Blood changes areoneoftheearliestsignsofleadaccumulationandarecharacteristic,consistingofamicrocytic,hypo-chromicanemiaassociatedwithadistinctivepunctatebasophilic stippling ofredcells.Thesechangesinthebloodstemfromtheinhibitionofhemesynthesisinmarrowerythroidprogenitors.Anotherconsequenceofthisblockadeisthatzinc-protoporphyrinisformedinsteadofheme.Thus,elevatedbloodlevelsofzincprotoporphyrinoritsproduct,freeredcellprotoporphyrin,areimportantindicatorsofleadpoisoning.
Brain damage ispronetooccurinchildren.Theanatomicchangesunderlyingthemoresubtlefunctionaldeficitsareilldefined;atthemoresevereendofthespectrum,changesincludebrainedema,demyelinationofthecerebralandcerebellarwhitematter,andnecrosisofcorticalneuronsaccompaniedbydiffuseastrocyticproliferation.Inadults,theCNSisless-oftenaffected,butfrequentlyaperipheral demyelinating neuropathy appears,typicallyinvolvingmotorneuronsinnervatingthemostcommonlyusedmuscles.Thus,theextensormusclesofthewristandfingersareoftenthefirsttobeaffected,followedbyparalysisoftheperonealmuscles(wristdrop andfootdrop).
TheGI tract alsoisasiteofmajorclinicalmanifestations.Lead“colic”ischaracterizedbyextremelysevere,poorlylocalizedabdominalpain.
Thekidneys maydevelopproximaltubulardamagewithintranuclearleadinclusions.Chronicrenaldamageleadseventuallytointerstitialfibrosisandpossiblyrenalfailureandfindingssuggestiveofgout(“saturninegout”).Otherfeaturesofleadpoisoningareshownin
Fig.8.4
Mercury, like lead, binds to sulfhydryl groups in certain proteins with high affinity, leading to damage in the CNS and several other organs such as the GI tract and the kidneys. Humans have used mercury in many ways throughout history, including as a pigment in cave paintings, a cosmetic, a remedy for syphilis, and a component of diuretics. Poisoning from inhalation of mercury vapors has long been recognized and is associated with tremor, gingivitis, and bizarre behavior, such as that of the “Mad Hatter” in Lewis Carroll’s Alice in Wonderland (mercury formerly was used in hat-making).
Today, the main sources of exposure to mercury are contaminated fish and dental amalgams, which release mercury vapors. In some areas of the world, mercury used in gold mining has contaminated rivers and streams. Inorganic mercury from the natural degassing of the earth’s crust or from industrial contamination is converted to organic compounds such as methyl mercury by bacteria. Methyl mercury enters the food chain, and in carnivorous fish such as swordfish, shark, and bluefish, mercury levels may be 1 million times higher than in the surrounding water. Almost 90% of the ingested mercury is absorbed in the GI tract. The consumption of contaminated fish from the release of methyl mercury in Minamata Bay and the Agano River in Japan, and the consumption of bread containing grain treated with a methyl mercury–based fungicide in Iraq, caused widespread morbidity and many deaths.
The medical disorders associated with the Minamata episode became known as “Minamata disease” and include cerebral palsy, deafness, blindness, and major CNS defects in children exposed in utero. The developing brain is extremely sensitive to methyl mercury; for this reason, the CDC in the United States has recommended that pregnant women avoid the consumption of fish known to contain mercury.