Lead poisoning

Lead poisoning is a medical condition, also known as saturnism, plumbism or painter's colic, caused by increased  blood lead levels.

History
Lead was first mined in Asia Minor (today Turkey) about 6500 BC. A 6000- to 8000-year-old lead necklace was found in the ancient city site of Anatolia. Lead's easy workability, low melting point and corrosion resistance were among its attractions.

Lead toxicity was first recognized as early as 2000 BC. Nicander of Colophon wrote of lead-induced anemia and colic in 250 BC. Gout, prevalent in affluent Rome, is thought to be the result of lead, or leaded eating and drinking vessels. Lead was used in makeup. Lead sugar (lead acetate) was used to sweeten wine, and the gout that resulted from this was known as saturnine gout.

Aulus Cornelius Celsus, writing ca. 30 AD, listed white lead among poisons with antidotes (beside cantharides, hemlock, hyoscyamus, poisoned mushrooms, and a swallowed leech), and claimed it could be remedied by mallow or walnut juice rubbed up in wine - an interesting idea. Despite his awareness of lead's toxicity, citing many contemporary authorities, Celsus recommended its use in a wide range of ointments applied to wounds to stop bleeding and reduce infection or inflammation.

Julius Caesar's engineer, Vitruvius, who also served his successor Caesar Augustus, reported, "Water is much more wholesome from earthenware pipes than from lead pipes. For it seems to be made injurious by lead, because white lead paint is produced from it; and this is said to be harmful to the human body."

In 17th-century Germany, an Ulm physician noticed that monks who did not drink wine were healthy, while wine drinkers developed colic. The culprit was a white oxide of lead, litharge, added to sweeten the wine.

Chinese alchemists found that lead could be rendered harmless by soaking it in blood and firing it, when this process was repeated several times it provided a protective coat that lead could not pass. The only notable use of this measure was by martial artists so they could use the heavy metal as weights for training.

Today, most exposure in developed countries is the result of occupational hazards, leaded paint, and leaded gasoline (which continues to be phased out in most countries).

The term "lead poisoning" is sometimes used as a dysphemism for gunshot wounds, as almost all bullets are mainly composed of lead.

Symptoms and effects
The symptoms of chronic lead poisoning include neurological problems, such as reduced IQ, or nausea, abdominal pain, irritability, insomnia, metal taste in oral cavity, excess lethargy or hyperactivity, headache and, in extreme cases, seizure and coma. There are also associated gastrointestinal problems, such as constipation, diarrhea, vomiting, poor appetite, weight loss, which are common in acute poisoning. Other associated effects are anemia, kidney problems, and reproductive problems.

In humans, lead toxicity sometimes causes the formation of a bluish line along the gums, which is known as the "Burton's line", although this is very uncommon in young children. Blood film examination may reveal "basophilic stippling" of red blood cells, as well as the changes normally associated with iron deficiency anemia (microcytosis and hypochromia).

A direct link between early lead exposure and extreme learning disability has been confirmed by multiple researchers and child advocacy groups.

Biological role
Lead has no known biological role in the body. The toxicity comes from its ability to mimic other biologically important metals, the most notable of which are calcium, iron and zinc. Lead is able to bind to and interact with the same proteins and molecules as these metals, but after displacement, those molecules function differently and fail to carry out the same reactions, such as in producing enzymes necessary for certain biological processes.

Most lead poisoning symptoms are thought to occur by interfering with an essential enzyme Delta-aminolevulinic acid dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the cofactor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form a Heme. Genetic mutations of ALAD cause the disease porphyria, a disease which was highlighted in the movie The Madness of King George. Lead poisoning is sometimes mistaken for porphyria but the distinction is that lead poisoning usually causes anemia while true porphyria does not.

An article on Lead Encephalopathy on Emedicine states:

Lead also interferes with excitatory neurotransmission by glutamate, which is the transmitter at more than half the synapses in the brain and is critical for learning. The glutamate receptor thought to be associated with neuronal development and plasticity is the N-methyl-D-aspartate (NMDA) receptor, which is blocked selectively by lead. This disrupts long-term potentiation, which compromises the permanent retention of newly learned information.

The January 2004 edition of Scientific American magazine contained an article on Schizophrenia that said the latest research:

... implies that their brain circuits reliant on NMDA receptors are out of kilter. If reduced NMDA receptor activity prompts schizophrenia's symptoms, what then causes this reduction? The answer still remains unclear.

However, a Johns Hopkins report by Tomas Guilarte stated:

It has been known for some time that lead is a potent inhibitor of the NMDA receptor, a protein known to play an important role in brain development and cognition. In this study we demonstrate that lead exposure decreased the amount of NMDA receptor gene and protein in a part of the brain called the hippocampus.

Ezra Susser and his colleagues at Columbia University in New York followed 12,000 children born in Oakland, California, between 1959 and 1966, whose mothers had given samples of blood serum while they were pregnant, which were frozen and stored for later analysis. They found that children who had been exposed to high levels of lead in the womb were more than twice as likely to go on to develop schizophrenia. Their research was presented at the 2004 annual meeting of the American Association for the Advancement of Science in Seattle, Washington.

Occurrence
Outside of occupational hazards, the majority of lead poisoning occurs in children under age twelve. The main sources of poisoning are from ingestion of lead contaminated soil (this is less of a problem in countries that no longer have leaded gasoline) and from ingestion of lead dust or chips from deteriorating lead-based paints. This is particularly a problem in older houses where the sweet-tasting lead paint is likely to chip, but deteriorating lead-based paint can also powder and be inhaled. Small children also tend to teeth and suck on painted windowsills as they look outside. In most American states, landlords and those selling such houses are required to inform the potential residents of the danger.

Lead has also been found in drinking water. It can come from plumbing and fixtures that are either made of lead or have trace amounts of lead in them. Exposure to lead may also come from bullet fragments in game meat hunted with lead bullets.

Lead can also be found in some imported cosmetics such as Kohl, from the Middle East, India, Pakistan, and some parts of Africa, and Surma from India. There are also risks of elevated blood lead levels caused by folk remedies like Azarcon which contains 95 percent lead and is used to "cure" empacho. For more information about less common causes of elevated blood lead levels, see footnote.

Measurement
One measure of lead in the body is the blood lead level (BLL), measured in micrograms of lead per deciliter of blood (μg/dL). Nearly everyone has a measurable BLL. The Centers for Disease Control and Prevention (CDC) states that a BLL of 10 μg/dL or above is a cause for concern. However, lead can impair development even at BLLs below 10 μg/dL. However, BLL measures current exposure to lead, but lead may also be incorporated into bone from prior exposures that will not show in BLLs until this bone-lead becomes "mobilized" through pregnancy or fracture healing. A fetus can be poisoned in utero if its mother had high bone-lead from either childhood exposure or a later occupational or other exposure that is subsequently mobilized by the fetal need for calcium. K-fluorescent X-ray metering can measure bone-lead.

The average person has less than 10 micrograms per deciliter, or 100 parts per billion, ppb, of lead in their blood. People who have been exposed to an unusual amount of lead will have blood lead levels higher than 200 ppb&mdash;most clinical symptoms of lead poisoning begin at around 100 ppb. The effect on children's IQ has been noted at very low levels.

Treatment
Although the most important part of treating lead poisoning is decreasing exposure to lead, there are some forms of chelation therapy that can be used to reduce existing BLL levels:
 * DMSA
 * EDTA
 * British anti-Lewisite

Additionally, vitamin C (ascorbic acid), is also thought to act as a weak (according to some sources) chelating agent, though high serum levels of vitamin C have been associated with a decreased prevalence of elevated blood lead levels.

There are also homeopathic remedies that purport to cure lead poisoning. Asa Herschoff, MD claims that Alumina helps antidote and eliminate lead from the body, and can help mental confusion, memory loss, dullness, lethargy and loss of identity, as well as high blood pressure and kidney disease. Causticum is also a general antidote, particularly indicated for nerve paralysis and urinary weakness.

Famous cases of lead poisoning

 * Much of Rome's affluent class suffered from lead-induced gout.
 * The Devon colic was caused by the presence of lead in cider in 18th century Devon.
 * Many historians have believed that Ludwig van Beethoven suffered from lead poisoning. This belief has been confirmed in 2005 by tests done at Argonne National Laboratory in the US on skull bone fragments, confirming earlier tests on hair samples.
 * Francisco Goya was considered skilled but unremarkable until he contracted lead poisoning in his late forties and painted a series of disturbing paintings called "the Caprices."
 * George Frideric Handel is believed to have acquired saturnine gout through port wine.
 * Lead shot for hunting ducks and other waterfowl in wetland areas is often restricted because waterfowl can ingest spent shot while feeding from the bottom of lakes and ponds. Non-toxic alternatives such as bismuth or powdered metal/polymer shot is manufactured specifically for use in restriced habitat areas.
 * Operation of a smelter in Trail, British Columbia contributed to higher than average blood lead levels in children living in Trail compared to nearby communities.
 * In 1845, a crew of 128 gathering magnetic data in the Canadian Arctic, under the leadership of John Franklin, are thought to have died from lead poisoning among other things. The canned food on board was sealed in tin cans with lead solder. The lead is thought to have leaked into the food and driven the men mad.