Lead and learning

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Lead and learning

• Anil T. Mangla

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Agenda

• History of lead
• Routes of exposure
• Signs and Symptoms of Lead Poisoning
• ISDH requirements and recommendations
• Current medical treatment
• How can you prevent lead poisoning?

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What is lead?

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Properties of lead

• Lead is a bluish-white lustrous metal
• It is very soft, highly malleable, ductile, and a
  relatively poor conductor of electricity
• It is very resistant to corrosion but tarnishes
  upon exposure to air
• Lead pipes bearing the insignia of Roman
  emperors, used as drains from the baths, are
  still in service

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History

• In 1892 lead poisoning in Children was first
  reported in Australia
• In 1909 France, Belgium and Austria banned
  white-lead interior paint
• In 1922 Tunisia and Greece followed the ban
• In 1926 Great Britain and Sweden banned lead
  interior paint
• 1927 Poland banned all lead-based paint
• 1931 Spain and Yugoslavia

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History

• In December 1943 the issue of lead poisoning from
  paint among children, already familiar to those
  in the industry and to some pediatricians and
  public health professionals, became national
  news. Time magazine reported on an article by
  pediatrician Randolf Byers and psychologist
  Elizabeth Lord in the American Journal of Disease
  of Children. The time article noted that
• When children chewed the painted surfaces, a
  variety of physical and nervous disorders
  resulted. All but one child, Dr Lord
  discovered, were school failures. Only five had
  normal IQs and four of the five were so erratic
  that they could not learn easily.

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Lead 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

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Lead 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

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Understanding Units

• Measure of weight.
• 1,000,000 ?g 1 gram (g), 1000g 1Kg 2.2lbs
• A penny weighs about 2 grams
• If a penny is cut into 2 million pieces, one
  piece would weigh 1 ?g
• Measure of volume.
• 1 dL 0.1L 100mL 0.2 pints about 1/2 cup
• A person weighing 165 pounds has about60
  deciliters of blood

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Blood Lead Levels
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Routes of Exposure to Lead

• Eating (Ingestion)
• Lead particles on hands transferred to food,
  drinks and children sucking on their fingers
• 20 absorbed in adults
• 70 absorbed in children and pregnant women
• Breathing (Inhalation),
• Lead particles in the air

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Lead Distribution in the body

• Blood
• Soft Tissue
• Mineralized Tissue

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Medical Effects of Lead Poisoning

• Brain damage
• Kidney disease
• Hemoglobin synthesis

• Hypertension
• Decreased fertility
• Reproductive complications

Some health effects of lead poisoning such as
cognitive ability is non-reversible, Rogan et al,
2001
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Signs and Symptoms

• Tiredness
• Sleep problems
• Dizziness
• Irritability
• Nervousness
• Headaches
• Difficulty concentrating
• Depression
• Forgetfulness
• Hyperactivity (children)
• Numbness

• Wrist or foot drop
• Weakness
• Clumsiness
• Joint and muscle pain
• Vomiting
• Loss of Appetite
• Stomach aches
• Constipation
• Metal taste in mouth
• Problems having healthy children

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Effects of Lead

• Children
• Even small doses of lead are dangerous
• Toddlers (1-3 years) especially at risk because
  they crawl on floor and put things in mouth
• May affect ability to learn
• Poor muscle and bone development
• Coordination problems
• Speech and language problems

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Effects of Lead

• Nervous System
• Most affected by lead
• Damage can be permanent
• Lead can damage the brain and destroybrain cells
• Damage can result in depression, irritability,
  forgetfulness, clumsiness, learning disability
• High exposure can result in hallucinations, coma,
  and even death

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Studies on lead toxicity and learning

• Canfield et al measured BLL in children at
  6,12,18,24,36,48 and 60 months of age
• Administered the Stanford-Binet intelligence test
  at 3 and 5 years of age
• Decrease in IQ by 4.6 point with BLLgt10mg/dL
• Decrease in IQ by 7.4 points with BLLlt 10mg/dL
• Results adjusted for confounders

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Studies on lead toxicity and learning

• Howard Ho et al and Rojo et al at Harvard using
  umbilical cord blood in children that had BLL
  between 10 and 25mg/dL
• Significant lower scores on test of cognitive
  development
• First trimester of pregnancy may be the hazard
  period of prenatal exposure for the infants
  mental development at 24 months

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Findings and conclusions

• Increased blood lead levels is inversely and
  significantly associated with IQ

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Lead Poisoning and educational Outcomes
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Mechanism of nerve impulse

• Pain receptors sense the stimulus        
• The receptors initiate a nerve impulse/action to
  the sensory neurons.
• The sensory neurons transmits the impulses to the
  spinal cord.
• Once these potentials reach the end of the
  sensory neuron it causes the release of a
  neurotransmitter into the synapse. (gap between
  neurons)
• The motor neuron transfers the impulse back to
  the effectors/muscles in the hand. While this is
  happening, other interneurons in the spinal cord
  transmit a message to the brain.

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Neurotransmitters

• Acetylcholine
• Nerve impulses
• Dopamine
• Emotion
• Gama-aminobutaric acid (GABA)
• Growth
• Glutamate
• Brain Development

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Mode of Action

• Ca2 and Pb2 are both divalents
• Pb2 mimics and the action of Ca2
• Increases neurotransmitter release from nerve
  endings

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Blood Brain Barrier

• Lead increases the permeability to the BBB
• Lead decreases the selectivity of molecules
  entering the brain

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Kidneys

• Filter and remove waste products from the blood
• 65 of lead in blood is filtered in kidneys
• Lead can damage kidneys
• Often damage is not detected until its too late
• Can cause kidney failure

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Kidneys

• The functional units in the kidney are called
  nephrons
• There are about 1.3 million nephrons in each
  kidney
• Each nephron has two main parts, the glomerulus
  and the tubules

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Kidneys

• The kidney's primary function in the body is to
  concentrate waste substances
• Metals are elements
• Metals cannot be broken down to reduce toxicity

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Mechanism

• Lead causes damage in the tubules where it
  inhibits the functions of the mitochondria
• Eventually the cells are not able to reabsorb
  substances like they are supposed to like sodium,
  potassium, phosphorus
• Lead can also bind with proteins and form protein
  inclusion bodies

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Types of Disease

• Chronic glomerulonephritis 48
• Interstitial nephritis 17
• Hypertensive nephropathy 13
• PKD 7
• Unknown 15

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Effects of Lead

• Hematology
• Lead damages the red blood cells
• Prevents cells from carrying oxygen
• Reduces the synthesis of hemoglobin
• Effects the Renin-Angiotensin system

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Mechanism
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Heme Biosynthesis

• Effects several enzymes steps
• This increases the amount of erythrocyte
  protoporphyrin and zinc protoporphyrin
• Control has been shown to be exerted on
  ferrochelatase

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Effects of Lead

• Bone Tissue
• Lead from blood is deposited in bones
• Prevents calcium release into blood
• Blocks production of new blood cells
• Bones and teeth store 95 of lead in body
• Stored in bone tissues for over 30 years
• Under stress, lead is released from bone tissue

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Effects of Lead

• Female Reproductive Health Pregnancy
• Reduces fertility
• Affects menstruation and menopause
• Lead passes through placenta to fetus
• May cause brain damage to fetus
• May cause miscarriage or premature birth
• May be released from bones back to blood

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Effects of Lead

• Male Reproductive System
• Decreased libido
• Infertility
• Damage to sperm, decreased motility
• Increases spouses chance of miscarriage,
  premature birth, and birth defects in child

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Available Tests

• Blood lead level (BLL) test
• Zinc protporphyrin (ZPP) test
• BLL test shows exposure within last 6-8 weeks
  (?g/dL)
• ZPP for a more accurate Blood Lead Level in
  Adults.

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Medical conditions in Children
Blood Lead Level
Possible Health Effects
10 ?g/dL 20 ?g/dL 40 ?g/dL 50 ?g/dL 100
?g/dL and over
Slight loss in IQ hearing and growth
problems Moderate 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
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Treatment

• Ensure that the patient is removed from the
  source of exposure
• Initial generic poisoning techniques
• Blood filtration techniques
• Chelators and metal antidotes

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Treatment

• Calcium Disodium EDTA (Ca Na2 EDTA)
• Calcium Disodium Versenate (Versenate)
• d-Penicillamine (penicillamine or Cupramine)

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Intravenous

• Patient is well hydrated
• Caution for renal impairment
• 60-80mg/kg twice a day for 5 days

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Mechanism

• They all are ligands
• The ligands present on chelators include groups
  such as OH, -SH or NH
• They bind irreversibly to Pb 2
• Removed through urine

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Intramuscular

• Allergy to peanuts
• Glucose-6-Phosphate Dehydrogenase(G6PD)
  deficiency
• Very painful procedure
• Mixed with 1 procaine

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Nutrition as Therapy

• Diets high in iron and calcium
• Examples of foods high in iron
• Cheese, fish, meat, eggs, spinach, beans,
  raisins, almonds, etc
• Examples of foods high in calcium
• Milk, cheese, ice cream, yogurt, bread, fish,
  meat, beans, broccoli, fruits, nuts, etc

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Acknowledgements

• Feldman et al., Principles of Neuropsychopharmacol
  ogy, Sinauer Associates, Inc
• Steven G. Gilbert
• Curtis et al Behavioral and Brain Science,
  (1996) 193
• www.komsta.net/chemwalls/ hemoglobin-1280.jpg
• Janet McCabe and Dave McCommick

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Questions?
Dr. Anil T. Mangla, PhD., MPH Epidemiologist 317-2
34-2273 amangla_at_isdh.IN.gov

• Childhood Lead Poisoning Prevention Program
• Indiana State Department of Health
• 2 N. Meridian Street
• Indianapolis, IN 46204-3003
• Tel. [phone]
• Fax. [phone]