Post on 12-Jan-2016
Iron and Metals Iron and Metals & Metalloids& Metalloids
Chapters 179 & 184Chapters 179 & 184
Arthur Amin OlyaiArthur Amin Olyai
Iron Physiology and Iron Physiology and PharmacologyPharmacology
Approx. 30 000 calls to Poison center Approx. 30 000 calls to Poison center yearlyyearly
Usually involves young children < 6 Usually involves young children < 6 y/oy/o
Risk of death without aggressive Risk of death without aggressive measuresmeasures
Less toxicity form overdose today Less toxicity form overdose today because of recent changes in iron because of recent changes in iron formulation and dispensing practices formulation and dispensing practices
Iron Physiology and Iron Physiology and pharmacologypharmacology
Average male 4 g storageAverage male 4 g storage Body stores iron in hemoglobin (2/3), Body stores iron in hemoglobin (2/3),
myoglobin, cytochromes, other myoglobin, cytochromes, other enzymes/cofactors and ferritin.enzymes/cofactors and ferritin.
Excess Iron is toxicExcess Iron is toxic body protects body protects itself by serum protein binding, reg. itself by serum protein binding, reg. of GI absorption, and intracellular of GI absorption, and intracellular storagestorage
Iron Physiology and Iron Physiology and pharmacologypharmacology
Fe2+ is better absorbed then Fe 3+(most Fe2+ is better absorbed then Fe 3+(most dietarydietary Broken down via ferri- Broken down via ferri-reductacse)reductacse)
Fe2+ transporter into enterocyte via Fe2+ transporter into enterocyte via DMT1DMT1
converted to ferritin converted to ferritin If Iron needed moved out of enterocyte as If Iron needed moved out of enterocyte as
transferrintransferrin Body is also available to slough intestinal Body is also available to slough intestinal
cells containing iron if neededcells containing iron if needed
Iron Physiology and Iron Physiology and PharmacologyPharmacology
Usu no free iron exists in bodyUsu no free iron exists in body Transferrin regulates how much iron Transferrin regulates how much iron
is transported from ferritin , GI tract is transported from ferritin , GI tract to liver and spleen for processingto liver and spleen for processing
Transferrin can bind up to 4500 iron Transferrin can bind up to 4500 iron moleculesmolecules
TIBC TIBC mostly amount of transferrin mostly amount of transferrin
Iron Physiology and Iron Physiology and PharmacologyPharmacology
Iron is potent catalyst for oxidants/free Iron is potent catalyst for oxidants/free radicalsradicalsorgan damage membrane lipid organ damage membrane lipid peroxidationperoxidation
Iron is GI irritantIron is GI irritant diarrhea,vomiting,abd diarrhea,vomiting,abd pain, mucosal ulceration, bleedingpain, mucosal ulceration, bleeding
Excess free iron enters mitochondriaExcess free iron enters mitochondriainhib. inhib. Oxydative phosphorilationOxydative phosphorilation metabolic metabolic (lactic ) acidosis(lactic ) acidosis
Results: Coagulopathy, hepatotox., Results: Coagulopathy, hepatotox., myocardial and vascul. dysfunction, myocardial and vascul. dysfunction, encephalopathyencephalopathy
FerrochelFerrochel
Iron Toxic DoseIron Toxic Dose
Elemental iron amount ingested is Elemental iron amount ingested is keykey usu prep. contain 12-33% usu prep. contain 12-33%
FeSo4(20%) vs ped. MVI (10-18%)FeSo4(20%) vs ped. MVI (10-18%) Tox effect >10-20 mg/kgTox effect >10-20 mg/kg Mod Tox. 20-60 mg/kgMod Tox. 20-60 mg/kg Severe over 60mg/kgSevere over 60mg/kg
Iron Laboratory Iron Laboratory AssessmentAssessment
Be careful about using iron levels to Be careful about using iron levels to direct managementdirect management Deferox on board?Deferox on board? What iron prep was ingested?What iron prep was ingested?
300-500microgr.300-500microgr. signif. GI tox. signif. GI tox. 500-1000microgr.500-1000microgr.mod sytemic mod sytemic
toxicitytoxicity > 1000microgr.> 1000microgr. signif. morbidity signif. morbidity
Iron Laboratory Iron Laboratory AssessmentAssessment
Some studies suggest WBC count > Some studies suggest WBC count > 15 000 and glucose level > 150 may 15 000 and glucose level > 150 may indicate iron tox. (controversial)indicate iron tox. (controversial)
TIBC little valueTIBC little value Xray may show tabletsXray may show tablets GI GI
decontaminationdecontamination
Clinical FeaturesClinical Features Clinically local toxicity vs systemis tox.Clinically local toxicity vs systemis tox. Traditionally five stages seenTraditionally five stages seen
Stage 1 <6 hoursStage 1 <6 hours Gi symptoms usu within 6 hoursGi symptoms usu within 6 hours Vomiting a/w acute iron intox.Vomiting a/w acute iron intox.
Stage 2 6-12 hoursStage 2 6-12 hours Latent stage – symptoms may resolveLatent stage – symptoms may resolve false false
reassurancereassurance Volume loss/ worsening met acidosisVolume loss/ worsening met acidosis
Stage 3 first 24 hStage 3 first 24 h Intracell disruption of metabolismIntracell disruption of metabolism shock and lactic shock and lactic
acidosisacidosis Iron induced coagulopathy (possibly Iron induced coagulopathy (possibly
biphasic)biphasic)bleeding + hypovolemiableeding + hypovolemia Stage 4 2-5 daysStage 4 2-5 days
Hepatic stage of iron poisoningHepatic stage of iron poisoning Stage 5 4-6 weeks Stage 5 4-6 weeks
Delayed sequelaeDelayed sequelae Gi Obstruction Gi Obstruction
Iron TreatmentIron Treatment Pt no or minimal symptoms/normal Pt no or minimal symptoms/normal
vitalsvitals stabilize ABC observe 6h stabilize ABC observe 6h GI decontamination/Chelation via GI decontamination/Chelation via
DeferoxamineDeferoxamine Dialysis not effectiveDialysis not effective Antiemetics may be usedAntiemetics may be used If hypotensiveIf hypotensivesymptomatically symptomatically
supportsupport If coagul.If coagul.Vit K/FFPVit K/FFP Consider CBC CMP LFT Type and crossConsider CBC CMP LFT Type and cross ABG not necessary in mild casesABG not necessary in mild cases
GI DecontaminationGI Decontamination Ipecac –not usedIpecac –not used Active Charcoal does not absorb ironActive Charcoal does not absorb iron Orogastric lavage Orogastric lavage
if ingestion within 60 minif ingestion within 60 min More useful smaller pillsMore useful smaller pills Pills on xray may suggest progressive Pills on xray may suggest progressive
tox.tox. Whole bowel irrigation-polyethylene Whole bowel irrigation-polyethylene
glycol solution via NGglycol solution via NG 250-500 ml/h in children250-500 ml/h in children 2 liters in adults2 liters in adults
DeferoxamineDeferoxamine Chelating agent dicovered in 1960sChelating agent dicovered in 1960s Streptomyces pilosusStreptomyces pilosus Removes critical amount of iron-Removes critical amount of iron-
preferantially free iron to restore proper preferantially free iron to restore proper cell. functioncell. function
Dose:Dose: IM IM
90mg/kg max 1 gr in children and 2 gr adults90mg/kg max 1 gr in children and 2 gr adults Repeat 4-6 hRepeat 4-6 h Volume factor Volume factor
If Dehydrated/hypotensive IV If Dehydrated/hypotensive IV Second IV line recommendedSecond IV line recommended 5-15mg/kg/h max 6-8gr daily5-15mg/kg/h max 6-8gr daily A/w mucormycosis, RI, pulm.tox.,Yersinia A/w mucormycosis, RI, pulm.tox.,Yersinia
enterocoliticaenterocolitica
Determination of Determination of Efficacy and Duration Efficacy and Duration
of Txof Tx Controversail- Clinical DxControversail- Clinical Dx Multiple urine samples before Multiple urine samples before
and after txand after tx Vin –rose color changeVin –rose color change Deferoxamine challenge test-Deferoxamine challenge test-
controversialcontroversial
Metal & MetalloidsMetal & Metalloids
Usu not acute toxicityUsu not acute toxicity A/w signif. Morbidity&mortalityA/w signif. Morbidity&mortality 4 sytems usu affected 4 sytems usu affected
Neuro (consider TCA overdose in Neuro (consider TCA overdose in approp. setting)approp. setting)
GIGI HematologicHematologic RenalRenal
The importance of index caseThe importance of index case
Lead EpidemiologyLead Epidemiology M/c chronic metal poisoningM/c chronic metal poisoning Environmental contaminantEnvironmental contaminant Inc. levels in 1 to 5 y/o a/wInc. levels in 1 to 5 y/o a/w
Urban dwelling, built before Urban dwelling, built before 1974,poverty, nonhisp. Black race, high 1974,poverty, nonhisp. Black race, high pop densitypop density
Less lead tox in community 2nd to Less lead tox in community 2nd to bans on household/industrial bans on household/industrial productsproducts
Inorganic lead (multisys) vs organic Inorganic lead (multisys) vs organic lead (CNS predominate)lead (CNS predominate)
Inorganic Lead Inorganic Lead Absorption by Resp./Gi tract Absorption by Resp./Gi tract
occasionally if bullet in contact with occasionally if bullet in contact with body fluid (esp.consider release at body fluid (esp.consider release at injury siteinjury site
Deficiencies of Ca2+,Iron, Cu, Zinc Deficiencies of Ca2+,Iron, Cu, Zinc predispose to Inc. Absorption of Leadpredispose to Inc. Absorption of Lead
90% stored in bone but also in soft 90% stored in bone but also in soft tissue and bloodtissue and blood
Can cross placenta/ consider inc. bone Can cross placenta/ consider inc. bone turn over in pregnancyturn over in pregnancy
Half life is 30 yearsHalf life is 30 years
PathophysiologyPathophysiology CNS (Younger more susceptible)CNS (Younger more susceptible)
Progressive astroctye injuryProgressive astroctye injuryBBB disruption cerebral BBB disruption cerebral edema/seizuresedema/seizures
Decr. CamP/protein phoph.Decr. CamP/protein phoph.decr. memory an learning decr. memory an learning Altered Ca metabo.Altered Ca metabo. altered neurotransmitter release altered neurotransmitter release
PNSPNS Primary segm/ 2ndary axonal degen.Primary segm/ 2ndary axonal degen. Motor nerves m/c involvedMotor nerves m/c involved
Hematopoietic ( basophilic stippling)Hematopoietic ( basophilic stippling) Porphyrin metab./lead induced anemiaPorphyrin metab./lead induced anemia Exacerbated by Iron defic. Exacerbated by Iron defic. Inhibition of RBC nucleotidases (degrad. cell. product)Inhibition of RBC nucleotidases (degrad. cell. product)
KidneyKidney Fanconi syndromeFanconi syndrome partial F. if chronic if longer then 13 partial F. if chronic if longer then 13
yearsyears Aminoaciduria,Glycosuria,Phosphaturia,RTAAminoaciduria,Glycosuria,Phosphaturia,RTA
LiverLiver Tox hepatitis, mild inc LFTs,Tox hepatitis, mild inc LFTs, Depr. reproduc. sys.-low sperm count and func., PMR, clinical Depr. reproduc. sys.-low sperm count and func., PMR, clinical
hypothyroidismhypothyroidism In Infants colicky abdominal painIn Infants colicky abdominal pain
DiagnosisDiagnosis History of exposure/hobby/environmental History of exposure/hobby/environmental
most imp. clue.:most imp. clue.: Pt may complain of metallic tastePt may complain of metallic taste On PE bluish gray gingival lead linesOn PE bluish gray gingival lead lines Arthralgias, Generalized Arthralgias, Generalized
weakness/weightloss/Delayed cognitive weakness/weightloss/Delayed cognitive development (PbB>10microg/dL)development (PbB>10microg/dL)
Mimics many other cond. thalassemia, other toxins, Mimics many other cond. thalassemia, other toxins, sickle cell etc.sickle cell etc.
Comb. Abdominal & Neuro dysfunc & Anemia Comb. Abdominal & Neuro dysfunc & Anemia should raise suspicionshould raise suspicion
CaNa2+-EDTA prov. test not used anymoreCaNa2+-EDTA prov. test not used anymore Labs: Labs:
Xray-lead bandsXray-lead bandsfailure bone remodelingfailure bone remodeling Anemia (normo or micro) and basophilic stippling Anemia (normo or micro) and basophilic stippling
(nonspecific), Inc retic count, Inc serum free (nonspecific), Inc retic count, Inc serum free hemoglobinhemoglobin
Inc. PbB levelsInc. PbB levels
Tx Inorganic LeadTx Inorganic Lead Standard life support measuresStandard life support measures SeizuresSeizuresBZN, Phenobarb., Gen BZN, Phenobarb., Gen
anaesthesia anaesthesia Whole Bowel Irrig.(Polyethylene Whole Bowel Irrig.(Polyethylene
glycol)glycol) if Xray ind. lead flecks etc.if Xray ind. lead flecks etc.tx until cleartx until clear 500-2000ml/h po adult vs 100-500ml/h 500-2000ml/h po adult vs 100-500ml/h
po childrenpo children If fishing sinkersIf fishing sinkerssx consultsx consult IV FluidsIV Fluids avoid cerebral edema avoid cerebral edema Lumbar puncLumbar punccareful, may ppc careful, may ppc
herniationherniation
ChelationChelation
If encephalopthy or sympt. with If encephalopthy or sympt. with PbB level elevated (>100 adult/>70 PbB level elevated (>100 adult/>70 children) children) BAL & CaNa2+-EDTA tx immediatelyBAL & CaNa2+-EDTA tx immediately
If mild sympt. or asympt.(PbB 70-If mild sympt. or asympt.(PbB 70-100 adults/45-69 children)100 adults/45-69 children) DMSADMSA
Asymptomatic (PbB less then 70 Asymptomatic (PbB less then 70 adult/45 children)adult/45 children) Tx not indictaed/remove sourceTx not indictaed/remove source
ChelationChelation M/C chelation agents usedM/C chelation agents used
BALBAL DMSA with or without CaNa2+-EDTADMSA with or without CaNa2+-EDTA Po administration-allows GI absorptionPo administration-allows GI absorption High costHigh cost Bind lead via sulfhydryl groupsBind lead via sulfhydryl groups No signif. Side effects/ minimal essential Vitamin No signif. Side effects/ minimal essential Vitamin
absortionabsortion D-penicillamine- less effective, less expensiveD-penicillamine- less effective, less expensive If EncephalopathicIf Encephalopathic 85% suffer some permanent CNS 85% suffer some permanent CNS
symptomssymptoms If Nephropathy If Nephropathy usu partially reversibleusu partially reversible GI symptoms GI symptoms usu resolve over 1-16 weeksusu resolve over 1-16 weeks DispositionDisposition
Remove source otherwise admitRemove source otherwise admit Admit Children over or equal to 70microg/dLAdmit Children over or equal to 70microg/dL Admit adults with CNS symptomsAdmit adults with CNS symptoms
Organic LeadOrganic Lead A/w Tetraethyl leadA/w Tetraethyl lead found in leaded found in leaded
gasgas Usu CNS effectsUsu CNS effects
Ranges from irritability,insomnia, Ranges from irritability,insomnia, restlessness,n,v,tremors, chorea, restlessness,n,v,tremors, chorea, convulsions, maniaconvulsions, mania persistent organic persistent organic psychosis,dementiapsychosis,dementia
Heptic, Muscle and renal damage can occurHeptic, Muscle and renal damage can occur Anemia usu not presentAnemia usu not present Blood levels may be normalBlood levels may be normal Tx remove source, symptomatic tx, and Tx remove source, symptomatic tx, and
chelate if PbB levels elevated onlychelate if PbB levels elevated only A/w gasoline sniffingA/w gasoline sniffing
ArsenicArsenic Tasteless & odorlessTasteless & odorless M/c acute metal poisoningM/c acute metal poisoning 22ndnd leading cause of chronic metal leading cause of chronic metal
tox.tox. Elemental, inorganic and organic Elemental, inorganic and organic
salts, and gaseous formssalts, and gaseous forms Found in many compound Found in many compound
/industry/industry Often tools for homo or suicideOften tools for homo or suicide
PharmocologyPharmocology Absortion:Absortion:
GI, respiratory, skin, or parenteral routeGI, respiratory, skin, or parenteral route Arsenate (As 5+)easier absorbed Arsenate (As 5+)easier absorbed
GI/mucous membranesGI/mucous membranes Arsenite (As3+)easier absorbed Arsenite (As3+)easier absorbed
skin/lipophilicskin/lipophilic Binding serum proteins/erythro&leukocytesBinding serum proteins/erythro&leukocytes 24h redistr. Liver,kidney,spleen, 24h redistr. Liver,kidney,spleen,
lung,Gi,muscles nervous syslung,Gi,muscles nervous syshair nails & hair nails & bonesbones
ExcretionExcretion Renal/ rate determines toxicity/arsenate more Renal/ rate determines toxicity/arsenate more
toxic due to slower excretedtoxic due to slower excreted Arsenic crosses placenta Arsenic crosses placenta TeratogenicTeratogenic
Pathophysiology of Pathophysiology of ArsenicArsenic
Binds reversibly to tissues and Binds reversibly to tissues and enzyme systems via sulfhydryl enzyme systems via sulfhydryl groups groups
Small blood vessels dilated and Small blood vessels dilated and become more permeablebecome more permeable
Inflammation & necrosis of GI tractInflammation & necrosis of GI tract Cerebral edema and hemorrhageCerebral edema and hemorrhage Myocardial tissue destructionMyocardial tissue destruction Fatty degen. Of liver & spleenFatty degen. Of liver & spleen Peripheral axonal degener./2ary Peripheral axonal degener./2ary
demylinationdemylination
Acute toxicityAcute toxicity Symptoms usu occur within 30 minSymptoms usu occur within 30 min Hallmark: gastroenteritis with Hallmark: gastroenteritis with
severe nausea, vomiting, & cholera –severe nausea, vomiting, & cholera –like diarrhealike diarrhea
Metallic taste in mouthMetallic taste in mouth Hypotension & tachycardiaHypotension & tachycardia ECG nonspecific ST-segand T-wave ECG nonspecific ST-segand T-wave
changes, prolonged QTchanges, prolonged QT Vtach with torsades de pointesVtach with torsades de pointes Acute encephalopathy, ARF, Acute encephalopathy, ARF,
rhabdomyolysis and deathrhabdomyolysis and death
Chronic ToxicityChronic Toxicity Peripheral neuropathy (mostly sensory)Peripheral neuropathy (mostly sensory)stocking-stocking-
glove distributionglove distribution Ascending paralysisAscending paralysis Skin rash (mobilliform)Skin rash (mobilliform) Nonspecific malaise and weaknessNonspecific malaise and weakness Hyperpigmentation, hyperkeratosis of palms and Hyperpigmentation, hyperkeratosis of palms and
solessoles H/o gastroenteritis 1-6 weeks earlierH/o gastroenteritis 1-6 weeks earlier Mees lines-nailsMees lines-nails Nasal septum perforationNasal septum perforation Nonspecific syptomsNonspecific syptoms
Weakness, muscle aches,abd pain,memory Weakness, muscle aches,abd pain,memory loss,personality changes, periorbital&extremity loss,personality changes, periorbital&extremity edema, decreased hearingedema, decreased hearing
CNS syptoms-delerium, CNS syptoms-delerium, hallucinations,disorientation/confabulationhallucinations,disorientation/confabulation
Ca- squamous cell & basal skin Ca, resp. tract Ca- squamous cell & basal skin Ca, resp. tract Ca,hepatic angiosarcoma, and leukemiaCa,hepatic angiosarcoma, and leukemia
DxDx Acute arsenic poisoning suspect if Acute arsenic poisoning suspect if
hypotesnion & preceded severe gastroenteritishypotesnion & preceded severe gastroenteritis Abd xray_radiopaque flecksAbd xray_radiopaque flecks Lab:Lab:
Normocytic,normochromic, or megaloblastic Normocytic,normochromic, or megaloblastic anemiaanemia
ThrombocytopeniaThrombocytopenia WBC count up in acute and down in chronic tox.WBC count up in acute and down in chronic tox. Eosionphilia up to 21%Eosionphilia up to 21% Basophilic stippling of RBCsBasophilic stippling of RBCs Elevated retic countElevated retic count
ECG prolonged QTECG prolonged QT 24h urine arsenic levels-measure after 5 days 24h urine arsenic levels-measure after 5 days
of seafood free diet (normal is less then of seafood free diet (normal is less then 0.05mg/L)0.05mg/L)
Hair and nail testingHair and nail testing
Differential DxDifferential Dx Septis shockSeptis shock EncephalopathyEncephalopathy Peripheral neuropathy/Guillain-BarrePeripheral neuropathy/Guillain-Barre Addison dzAddison dz Hypo/hyperthyroidismHypo/hyperthyroidism Korsakoff syndr.Korsakoff syndr. Gastroenteritis/cholera like diarrheaGastroenteritis/cholera like diarrhea PorphyriaPorphyria Other metal tox. thallium & mercuryOther metal tox. thallium & mercury
TreatmentTreatment Ensure resp.& Circulatory funcEnsure resp.& Circulatory func
Hemodyn. MonitoringHemodyn. Monitoring Usu 2ndary to hypovolemia (usu Usu 2ndary to hypovolemia (usu
crystalloids/pressors as needed)crystalloids/pressors as needed) Avoid overhydrationAvoid overhydration Vtach-tx with lido, amiodarone, & defibrillationVtach-tx with lido, amiodarone, & defibrillation Avoid drugs prolong QTAvoid drugs prolong QT Replace Mg,K,CaReplace Mg,K,Ca
Gastrointestinal lavage and activated charcoalGastrointestinal lavage and activated charcoal Chelation therapy Chelation therapy
BAL –admin immediate/ tx may exceed 19 day txBAL –admin immediate/ tx may exceed 19 day tx DMSA less toxic/ may be substituted or for chronicDMSA less toxic/ may be substituted or for chronic D-penicillamine not useful in arsenic toxD-penicillamine not useful in arsenic tox 24 urine arsebic level to guide for further tx24 urine arsebic level to guide for further tx
Tx seizures with BZN phenobarb. or gen anesthesiaTx seizures with BZN phenobarb. or gen anesthesia Consider homocide/suicideConsider homocide/suicide Hemodialysis- rarely used only in ARF can remove Hemodialysis- rarely used only in ARF can remove
small amountssmall amounts
DispositionDisposition
Admit if acute or life threatening Admit if acute or life threatening known or suspected arsenic known or suspected arsenic poisoningpoisoning
All chronically poisoned pt requiring All chronically poisoned pt requiring BALBAL
Suicidal or homocidal ideationSuicidal or homocidal ideation
ArsineArsine Colorless, nonirritating gasColorless, nonirritating gas Found in semiconductor industry, ore Found in semiconductor industry, ore
smelting, refinery, or arsenic containing smelting, refinery, or arsenic containing insecticidesinsecticides
Attaches to hemoglobin via sulfhydryl Attaches to hemoglobin via sulfhydryl groupsgroups
Hemolytic anemia, abd pain Hemolytic anemia, abd pain ARF(hemoglobinuria)ARF(hemoglobinuria)
Tx with blood transfusion, exchange Tx with blood transfusion, exchange transfusions, and hemodialysis for ARFtransfusions, and hemodialysis for ARF
Chelation tx ie BAL not usedChelation tx ie BAL not used
MercuryMercury Inorganic vs organic formsInorganic vs organic forms Inorganic form subdividedInorganic form subdivided
Elem. MercuryElem. Mercury MercurousMercurous Mercuric saltMercuric salt
OrganicOrganic Short chained alkylsShort chained alkyls
More toxic to humansMore toxic to humans Methyl mercuryMethyl mercury Ethyl mercuryEthyl mercury Dimethylmercury- lethal in small amountsDimethylmercury- lethal in small amounts
Long chained alkylsLong chained alkyls
PharmocologyPharmocology Elem mercury (Inorganic) & Long chained alkyls Elem mercury (Inorganic) & Long chained alkyls
(organic)(organic) Long chained organic alkyls are Long chained organic alkyls are
biotransformed/resemble inorganic mercury biotransformed/resemble inorganic mercury poisoningpoisoning
Crosses BBBCrosses BBBtrapped in CNStrapped in CNS Usu inhaled or absorbed via skinUsu inhaled or absorbed via skin IM injectionIM injection
Abscess and granuloma formAbscess and granuloma form Delayed toxDelayed tox
IV injectionIV injection PE & DVTPE & DVT
Mercuric salts (inorganic) & short chained alkyls Mercuric salts (inorganic) & short chained alkyls (organic)(organic) Absorbed via GIAbsorbed via GI Mercuric salts deposit in liver, kidney, & spleenMercuric salts deposit in liver, kidney, & spleen Organic mercury-short chained type cross Organic mercury-short chained type cross
membranes accum. additionally in RBCs, CNS and membranes accum. additionally in RBCs, CNS and fetusfetus
PathophysiologyPathophysiology
Binds sulfhydryl groups- protein and Binds sulfhydryl groups- protein and enzyme sys affectedenzyme sys affected
Methyl mercury inhib choline acetyl Methyl mercury inhib choline acetyl transferasetransferase interferes with Ach interferes with Ach production/deficiencyproduction/deficiency
Mercuric salt Mercuric salt Proximal RTAProximal RTA
Clinical FeaturesClinical Features Depend on form ingestionDepend on form ingestion Usu neuro, Gi,& renal effectsUsu neuro, Gi,& renal effects CNS effectCNS effect
M/c 2ndary to short chain alkylsM/c 2ndary to short chain alkylsCNS terratogenic effectCNS terratogenic effect Elemental mercury may also cause it (vs mecury salts no Elemental mercury may also cause it (vs mecury salts no
effect)effect) Various sympt.Various sympt.
Erethism,anxiety,depression,irritability,mania, sleep Erethism,anxiety,depression,irritability,mania, sleep disturbance,shyness,memory loss,tremordisturbance,shyness,memory loss,tremor
Paresthesia,ataxia, muscle rigidity/spasticity,&hearing Paresthesia,ataxia, muscle rigidity/spasticity,&hearing and visual impairmentand visual impairmentusu short chain alkylsusu short chain alkyls
GI effectGI effect M/c 2ndary to M/c 2ndary to mecury salts a/w errosive gastroenteritis, mecury salts a/w errosive gastroenteritis,
abdominal pain, cardiovasc.collapseabdominal pain, cardiovasc.collapse Elemental and short chain alkyls only mild GI effects- Elemental and short chain alkyls only mild GI effects-
stomatitis, gingivitis, excessive salivationstomatitis, gingivitis, excessive salivation Renal effectsRenal effects
Elemental and organic- glomerular and tubular damageElemental and organic- glomerular and tubular damage Mercury salts ATN within 24 hMercury salts ATN within 24 h
Pneumonitis, ARDS, progressive pulmonary fibrosisPneumonitis, ARDS, progressive pulmonary fibrosis Elementalmercury inhalationElementalmercury inhalation
AcrodyniaAcrodynia
Immune mediated condition Immune mediated condition develops in children exposed to all develops in children exposed to all form mercury except short chain form mercury except short chain alkylsalkyls
Generalized rash, fever, irritability, Generalized rash, fever, irritability, splenomegaly, & generalized splenomegaly, & generalized hypotonia with weakness pelvic and hypotonia with weakness pelvic and pectoral musclespectoral muscles
Swallowing glass thermometer Swallowing glass thermometer usu does not produce adverse usu does not produce adverse effect unless GI tract is damaged effect unless GI tract is damaged or contains fistulasor contains fistulas
DiagnosisDiagnosis Exposure HistoryExposure History Constellation S&S tremor, erethism, or Constellation S&S tremor, erethism, or
acrodyniaacrodynia Ingestion of mercuric chloride rapid fatal Ingestion of mercuric chloride rapid fatal
course/erosive gastritiscourse/erosive gastritis Often dx is subtleOften dx is subtle Labs:Labs:
Obtain 24 h urine mercury level (5 day seafood Obtain 24 h urine mercury level (5 day seafood free diet) except for short chain alkyls (biliary free diet) except for short chain alkyls (biliary excretion)excretion)
10-15 microg/L normal over 20 10-15 microg/L normal over 20 toxtox Levels may be artificially low in chronicLevels may be artificially low in chronic Whole blood levels (merc. Concentr. In RBCs) Whole blood levels (merc. Concentr. In RBCs)
usu below 1.5micog/dLusu below 1.5micog/dL MRI: atrophy visual cortex, cerebellar MRI: atrophy visual cortex, cerebellar
vermis & hemisphere, and postcentral vermis & hemisphere, and postcentral cortexcortex
Differential DiagnosisDifferential Diagnosis HypothyroidismHypothyroidism Apathetic hyperthyroidismApathetic hyperthyroidism Metabolic encephalopathyMetabolic encephalopathy Senile DementiaSenile Dementia Lithium, theoph., & Phenytoin toxLithium, theoph., & Phenytoin tox Parkinsons dzParkinsons dz Carbon monox. PoisoningCarbon monox. Poisoning Lacunar infarctLacunar infarct Cerebellar dzCerebellar dz Ethanol and sedative-hypnotic drug Ethanol and sedative-hypnotic drug
withdrawalwithdrawal Iron, arsenic, phosphorus acid or alkali Iron, arsenic, phosphorus acid or alkali
poisoningpoisoning
TreatmentTreatment Removal exposureRemoval exposure Supportive therapySupportive therapy Gastric lavage & activated charcoal (cathartic not Gastric lavage & activated charcoal (cathartic not
indicated)indicated) Neostigmine may improve motor function in Neostigmine may improve motor function in
methyl mercury poisoningmethyl mercury poisoning BAL contraindicated in methyl mercury poisoningBAL contraindicated in methyl mercury poisoning
Exacerbates CNS symptomsExacerbates CNS symptoms DMSA may be useful in short chain alkylsDMSA may be useful in short chain alkyls
Given as second line agent after Gi decontam.Given as second line agent after Gi decontam. BAL preffered chelator for mercury saltsBAL preffered chelator for mercury salts
Adjust dose to clinical response and side effect Adjust dose to clinical response and side effect developmentdevelopment
Hemodialysis- can dialyze BAL-mercury complexHemodialysis- can dialyze BAL-mercury complex Plasma exchange transfusion may be usefulPlasma exchange transfusion may be useful
DispositionDisposition
All ingestions of mercury saltsAll ingestions of mercury salts All patients known to have or All patients known to have or
suspected to have inhaled elemental suspected to have inhaled elemental mercury vapor with pulm. injurymercury vapor with pulm. injury
All patients receiving BAL therapyAll patients receiving BAL therapy
QuestionsQuestions
1.Which statement concerning iron 1.Which statement concerning iron toxicity is false:toxicity is false:
A.Some studies suggest WBC count > A.Some studies suggest WBC count > 15 000 may indicate toxicity15 000 may indicate toxicity
B. Glucose level > 150 may indicate B. Glucose level > 150 may indicate iron tox. C.TIBC little valueiron tox. C.TIBC little value
D.Xray may show tabletsD.Xray may show tablets E.Nonelemental iron amount ingested E.Nonelemental iron amount ingested
is keyis key
QuestionsQuestions
2.Which of the following is incorrect 2.Which of the following is incorrect about treatment in iron toxicityabout treatment in iron toxicity
A. GI decontamination/Chelation via A. GI decontamination/Chelation via Deferoxamine is commonly doneDeferoxamine is commonly done
B.Dialysis is very effectiveB.Dialysis is very effective C.Antiemetics may be usedC.Antiemetics may be used D.If hypotensive support D.If hypotensive support
symptomatically symptomatically E.If coagulopthic give Vit K/FFPE.If coagulopthic give Vit K/FFP
QuestionsQuestions 3. Which of the following is incorrect in 3. Which of the following is incorrect in Chelation therapy Chelation therapy
in arsenic poisoning in arsenic poisoning
A. BAL is administer immediate A. BAL is administer immediate
B. Treatment may exceed 19 daysB. Treatment may exceed 19 days
B. DMSA is less toxicB. DMSA is less toxic
C. D-penicillamine is not useful in treatment of arsenic C. D-penicillamine is not useful in treatment of arsenic poisoningpoisoning
D. 24 urine arsenic level are not usefulD. 24 urine arsenic level are not useful
QuestionsQuestions 4. Which of the following is not present in 4. Which of the following is not present in
the condition known as acrodyniathe condition known as acrodynia A.It is a immune mediated condition A.It is a immune mediated condition
develops in children exposed to all form develops in children exposed to all form mercury except short chain alkylsmercury except short chain alkyls
B.Generalized rashB.Generalized rash C.Fever and IrritabilityC.Fever and Irritability D.Splenomegaly, & generalized hypotonia D.Splenomegaly, & generalized hypotonia E. Weakness of abdominal and deltoid E. Weakness of abdominal and deltoid
musclesmuscles
QuestionsQuestions
5. The following are treatment 5. The following are treatment options in mercury poisoning exceptoptions in mercury poisoning except
A. All are correctA. All are correct B. Gastric lavage & activated charcoal and B. Gastric lavage & activated charcoal and
cathartic are usually not indicatedcathartic are usually not indicated C. Neostigmine may improve motor function C. Neostigmine may improve motor function
in methyl mercury poisoningin methyl mercury poisoning D.BAL contraindicated in methyl mercury D.BAL contraindicated in methyl mercury
poisoningpoisoning E.Hemodialysis- can dialyze BAL-mercury E.Hemodialysis- can dialyze BAL-mercury
complexcomplex
AnswersAnswers
1.E1.E 2.B2.B 3.D3.D 4.E4.E 5.A5.A
CaseCase