While Michiganders and anyone paying attention to the news lately know about the dangers of lead, it is probably less well known that lead poisoning and lead contamination affect people all across the United States, not just in Flint. In fact, according to the Center for Disease Control and Prevention (CDC), there are at least 4 million homes in the U.S. where children are being exposed to high levels of lead.

Some of the symptoms of lead poisoning in children, according to Mayo Clinic, are developmental delays, learning difficulties, irritability, loss of appetite, weight loss, sluggishness and fatigue, vomiting, abdominal pain and hearing loss.

Knowing the symptoms, though, does not take away the question of Why? What is it about lead that causes these health problems?

To understand the toxicity of lead, we must first understand how it is absorbed and stored in the body. Lyn Patrick provides an overview of the process in an “Alternative Medicine Review” article. When lead is ingested, the intestines absorb it and pass it along to the blood stream, which deposits the lead in the body’s bones and soft tissue (the liver, renal cortex, brain, lungs and spleen, specifically). Bone deteriorates as a person ages, releasing the stored lead back into the body. Thus, exposure to lead has lifelong consequences.

The three main body systems that lead negatively affects, according to the review article, are the central nervous system, the renal system (found in the kidney) and the cardiovascular system. Lead poisoning is especially problematic for the central nervous system — the brain and spinal cord — where it interferes with the ability of cells to communicate with each other by a process known as “signal transduction.”

Lead is a metal compound and exists in cells as charged particles (ions). It is chemically similar to another metal compound, calcium, which is an ion as well. Though calcium is well known for its role in bone structure, it is also crucial in cells to the proper functioning of enzymes.

In normal cells and in nerve cells, the abundance of calcium is used to signal that certain enzymes and molecules need to be made. Calcium binding to proteins and enzymes begins the signaling process that alerts normal cells to a deficiency in these molecules. Lead can mimic the way calcium binds to several enzymes, preventing them from signaling properly. This limits a cell’s ability to make essential molecules and, as a result, nerve cells aren’t well controlled and haphazardly send messages to other nerve cells.

One clear example of how lead influences signaling within the brain is based on how it affects the amount of a neurotransmitter called GABA. GABA is known to have a calming or quieting effect on the brain, and when GABA is absent or reduced, nervous (in both senses of the word) activity within the brain increases. Having less GABA to calm unnecessary brain activity may account for some of the behavioral disorders caused by long-term lead exposure.

Elevated levels of lead can also kill cells that form the protective tissue barrier around the brain, allowing the lead particles to infiltrate the brain and wreak havoc on the nerve cells there. A protein called albumin also enters the brain when the blood-brain barrier is absent, which damages the brain by causing it to swell. For all of these reasons, lead is particularly toxic to fetuses and young infants that are in the early stages of brain development. Young children are also more vulnerable to lead poisoning than adults because their brains are still developing. Lead’s interruption of the development process permanently alters brain function, and affected children often have difficulty learning.

In addition to the specific ways lead exposure affects the central nervous system, there are also more general ways that lead affects the body. One of the ways lead has a widespread effect is by inhibiting the production of an iron-binding molecule called “heme” (see Figure 1). Heme molecules are found in many proteins, and they give their name to the well-known protein hemoglobin, which uses the heme to bind and carry oxygen in the bloodstream.

Another set of proteins that contain heme is found in mitochondria, the organelles that high school biology teachers often call the “powerhouse of the cell.” Within the mitochondria, these proteins capture and move electrons using their heme groups, thus generating chemical energy in a way that is similar to how a watermill uses the flow of a stream to generate mechanical energy. A lack of heme in these proteins causes cellular energy production to slow down to potentially harmful levels.

The list of ways lead influences body systems is long and detailed, but interrupting cell signaling and inhibiting heme synthesis are two of the most significant effects. Even though scientists understand the biochemical reasons behind lead poisoning, it is still difficult to treat. And despite public awareness of its toxicity, lead is still found in pipes, paint and toys. It’s no wonder that, as the review article points out, the CDC views lead as the greatest environmental health risk to children in the United States.

References

CDC Lead Home Page: http://www.cdc.gov/nceh/lead/default.htm

Patrick, Lyn. “Lead Toxicity, A Review of the Literature. Part I: Exposure, Evaluation, and Treatment.” Alternative Medicine Review. 11.1 (2006): 2-22. Print.

Picture source: https://www.ebi.ac.uk/thornton-srv/databases/CoFactor/cofactor.php?cid=22