ZDRAVSTVENI UCINCI METALA

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ZDRAVSTVENI UCINCI METALA

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TEŠKI METALI IMAJU

• IZRAZITI AFINITET PREMA KISIKU I SUMPORU
• NA OVOJ SPOZNAJI POCIVA TOKSIKOLOGIJA TEŠKIH
  METALA

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OTROVANJE OLOVOM ? SATURNIZAM
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Toksicni teški metal

• kontaminant radnog i globalnog okoliša,
  posebice urbanih centara

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• Procjenjuje se da je opterecenje organizma naših
  suvremenika i do 1000x vece nego u naših
  predaka,
• iako ekspolatacija olovne rudace datira iz davne
  prošlosti ljudskog roda

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OLOVNI SJAJNIK ILI GALENIT (PbS)

• najcešca, ali toksikološki neinteresantna olovna
  rudaca, obzirom da je Pb vec vezan za S, pa je
  taj spoj NEOTROVAN

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OLOVNI KARBONAT ILI CERUSIT (PbCO3)

• OTROVAN,
• jer se u organizmu ion olova odvaja iz spoja i
  traži S

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In general, the older your home, the more likely
it has lead-based paint.  

• Paint.  Many homes built before 1978 have
  lead-based paint.  The federal government banned
  lead-based paint from housing in 1978.   
• In homes in the city, country, or suburbs. 
• Inside and outside of the house. 
• In soil around a home.
• Household dust. (Dust can pick up lead from
  deteriorating lead-based paint or from soil
  tracked into a home.)
• Drinking water. Your home might have plumbing
  with lead or lead solder. You cannot see, smell,
  or taste lead, and boiling your water will not
  get rid of lead.

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• The job. If you work with lead, you could bring
  it home on your hands or clothes. Old painted
  toys and furniture. 
• Food and liquids stored in lead crystal or
  lead-glazed pottery or porcelain. 
• Lead smelters or other industries that release
  lead into the air. 
• Hobbies that use lead, such as making pottery or
  stained glass, or refinishing furniture. 
• Folk remedies that contain lead, used to treat an
  upset stomach.

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Otrovni su OLOVNA PARA, DIM I PRAH

• Putevi unosa
• ? inhalacija ! (najvažniji put unosa u
  profesionalnoj toksikologiji)
• ? ingestija ! (put unosa važan u vicinalnoj
  toksikologiji)
• ? perkutano (unos zanemariv s oba aspekta)

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Inhalacija

• najopasniji put unosa ? Pb ulazi direktno
• u krv ?
• 95 ioniziranog Pb se veže na E te s tu
  prisutnim fosfatima stvara primarne, sekundarne i
  tercijarne spojeve, a 5 ostaje u plazmi i širi
  se po cijelom organizmu

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Najvažniji toksicni ucinak POREMECAJ SINTEZE
HEMOGLOBINA.
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Notes                                         
                                                  
                                                 
 
The mitochondria of the developing red cell are
responsible for the synthesis of protoporphyrin
which then combines with iron to form heme. This
is a stepwise process which begins with the
formation of delta aminolevulinic acid from
glycine and succinyl COA. The phosphorylated form
of pyridoxine, pyridoxal-5-phosphate, is an
essential cofactor in this reaction. The
subsequent sequence of porphobilinogen,
uroporphyrin, and coproporphyrin formation occurs
in the cytoplasm, after which there is an
intramitochondrial assembly of protoporphyrin and
iron to form heme. A schematic of the final
product, a protoporphyrin ring structure with its
central iron molecule is shown.
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Laboratorijska dg. saturnizma

• 1. odredivanje plumbemije
• The standard elevated blood lead level (BLL) for
  adults' is (25 µg/dl) This level recognizes that
  every adult has accumulated some lead
  contamination.
• The level for a child is much lower, currently it
  is (10 µg/dl)
• a worker's blood lead level (BLL, be maintained
  at or below forty (40 µg/dl)

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2.NESPECIFICNI TESTOVI, ALI OD VELIKOG PRAKTICNOG
ZNACAJA

• odredivanje d-DALK-a ZPP, EPP (eritrocitni
  protoporfirin), FPP (slobodni protoporfirin)
• Normalna aktivnost ako je d-DALK 15?mol/L i više
• Normala za EP 2,67 ?mol/L

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3.POTPUNO NESPECIFICNI SCREENING-TESTOVI

• E, retikulociti, Fe, bazofilni punktati

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Ingestija

• posude s olovnom glazurom u kom je kiseli sadržaj
  (vino, ukiseljeno povrce i sl.) ? kiselina otopi
  olovnu glazuru i nastaje olovna sol odnosne
  organske kiseline (tartarat, citrat, acetat) ?
  kod konzumenta se razvija slika trovanja

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Klinicka slika saturnizma

• 1. Gastrointestinalni oblik
• 2. Neuromuskularni oblik
• 3. Encefalopaticki oblik
• 4. Mješoviti oblik

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Najjopasniji organski spoj olova ?

• tetraetil-olovo lakohlapljiva tekucina, nakon
  inhalacije olovna encefalopatija, moguc letalni
  ishod

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? Djeca su posebno osjetljiva na olovo

• U novorodencadi i male djece apsorpcija Pb iz GI
  trakta je znacajno veca nego u odraslih, tako da
  raste važnost peroralnog puta unosa

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FETOTOKSICNOST Pb

• Dobro prolazi transplacentarnu barijeru,
• a prisutan je i u majcinom mlijeku

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• BLLs of workers (both male and female workers)
  who intend to have children should be maintained
  below 30 µg/dl to minimize lead poisoning of the
  parents and their future children.

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Teratogeni ucinci

• spontani pobacaji,
• prijevremeni porodaji,
• kongenitalne anomalije

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• Do druge godine života djeca profesionalno
  izloženih roditelja pokazuju na testovima
  inteligencije izrazito slabije rezultate od
  svojih vršnjaka,
• ali se kasnije te razlike gube
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Th. saturnizma

• kelatni spojevi
• najcešce CaNa2EDTA

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OTROVANJE ŽIVOM ? MERKURIJALIZAM
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What are sources of exposure to elemental mercury?

• Sources of elemental mercury include broken
  mercury thermometers, broken fluorescent light
  bulbs, dental amalgam fillings, mercury
  containing latex paints, extraction of gold from
  ore using mercury, and contaminated clothing from
  workers in thermometer making plants. Elemental
  mercury is also used as a Mexican folk medicine
  to treat "empacho," a chronic stomach disorder.

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S toksikološkog aspekta treba razlikovati

• 1. elementarnu Hg (ne može stvarati kemijske
  veze!!)
• 2. anorganske Hg-spojeve (toksicnost se osniva na
  stvaranju merkuri-iona)
• 3. organske Hg-spojeve (toksicnost potenciraju
  alkilni radikali)

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• "You wouldnt take a leaky thermometer, put it in
  your mouth, and leave it there 24 hours a day,
  365 days a year. Yet thats exactly what happens
  when an amalgam filling is installed in your
  mouth."----Dr Michael Ziff.

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Toxicity of ThimerosalAn Organic Mercurial Added
To Vaccines

• Is this any place to put a toxic organic mercury
  compound?

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Paul J. Dunn, MD,

• "On average, Chicago rainwater had mercury levels
  12 times higher than that human standard."
• Amalgam is 50 mercury. With chewing, mercury
  vapor is released and readily absorbed.

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Paul J. Dunn, MD,

• Incidentally, anyone who still has amalgam
  fillings in their mouth should not use the
  supplement lipoic acid because it mobilizes
  mercury into other parts of the body.
• In my own practice I have had several patients
  who had no amalgam fillings in their mouth but
  their hair mineral analyses showed high levels of
  mercury. . . . In each instance, fish had been
  frequently consumed over a long period.

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Putevi unosa

• ? inhalacija Hg para i prašine (NAJVAŽNIJI PUT
  UNOSA U PROFESIONALNOJ TOKSIKOLOGIJI !)
• ? perkutano (metil-Hg spojevi i kroz intaktnu!!!)
• ? ingestija (predominantno konzumacija ribe)
• ? transplacentarno (organski Hg spojevi)

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A)PROFESIONALNA TROVANJA ANORGANSKIM HG-SPOJEVIMA

• 2 kardinalna sindroma
• 1. orofaringealni sy (hipersalivacija,
  gingivitis, ispadanje zubi)
• 2. neuropsihicki u 3 moguca oblika
• ? astenicko-vegetativni oblik ili
  mikromerkurijalizam(nespecificni simptomi)
• ? živin tremor
• ? živin eretizam

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Pulmonalne toksicne manifestacije

• akutna intersticijska pneumonija,
• bronhitis,
• bronhiolitis

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Nefrotoksicne manifestacije

• proteinurija,
• nefrotski sindrom
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B) TROVANJA ORGANSKIM HG-SPOJEVIMA

• organski spojevi žive uspijevaju svojim manjim
  dijelom prijeci cerebralnu barijeru, ali se potom
  jednoliko rasporeduju i akumuliraju u mozgu ?
  loša prognoza

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Koža

• fenilni i metoksi-etilni spojevi!)
• dermatitis, u fulminantnim oblicima sa
  nekroticnim lezijama

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Bubreg, orofarinks- kao kod anorganske Hg

• respiratorni trakt - iritacija dišnih puteva,
  toksicni edem pluca

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• jetra - nakon latencije od nekoliko sati moguca
  akutna žuta distrofija jetre

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POZNATI EKOLOŠKI AKCIDENTI VEZANI UZ TROVANJE
ŽIVOM

• ? zaljev Minamata, Japan, 1953.g.
• ? trudnice konzumirale ribu otrovanu metil-Hg,
  koja je "iscurila" iz tamošnjeg pogona
  ?uslijedila epidemicka pojava mentalne
  retardacije, cerebralne paralize i zastoja u
  rastu i razvoju njihove novorodencadi
•  

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? Irak , 1971./72.

• ? masovno trovanje Hg-om nakon konzumacije kruha,
  pri cemu su elementarne žitarice bile tretirane
  fungicidom s metil-Hg ? ozbiljni centralni i
  periferni neurološki poremecaji kod potomaka
  otrovanih majki, gubitak sluha i vida

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ŽIVA KAO REPRODUKCIJSKI TOKSIN

• u ruralnih populacija, koje koriste metil-Hg kao
  pesticid, fertilitetna stopa znacajno smanjena,
  što se pripisuje subfertilitetu/infertilitetu oba
  izložena partnera

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• ?U žena stomatoloških struka, koje profesionalno
  rade sa Hg? povecana incidencija reprodukcijskih
  poremecaja

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• ?Znacajno veca ucestalost spontanih pobacaja u
  žena ciji su partneri profesionalno izloženi Hg-u
  ? linearna korelacija sa prekoncepcijskom konc.Hg
  u urinu izloženih muškaraca
• ? halogenirani spojevi Hg dokazano smanjuju
  motilitet spermija i uzrokuju morfološke
  abnormalnosti spermija ? po prekidu ekspozicije
  motilitet se izgleda normalizira, ali morfologija
  NE!

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• LAB. DG. MERKURIJALIZMA
• ?Hg u urinu 
• ? u uzorcima vlasišta

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TH. MERKURIJALIZMA

• ?Prije transporta i hospitalizacije obavezna
  dekontaminacija.  
• ?Prva pomoc kisik, mirovanje, kod ingestionih
  otrovanja izazivanje povracanja
• ?Obzirom na visoku toksicnost obavezna i zaštita
  spasioca, SVE OTROVANE ILI IZLOŽENE PREVESTI U
  BOLNICKU USTANOVU!

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• ?Lijecenje simptomatsko i suportivno, nema
  specificnog antidota !!!
• ? Kod vrlo teških otrovanja može se pokušati
  kelatna th. (Dimerkaprol ? di-merkapto-propanol ?
  BAL) i.m. svakih 6 sati opetovano 4-6 puta, ali
  nema stvarnog dokaza djelotvornosti

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Sve najbolje!!!
VAŠA PROFA