lead & mercury toxicity2

8/8/2019 Lead & Mercury Toxicity2

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Lead Toxicity



± Lead may be the oldest recognized chemical toxin.

± It has been used in making batteries, pottery, solder, pesticides, cooking

utensils, plumbing, and ³the one that is getting so much attention now´

household paint.

± Another big source of lead in the environment comes from gasoline thatcontains lead.



A. Nature of Jobs exposed to

Lead

Battery manufacturing

Chemical industry




Lead

Building construction

Pipe fitters




Lead

Plastic industry



Major O at ons and Industr s ssociat d it

ad O r osur

att r anuf actur ing

ical industr onstr uction or r s

D olition or r s

Fir ing-r ange instr uctor s

Foundr or er s

Gas-station attendants

Gasoline additives r od.

eweler s

ead iner s

ead smelter s and r ef iner s

igment manuf actur ing

ipe f itter s lastics industr

otter wor er s

r inter s

Radiator r epair

Rubber industr

Solder ing of lead pr od.

Solid waste pr oduction

Stained-glass maker s

Welder s

. Natur e of obs exposed to

ead



B. Clinical Presentation

Pharmacokinetics Absorption:

The two principal exposure routes are

respiratory system inhaled in dust and fumes

gastrointestinal system especially ingestion of contaminated

food. The ma jor target organs are the central and peripheral nervous

systems, kidneys, and blood.

Distribution:

95% of lead exists in the BCs (half -life = 35 days)

± About 10% of the total body lead burden equilibriates in soft tissue

(half -life = 40 days).

± 90% of the total body lead burden existing in skeleton (half -life =

20-30 years).

Elimination:

The kidney accounts for 75% of daily lead loss.



A. Hematologic effects

± Impaired heme biosynthesis

± lead blocks the conversion of d-aminolevulinic acid to

porphobilinogen

± Lead inhibits the enzyme (ferrochelatase) during the

formation of heme; results in elevated free

erythrocyte protoporphyrin ( EP) levels

Pathophysiology



Signs & Symptoms

A. Hematologic effects

± Anemia most common

± Basophilic stippling

uncommon but highly

suggestive of lead

intoxication. Eosinophilia in

lead-intoxicated patients



B. Neurologic effects

± In adults, peripheral neuropathy is the most commonmanifestation

± encephalopathy appears more frequently in children(passes the BBB more easily in children)

± Cerebral edema is a late complication of leadencephalopathy,

±S

ubtle neuropsychiatric changes (e.g. hyperactivity,learning disorders, and fine motor dysfunction) mayrepresent subclinical neuropathy.

Pathophysiology



B. Neurologic effects

± classic motor neuropathy

± Extensor weakness (wrist drop) at high levels ± paresthesias are uncommon

± Motor conduction velocities and distal latency may beprolonged, but sensory conduction velocities are usuallynormal

± Acute encephalopathy occurs infrequently in adults ±seizures, obtundation, and confusion are the mostcommon signs

± Subtle effects on personality, memory, learning, reactiontime, psychomotor function, and motor coordination

Signs & Symptoms



seizure confusion



C. Renal effects

± Lead toxicity produces lesions of the proximal tubule

and loops of Henle

± A anconi syndrome develops, which includes

aminoaciduria, phosphaturia, glycosuria, and renal

tubular acidosis.

± Lead decreases tubular secretion of uric acid, causing

higher incidence of gout

Pathophysiology



C. Renal effects

± enal disease can be

asymptomatic until thelate stages and may not

be detected without

specific testing.

Signs & Symptoms



D. Endocrine Effects

± Lead impedes vitamin conversion into its hormonal form,1,25-dihydroxyvitamin , impairing cell growth, maturation,and tooth and bone development.

± Chronic lead exposure could adversely affect the thyroid

over time.

E. Cardiovascular (Hypertension) Effects

± onset and development of hypertension ± systolic blood pressure may rise 1±2 mm with each

doubling of blood lead,

± blood lead can account for a 1 to 2% variance in bloodpressure

± renal failure and hypertension can exacerbate each other

Pathophysiology



F. Reproductive and Developmental Effects

M ale Reproductive Effects

± decrease sperm count totals

± increase abnormal sperm frequencies

± Long-term lead exposure ± may diminish sperm concentrations, total sperm

counts, and total sperm motilityP regnancy Outcomes

± increased frequency of miscarriages and stillbirths (chronic exposure)

Developmental Effects

± pregnancy issues (e.g., premature births and low birth weights)

± congenital abnormalities ± postbirth effects on growth or neurologic development

± readily crosses the placenta, adversely affects fetus viability as well as fetal and

early childhood development

± Prenatal exposure to low lead levels increases risk of reduced birth weight and

premature birth

Pathophysiology



General ign and Sy pto of Lead Toxi ity

Mild Moderate Se ere

Myalgia

Irr itability

Pare the ia

Mild fatigue

Inter ittent abdo inal

pain

Lethargy

Heada he

Tre or

Vo iting

General fatigue

Diffu e abdo inal pain

Weight lo

Lo of libido

Con tipation

En ephalopathy

Motor neuropathy

Sei ure

Co a

Abdo inal oli

Lead line

Oligur ia



Diagnosis

A. hole Blood Lead concentration

Most widely used screening test Best measure for recent exposure

Interpretation of lead levels:

less than 10 ug/dL - not considered indicative of lead poisoning

10-14 ug/dL - border zone

15-19 ug/dL - mandates more careful follow-up

20-69 ug/dL - calls for full medical evaluation, detailed enviromentaland behavioral history, physical examination, and test for iron-deficiency

70 ug/dL constitutes medical emergency

B. ree Erythrocyte Protoporphyrin Test ( EP)

best screening test for chronic but not acute lead intoxication

Elevation of EP persists long after the cessation of lead exposure

All children between 9 months and 6 years of age should receive aEP test

better measure of body-lead burden than blood-lead but still, bothtests should be used

EP level higher than 35 ug/dL and a blood-lead level higher than 10ug/dL indicate excess lead exposure and require further medicalevaluation and environmental investigation



C. Zinc Protoporphyrin Test (ZPP) used to screen and monitor chronic exposure to lead

ZPP levels begin to increase at blood-lead concentrations of 15-25ug/dL in children, 20-25 ug/dL in female adults, and 30-40 ug/dL inadult males

sensitive to an elevated body-lead burden than blood-lead -- leadlevels tend to vary day to day in the blood because lead moves from

the blood into organs and bones compared to blood lead, ZPP is not affected by environmental lead

present at the time of collection

D. D- Aminolevulinate Dehydratase Activity (ALA-D)

Lead decreases the activity of this enzyme which is present in theerythrocyte

used for monitoring occupational lead exposure not as sensitive and readily available as BLL

should only be used in monitoring cases with moderate to severelead poisoning

Diagnosis



A. ut decontamination

B. Elimination enhancement

± hemodialysis enhance excretion of calcium disodium EDTA chelated lead

± whole bowel irrigation remove lead from I tract

C.S

upportive measures ± screening: free erythrocyte protoporphyrin test

± radiology

± blood-lead levels: 20-24 ug/dL, 25-44 ug/dL, 45-69 ug/dL, >70 ug/dL

D. Antidotes

± calcium disodium EDTA

± dimercaprol

± DMPS

± DMS A

± D-penicillamine

Treatment



Mercury Toxicity



± Mercury is a metal found in various forms:

a. rganic mercury

Mercury combined with carbon

b. Inorganic mercury

Compounds which contain mercury in combination with non-carbonsubstances such as chlorine, oxygen, or sulfur

c. Elemental mercury

± Common ways in which people are exposed include breathing

contaminated air, eating contaminated fish, and through the use of mercury

based amalgams (fillings) in dental treatments.

± Can also enter the body through direct skin contact




Mercury

Battery manufacturing

Disinfectant industry




Mercury

armer

ur makers




Mercury

Insecticide makers Embalmers



B. Clinical PresentationPharmacokinetics

Absorption:

± mercury distributes to all parts of the body on absorption (peak over 1-2 days)

± widely distributed to the liver, kidney, blood and muscle

± After inhalation, elemental mercury is readily absorbed through the alveolar

membrane and is transported by blood to the brain and other tissues of the

nervous system.

Distribution:

± Elemental mercury easily penetrates the BBB and accumulates in brain tissue

± same areas of the brain are affected by both inorganic and organic mercury

± High levels accumulate in the cerebellum, brain stem (inferior olive nucleus,

subthalamic nucleus) and choroid plexus.

Elimination:

± converted in blood to mercuric ions, then excreted in the urine and feces.

± Elimination of elemental mercury primarily in the urine (half -life = 60 days).

± The loss of mercury from the lungs (half -life = 1.7 days), from the kidney (half -

life = 64 days), and from the head (half -life = 21 days).



Pathophysiology

A. Elemental mercury (Hg)

± Its lipid-soluble property allows for easy passage through the alveoli into thebloodstream and red blood cells ( BCs)

± as a vapor, has the ability to penetrate the CNS, where it is ionized and

trapped, attributing to its significant toxic effects.

± not well absorbed by the I tract and, therefore, when ingested (eg,

thermometers), is only mildly toxic.

B. Inorganic mercury ± highly toxic and corrosive

± gains access to the body orally or dermally

± accumulates mostly in the kidney, causing significant renal damage

± poor lipid solubility limits CNS penetration, but slow elimination and chronic

exposure allow for significant CNS accumulation of mercuric ions and

subsequent toxicity.C. rganic mercury

± absorbed more completely from the I tract than inorganic salts

± has high lipid solubility and is distributed uniformly throughout the body,

accumulating in the brain, kidney, liver, hair, and skin

± also cross the BBB and placenta and penetrate erythrocytes



Signs and Symptoms

Three signs characterize the diagnosis of industrial mercurialism:

gingivitis, tremor of extremities, and emotional instability.

A. Neurologic Effects

± Tremor, rigidity and truncal unsteadiness impairing gait may

produce a Parkinsonian syndrome (basal ganglia and cerebellum

involved) ± Defects in memory (temporal lobe involved)

B. Ophthalmologic Effects

± brown reflex ± bilateral, symmetrical and varies in intensity from

light brown to coffee brown (mercurialentis).

± ine punctate opacities present bilaterally and most evident inanterior cortex of lens.

± ell-marked vascularity is observed at the corneo-scleral junction.



Signs and Symptoms

C . Renal Effects ± overt renal tubular damage

± The nephro-toxicity manifested as an acute tubular necrosis or as

an immune complex glomerulo-nephritis.

± two types of proteinuria

lomerular proteinuria - characterized by the leakage of serum proteins(predominantly high-molecular weight) through damaged glomeruli

Tubular proteinuria - consists of a variety of proteins and enzymes.

Many of these markers are low-molecular weight proteins normally

filtered through the glomerulus and then reabsorbed in the proximal

tubules.



Chronic, Low-Dose E posure

y Erethism (ner ousness, irritabilit ,mood instabilit , blushing)

y remor

y Personalit change

y Suicidal tendenc

y Paraesthesia

y Impaired hearingy Speech disorders

y Visual disturbance

y Abnormal refle es

y Disturbed gait

y ingi itis (inflammation of the gums)

y Impaired ner e conduction

y enal damage

y Ad erse outcome of pregnancy Infertilit

y Pneumonitis (lung disease)

y lioblastoma (brain cancer)

y Immune s stem d sfunction

Clinical Symptoms of Mercury Toxicity



Clinical Symptoms of Mercury Toxicity

Acute, High-Dose Exposure

astroenteritis (stomach upset)

Mouth pain Abdominal pain

Vomiting

Excessive salivation Anuria (urine production stops)

Uraemia (urine products appearing in the

blood)

Nephritis (kidney disease leading to

kidney failure) Anorexia (lack of appetite)

Ataxia (difficulty in moving)



A. ut decontamination

± should be with protected airway

B. ral Chelation Therapy

± attaching--or chelating--to metallic ions and minerals, then move

them into the body's waste disposal pathways and flush them out. Dimercaprol

DMPS

DMS A

D-Penicillamine

Treatment

lead & mercury toxicity2

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