Lead and learningLead and learning

Anil T. ManglaAnil T. Mangla

ICLPPPICLPPP 22

AgendaAgenda

History of leadHistory of leadRoutes of exposureRoutes of exposureSigns and Symptoms of Lead PoisoningSigns and Symptoms of Lead Poisoning ISDH requirements and recommendationsISDH requirements and recommendationsCurrent medical treatmentCurrent medical treatmentHow can you prevent lead poisoning?How can you prevent lead poisoning?

ICLPPPICLPPP 33

What is lead?What is lead?

ICLPPPICLPPP 44

Properties of leadProperties of lead

Lead is a bluish-white lustrous metalLead is a bluish-white lustrous metal It is very soft, highly malleable, ductile, It is very soft, highly malleable, ductile,

and a relatively poor conductor of and a relatively poor conductor of electricityelectricity

It is very resistant to corrosion but It is very resistant to corrosion but tarnishes upon exposure to air tarnishes upon exposure to air

Lead pipes bearing the insignia of Roman Lead pipes bearing the insignia of Roman emperors, used as drains from the baths, emperors, used as drains from the baths, are still in serviceare still in service

ICLPPPICLPPP 55

HistoryHistory In 1892 lead poisoning in Children was first In 1892 lead poisoning in Children was first

reported in Australiareported in Australia In 1909 France, Belgium and Austria banned In 1909 France, Belgium and Austria banned

white-lead interior paintwhite-lead interior paint In 1922 Tunisia and Greece followed the banIn 1922 Tunisia and Greece followed the ban In 1926 Great Britain and Sweden banned lead In 1926 Great Britain and Sweden banned lead

interior paintinterior paint 1927 Poland banned all lead-based paint 1927 Poland banned all lead-based paint 1931 Spain and Yugoslavia1931 Spain and Yugoslavia

ICLPPPICLPPP 66

HistoryHistory In December 1943 the issue of lead poisoning from paint In December 1943 the issue of lead poisoning from paint

among children, already familiar to those in the industry among children, already familiar to those in the industry and to some pediatricians and public health and to some pediatricians and public health professionals, became national news. professionals, became national news. Time magazineTime magazine reported on an article by pediatrician Randolf Byers and reported on an article by pediatrician Randolf Byers and psychologist Elizabeth Lord in the American Journal of psychologist Elizabeth Lord in the American Journal of Disease of Children. The time article noted that:Disease of Children. The time article noted that:

When children chewed the painted surfaces, a variety of When children chewed the painted surfaces, a variety of physical and nervous disorders resulted. “All but one physical and nervous disorders resulted. “All but one child, Dr Lord discovered, were school failures. Only five child, Dr Lord discovered, were school failures. Only five had normal IQ’s and four of the five were so erratic that had normal IQ’s and four of the five were so erratic that they could not learn easily.”they could not learn easily.”

ICLPPPICLPPP 77

Lead Based PaintLead Based Paint 1887 - US medical authorities diagnose childhood lead

poisoning 1904 - Child lead poisoning linked to lead-based paints 1914- Pediatric lead-paint poisoning death from eating

crib paint is described 1921 - National Lead Company admits lead is a poison 1922 - League of Nations bans white-lead interior paint;

US declines to adopt 1943- Report concludes eating lead paint chips causes

physical and neurological disorders in children 1971- Lead-Based Paint Poisoning Prevention Act

passed

ICLPPPICLPPP 88

Lead In GasolineLead In Gasoline 1854 - Tetraethyl lead discovered by German chemist 1921 - Midgley discovers that tetraethyl lead curbs

engine knock 1922 - Public Health Service warns of dangers of lead

production, leaded fuel 1923 - Leaded gasoline goes on sale in selected markets 1936 - 90 percent of gasoline sold in US contains Ethyl 1972 - EPA gives notice of proposed phase out of lead in

gasoline. 1986 - Primary phase out of leaded gas in US completed 1994 - Study shows that US blood-lead levels declined by

78 percent from 1978 to 1991

ICLPPPICLPPP 99

Understanding UnitsUnderstanding Units

Measure of weight.Measure of weight. 1,000,000 1,000,000 g = 1 gram (g), 1000g = 1Kg = 2.2lbsg = 1 gram (g), 1000g = 1Kg = 2.2lbs

A penny weighs about 2 gramsA penny weighs about 2 grams If a penny is cut into 2 million pieces, one piece If a penny is cut into 2 million pieces, one piece

would weigh 1 would weigh 1 gg

Measure of volume.Measure of volume. 1 1 dLdL = 0.1L = 100mL= 0.2 pints = about 1/2 cup = 0.1L = 100mL= 0.2 pints = about 1/2 cup A person weighing 165 pounds has aboutA person weighing 165 pounds has about

60 deciliters of blood60 deciliters of blood

ICLPPPICLPPP 1010

Blood Lead LevelsBlood Lead Levels40

30

25

20

15

10

0

5

10

15

20

25

30

35

40

Blo

od

Lea

d L

evel

s (u

g/d

L)

73 75 85 86 86 90

Year

BLL

ICLPPPICLPPP 1111

Routes of Exposure to LeadRoutes of Exposure to Lead

Eating (Ingestion)Eating (Ingestion) Lead particles on hands transferred Lead particles on hands transferred

to food, drinks and children sucking to food, drinks and children sucking on their fingers on their fingers

20% absorbed in adults20% absorbed in adults 70% absorbed in children and 70% absorbed in children and

pregnant womenpregnant women

Breathing (Inhalation), Breathing (Inhalation), Lead particles in the airLead particles in the air

ICLPPPICLPPP 1212

ICLPPPICLPPP 1313

ICLPPPICLPPP 1414

Lead Distribution in the bodyLead Distribution in the body

BloodBlood

Soft TissueSoft Tissue

Mineralized Tissue Mineralized Tissue

ICLPPPICLPPP 1515

Medical Effects of Lead Medical Effects of Lead PoisoningPoisoning

Brain damageBrain damage Kidney diseaseKidney disease Hemoglobin Hemoglobin

synthesissynthesis

HypertensionHypertension Decreased fertilityDecreased fertility Reproductive Reproductive

complicationscomplications

Some health effects of lead poisoning suchas cognitive ability is non-reversible, Rogan et al, 2001

ICLPPPICLPPP 1616

Signs and SymptomsSigns and Symptoms

TirednessTiredness Sleep problemsSleep problems DizzinessDizziness IrritabilityIrritability NervousnessNervousness HeadachesHeadaches Difficulty concentratingDifficulty concentrating DepressionDepression ForgetfulnessForgetfulness Hyperactivity (children)Hyperactivity (children) NumbnessNumbness

Wrist or foot dropWrist or foot drop WeaknessWeakness ClumsinessClumsiness Joint and muscle painJoint and muscle pain VomitingVomiting Loss of AppetiteLoss of Appetite Stomach achesStomach aches ConstipationConstipation Metal taste in mouthMetal taste in mouth Problems having Problems having

healthy childrenhealthy children

ICLPPPICLPPP 171710

Effects of LeadEffects of LeadChildrenChildren

Even small doses of lead are dangerousEven small doses of lead are dangerousToddlers (1-3 years) especially at risk Toddlers (1-3 years) especially at risk

because they crawl on floor and put things because they crawl on floor and put things in mouthin mouth

May affect ability to learnMay affect ability to learnPoor muscle and bone developmentPoor muscle and bone developmentCoordination problemsCoordination problemsSpeech and language problemsSpeech and language problems

ICLPPPICLPPP 1818

Effects of LeadEffects of Lead

Nervous SystemNervous System Most affected by leadMost affected by lead Damage can be permanentDamage can be permanent Lead can damage the brain and destroyLead can damage the brain and destroy

brain cellsbrain cells Damage can result in depression, irritability, Damage can result in depression, irritability,

forgetfulness, clumsiness, learning disabilityforgetfulness, clumsiness, learning disability High exposure can result in hallucinations, coma, High exposure can result in hallucinations, coma,

and even deathand even death

ICLPPPICLPPP 1919

Studies on lead toxicity and learningStudies on lead toxicity and learning

Canfield Canfield et alet al measured BLL in children at measured BLL in children at 6,12,18,24,36,48 and 60 months of age6,12,18,24,36,48 and 60 months of age

Administered the Stanford-Binet intelligence Administered the Stanford-Binet intelligence test at 3 and 5 years of age:test at 3 and 5 years of age:Decrease in IQ by 4.6 point with BLL>10Decrease in IQ by 4.6 point with BLL>10g/dLg/dLDecrease in IQ by 7.4 points with BLL< 10Decrease in IQ by 7.4 points with BLL< 10g/dLg/dL

Results adjusted for confoundersResults adjusted for confounders

ICLPPPICLPPP 2020

Studies on lead toxicity and learningStudies on lead toxicity and learning

Howard Ho Howard Ho et alet al and Rojo and Rojo et alet al at Harvard at Harvard using umbilical cord blood in children that using umbilical cord blood in children that had BLL between 10 and 25had BLL between 10 and 25g/dLg/dLSignificant lower scores on test of cognitive Significant lower scores on test of cognitive

developmentdevelopmentFirst trimester of pregnancy may be the First trimester of pregnancy may be the

hazard period of prenatal exposure for the hazard period of prenatal exposure for the infants mental development at 24 monthsinfants mental development at 24 months

ICLPPPICLPPP 2121

Findings and conclusionsFindings and conclusions

Increased blood lead levels Increased blood lead levels is inversely and significantly is inversely and significantly

associated with IQassociated with IQ

ICLPPPICLPPP 2222

Lead Poisoning and educational Lead Poisoning and educational OutcomesOutcomes

           

               

ICLPPPICLPPP 2323

Mechanism of nerve impulseMechanism of nerve impulse Pain receptors sense the Pain receptors sense the

stimulus        stimulus         The receptors initiate a nerve The receptors initiate a nerve

impulse/action to the sensory impulse/action to the sensory neurons.neurons.

The sensory neurons transmits the The sensory neurons transmits the impulses to the spinal cord.impulses to the spinal cord.

Once these potentials reach the Once these potentials reach the end of the sensory neuron it end of the sensory neuron it causes the release of a causes the release of a neurotransmitter into the synapse. neurotransmitter into the synapse. (gap between neurons)(gap between neurons)

The motor neuron transfers the The motor neuron transfers the impulse back to the impulse back to the effectors/muscles in the hand. effectors/muscles in the hand. While this is happening, other While this is happening, other interneurons in the spinal cord interneurons in the spinal cord transmit a message to the brain.transmit a message to the brain.

ICLPPPICLPPP 2424

NeurotransmittersNeurotransmitters

AcetylcholineAcetylcholine Nerve impulsesNerve impulses

DopamineDopamine EmotionEmotion

Gama-aminobutaric Gama-aminobutaric acid (GABA)acid (GABA) GrowthGrowth

GlutamateGlutamate Brain DevelopmentBrain Development

ICLPPPICLPPP 2525

Mode of ActionMode of Action CaCa2+2+ and Pb and Pb2+2+ are are

both divalentsboth divalents

PbPb2+2+ mimics and the mimics and the action of Caaction of Ca2+2+

Increases Increases neurotransmitter neurotransmitter release from nerve release from nerve endingsendings

ICLPPPICLPPP 2626

Blood Brain BarrierBlood Brain Barrier Lead increases the Lead increases the

permeability to the permeability to the BBBBBB

Lead decreases the Lead decreases the selectivity of selectivity of molecules entering molecules entering the brainthe brain

ICLPPPICLPPP 2727

KidneysKidneys Filter and remove Filter and remove

waste products from waste products from the bloodthe blood

65% of lead in blood is 65% of lead in blood is filtered in kidneysfiltered in kidneys

Lead can damage Lead can damage kidneyskidneys

Often damage is not Often damage is not detected until it’s too detected until it’s too latelate

Can cause kidney Can cause kidney failurefailure

ICLPPPICLPPP 2828

KidneysKidneys

The functional units in The functional units in the kidney are called the kidney are called nephronsnephrons

There are about 1.3 There are about 1.3 million nephrons in million nephrons in each kidneyeach kidney

Each nephron has Each nephron has two main parts, the two main parts, the glomerulus and the glomerulus and the tubulestubules

ICLPPPICLPPP 2929

KidneysKidneys

The kidney's primary The kidney's primary function in the body is function in the body is to concentrate waste to concentrate waste substancessubstances

Metals are elementsMetals are elements Metals cannot be Metals cannot be

broken down to broken down to reduce toxicityreduce toxicity

ICLPPPICLPPP 3030

MechanismMechanism Lead causes damage in Lead causes damage in

the tubules where it the tubules where it inhibits the functions of inhibits the functions of the mitochondriathe mitochondria

Eventually the cells are Eventually the cells are not able to reabsorb not able to reabsorb substances like they are substances like they are supposed to like sodium, supposed to like sodium, potassium, phosphoruspotassium, phosphorus

Lead can also bind with Lead can also bind with proteins and form protein proteins and form protein inclusion bodiesinclusion bodies

ICLPPPICLPPP 3131

Types of DiseaseTypes of Disease

Chronic Chronic glomerulonephritis 48%glomerulonephritis 48%

Interstitial nephritis 17%Interstitial nephritis 17% Hypertensive Hypertensive

nephropathy 13%nephropathy 13% PKD 7%PKD 7% Unknown 15%Unknown 15%

ICLPPPICLPPP 3232

Effects of LeadEffects of Lead

HematologyHematologyLead damages the red blood cellsLead damages the red blood cellsPrevents cells from carrying oxygenPrevents cells from carrying oxygenReduces the synthesis of hemoglobinReduces the synthesis of hemoglobinEffects the Renin-Angiotensin systemEffects the Renin-Angiotensin system

ICLPPPICLPPP 3333

Mechanism Mechanism

ICLPPPICLPPP 3434

Heme BiosynthesisHeme Biosynthesis

Effects several Effects several enzymes stepsenzymes steps

This increases the This increases the amount of erythrocyte amount of erythrocyte protoporphyrin and protoporphyrin and zinc protoporphyrinzinc protoporphyrin

Control has been Control has been shown to be exerted shown to be exerted on on ferrochelataseferrochelatase

ICLPPPICLPPP 3535

Effects of LeadEffects of Lead

Bone TissueBone TissueLead from blood is deposited in bonesLead from blood is deposited in bonesPrevents calcium release into bloodPrevents calcium release into bloodBlocks production of new blood cellsBlocks production of new blood cellsBones and teeth store 95% of lead in bodyBones and teeth store 95% of lead in bodyStored in bone tissues for over 30 yearsStored in bone tissues for over 30 yearsUnder stress, lead is released from bone Under stress, lead is released from bone

tissuetissue

ICLPPPICLPPP 3636

Effects of LeadEffects of Lead

Female Reproductive Health & Female Reproductive Health & PregnancyPregnancy Reduces fertilityReduces fertility Affects menstruation and menopauseAffects menstruation and menopause Lead passes through placenta to fetusLead passes through placenta to fetus May cause brain damage to fetusMay cause brain damage to fetus May cause miscarriage or premature birthMay cause miscarriage or premature birth May be released from bones back to bloodMay be released from bones back to blood

ICLPPPICLPPP 3737

Effects of LeadEffects of Lead

Male Reproductive SystemMale Reproductive SystemDecreased libidoDecreased libido InfertilityInfertilityDamage to sperm, decreased motilityDamage to sperm, decreased motility Increases spouses chance of miscarriage, Increases spouses chance of miscarriage,

premature birth, and birth defects in childpremature birth, and birth defects in child

ICLPPPICLPPP 3838

Available TestsAvailable Tests

Blood lead level (BLL) testBlood lead level (BLL) testZinc protporphyrin (ZPP) testZinc protporphyrin (ZPP) testBLL test shows exposure within last 6-8 BLL test shows exposure within last 6-8

weeks (weeks (g/dL)g/dL)ZPP for a more accurate Blood Lead ZPP for a more accurate Blood Lead

Level in Adults.Level in Adults.

ICLPPPICLPPP 3939

10 g/dL

20 g/dL

40 g/dL

50 g/dL

100 g/dLand over

Slight loss in IQ; hearing and growth problemsModerate loss in IQ; hyperactivity; poor attention span; difficulty learning; language and speech problems; slower reflexes

Poor bone and muscle development; clumsiness; lack of coordination; early anemia; decreased red blood cells; tiredness; drowsiness

Stomach aches and cramps; anemia; destruction of red blood cells; brain damage

Swelling of brain; seizures; coma; death

Medical conditions in ChildrenMedical conditions in ChildrenBlood

Lead Level Possible Health Effects

ICLPPPICLPPP 4040

TreatmentTreatment

Ensure that the patient is removed from Ensure that the patient is removed from the source of exposurethe source of exposure

Initial ‘generic’ poisoning techniquesInitial ‘generic’ poisoning techniques Blood filtration techniquesBlood filtration techniques Chelators and metal antidotesChelators and metal antidotes

ICLPPPICLPPP 4141

TreatmentTreatment Calcium Disodium EDTA Calcium Disodium EDTA

(Ca Na2 EDTA) (Ca Na2 EDTA)

Calcium Disodium Calcium Disodium Versenate (Versenate) Versenate (Versenate)

d-Penicillamine d-Penicillamine (penicillamine or (penicillamine or

Cupramine)Cupramine)

ICLPPPICLPPP 4242

IntravenousIntravenous

Patient is well Patient is well hydratedhydrated

Caution for renal Caution for renal impairmentimpairment

60-80mg/kg twice a 60-80mg/kg twice a day for 5 daysday for 5 days

ICLPPPICLPPP 4343

MechanismMechanism They all are ligandsThey all are ligands The ligands present The ligands present

on chelators include on chelators include groups such as –OH, groups such as –OH, -SH or –NH-SH or –NH

They bind irreversibly They bind irreversibly to Pb to Pb 2+2+

Removed through Removed through urineurine

ICLPPPICLPPP 4444

IntramuscularIntramuscular

Allergy to peanutsAllergy to peanuts Glucose-6-Phosphate Glucose-6-Phosphate

Dehydrogenase(G6PDehydrogenase(G6PD) deficiencyD) deficiency

Very painful Very painful procedureprocedure

Mixed with 1% Mixed with 1% procaineprocaine

ICLPPPICLPPP 4545

Nutrition as TherapyNutrition as Therapy

Diets high in iron and calciumDiets high in iron and calciumExamples of foods high in ironExamples of foods high in iron

Cheese, fish, meat, eggs, spinach, beans, Cheese, fish, meat, eggs, spinach, beans, raisins, almonds, etcraisins, almonds, etc

Examples of foods high in calciumExamples of foods high in calciumMilk, cheese, ice cream, yogurt, bread, Milk, cheese, ice cream, yogurt, bread,

fish, meat, beans, broccoli, fruits, nuts, etcfish, meat, beans, broccoli, fruits, nuts, etc

ICLPPPICLPPP 4646

AcknowledgementsAcknowledgements

Feldman et al., Principles of Neuropsychopharmacology, Feldman et al., Principles of Neuropsychopharmacology, Sinauer Associates, IncSinauer Associates, Inc

Steven G. Gilbert Curtis et al; Behavioral and Brain Science, (1996) 19:3 www.komsta.net/chemwalls/ hemoglobin-1280.jpg

Janet McCabe and Dave McCommick

ICLPPPICLPPP 4747

Questions?Questions?Childhood Lead Poisoning Prevention ProgramChildhood Lead Poisoning Prevention Program

Indiana State Department of HealthIndiana State Department of Health2 N. Meridian Street2 N. Meridian Street

Indianapolis, IN 46204-3003Indianapolis, IN 46204-3003Tel. 317-233-1250Tel. 317-233-1250Fax. 317-233-1630Fax. 317-233-1630

Dr. Anil T. Mangla, PhD., MPHDr. Anil T. Mangla, PhD., MPHEpidemiologistEpidemiologist317-234-2273317-234-2273

amangla@isdh.IN.govamangla@isdh.IN.gov