Lead Poisoning Physical Properties Lead (Pb) has been used by
humans for at least 7000 years, because it is widespread, easy to
extract, and easy to work with. It is highly malleable and ductile
as well as easy to smelt. Leads elemental symbol Pb, is an
abbreviation of its Latin name plumbum. Metallic lead (Pb0) is
resistant to corrosion and can combine other metals to form various
alloys(Lead alloys are used in batteries, shields from radiation,
water pipes, and ammunition) Inorganic Lead Organic Lead Lead has
no known biological function.
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Uses and Sources of Lead: Lead paint: Food containers(painted
with lead-based paint or lead-containing glaze, canned foods)
Petrol (tetraethyl lead) Toys and Jewelry Herbal remedies from
India, China, and other parts of Asia may be potential sources of
lead exposure.
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Uses and Sources of Lead: Soil: Exposure to soil that contains
particulate lead has been shown to be significantly hazardous for
children, who are more commonly exposed by ingestion of house dust
or soil than by paint chips. Water: Drinking water is also a major
source of lead Exposure. Occupational sources: Remodeling
construction Smelters Battery factories Ammunition. Soil: Exposure
to soil that contains particulate lead has been shown to be
significantly hazardous for children, who are more commonly exposed
by ingestion of house dust or soil than by paint chips. Water:
Drinking water is also a major source of lead Exposure.
Occupational sources: Remodeling construction Smelters Battery
factories Ammunition factories Ceramic glazes.
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Contribution of Sources
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Toxicokinetics Absorption of Lead: GI: Children absorb lead
well orally (~50%) adults poorly (~10%). Lead absorption is
enhanced if diet is poor in iron or calcium. High fat intake and
inadequate calories have also been associated with enhanced lead
absorption. Respiratory: Inorganic lead Skin: Organic lead
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Toxicokinetics Distribution: 95% in bone (%70 in children) 4%
in soft tissue (brain, liver, kidneys, bone marrow) 1% blood Lead
readily crosses the placenta
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Toxicokinetics Half-life Of Lead 25 DAYS -- BLOOD 40 DAYS --
SOFT TISSUE 20 YEARS -- BONE
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Toxicokinetics Hepatic Metabolism/Excretion Inorganic lead is
not metabolized but is excreted unchanged. Organic or
alkyl-lead,(leaded gasoline, also identified as tetraethyl- and
tetramethyl-lead) undergoes oxidative dealkylation to the highly
neurotoxin metabolites, triethyl- and trimethyl-lead. The major
route of excretion of absorbed lead is the kidney. Urine: %65 Bile:
%35 Children excrete less of their daily uptake than adults, with
an average retention in adults of %1-4 versus %33 in children.
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Toxic Effects of Lead Nervous System Neurological,
Neurobehavioral, and Developmental Effects in Children Clinically
overt lead encephalopathy may occur in children with high exposure
to lead, probably at BLL of 70 g/dL or higher. Symptoms of lead
encephalopathy: Lethargy Vomiting Irritability Loss of appetite
Dizziness Progressing to obvious ataxia, and a reduced level of
consciousness, which may progress to coma and death
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Toxic Effects of Lead Neurological, Neurobehavioral, and
Developmental Effects in Children The pathological findings at
autopsy are severe edema of the brain due to extravasations of
fluid from capillaries in the brain. This is accompanied by the
loss of neuronal cells and an increase in glial cells. Recovery is
often accompanied by sequelae including epilepsy, mental
retardation, and, in some cases, optic neuropathy and blindness.
Most studies report a 2- to 4-point IQ deficit for each g/dL
increase in BLL within the range of 5 35 g/dL.
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Toxic Effects of Lead Neurological, Neurobehavioral, and
Developmental Effects in Children Lead can affect the brain by
multiple mechanisms: Lead may act as a surrogate for calcium and/or
disrupt calcium homeostasis. Lead affects virtually every
neurotransmitter system in the brain, including glutamatergic,
dopaminergic, and cholinergic systems. (All these systems play a
critical role in synaptic plasticity and cellular mechanisms for
cognitive function, learning, and memory.)
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Toxic Effects of Lead Neurotoxic Effects in Adults CNS :
Fatigue, irritability, lethargy, insomnia, headache, difficulty
concentrating, memory loss and tremor. Sever lead intoxication can
result in an encephalopathy characterized by depressed
consciousness, seizure, and coma, in association with cerebral
edema. PNS: More than a half-century ago, foot drop and wrist drop
characterized the house painter and other workers with excessive
occupational exposure to lead. Axonopathy motor disturbance Upper
extremities, extensor
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Toxic Effects of Lead Hematologic Effects Lead has multiple
hematologic effects,ranging from increased urinary porphyrins,
coproporphyrins, -aminolevulinic acid (ALA), and zinc-
protoporphyrin to anemia.
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Toxic Effects of Lead Renal Toxicity Acute lead nephrotoxicity
consists of proximal tubular dysfunction and can be reversed by
treatment with chelating agents. Chronic lead nephrotoxicity
consists of interstitial fibrosis and progressive nephron loss,
azotaemia and renal failure. Fanconlike syndrome A characteristic
microscopic change is the presence of intranuclear inclusion
bodies.
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Toxic Effects of Lead Effects on Cardiovascular System The most
important manifestation of lead toxicity on the cardiovascular
system is hypertension. The pathogenesis of lead-induced
hypertension is multifactorial including: (1) Inactivation of
endogenous nitric oxide and cGMP, possibly through lead-induced
reactive oxygen species. (2) Changes in the
renninangiotensinaldosterone system, and increases in sympathetic
activity, important humoral components of hypertension. (3)
Alterations in calcium-activated functions of vascular smooth
muscle cells including contractility by decreasing Na+/K+-ATPase
activity and stimulation of the Na+/Ca++ exchange pump. (4)
Possible rise in endothelin and thromboxane.
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Toxic Effects of Lead Reproductive system Impairment of both
male and female reproductive function is associated with over
plumbism. Gastrointestinal Lead colic is a major gastrointestinal
symptom of severe lead poisoning, and is characterized by abdominal
pain, nausea, vomiting, constipation, and cramps. It is rarely seen
today.
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Toxic Effects of Lead Bone Effects Lead has an extremely long
half-life in bone, accounting for over 90% of the body lead in
adults. Lead can affect bone by interfering with metabolic and
homeostatic mechanisms including parathyroid hormone, calcitonin,
vitamin D, and other hormones that influence calcium metabolism.
Lead substitutes for calcium in bone. Lead is known to affect
osteoblasts,osteoclasts, and chrondrocytes and has been associated
with osteoporosis and delays in fracture repair. In children
exposed to lead, a higher bone mineral density (BMD) was
observed.
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Carcinogenicity 2B. Agent is possibly carcinogenic to humans
Human epidemiology data weak Animal data positive
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Children Vulnerability CHILDREN are more vulnerable exposure
than ADULTS Size Consume More Food Inhale More Air Developing
Nervous System Increased need for Calcium
Clinical Presentation Blood lead concentration (g/L) Children:
1000 GI Tract NilAbdominal pain Constipation Abdominal pain,
constipation, weight loss, loss of appetite Abdominal colic,
vomiting Blood Subclinical inhibition of RBC enzymes Mild
anaemiaSevere anaemia CNS Effects on IQ in children? Mild fatigue,
irritability, slowed motor neurone conduction Fatigue, poor
concentration [Peripheral neuropathy] Encephalopathy - delirium -
ataxia - fits - coma Other NilMuscle pain Hypertension,
nephrotoxicity, lowered Vit D metabolism Hypertension,
nephrotoxicity, lowered Vit D metabolism
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IDENTIFY & REMOVE from SOURCE Nutrition Therapy: Diets high
in iron and calcium Examples of foods high in iron are: *Cheese,
fish, meat, eggs, beans, spinach, raisins Examples of foods high in
calcium are: * Milk, cheese, ice cream, yogurt, bread, fish, meat,
broccoli, fruit, nuts
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Consider the use of chelation therapy - Chelaton terapy is
wildely recomended for asymptomatic children with BLL >450g/l
Increase lead excretion,reduce blood cocentration,and reverse
hemotologic markers of toxcity.
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EDTA - Sodium Calcium Edetate 1000-1500 mg/m2/d, IV,IM IV for
severe toxicity, particularly encephalopathy Well tolerated,
Chelation Therapy Guidelinesa Condition, BPb (
g/dL)DoseRegimen/Comments Adults EncephalopathyBAL 450 mg/m2/d75
mg/m2 IM every 4 h for 5 d CaNa2EDTA 1500 mg/m2/d Continuous
infusion or 2-4 divided IV doses for 5 d (start 4 h after BAL)
Symptoms suggestive of encephalopathy or >100 BAL 300-450
mg/m2/d50-75 mg/m2 every 4 h for 3-5 d CaNa2EDTA 1000-1500 mg/m2/d
Continuous infusion or 2-4 divided IV doses for 5 d (start 4 h
after BAL) Base dose, duration on BPb, severity of symptoms Mild
symptoms or 70-100 Succimer 700-1050 mg/m2/d 350 mg/m2 tid for 5 d,
then bid for 14 d Asymptomatic and
Children Encephalopathy BAL 450 mg/m2/d75 mg/m2 IM every 4 h
for 5 d CaNa2EDTA 1500 mg/m2/d Continuous infusion or 2-4 divided
IV doses for 5 d (start 4 h after BAL) Symptomatic or > 69 BAL
300-450 mg/m2/da50-75 mg/m2 every 4 h for 3-5 d CaNa2EDTA 1000-1500
mg/m2/da Continuous infusion or 2-4 divided IV doses for 5 d (start
4 h after BAL) Base dose, duration on BPb, severity of symptoms
Asymptomatic: 45-69 Succimer 700-1050 mg/m2/d 350 mg/m2 tid for 5
d, then bid for 14 d or CaNa2EDTA, 1000 mg/m2/d Continuous infusion
or 2-4 divided IV for 5 d (or rarely, D-penicillamine) 20-44
Routine chelation not indicated If succimer used, same regimen as
per above group Attempt exposure reduction