Lead Poisoning Pathophysiology

Lead circulates in the body bound to red blood cells. O nly a small fraction is present in the plasma. However, if the level of lead in the blood exceeds 2.9 µmol/L, red cell binding becomes saturated, meaning the fraction of lead in plasma begins to increase. Lead in the plasma gradually gets distributed to various organs and tissues. B ecause the process is slow, it usually takes long-term exposure over months or years before clinical toxicity occurs.

More than 90% of lead is stored in the bones, where it can remain for decades serving as an ongoing source of lead to tissues, long after a person is no longer exposed to lead or after they have received chelation therapy.

The clinical toxicity eventually observed as a result of lead poisoning occurs due to lead distribution to target tissues, especially the nervous system, bone marrow and kidneys. Lead poisoning results in various different health problems including hypertension, coronary artery disease, peripheral artery disease and stroke, although the underlying mechanisms involved are not fully understood.

Lead is highly toxic to the proximal renal tubules, which can lead to a condition called Fanconi syndrome. This is a disorder where substances that would normally be absorbed into the bloodstream such as amino acids, phosphate and glucose are instead released into the urine.

The exact pathophysiologic mechanism of lead poisoning is not yet clear, but it is known that lead competes with other minerals in cellular systems, especially calcium and zinc. It therefore disrupts several cellular processes that depend on these minerals. Examples include:

1. In vitro, lead inhibits calcium uptake and disrupts mitochondrial function.
2. At the presynaptic nerve terminal, lead interferes with neurotransmitter functions that requires calcium.
3. Lead inhibits the calcium-dependent protein kinase C, which is essential to brain function
4. Two major enzymes involved in heme synthesis are inhibited by lead as it competes with zinc, possibly leading to a wide variety of effects on the different processes that depend on heme.

Lead poisoning has more damaging effects on children than it does on adults because children absorb five times more lead when exposed than adults do. The lead can also cause serious neurodevelopmental problems in children due its damaging effects on growing nerve cells and the developing brain. In children exposed to lead from birth onward, the level of lead in the blood peaks at around 18 to 24 months, which is a key period in terms of neurological development, when children are rapidly acquiring various different skills. Synapse formation between nerve cells (synaptogenesis) is also rapid during this period and some studies have indicated that inhibition of this process is one of the main pathological mechanisms that leads to nervous system injury in children.