, and day care center. Occupational history of all home occupants Past living conditions Siblings or playmates who have been diagnosed with lead poisoning Use of imported or glazed ceramics.

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Physical Examination Neurological Hematological Cardiovascular Gastrointestinal Renal Check blood pressure to evaluate whether the patient is hypertensive and pay attention to the renal system in those who are positive for hypertension. Check for a blue-black line on the gums (lead line). This is rarely seen, but if present, usually indicates severe and prolonged lead poisoning. For children : Evaluate hearing, speech, and other developmental milestones. Assess the nutritional status. Evaluation of patients exposed to lead cont.

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Signs and Symptoms Lowest Exposure: Impaired Abilities (patient may appear asymptomatic) Decreased learning and memory Lowered IQ Decreased verbal ability Impaired speech and hearing functions Early signs of hyperactivity or ADHD Low Exposure Dose Signs and Symptoms Myalgia or paresthesia Mild fatigue Irritability Lethargy Occasional abdominal discomfort Evaluation of patients exposed to lead cont.

Evaluation of patients exposed to lead cont.:

Signs and Symptoms Moderate Exposure Dose Arthralgia General fatigue Difficulty concentrating/Muscular exhaustibility Tremor Headache Diffuse abdominal pain Vomiting Weight loss Constipation High Exposure Dose Signs and Symptoms Paresis or paralysis Encephalopathy—may abruptly lead to seizures, changes in consciousness, coma, and death Lead line (blue-black) on gingival tissue Colic (intermittent, severe abdominal cramps) Evaluation of patients exposed to lead cont.

Evaluation of patients exposed to lead cont.:

Investigations Blood Lead Levels They respond relatively rapidly to abrupt or intermittent changes in lead intake. However with high or chronic past exposure, BLLs often under-represent the total body burden because most lead is stored in the bone and may have “normal” levels in the blood. One exception is patients with a high body burden under physiological stressful circumstances whose BLLs may be elevated from the release of lead stored in bones. Evaluation of patients exposed to lead cont.

Evaluation of patients exposed to lead cont.:

Investigations Erythrocyte protoporphyrin (EP) & Zinc protoporphyrin (ZP) EP/ZPP assays are used at times as a complement to venous BLL testing and are required by OSHA for some workplace testing. Normal values of ZPP are usually below 35 μg/dL. EP is also elevated in iron deficiency anemia jaundice sickle cell other hemolytic anemias In erythropoietic protoporphyria, an extremely rare disease, EP is markedly elevated (usually above 300 μg/dL). Evaluation of patients exposed to lead cont.

Evaluation of patients exposed to lead cont.:

Other investigations include: Complete blood count (CBC)►►anemia Long bone radiographs for children ►►can show “Lead Lines”. These are lines of increased density on the metaphysis growth plate of the bone, showing radiological growth retardation. Evaluation of patients exposed to lead cont.

Treatment of lead toxicity :

Treatment of lead toxicity

Treatment of lead toxicity cont. :

Treatment of lead toxicity cont.

Treatment of lead toxicity cont. :

Common Chelating Agents Used in Treating Children With High BLLs Product Name Generic Name Chemical Name Abbreviation Treatment of lead toxicity cont.

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