– both kids and adults, Ý [Pb] causes swelling of the brain, Ý intracranial pressureÞ herniation, ischemia, ultimately to coma. Rare in adults because a high concentration is needed. More common in kids because they’ll eat lead paint chips and children absorb a greater percentage of ingested lead compared to adults.
Colic
– abdominal pain and rigidity relieved by IV Ca2+
Peripheral neuropathy
– affects mainly wrist and foot extensors, ß nerve conduction velocity can be seen in kids and adults with lower levels of exposure. In adults there is motor neuron degeneration with "dying back" and segmental demyelination.
Hearing loss
– seen in children even after low doses, affects higher frequencies > lower frequencies.
Neurobehavioral changes
Adults – low chronic exposure can lead to fatigue and impaired concentration. Children – hyperactivity, shortened attention span, impulsive behavior, easy distractibility, all seen at much lower levels than were previously thought to be harmful. Exposure (as measured by teeth lead levels) was linked to learning deficit (as measured by IQ tests, speech and language processing, attention, and classroom performance) and decreased performance in high school (~11 years later!) Other studies show an inverse relationship between blood lead levels and IQ.
Effects of Different Concentrations of Lead in Blood
5
mg/dl - transplacental transfer occurs
10
mg/dl - ß IQ, hearing, and growth in children; hypertension in adults
12
mg/dl - developmental toxicity in children
15
mg/dl - Ý erythrocyte protoporphyrin in children and women
20
mg/dl - ß nerve conduction velocity in children
25
mg/dl - Ý erythrocyte protoporphyrin in men
30
mg/dl - ß vitamin D metabolism in children; Ý systolic blood pressure in men; ß hearing acuity
40
mg/dl - ß hemoglobin synthesis in children; peripheral neuropathies and nephropathy in adults; infertility in men
50
mg/dl - ß hemoglobin synthesis in adults
60
mg/dl - colic in children
70
mg/dl - frank anemia in children; sustained levels of greater than 70 mg/dl in adults lead to decreased longetivity
75
mg/dl - nephropathy; frank anemia in adults
80
mg/dl - encephalopathy in children
100
mg/dl - encephalopathy in adults
130
mg/dl - death in children
Lead as an Environmental Neurotoxin
History of many environmental neurotoxins
– lead has only been a part of the human experience for a short period of time, whereas Ca2+ (which Pb2+ mimics in body) has been around for all evolution. Since the Greeks started mining silver (often found with lead) 5000 yrs ago, there has been a steady Ý in worldwide lead production (currently >106 tons/yr)
Differential Response (pregnant women/children vs. Adults)
– In the human body, inorganic lead is directly absorbed, distributed, and excreted. Inhaled lead is completely absorbed from lower respiratory tracts. In the GI tract, only 10-15% of ingested lead is typically absorbed, but in pregnant women or children GI absorption can be ~50%. Iron or calcium deficiencies also significantly Ý GI absorption of lead. Also important for pregnant women is that the insult of pregnancy on the body leads to resorption of bone stores of calcium so lead sequestered in bones becomes liberated and is a threat to both the woman and fetus (Pb crosses placental barrier)
Pathophysiology
– The lead ion mimics Ca2+. Once in the blood, Pb2+ is distributed to soft tissue (kidneys, bone marrow, liver, and brain) and mineralized tissue (95% of Pb burden of adults is in their mineralized tissue). Pb2+ enters nerve terminals like Ca2+ during synaptic activity and interferes with a wide variety of calcium related signal transduction mechanisms. Lead reduces neurotransmitter release at cholinergic and other synapses. Developmental morphogenesis dependent on synaptic activity would be expected to be impaired. It is hypothesized that lead-associated learning deficits are due to lead-related interference at NMDA glutamate receptors and with dopamine neurotransmission.
Exposure vs. Hazard
– Lead has been in the earth since day 1, however until it was uncovered and made accessible to humans it was not a problem. Lead is hazardous all the time but only a problem if a person is exposed to it. This century there have been 2 periods of high lead exposure: leaded paint and leaded gas.
+/- Reversibility
– The irreversibility of chronic lead neurotoxicity and the limited effectiveness of medical treatment (predominantly chelation) makes prevention the major option for dealing with lead neurotoxicity.
Sources
– Lead levels in the soil (especially from auto emissions of leaded gasoline) are related to childhood exposure. Once leaded gasoline was banned, there was a corresponding ß in children’s blood lead levels, since children (and some adults) like to put dirt and dirty things in their mouths. Similarly, leaded paint, used in the 1st half of this century, is a source of lead exposure that affects children who live in older homes in poor repair. Other minor sources of exposure include: occupational (plumbers, auto repair, etc), certain types of ceramics, hobbies (shootin’n’fishin’), and substance abuse (gasoline sniffing/moonshine). "Folk remedies" and "Health foods" may also have Pb.
Primary vs. Secondary Effects
– Lead reduces neurotransmitter release at cholinergic and other synapses, a primary effect. Therefore, developmental morphogenesis dependent on synaptic activity would be expected to be impaired, a secondary effect.
Public Health
– need to treat patient (remedial education), family (limit future exposure), community (use Public Health agencies), and planet (all these efforts won’t work if the world keeps using leaded gasoline)