clinical toxicology

2.  Leadisthecommon
estmetalinvolvedinchronicpoisoning.
Itwasoneofthefirstmetalsknowntom
a
n
andhasbeenwidelyusedduringthelasttwo
thousandyearsfordomestic,industrial,andtherapeuticpurposes.
 Leadisabundantinsoil,beingdistributedthroughouttheearth’scrust.

3.  ThemainuseofPbisintheproductionofstoragebatteriesandinsheathing
electriccables.
 Itisalsousefulasprotectiveshieldingfromx-raysandradiationfromnuclearreactors.
 Certainfolkmedicines(eg,theMexicanremediesandsomeIndianAyurvedic
preparations)maycontainhighamountsofleadsalts.

4.  Leadacetate(sugaroflead)hasbeenusedintherapeutics,
 leadcarbonate(whitelead)isstillusedinpaints,
 lead oxide (litharge) is essential for glazing of pottery and enamel ware, and
Tetraethylleadismixedwithpetrolasanantiknocktopreventdetonationininternal
combustionengines.
 A
m
on
g cosm
etics,leadtetro
xide is th
e m
ost com
m
oncom
poun
din“Sin
door”
an
dleadsulfidein“Surma”

5.  Candlewithlead-containingwicks
 Ayurvedicmedicines
 Paint
 Retainedbullets
 Ink
 Automobile storage battery casing;battery repairshops
 Ceramicglazes
 Leadpipes
 Silverjewelleryworkers
 Renovation/modernisationofoldhomes.

6.  Pbtoxicityaffects virtuallyallorgansandsystemsofthebody
 TheproposedmechanismofPbtoxicityinvolvesitsabilitytoinhibitormimictheactionofcations
suchascalcium,zinc,andiron,andtointerferewithvitalproteinsbybindingtosulfhydryl,amine,
phosphate,andcarboxylgroups.
 PbincreasesintracellularlevelsofCalciuminbraincapillaries,neurons,hepatocytes,andarteriesthat
triggersmoothmusclecontraction,therebyinducinghypertension

7.  Pbinterfereswithhemebiosynthesisbyinterferingwithferrochelatase,A
L
A
S
(aminolevulinicacidsynthetase),andA
L
A
D(aminolevulinicaciddehydrase).Therefore,
decreasedhemoglobinandanemiaresultsinindividualsexposedtoexcessivePb
 Leadincreaseshaemolysisasaresultofwhichimmatureredcellsarereleasedintocirculation
suchasreticulocytesandbasophilic stippledcells (theresultofaggregationof
ribonucleicacidduetoinhibitionoftheenzymepyrimidine-5-nucleotidasewhichnormally
eliminatesdegradedR
N
A
)

8.  Inthenervoussystem,PbsubstitutesforCaasasecondarymessengerinneurons,blocking
voltage-gatedCachannels,inhibitinginfluxofCaandsubsequentreleaseof
neurotransmitter.Theresultisaninhibitionofsynaptictransmission.
 Pbinhibitsglutamateuptakeandglutamatesynthetaseactivityinastroglia,thus
inhibitingtheregenerationofglutamate,amajorexcitatoryneurotransmitter
 Thisleadstodecreasednerveconduction,increasedpsychomotoractivity,lowerIQ,
andbehavioural/learningdisorders.

9.  Leadalsohasdeleteriouseffectso
ntheC
V
S(hypertensionandmyocarditis),kidney
(nephritis),andreproductiveorgans(infertility).
 Inaddition,leadcandecreaseuricacidrenalexcretion,therebyraisingblooduratelevels
andpredisposingtogout

10. Thisisnotreallyrelevanttoleadsinceacute
poisoningisveryrare.
Theaveragelethaldoseissaidtobe10gm/70kgformostleadsalts,whileitis100mg/kgfor
tetraethyllead.
 Todaytheacceptedupperlevelforbloodlead(BL)isfixedas35mcg/100ml.
 Howevertherearereportsthatadverseeffectsespeciallyo
nthehaematopoieticsystemcan
occuratlevelsaslowas10mcg/100ml.

11.  NeurobehaviouraldisordersinchildrencanoccuratB
L
aslowas25mcg/100ml.
 Hence,thecurrentlyevenlevelsaslowas10mcg/100m
lasunacceptable,
especiallyinchildren.

12. Absorption
Leadisabsorbedthroughallportalsofentry
 Occupationalexposureresultsmainlyfrominhalation,whileinmostothersituationsthem
o
d
eof
intakeisingestion.
 Tetraethylleadcanbeabsorbedrapidlythroughintactskin.
 About 5–15 of ingested lead is absorbed byadults with less than 5 retained.
 Children,however,absorbapproximately 5
0 of ingested lead and retainabout 3
0 .

13. Distribution
 lead is distributed amon
gthreecompartments:blood, softtissuesandthemineralizing
tissues(bonesandteeth).
 Leadis distributed to those areas of the skeleton which are growing mostrapidly.
 These include the radius,tibia, andfemur,which are the mostmetabolicallyactive
 itisstoredinthebonesasphosphateandcarbonate.

14.  Inchildrenabout70
tissues.
oftotalbodyleadisskeletal,whileinadultsover95
isin
osseous
 Significantamountsofskeletalleadarereleasedfromboneintothebloodstreamperiodicallyresulting
insymptomsoftoxicity.
 Theconditionsfavouringthisincludeacidosis,fevers,alcoholicintake,andevenexposureto
sunlight.
Elimination
 Excreted primarily in the urine (about 65 ) andbile (about 35 ).

15. Acute poisoning
 Thisisrare.Man
yreportedcasesofacutepoisoningmayactuallybeexacerbationsofchronic
leadpoisoningwhensignificantquantitiesofleadaresuddenlyreleasedintothebloodstream
frombone.
 Symptomsincludemetallictaste,abdominalpain,constipationordiarrhoea(stoolsmaybe
blackishduetoleadsulfide),vomiting,hyperactivityorlethargy,ataxia,behaviouralchanges,
convulsions,andcoma.

16. Chronic Poisoning
 Subacuteorchronicexposureismorec
o
m
m
o
n
thanacutepoisoning
 Constitutionaleffectsincludefatigue,malaise,irritability,anorexia,insomnia,weightloss,decreased
libido,arthralgias,andmyalgias.
 Hypertensionmaybeassociatedwithleadexposureinsusceptiblepopulations
 Gastrointestinaleffectsincludecrampyabdominalpain(leadcolic),nausea,constipation,or(less
commonly)diarrhea.

17.  Centralnervoussystemmanifestationsrangefromimpairedconcentration,headache,diminishedvisual-
motorcoordination,andtremortoovertencephalopathy(alife-threateningemergencycharacterizedby
agitateddeliriumorlethargy,ataxia,convulsions,andcoma).
 Chroniclow-levelexposureininfantsandchildrenmayleadtodecreasedintelligenceandimpaired
neurobehavioraldevelopment,stuntedgrowth,anddiminishedauditoryacuity
 Peripheralmotorneuropathy,affecting mainlytheupperextremities,cancausesevereextensormuscle
weakness(“wristdrop”)

18.  Hematologiceffectsincludenormochromicormicrocyticanemia,whichmaybe
accompaniedbybasophilicstippling.Hemolysismayoccur.
 Nephrotoxiceffectsincludereversibleacutetubulardysfunctionandchronic
interstitialfibrosis.Hyperuricemiaandgoutmayoccur.
 Adversereproductiveoutcomesmayincludediminishedoraberrantspermproduction,
increasedrateofmiscarriage,pretermdelivery,decreasedgestationalage,lowbirth
weight,andimpairedneurologicdevelopment.

19. MildToxicity(BL4
0to6
0
mcg/100ml):
ModerateToxicity(BL6
0to
100mcg/100ml):
SevereToxicity(BLmorethan100
mcg/100ml):
Myalgia
Paraesth
esia
Fatigue
Irritability
Abdominaldiscomfort
–Arthralgia(especially
nocturnal)
– Muscularexhaustibility
–Tremor
– Headache
– Diffuseabdominalpain
–Anorexia,metallictaste,
vomiting
– Constipation
–Weightloss
– Hypertension.
–Leadpalsy:wristdrop)orfootdrop.
–Abluishblackleadlineongums
(Burton’sline)
–Leadcolic:intermittentsevere
abdominalcramps.
–Leadencephalopathy:Itismore
c
o
m
m
o
n
inchildrenandisoften
associatedwithorganicleadtoxicity,
especiallytetraethylleadorTEL.

21.  T
E
L
ismorelipidsolubleandisdistributedwidelyinlipophilictissuessuchasthebrain
 T
E
L
ismetabolisedtotriethylleadwhichisthemajortoxicc
o
m
p
ou
n
dwhichleadstosudden
onsetofvomiting,irritability,headache,ataxia,vertigo,convulsions,psychotic
manifestations,coma,anddeath.
 Mortalityrateisaround25.Evenifrecoveryoccurs,thereisoftenpermanent brain
damage manifesting as mental retardation, cerebral palsy, optic neuropathy,
hyperkinesis,andperiodicconvulsions.

22.  F
E
P
andZ
n
p
levels(>50mcg/100ml)—AnelevatedF
E
P
levelindicatesimpairmentofthehaeme
biosyntheticpathwayandmayresultfromleadpoisoningorirondeficiency.
 Inordertoconfirmwhetheritisduetotheleadpoisoning,theB
L
mustbeestimated
 TodayZ
n
PlevelsaremorecommonlystudiedthanF
E
P
 Urinelevelsofaminolaevulinicacid(ALA)canalsoserveasasensitiveindicatorofleadpoisoning.
 Completebloodcountandperipheralsmear-includelowhaematocritandhaemoglobinvalues,peripheral
smearmayeitherbenormochromicorhypochromic,Basophilicstipplingandmicrocytic.
 Hypochromiaandbasophilicstipplingarestronglysuggestiveofleadintoxication

23.  Bloodleadlevelsreflectrecentexposureorexposureoveraperiodofupto3to5weeks.
 Inindividualswithhighorchronicpastexposure,B
Lusuallyunderrepresentsthetotalbodyburden
becausemostleadisstoredintheboneandmaybefoundatnormallevelsintheblood.
 Therecommendedmethodsofestimatingbloodleadlevel(BL)include
 Atomicabsorptionspectroscopy(AAS)
 Electrothermalatomicabsorptionspectroscopy(EAAS),
 Anodicstrippingvoltammetry(ASV)
 Inductivelycoupledplasmaatomicemissionspectroscopy(ICPAES)
 X-rayfluorescencespectroscopy.
 Fastneutronactivationanalysis(
F
N
A
A
)
 Massspectrometry(MS),andmicrowaveplasmadetection

24.  E
A
A
SandA
S
Varethemethodsofchoice.
 Inrecentyears,ICP-AEShasbecomethetechniqueofchoiceowingtosuperiorspecificityandsensitivity
U
R
I
N
E
 A
L
A
inurine
 Urineleadlevel:Ifthisisabove150mcg/litreitisasignificantfinding,butitis
unfortunatelynotveryreliable
 CalciumdisodiumE
D
T
Amobilisationtest:Thistestisdonemainlyinchildrentofindoutwhetherachild
whoseB
L
isbetween25and41mcg/100m
lwillrespondtochelationtherapywithabriskleaddiuresis..

25.  ChildrenwhoseB
L
ismorethan45mcg/100m
lshouldnotreceivethisprovocativetest.
 A
n8
hourC
a
N
a
2
E
D
T
Achelationprovocativetestisconsideredpositiveiftheleadexcretionratiois
morethan0.6(thoughsomecliniciansuseacut-offof0.5).
 Urineporphyrin
 X-Ray
 Radiography-leadlinesinlongandflatbones.

27.  Treat seizures and coma iftheyoccur.
 Provideadequatefluidstomaintainurineflow(optimally1–2mL/kg/h)butavoid
overhydration,whichmayaggravatecerebraledema
 Patientswithincreasedintracranialpressuremaybenefitfromcorticosteroids(eg,
dexamethasone,10m
g
IV)andmannitol(1–2g/kgIV).

28.  Treatmentwithchelatingagentsdecreasesbloodleadconcentrationsandincreasesurinarylead
excretion.
Severeacutepoisoningwithencephalopathy
 B
A
L
4mg/kgimmediately(inchildren)
 CaNa2E
D
T
A75mg/kg/dayIVinfusion
Severeacutepoisoningwithoutencephalopathy
 B
A
L
12mg/kg/day.
 E
D
T
A5
0mg/kg/day.
Moderate poisoning:
 E
D
T
A
5
0
mg/kg/day
Mild poisoning
 D-Penicillamine3
0mg/kg/day

29. Acute ingestion
 Administeractivatedcharcoal(althoughefficacyisunknown).
 Iflead-containingmaterialisstillvisibleo
nabdominalx-rayafterinitial treatment,
considerwhole-bowelirrigation.
 Considerendoscopicorsurgicalremovalofleadforeignbodiesthatexhibitprolonged
gastrointestinalretention

30.  There is no role for dialysis, hemoperfusion, or repeat-dose charcoal.