2. Lead
• Lead poisoning is one of the oldest occupational
and environmental diseases in the world.
Lead has widespread commercial application:
• production of storage batteries
• ammunition
• metal alloys
• solder
• glass
• plastics
• pigments
• ceramics
3. Lead
Lead may have subtle
subclinical adverse effects
on neurocognitive function
and on blood pressure
even at low blood lead
concentrations.
4. Pharmacokinetics
Inorganic lead is slowly, but
consistently absorbed via the
respiratory and gastrointestinal tract.
Inorganic lead is poorly absorbed
through the skin.
5. Pharmacokinetics
• Absorption of lead dust via the
respiratory tract is the most
common cause of industrial
poisoning.
• The intestinal tract is the primary
route of entry in nonindustrial
exposure.
6. Pharmacokinetics
• Adults absorb about 10-15% of the
ingested amount.
• Young children absorb up to 50%.
• Low dietary calcium, iron deficiency
and ingestion on an empty stomach
are associated with increased lead
absorption.
9. Pharmacokinetics
• Lead crosses the placenta and poses
a potential hazard to the fetus.
The kinetics of lead clearance:
• half-life for blood and soft tissues is
1-2 months
• half-life for skeleton is years to
decades
10. Pharmacokinetics
• 70% of eliminated lead is in the urine.
• Lesser amounts are excreted through
the bile, skin, hair, nails, sweat and
breast milk.
• The fraction not undergoing prompt
excretion (up to 50%) may be
incorporated into the skeleton.
11. Pharmacokinetics
In patients with high bone
lead burdens, slow release
from the skeleton may
elevate blood lead
concentrations for years after
exposure ceases.
15. Multisystemic toxic effects of the lead
are based on several mechanisms:
• inhibition of enzymatic function
• interference with the action of essential
cations (calcium, iron, zinc)
• generation of oxidative stress
• changes in gene expression
• alterations in cell signaling
• disruption of the integrity of cell´s and
organelles membranes
16. Nervous system
The developing central nervous
system of the fetus and young
child is the most sensitive target
organ for lead´s toxic effect.
Blood lead concentrations even
less than 5 mcg/dL may result in
subclinical deficits in
neurocognitive function in lead-
exposed young children.
21. Peripheral neuropathy
• It may appear after chronic high dose
lead exposure.
• Usually months to years of blood lead
concentrations >100 mcg/dL.
• It is predominantly motor in
character: painless weakness of the
extensors, particularly in the upper
extremity with classic wrist drop.
22.
23. Blood
Lead can induce normocytic or microcytic
hypochromic anemia.
Lead interferes with heme synthesis by
blocking the incorporation of iron into
protoporphyrin IX.
Lead also inhibits the function of enzymes in
the heme synthesis pathway: aminolevulinic
acid dehydratase, ferrochelatase.
24. Blood
• Lead can also increase erythrocyte
membrane fragility and decrease
red cell survival time.
• Frank hemolysis may occur with
high exposure.
• Basophilic stippling on the
peripheral blood smear!
26. Kidneys
• Chronic high-dose lead exposure
(>80 mcg/dL) for months to years
may result in renal interstitial
fibrosis and nephrosclerosis.
• Lead nephropathy may have a
latency period of years.
27. Kidneys
Lead may alter uric
acid excretion by
the kidney resulting
in recurrent bouts of
gouty arthritis called
saturnine gout.
Health.wikinut.com
28. Kidneys
• Acute high dose lead exposure
sometimes produces transient
azotemia caused by intrarenal
vasoconstriction.
• There is association between blood
lead concentrations and serum
creatinine (and creatinine clearance).
30. Reproductive organs
• High dose lead exposure is a risk
factor for stillbirth or spontaneous
abortion.
• Even low level lead exposure can
increase risk for low birht weight,
preterm delivery and spontaneous
abortion.
31. Reproductive organs
Prenatal exposure to low levels of lead
(maternal blood lead 5-15 mcg/dL) is
associated with decrements in physical
and cognitive development.
In males, blood lead conc. >40 mcg/dL
are associated with diminished or
aberrant sperm production.
34. Gastrointestinal tract
• In heavily exposed individuals with
poor dental hygiene, the reaction of
circulating lead with sulfur ions
released by microbial action, may
produce DARK DEPOSITS OF
LEAD SULFIDE at the gingival
margin: GINGIVAL LEAD LINES.
36. Cardiovascular system
Lead exposure elevates blood
pressure in susceptible
individuals.
Blood lead concentration is
linked with increases in systolic
and diastolic blood pressure.
37. Cardiovascular system
• Low to moderate levels of lead exposure
are risk factors for increased
cardiovascular mortality.
• The pressor effect of lead may be
mediated by an interaction with calcium
mediated concentration of vascular smooth
muscle, generation of oxidative stress and
an associated interference in nitric oxide
signaling pathways.
38. MAJOR FORMS OF LEAD
INTOXICATION
Inorganic lead poisoning: acute and chronic
Organolead poisoning
39. Acute inorganic lead poisoning
• Uncommon today.
• It can happen as industrial inhalation
of large quantities of lead oxide
fumes in workers.
• In children, from ingestion of a large
oral dose of lead (toys coated or
fabricated from lead, contaminated
food or drink).
40. Acute inorganic lead poisoning
• The onset of severe symptoms
occurs several days or weeks of
recurrent exposure: encephalopathy
and colic symptoms.
• There may be evidence of hemolytic
anemia and elevated hepatic
aminotransferases.
41. Acute inorganic lead poisoning
• Acute inorganic lead poisoning may be
mistaken for appendicitis, peptic ulcer,
biliary colic, pancreatitis or infectious
meningitis.
• Subacute presentation may be mistaken
for a flu-like viral illness: headache,
fatigue, intermittent abdominal cramps,
myalgias and arthralgias.
43. Chronic inorganic lead poisoning
Lead poisoning should be
suspected in patient presenting
with:
• ABDOMINAL PAIN
• HEADACHE
• ANEMIA
44. Chronic inorganic lead poisoning
Less commonly, but very
important for diagnosis of lead
poisoning are:
• MOTOR NEUROPATHY
• GOUT
• RENAL INSUFFICIENCY
45. Chronic inorganic lead poisoning
This diagnosis should be
considered in any child with:
• NEUROCOGNITIVE DEFICITS
• GROWTH RETARDATION
• DEVELOPMENTAL DELAY
46. Chronic inorganic lead poisoning
• Measuring lead in whole blood is not
a reliable marker of recent or
cumulative lead exposure, but it is
usefull diagnostic tool.
• Most patients with lead-related
disease have blood lead
concentrations higher than the
normal range.
48. Chronic inorganic lead poisoning
• Measurement of lead excretion in the
urine after a single dose of a
chelating agent (chelation challenge
test) reflects the lead content of soft
tissues.
• It is not a reliable marker of long term
lead exposure, remote past exposure
or skeletal lead burden.
49. Chronic inorganic lead poisoning
• The finding of a blood lead
concentration of 30 mcg/dL or
more with no concurrent increase
in zinc protoporphyrin suggests
that the lead exposure was of
recent onset.
51. Treatment
• Lead encephalopathy is a medical
emergency that requires intensive
supportive care.
• Cerebral oedema may be improved
with corticosteroids and mannitol.
• Anticonvulsants are required for the
treatment of convulsions.
52. Treatment
Radiopacities on abdominal radiographs may
suggest the presence of retained lead objects.
Gastrointestinal decontamination is necessary
in this case.
Adequate urine flow should be maintained.
Overhydration should be avoided.
55. Treatment
• Parenteral chelation is limited to 5 or
fewer days, at which time oral
treatment may be instituted.
• Succimer is peroral chelator.
• In lead intoxication without
encephalopathy, treatment may be
initiated with succimer.
56. Treatment
• Goal of chelation is resolution of
symptoms or return of the blood lead
concentration to the premorbid range.
• In chronic lead poisoning, cessation
of chelation may be followed by an
upward rebound in blood lead
concentration as the lead re-
equilibrates from bone lead stores.
59. Prevention
• The longer-term goal should be for
workers to maintain blood lead levels
at lower than 10 mcg/dL.
• For pregnant women goal is to avoid
occupational or avocational exposure
that would result in blood lead levels
higher than 5 mcg/dL.
60. Organolead poisoning
• Today very rare.
• Organolead compounds like lead
stearate and lead naphthenate are
still used in some commercial
processes.
• Organolead compounds are well
absorbed through the respiratory
tract and skin.
61. Organolead poisoning
Organolead compounds target the
central nervous system and produce
dose-dependent effects:
• neurocognitive deficits
• insomnia, delirium, hallucinations
• tremor, convulsions
• death
62. Treatment
Decontamination of the skin and
prevention of further exposure!
Treatment of seizures with
anticonvulsants.
Empiric chelation if high blood lead
concentrations are present.
63. Literature
• Katzung, Masters, Trevor. Basic
and clinical pharmacology.
• Gutemberg.org
• Pinterest.com
• Health.wikinut.com
• Portal.dentistry.vcu.edu
