Neuropathy of Lead

1. References: 1)   Subclinical neurophysiological effects of lead: A review on peripheral, central, and autonomic nervous system effects in lead workersAmerican Journal of Industrial MedicineVolume 37, Issue 2, Date: February 2000, Pages: 193-204Shunichi Araki, Hajime Sato, Kazuhito Yokoyama, Katsuyuki Murata 2)   Neuropathies associated with excessive exposure to leadMuscle & NerveVolume 33, Issue 6, Date: June 2006, Pages: 732-741Ruth M. Thomson, Gareth J. Parry 3)   The Influence of Milk Intake on The Lead Toxicity to The Sensory Nervous System in Lead WorkersNeuroToxicology,  Volume 25, Issue 6, December 2004, Pages 941-949Hung-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 403-431Alan S. Kaufman 5) Neuropsychological function in children with blood lead levels <10 μg/dL NeuroToxicology, Volume 28, Issue 6, November 2007, Pages 1170-1177Pamela J. Surkan, Annie Zhang, Felicia Trachtenberg, David B. Daniel, Sonja McKinlay, David C. Bellinger 6) Effects of Lead Salts on the Uptake, Release, and Binding of -Aminobutyric Acid: The Importance of Buffer CompositionJournal of NeurochemistryVolume 52, Issue 2, Date: February 1989, Pages: 433-440Colleen 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 StudyJournal of NeurochemistryVolume 65, Issue 4, Date: October 1995, Pages: 1631-1635Subbarao V. Kala 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 low-levels 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? \ Neuropathy of Lead Toxicological Profile for Lead (1989) 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 is a summary of the data found in journal #1 regarding discoveries in subclinical lead poisoning on different aspects of the nervous system: 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) The Bigger Brain 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 common symptom of lead poisoning. Conversely, in adults, encephalopathy is 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). This difference of neuropathy susceptibility is usually explained for two reasons. The first reason is that calcium (and lead) is actively used and transported more by growing children than adults. This gets the lead to the brain faster and ultimately causes edema (4). The other reason is that child lead poisoning usually results from ingesting a large amount of lead. These large blood-lead levels increase the permeability of the blood-brain barrier, which ultimately causes edema. On the other hand, adults usually experience 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 levels of lead causes more motor naturopathic problems, while long-term exposure (>10 years) causes sensory, motor, and autonomic neuropathy (2). This length-dependent neuropathy usually starts as distal weakness but it can occur in proximal areas. Peripheral To detect lead’s influence on the peripheral nervous system, a nerve conduction voltage (NCV) was measured in volunteers with around 60 ug/Pb per dL blood. In 1976, Araki and Honma proved that low-levels of lead exposure can slow the peripheral nerve conduction velocities (NCV) and that there were discoveries linking blood lead levels and poor NCV (1). In 1992, Yokoyama and Araki further suggested the reduced NCV were from lead damaged axons which thus gave poor reflex and causes wrists drops. Central In 1979, Fox and Sillman indicated that lead selectively affects the rods to decrease night vision but not the cones. In 1993, Otto and Fox showed that blood lead levels between 40 and 50 ug/dL inteferes with the auditory pathway from the acoustic nerve to the brainstem. Autonomic In 1991, two independent Japanese groups reported lead’s adverse effects on cardiac autonomic functions in workers with a mean blood lead level of 36 um/dL. Acetylcholine Acetylcholine is a neurotransmitter responsible for contractions that 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.. 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 presynaptic terminals and inhibits the evoked transmitter release (6). Lead also causes the overproduction of ALA which blocks GABA and can cause seizures, stress, and anxiety. Protein Kinase C Protein kinase C regulates long-term memory storage and helps regulate membrane channels (Ch 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. 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) Krishna Bharani Science and Society 12/11/08 Background Picture - http://amayathinking.wordpress.com/