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

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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

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AnswersAnswers

1.E1.E 2.B2.B 3.D3.D 4.E4.E 5.A5.A

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