Transcript Lead - It’s Everywhere

Alan M. Ducatman, MD, MSc
West Virginia University
School of Medicine
What is Lead?
Lead is a blush gray metallic element which occurs
naturally (in small amounts) in the earth’s crust.
It is dense, hence its use as a ballast, ammunition, or
radiation shield.
Lead is insoluble in water, but some salts are soluble.
Significant Health Characteristics of Lead
Lead has a low melting point and can easily
be aerosolized by heating.
Lead can be formed into organic compounds
by some organisms, and some organic
compounds (such as “leaded gasoline”) have
industrial uses.
Historic Production of Lead
1. 3500 BC-1450 AD: Mostly mined as a
byproduct of silver extraction, and mostly
converted to… SMOKE.
2. 1450-1750 AD: Byproduct of copper smelting.
3. Industrial Revolution: Byproduct of coal and
combustion. Taller stacks spread pollution. Peak
emissions 1970-80 (400,000 tons/yr).
Historic Production of Lead
Lead in paints (never permitted in some alert
countries). Banned 1978 in the U.S.
Automobile (1923 - depends on country)
Emission byproduct of leaded gasoline.
Improved Lead Levels in the US
Blood lead levels in children <6 years old
showed an approximately 80% decline from the
1970’s to 1994, and a continuing drop from
1994-1998.
Geometric Mean
1994
2.7
1996
1998
2.0
% with elevated BLLS
>10 >15 >20 μg/dL
10.5
3.9
1.9
8.6
3.2
1.5
7.6
2.7
1.2
Approximate # of children tested= 1.2 million yearly
From: MMWR 2000;49:1133-1137
Childhood Risk Factors for
Elevated BLLs (>10μg/dl)
Pre-1946 Housing
Non-Hispanic Black
Mexican American
White
21.9%
13.0%
5.6%
Low Income
High Income
16.4%
0.9%
NHANES III, and CDC Recommendations for BL Screening of Young
Children (Dec. 2000)
Lead- It’s Everywhere
USES OF Pb
Storage batteries
Cable
Radiation shielding
Galvanizing
Annealing
Plating
Paint
Soldering
Glass
Insecticides
Automobile radiators
Brass and bronze Production
Construction
Ammunition
Printing
Plastics
Television electronics
Petroleum
Sources of Lead- Air
Uncontaminated
Contaminated
1-2 μg/m3
4-16 μg/m3
Near Smelter
SOURCES OF LEAD- Water
Uncontaminated
Standards vary Internationally.
In U.S. <15 μg/L 99% of water supplies
SOURCES OF LEAD- Food
Uncontaminated
Mixed Diet
9.43 μg/kg/day
Bottled Baby Food
3.5 μg/L
Contaminated
Older Canned Baby Food
202 μg/L
Bone Meal
60-190 μg/g
_______________________________________________
Compare this to a paint chip 100,000 μg/g or more
Paint Chip
100,000 μg/g or more
Lead- It’s Everywhere
Unusual oral sources of lead:
Ceramic glazes, art pottery, primitive
equipment for making maple syrup,
crystal glass used to contain alcohol
products, certain cosmetics applied to
hands or face, some candle wicks, folk
medicines, used lead radiators,
moonshine liquor.
Lead- It’s Everywhere
What is Lead Paint?
Lead paint uses LEAD as a pigment.
It was advantageous to do this because it “sticks”
(coats or penetrates) well.
There are 2 typesWhite lead (basic lead carbonate)
Red lead (a form of lead oxide)
SOURCES OF LEAD- Soil
Uncontaminated
Remote area
2-200 µg/g
Contaminated
Urban residential mean
585 µg/g
City parks
194 - 3,357 µg/g
Near smelter mean
7,600 µg/g
SOURCES OF LEADHouse Dust
Uncontaminated- New inner-city home
Floor Surface- 2-24 µg/sq ft
Contaminated- Old inner-city home
Floor Surface- 33-486 µg/sq ft
How does lead enter the body?
1. Respiratory
Breathing in dust that contain lead.
Lead is absorbed and distributed to
other parts of the body via the
bloodstream.
How Does Lead Enter the Body?
2. Ingestion
Adults absorb about 6% of ingested lead.
Fasting adults absorb more.
Children absorb much more lead
(30-50% if well fed, and more, if fasting or
malnourished).
How Does Lead Enter the Body?
3. Skin
Skin is relatively impervious to lead, lead
oxides , or lead salts. Some may get through
scrapes or wounds, but organic leads (such
as in leaded gasoline), will go through skin
into the bloodstream quite well.
Does the Route of Entry Matter?
• Lead, lead salts, lead oxide, all have same
toxicity (whether inhaled or ingested), but
more is absorbed when inhaled.
• Organic lead has greater affinity for CNS –
therefore skin absorption may be
SERIOUS
Lead Metabolism and Nutrition
Low dietary intake of vitamin D, vitamin
C, and iron enhance absorption and
retention of lead in the body.
It is believed that vitamin D modifies leadbone metabolism, while vitamin C and
iron may also modify excretion.
Cheny L, et al AJ Epi 1998:147:1162-1174
Where does lead go once in the body?
1. Lead is absorbed into the bloodstream rapidly.
2. It then travels to “soft tissue” such as kidneys, lungs,
brain, spleen, muscles, and heart.
3. After several weeks, most lead moves into bones and
teeth (and some into hair).
•
•
About 94% of adults total lead burden is in bones and teeth
Only about 73% for children
4. Lead in bones and teeth equilibrates over time and
circumstance with other “compartments”.
Lead Compartments
BONE
10 Days

TEETH

BLOOD
27 Days

URINE

SOFT TISSUE
30-40 Days

BILE, HAIR,
SWEAT, NAIL
Figure 2.5 A simple three-compartment model for absorption,
retention, and elimination of lead in humans. Quantitative
estimates apply to adult males . Source: derived from Rabinowitz
et al. (1975)
How Does Lead Get
Out of the Body
•
•
•
•
•
Kidneys- urine
Bowels- stool
Glandssweat
Breastbreast milk
Hair, nails, teeth (very slow turnover)
• It takes >10 years to turn over one half the body’s stored
lead. Bone source slowly leaches into the blood.
What Does Lead Do?
Lead inhibits certain types of enzymes,
Particularly enzymes dependant upon
sulfhydryl groups.
Organ systems affected include:
Neurologic
Endocrine (including BP)
Reproductive Musculoskeletal
Blood
Renal
GI
Microcytic Anemia
with Basophilic Stippling
Larger area is a thick thick smear to demonstrate the frequency of
basophilic stippling
Alternative tests to blood lead
• Erythrocyte protoporphyrin and zinc
protoporphyrin tend to become elevated as
lead-induced hemoglobin salvage increases.
• These tests are neither sensitive nor specific
for detecting lead exposure. They have
limited usefulness in the diagnosis,
surveillance, or treatment of lead exposure
and lead poisoning.
CNS Symptoms in Adults
Early
Later
Chronic
Irritability
Ataxia
Hearing Loss
Impaired
Judgment
Depression
Hallucinations
Seizure
Diminished
Judgment
↓ Memory
↓ Dexterity
Death
↓Cognition
Peripheral Neuropathy in
Lead Poisoning
Distal Symmetric Axonal Polyneuropathy:
Wrist Drop
Foot Pain
Joint Pain
Dexterity
Cognitive Performance Deficits
* in Lead- Exposed Children
Deficits:
Psychomotor performance
Auditory and language processing
Sustained attention & concentration
Measured outcomes:
Less likely to graduate High School
More likely to be convicted of felonies
*Deficits consistent across cultures and controlled for SES
Lead Poisoned Children as
Young Adults
A 20-year follow up by ATSDR of 917 lead
poisoned children (mean 50 ug/dl) measured
lead bone storage by tibial KXRF.
Diminished were:
1. Sural nerve sensory and peroneal motor evoked response
amplitude.
Vibro-tactile thresholds: Fingers and toes
Standing coordination
2. Hand-eye coordination in several types of test performance
(Trails B, Symbol Digit, Learning Error).
Lead Exposure in utero
• Lead crosses the placenta in plasma.
• Pregnancy (and lactation) causes lead release from
bone stores into plasma
• Plasma lead is about 1% of circulating blood lead.
• Epidemiologic effects on CNS have been
documented.
• Peak transfer is at 12-14 weeks gestation
Lead Outcomes in Children
Exposed in Utero
High Dose
Lower Dose
Spontaneous Abortion
Stillbirth
Low Birth Weight
Neuropsychologic
Problems
Additional risk
from breast milk
Lead and Adult Reproduction
Reproductive
Females
- Miscarriage, still birth
- Inability to conceive
Males
- Decreased libido
- Decreased fecundity
- Sperm abnormalities: counts, abnormal forms
Dose response relationship
Lead & Bones
Lead & Hypertension
Lead and the Kidney
Acute and Chronic Disease
1. Lead nephropathy (Fanconi syndrome) is
characterized by aminoacidura, glucosuria,
phosphaturia with hypophosphatemia, and
deceased uric acid excretion.
2. Chronic kidney disease may also arise,
sometimes associated with gout.
Other Organ Systems Affected
by Lead
Hearing (8th nerve damage)
Gout
GI- Anorexia, colic
Endocrine- Vitamin D Metabolism
Genotoxicity
Key Aspects of the Clinical History*
Home environment (or environment where a child visits)
Home remodeling (occupational histories: all family members)
Hobbies, making glazed ceramics, fishing sinkers
Unusual medications, cosmetics
For children, the vast majority of sources will be paint.
For adults, it will be occupation.
For adults and children, home remodeling is an issue
Occupational Histories All family members
*The exposure history provides the key to successful Rx!
Key Presenting Symptoms
Mild
Moderate
Severe
Fatigue
Paresthesia
Paralysis
Irritability
Myalgia
Colic
Arthralgia
Headache
Tremor
GI Distress
Physical Findings
Early
Wrist Drop
Distal Sensation
Proprioception
Vibration Sense
Chronic
Transverse Nail Lines
Blue-Black Gum Lines
Detecting Lead Poisoning in
Young Children
CDC
“Preventing Lead Poisoning in Young Children”
Oct- 1991
Initial Test (12 months)
Surveillance Strategy
<10 µg/dl
10-14 µg/dl
Repeat at 24 months Retest in 1-3 months
>15 µg/dl Individual Case Management
Medical Surveillance for Adult Workers
When: Exposure above “action level”
>30 days/yr
What: Triggers periodic exams and biologic monitoring
(including blood level)
Removal threshold: 50 µg/dl (repeated) or 60 µg/dl once.
Repeat testing: Monthly, depending on lead level
Adult Return to Work
• Lead poisoned workers can return to the
workplace when blood lead is <40 µg/dl.
• Symptomatic workers can remain out of the
workplace at lower levels.
• Workers whose blood lead is near 40 µg/dl
are most likely to be able to remain in the
workplace if they can perform modified duty
without lead exposure.
The Key to “Treatment”
of Lead Poisoning
Remove from exposure, or otherwise prevent
exposure.
Workplace
Substitution
Engineering
Personal Protection
Work Practices
Job Placement
Home
Move
Identify and Abate
Chelation Therapy
• For symptoms, or physical findings.
• May prevent dread acute consequences- seizure
• No longer believed to protect CNS in
asymptomatic children
• Must be considered in light of possible
complications- kidney damage and arrhythmia.
• Will cause increased lead absorption if exposure
persists.
Choice of Chelation Agents
Outpatient: Succimer
1050 mg/m²x 7 days
700 mg/m²x14-19 days
Inpatient: CaNa² -EDTA
1000 –1500 mg/m²/dx 5 days
Encephalopathy
Add: BAL 300-450 mg/m²/d x 3 days
In children
Social Danger:
Lowering blood level by oral chelation is not a substitute for
workplace hygiene!!
Prevention of Lead Poisoning
Prevention of lead poisoning is a superior
public health measure; medical treatment alone
is disappointing.
The key to treatment is cessation of exposure,
and the public health need is to consider and
find other possible victims.
Helpful Web Sites
• ATSDR
http://www.atsdr.cdc.gov/HEC/CSEM/lead/index.ht
ml
• ATSDR Toxicological Profiles
http://www.atsdr.cdc.gov/toxpro2.html
• ATSDR ToxFAQs ™
http://www.atsdr.cdc.gov/toxfaq.html
• CDC-NCEH
http://www.cdc.gov/nceh/lead/lead.htm
• NIOSH
http://www.cdc.gov/niosh/leadpg.html