Transcript Slide 1

References:
1) Subclinical neurophysiological effects of lead: A
review on peripheral, central, and autonomic nervous
system effects in lead workers
American Journal of Industrial Medicine
Volume 37, Issue 2, Date: February 2000, Pages: 193-204
Shunichi Araki, Hajime Sato, Kazuhito Yokoyama, Katsuyuki
Murata
2) Neuropathies associated with excessive exposure to
lead
Muscle & Nerve
Volume 33, Issue 6, Date: June 2006, Pages: 732-741
Ruth M. Thomson, Gareth J. Parry
3) The Influence of Milk Intake on The Lead Toxicity to
The Sensory Nervous System in Lead Workers
NeuroToxicology,
Volume 25, Issue 6, December 2004, Pages 941-949
Hung-Yi Chuang, Song-Yen Tsai, Kun-Yu Chao, Chen-Yu
Lian, Chun-Yuh Yang, Chi-Kung Ho, Trong-Neng Wu
4) How dangerous are low (not moderate or high) doses
of lead for children's intellectual development?
Archives of Clinical Neuropsychology,
Volume 16, Issue 4, May 2001, Pages 403-431
Alan S. Kaufman
5) Neuropsychological function in children with blood
lead levels <10 μg/dL
NeuroToxicology, Volume 28, Issue 6, November 2007,
Pages 1170-1177
Pamela J. Surkan, Annie Zhang, Felicia Trachtenberg, David
B. Daniel, Sonja McKinlay, David C. Bellinger
Introduction – A Lead-In
Since antiquity, mankind has used lead for both industrial and commercial uses. The malleability
and preservative properties of lead have made it ideal for pigments, glazes, piping, lubricants,
gasoline, and a plethora of other objects we see and use everyday. Today, “we are all exposed to
environmental lead but neuropathy remains confined to workers in industry that use lead or in which
lead is a by-product” (2).
Lead ion’s unique ionic radius and divalent charge allows it to masquerade as calcium and trick the
human body into absorbing lead in calcium’s place. However, lead’s extra electrons (in relation to
calcium) ultimately allow lead to interrupt calcium-dependent processes and cause various
imbalances in the body. In the nervous system, lead can indirectly disrupt hormonal triggers in the
brain, and lead can directly interfere with calcium triggers in the nerves.
While a great amount of lead has been removed from public use, we may still be exposed to lowlevels of lead from trace contaminants. Although we may not overtly feel the effects low-levels of
lead have on our body, our neurological systems can still be adversely affected.
Thus, we are required to ask, what are the effects of lead on our nervous system and what can we
do about it?
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6) Effects of Lead Salts on the Uptake, Release, and
Binding of -Aminobutyric Acid: The Importance of Buffer
Composition
Journal of Neurochemistry
Volume 52, Issue 2, Date: February 1989, Pages: 433-440
Colleen A. Drew, Ian Spence, Graham A. R. Johnston
7) Low Level Lead Exposure Decreases In Vivo Release
of Dopamine in the Rat Nucleus Accumbens: A
Microdialysis Study
Journal of Neurochemistry
Volume 65, Issue 4, Date: October 1995, Pages: 1631-1635
Subbarao V. Kala
Toxicological Profile for Lead (1989)
The Bigger Brain
Nerve picture http://en.wikipedia.org/wiki/Image:Complete_neuron_cell_diagram_en.svg
Low-Lead Levels Exposure
Detecting the symptoms and signs from low-level lead exposure can help us identify and treat
lead-poisoned individuals before they experience permanent neurological damages. The following
Lead is highly toxic to the human body, but it is difficult to find isolated
cases of lead neuropathy. In children, however, encephalopathy is an early and is a summary of the data found in journal #1 regarding discoveries in subclinical lead poisoning on
common symptom of lead poisoning. Conversely, in adults, encephalopathy is different aspects of the nervous system:
not usually present except in special cases of massive exposure. In adults, we
usually see neuropathy after “bone marrow suppression [anemia and
leukopenia, gastrointestinal tract effects (GI hemorrhage, diarrhea)], renal
effects (proteinuria, renal failure), hypertension and gout” (2).
To detect lead’s influence on the peripheral nervous system, a nerve conduction voltage (NCV) was
This difference of neuropathy susceptibility is usually explained for two
measured in volunteers with around 60 ug/Pb per dL blood.
reasons. The first reason is that calcium (and lead) is actively used and
In 1976, Araki and Honma proved that low-levels of lead exposure can slow the peripheral nerve
transported more by growing children than adults. This gets the lead to the
conduction velocities (NCV) and that there were discoveries linking blood lead levels and poor NCV
brain faster and ultimately causes edema (4). The other reason is that child
(1).
lead poisoning usually results from ingesting a large amount of lead. These
large blood-lead levels increase the permeability of the blood-brain barrier,
In 1992, Yokoyama and Araki further suggested the reduced NCV were from lead damaged axons
which ultimately causes edema. On the other hand, adults usually experience which thus gave poor reflex and causes wrists drops.
chronic exposure to small amounts of lead which cause neuropathy (2).
Lead neuropathy is ultimately dependent on the rate and amount of
exposure. Studies have shown that short-term exposure (a few years) of high
In 1979, Fox and Sillman indicated that lead selectively affects the rods to decrease night vision but
levels of lead causes more motor naturopathic problems, while long-term
not the cones.
exposure (>10 years) causes sensory, motor, and autonomic neuropathy (2).
In 1993, Otto and Fox showed that blood lead levels between 40 and 50 ug/dL inteferes with the
This length-dependent neuropathy usually starts as distal weakness but it can
auditory pathway from the acoustic nerve to the brainstem.
occur in proximal areas.
Peripheral
Central
Autonomic
Acetylcholine
In
1991,
two
independent
Japanese
groups
reported
lead’s
adverse
effects
on
cardiac
autonomic
Acetylcholine is a neurotransmitter responsible for contractions that
functions in workers with a mean blood lead level of 36 um/dL.
act as neuromodulator between the peripheral nervous system (PNS)
and the central nervous system (CNS). Lead can act as a calcium
trigger and cause mussel fatigue, shaking, dangling, and other
periphery problems. This usually only happens in adults with 80-100
ug/dL..
Dopamine
Dopamine controls movement and
emotional responses. Lead’s presence in
the body can produce dopaminergic
mechanism changes to disrupt behavior
parameters and provoke learning deficits
and impaired cognitive functions. (7)
Got Cure?
The best way to prevent lead neuropathy is to adhere to the regulatory
standards and to be vigilant in lead testing. Blood lead level testing should be
done quarterly in industries where lead exposure is not avoidable. This test
gives relevant information to lead exposure for the previous 3-5 weeks and
those with lead levels above 60 ug/dl should be retested in 2 weeks to
determine if additional medical attention is needed (2).
Trials done by H.Y. Chuang has shown that the intake of milk has a protective
effect in individuals who are exposed to lead. Chuang investigated the sensory
nervous function of Taiwanese lead industry workers with a current perception
threshold (CPT) test. The study showed that those who drank around 700g of
calcium (two bottles a day) had mild protection in nerves in the hand but not in
the feet. This was probably because the longer nerve fibers, weaker blood
barrier, made them more susceptible to toxins (3).
Chelation therapy along with termination of exposure is recommend for
treating elevated blood lead levels. Urination-inducing drugs like EDTA and
DMSA reduce the bodily burden of lead during the chelation therapy. It should
be noted that chelation treatments can dangerously mobilize un-reactive lead
stored in bones. (2)
GABA
Gama-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter
in the central nervous system. Its job is to secrete growth hormones
and control skeletal muscles by inhibiting ALA-dehydrase (ALAD).
However, when lead is in the system, lead competes with calcium at the
Protein Kinase C
presynaptic terminals and inhibits the evoked transmitter release (6).
Protein kinase C regulates long-term memory
Lead also causes the overproduction of ALA which blocks GABA and can
storage and helps regulate membrane channels (Ch
cause
seizures,
stress,
and
anxiety.
8, Fitch). Lead can affect protein kinase to increase
permeability of the blood brain barrier and cause
cerebral edema or seizures. This is very common in
children and lead can further cause learning
deficiencies if lead binds with protein kinase C.
Krishna Bharani
Science and Society
12/11/08
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