Lead and learning Anil T. Mangla
Agenda <ul><li>History of lead </li></ul><ul><li>Routes of exposure </li></ul><ul><li>Signs and Symptoms of Lead Poisoning...
What is lead?
Properties of lead <ul><li>Lead is a bluish-white lustrous metal </li></ul><ul><li>It is very soft, highly malleable, duct...
History <ul><li>In 1892 lead poisoning in Children was first reported in Australia </li></ul><ul><li>In 1909 France, Belgi...
History <ul><li>In December 1943 the issue of lead poisoning from paint among children, already familiar to those in the i...
Lead Based Paint <ul><li>1887 - US medical authorities diagnose childhood lead poisoning </li></ul><ul><li>1904 - Child le...
Lead In Gasoline <ul><li>1854 - Tetraethyl lead discovered by German chemist </li></ul><ul><li>1921 - Midgley discovers th...
Understanding Units <ul><li>Measure of weight. </li></ul><ul><ul><li>1,000,000   g = 1 gram (g), 1000g = 1Kg = 2.2lbs </l...
Blood Lead Levels
Routes of Exposure to Lead <ul><li>Eating (Ingestion) </li></ul><ul><ul><li>Lead particles on hands transferred to food, d...
 
 
Lead Distribution in the body <ul><li>Blood </li></ul><ul><li>Soft Tissue </li></ul><ul><li>Mineralized Tissue  </li></ul>
Medical Effects of Lead Poisoning <ul><li>Brain damage </li></ul><ul><li>Kidney disease </li></ul><ul><li>Hemoglobin synth...
Signs and Symptoms <ul><li>Tiredness </li></ul><ul><li>Sleep problems </li></ul><ul><li>Dizziness </li></ul><ul><li>Irrita...
Effects of Lead <ul><li>Children </li></ul><ul><ul><li>Even small doses of lead are dangerous </li></ul></ul><ul><ul><li>T...
Effects of Lead <ul><li>Nervous System </li></ul><ul><ul><li>Most affected by lead </li></ul></ul><ul><ul><li>Damage can b...
Studies on lead toxicity and learning <ul><li>Canfield  et al  measured BLL in children at 6,12,18,24,36,48 and 60 months ...
Studies on lead toxicity and learning <ul><li>Howard Ho  et al  and Rojo  et al  at Harvard using umbilical cord blood in ...
Findings and conclusions <ul><li>Increased blood lead levels is inversely and significantly associated with IQ </li></ul>
Lead Poisoning and educational Outcomes                            
Mechanism of nerve impulse <ul><li>Pain receptors sense the stimulus         </li></ul><ul><li>The receptors initiate a ne...
Neurotransmitters <ul><li>Acetylcholine </li></ul><ul><ul><li>Nerve impulses </li></ul></ul><ul><li>Dopamine </li></ul><ul...
Mode of Action <ul><li>Ca 2+  and Pb 2+  are both divalents </li></ul><ul><li>Pb 2+  mimics and  the action of Ca 2+   </l...
Blood Brain Barrier <ul><li>Lead increases the permeability to the BBB </li></ul><ul><li>Lead decreases the selectivity of...
Kidneys <ul><ul><li>Filter and remove waste products from the blood </li></ul></ul><ul><ul><li>65% of lead in blood is fil...
Kidneys <ul><li>The functional units in the kidney are called nephrons </li></ul><ul><li>There are about 1.3 million nephr...
Kidneys <ul><li>The kidney's primary function in the body is to concentrate waste substances </li></ul><ul><li>Metals are ...
Mechanism <ul><li>Lead causes damage in the tubules where it inhibits the functions of the mitochondria </li></ul><ul><li>...
Types of Disease <ul><li>Chronic glomerulonephritis 48% </li></ul><ul><li>Interstitial nephritis 17% </li></ul><ul><li>Hyp...
Effects of Lead <ul><li>Hematology </li></ul><ul><ul><li>Lead damages the red blood cells </li></ul></ul><ul><ul><li>Preve...
Mechanism
Heme Biosynthesis <ul><li>Effects several enzymes steps </li></ul><ul><li>This increases the amount of erythrocyte protopo...
Effects of Lead <ul><li>Bone Tissue </li></ul><ul><ul><li>Lead from blood is deposited in bones </li></ul></ul><ul><ul><li...
Effects of Lead <ul><li>Female Reproductive Health & Pregnancy </li></ul><ul><ul><li>Reduces fertility </li></ul></ul><ul>...
Effects of Lead <ul><li>Male Reproductive System </li></ul><ul><ul><li>Decreased libido </li></ul></ul><ul><ul><li>Inferti...
Available Tests <ul><li>Blood lead level (BLL) test </li></ul><ul><li>Zinc protporphyrin (ZPP) test </li></ul><ul><li>BLL ...
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 l...
Treatment <ul><li>Ensure that the patient is removed from the source of exposure </li></ul><ul><li>Initial ‘generic’ poiso...
Treatment <ul><li>Calcium Disodium EDTA (Ca Na2 EDTA)  </li></ul><ul><li>Calcium Disodium Versenate (Versenate)  </li></ul...
Intravenous   <ul><li>Patient is well hydrated </li></ul><ul><li>Caution for renal impairment </li></ul><ul><li>60-80mg/kg...
Mechanism <ul><li>They all are ligands </li></ul><ul><li>The ligands present on chelators include groups such as –OH, -SH ...
Intramuscular <ul><li>Allergy to peanuts </li></ul><ul><li>Glucose-6-Phosphate Dehydrogenase(G6PD) deficiency </li></ul><u...
Nutrition as Therapy <ul><li>Diets high in iron and calcium </li></ul><ul><li>Examples of foods high in iron </li></ul><ul...
Acknowledgements <ul><li>Feldman et al., Principles of Neuropsychopharmacology, Sinauer Associates, Inc </li></ul><ul><li>...
Questions? Childhood Lead Poisoning Prevention Program Indiana State Department of Health 2 N. Meridian Street Indianapoli...
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  • Lead and Learning

    1. 1. Lead and learning Anil T. Mangla
    2. 2. Agenda <ul><li>History of lead </li></ul><ul><li>Routes of exposure </li></ul><ul><li>Signs and Symptoms of Lead Poisoning </li></ul><ul><li>ISDH requirements and recommendations </li></ul><ul><li>Current medical treatment </li></ul><ul><li>How can you prevent lead poisoning? </li></ul>
    3. 3. What is lead?
    4. 4. Properties of lead <ul><li>Lead is a bluish-white lustrous metal </li></ul><ul><li>It is very soft, highly malleable, ductile, and a relatively poor conductor of electricity </li></ul><ul><li>It is very resistant to corrosion but tarnishes upon exposure to air </li></ul><ul><li>Lead pipes bearing the insignia of Roman emperors, used as drains from the baths, are still in service </li></ul>
    5. 5. History <ul><li>In 1892 lead poisoning in Children was first reported in Australia </li></ul><ul><li>In 1909 France, Belgium and Austria banned white-lead interior paint </li></ul><ul><li>In 1922 Tunisia and Greece followed the ban </li></ul><ul><li>In 1926 Great Britain and Sweden banned lead interior paint </li></ul><ul><li>1927 Poland banned all lead-based paint </li></ul><ul><li>1931 Spain and Yugoslavia </li></ul>
    6. 6. History <ul><li>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: </li></ul><ul><li>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 IQ’s and four of the five were so erratic that they could not learn easily.” </li></ul>
    7. 7. Lead Based Paint <ul><li>1887 - US medical authorities diagnose childhood lead poisoning </li></ul><ul><li>1904 - Child lead poisoning linked to lead-based paints </li></ul><ul><li>1914- Pediatric lead-paint poisoning death from eating crib paint is described </li></ul><ul><li>1921 - National Lead Company admits lead is a poison </li></ul><ul><li>1922 - League of Nations bans white-lead interior paint; US declines to adopt </li></ul><ul><li>1943- Report concludes eating lead paint chips causes physical and neurological disorders in children </li></ul><ul><li>1971- Lead-Based Paint Poisoning Prevention Act passed </li></ul>
    8. 8. Lead In Gasoline <ul><li>1854 - Tetraethyl lead discovered by German chemist </li></ul><ul><li>1921 - Midgley discovers that tetraethyl lead curbs engine knock </li></ul><ul><li>1922 - Public Health Service warns of dangers of lead production, leaded fuel </li></ul><ul><li>1923 - Leaded gasoline goes on sale in selected markets </li></ul><ul><li>1936 - 90 percent of gasoline sold in US contains Ethyl </li></ul><ul><li>1972 - EPA gives notice of proposed phase out of lead in gasoline. </li></ul><ul><li>1986 - Primary phase out of leaded gas in US completed </li></ul><ul><li>1994 - Study shows that US blood-lead levels declined by 78 percent from 1978 to 1991 </li></ul>
    9. 9. Understanding Units <ul><li>Measure of weight. </li></ul><ul><ul><li>1,000,000  g = 1 gram (g), 1000g = 1Kg = 2.2lbs </li></ul></ul><ul><li>A penny weighs about 2 grams </li></ul><ul><ul><li>If a penny is cut into 2 million pieces, one piece would weigh 1  g </li></ul></ul><ul><li>Measure of volume. </li></ul><ul><ul><li>1 dL = 0.1L = 100mL= 0.2 pints = about 1/2 cup </li></ul></ul><ul><ul><li>A person weighing 165 pounds has about 60 deciliters of blood </li></ul></ul>
    10. 10. Blood Lead Levels
    11. 11. Routes of Exposure to Lead <ul><li>Eating (Ingestion) </li></ul><ul><ul><li>Lead particles on hands transferred to food, drinks and children sucking on their fingers </li></ul></ul><ul><ul><li>20% absorbed in adults </li></ul></ul><ul><ul><li>70% absorbed in children and pregnant women </li></ul></ul><ul><ul><li>Breathing (Inhalation), </li></ul></ul><ul><ul><li>Lead particles in the air </li></ul></ul>
    12. 14. Lead Distribution in the body <ul><li>Blood </li></ul><ul><li>Soft Tissue </li></ul><ul><li>Mineralized Tissue </li></ul>
    13. 15. Medical Effects of Lead Poisoning <ul><li>Brain damage </li></ul><ul><li>Kidney disease </li></ul><ul><li>Hemoglobin synthesis </li></ul><ul><li>Hypertension </li></ul><ul><li>Decreased fertility </li></ul><ul><li>Reproductive complications </li></ul>Some health effects of lead poisoning such as cognitive ability is non-reversible, Rogan et al, 2001
    14. 16. Signs and Symptoms <ul><li>Tiredness </li></ul><ul><li>Sleep problems </li></ul><ul><li>Dizziness </li></ul><ul><li>Irritability </li></ul><ul><li>Nervousness </li></ul><ul><li>Headaches </li></ul><ul><li>Difficulty concentrating </li></ul><ul><li>Depression </li></ul><ul><li>Forgetfulness </li></ul><ul><li>Hyperactivity (children) </li></ul><ul><li>Numbness </li></ul><ul><li>Wrist or foot drop </li></ul><ul><li>Weakness </li></ul><ul><li>Clumsiness </li></ul><ul><li>Joint and muscle pain </li></ul><ul><li>Vomiting </li></ul><ul><li>Loss of Appetite </li></ul><ul><li>Stomach aches </li></ul><ul><li>Constipation </li></ul><ul><li>Metal taste in mouth </li></ul><ul><li>Problems having healthy children </li></ul>
    15. 17. Effects of Lead <ul><li>Children </li></ul><ul><ul><li>Even small doses of lead are dangerous </li></ul></ul><ul><ul><li>Toddlers (1-3 years) especially at risk because they crawl on floor and put things in mouth </li></ul></ul><ul><ul><li>May affect ability to learn </li></ul></ul><ul><ul><li>Poor muscle and bone development </li></ul></ul><ul><ul><li>Coordination problems </li></ul></ul><ul><ul><li>Speech and language problems </li></ul></ul>10
    16. 18. Effects of Lead <ul><li>Nervous System </li></ul><ul><ul><li>Most affected by lead </li></ul></ul><ul><ul><li>Damage can be permanent </li></ul></ul><ul><ul><li>Lead can damage the brain and destroy brain cells </li></ul></ul><ul><ul><li>Damage can result in depression, irritability, forgetfulness, clumsiness, learning disability </li></ul></ul><ul><ul><li>High exposure can result in hallucinations, coma, and even death </li></ul></ul>
    17. 19. Studies on lead toxicity and learning <ul><li>Canfield et al measured BLL in children at 6,12,18,24,36,48 and 60 months of age </li></ul><ul><li>Administered the Stanford-Binet intelligence test at 3 and 5 years of age: </li></ul><ul><ul><li>Decrease in IQ by 4.6 point with BLL>10  g/dL </li></ul></ul><ul><ul><li>Decrease in IQ by 7.4 points with BLL< 10  g/dL </li></ul></ul><ul><ul><li>Results adjusted for confounders </li></ul></ul>
    18. 20. Studies on lead toxicity and learning <ul><li>Howard Ho et al and Rojo et al at Harvard using umbilical cord blood in children that had BLL between 10 and 25  g/dL </li></ul><ul><ul><li>Significant lower scores on test of cognitive development </li></ul></ul><ul><ul><li>First trimester of pregnancy may be the hazard period of prenatal exposure for the infants mental development at 24 months </li></ul></ul>
    19. 21. Findings and conclusions <ul><li>Increased blood lead levels is inversely and significantly associated with IQ </li></ul>
    20. 22. Lead Poisoning and educational Outcomes                            
    21. 23. Mechanism of nerve impulse <ul><li>Pain receptors sense the stimulus         </li></ul><ul><li>The receptors initiate a nerve impulse/action to the sensory neurons. </li></ul><ul><li>The sensory neurons transmits the impulses to the spinal cord. </li></ul><ul><li>Once these potentials reach the end of the sensory neuron it causes the release of a neurotransmitter into the synapse. (gap between neurons) </li></ul><ul><li>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. </li></ul>
    22. 24. Neurotransmitters <ul><li>Acetylcholine </li></ul><ul><ul><li>Nerve impulses </li></ul></ul><ul><li>Dopamine </li></ul><ul><ul><li>Emotion </li></ul></ul><ul><li>Gama-aminobutaric acid (GABA) </li></ul><ul><ul><li>Growth </li></ul></ul><ul><li>Glutamate </li></ul><ul><ul><li>Brain Development </li></ul></ul>
    23. 25. Mode of Action <ul><li>Ca 2+ and Pb 2+ are both divalents </li></ul><ul><li>Pb 2+ mimics and the action of Ca 2+ </li></ul><ul><li>Increases neurotransmitter release from nerve endings </li></ul>
    24. 26. Blood Brain Barrier <ul><li>Lead increases the permeability to the BBB </li></ul><ul><li>Lead decreases the selectivity of molecules entering the brain </li></ul>
    25. 27. Kidneys <ul><ul><li>Filter and remove waste products from the blood </li></ul></ul><ul><ul><li>65% of lead in blood is filtered in kidneys </li></ul></ul><ul><ul><li>Lead can damage kidneys </li></ul></ul><ul><ul><li>Often damage is not detected until it’s too late </li></ul></ul><ul><ul><li>Can cause kidney failure </li></ul></ul>
    26. 28. Kidneys <ul><li>The functional units in the kidney are called nephrons </li></ul><ul><li>There are about 1.3 million nephrons in each kidney </li></ul><ul><li>Each nephron has two main parts, the glomerulus and the tubules </li></ul>
    27. 29. Kidneys <ul><li>The kidney's primary function in the body is to concentrate waste substances </li></ul><ul><li>Metals are elements </li></ul><ul><li>Metals cannot be broken down to reduce toxicity </li></ul>
    28. 30. Mechanism <ul><li>Lead causes damage in the tubules where it inhibits the functions of the mitochondria </li></ul><ul><li>Eventually the cells are not able to reabsorb substances like they are supposed to like sodium, potassium, phosphorus </li></ul><ul><li>Lead can also bind with proteins and form protein inclusion bodies </li></ul>
    29. 31. Types of Disease <ul><li>Chronic glomerulonephritis 48% </li></ul><ul><li>Interstitial nephritis 17% </li></ul><ul><li>Hypertensive nephropathy 13% </li></ul><ul><li>PKD 7% </li></ul><ul><li>Unknown 15% </li></ul>
    30. 32. Effects of Lead <ul><li>Hematology </li></ul><ul><ul><li>Lead damages the red blood cells </li></ul></ul><ul><ul><li>Prevents cells from carrying oxygen </li></ul></ul><ul><ul><li>Reduces the synthesis of hemoglobin </li></ul></ul><ul><ul><li>Effects the Renin-Angiotensin system </li></ul></ul>
    31. 33. Mechanism
    32. 34. Heme Biosynthesis <ul><li>Effects several enzymes steps </li></ul><ul><li>This increases the amount of erythrocyte protoporphyrin and zinc protoporphyrin </li></ul><ul><li>Control has been shown to be exerted on ferrochelatase </li></ul>
    33. 35. Effects of Lead <ul><li>Bone Tissue </li></ul><ul><ul><li>Lead from blood is deposited in bones </li></ul></ul><ul><ul><li>Prevents calcium release into blood </li></ul></ul><ul><ul><li>Blocks production of new blood cells </li></ul></ul><ul><ul><li>Bones and teeth store 95% of lead in body </li></ul></ul><ul><ul><li>Stored in bone tissues for over 30 years </li></ul></ul><ul><ul><li>Under stress, lead is released from bone tissue </li></ul></ul>
    34. 36. Effects of Lead <ul><li>Female Reproductive Health & Pregnancy </li></ul><ul><ul><li>Reduces fertility </li></ul></ul><ul><ul><li>Affects menstruation and menopause </li></ul></ul><ul><ul><li>Lead passes through placenta to fetus </li></ul></ul><ul><ul><li>May cause brain damage to fetus </li></ul></ul><ul><ul><li>May cause miscarriage or premature birth </li></ul></ul><ul><ul><li>May be released from bones back to blood </li></ul></ul>
    35. 37. Effects of Lead <ul><li>Male Reproductive System </li></ul><ul><ul><li>Decreased libido </li></ul></ul><ul><ul><li>Infertility </li></ul></ul><ul><ul><li>Damage to sperm, decreased motility </li></ul></ul><ul><ul><li>Increases spouses chance of miscarriage, premature birth, and birth defects in child </li></ul></ul>
    36. 38. Available Tests <ul><li>Blood lead level (BLL) test </li></ul><ul><li>Zinc protporphyrin (ZPP) test </li></ul><ul><li>BLL test shows exposure within last 6-8 weeks (  g/dL) </li></ul><ul><li>ZPP for a more accurate Blood Lead Level in Adults. </li></ul>
    37. 39. 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 Medical conditions in Children Blood Lead Level Possible Health Effects
    38. 40. Treatment <ul><li>Ensure that the patient is removed from the source of exposure </li></ul><ul><li>Initial ‘generic’ poisoning techniques </li></ul><ul><li>Blood filtration techniques </li></ul><ul><li>Chelators and metal antidotes </li></ul>
    39. 41. Treatment <ul><li>Calcium Disodium EDTA (Ca Na2 EDTA) </li></ul><ul><li>Calcium Disodium Versenate (Versenate) </li></ul><ul><li>d-Penicillamine (penicillamine or Cupramine) </li></ul>
    40. 42. Intravenous <ul><li>Patient is well hydrated </li></ul><ul><li>Caution for renal impairment </li></ul><ul><li>60-80mg/kg twice a day for 5 days </li></ul>
    41. 43. Mechanism <ul><li>They all are ligands </li></ul><ul><li>The ligands present on chelators include groups such as –OH, -SH or –NH </li></ul><ul><li>They bind irreversibly to Pb 2+ </li></ul><ul><li>Removed through urine </li></ul>
    42. 44. Intramuscular <ul><li>Allergy to peanuts </li></ul><ul><li>Glucose-6-Phosphate Dehydrogenase(G6PD) deficiency </li></ul><ul><li>Very painful procedure </li></ul><ul><li>Mixed with 1% procaine </li></ul>
    43. 45. Nutrition as Therapy <ul><li>Diets high in iron and calcium </li></ul><ul><li>Examples of foods high in iron </li></ul><ul><ul><li>Cheese, fish, meat, eggs, spinach, beans, raisins, almonds, etc </li></ul></ul><ul><li>Examples of foods high in calcium </li></ul><ul><ul><li>Milk, cheese, ice cream, yogurt, bread, fish, meat, beans, broccoli, fruits, nuts, etc </li></ul></ul>
    44. 46. Acknowledgements <ul><li>Feldman et al., Principles of Neuropsychopharmacology, Sinauer Associates, Inc </li></ul><ul><li>Steven G. Gilbert </li></ul><ul><li>Curtis et al ; Behavioral and Brain Science, (1996) 19:3 </li></ul><ul><li>www.komsta.net/chemwalls/ hemoglobin-1280.jpg </li></ul><ul><li>Janet McCabe and Dave McCommick </li></ul>
    45. 47. Questions? Childhood Lead Poisoning Prevention Program Indiana State Department of Health 2 N. Meridian Street Indianapolis, IN 46204-3003 Tel. 317-233-1250 Fax. 317-233-1630 Dr. Anil T. Mangla, PhD., MPH Epidemiologist 317-234-2273 [email_address]
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