Toxic

LEAD
 Sources of poisoning:
Lead is a heavy metal used in a wide variety of consumer
products and occupational setting.
It is derived from the Latin word plumbum.
The major routes of lead entry into the body are GI tract
(ingestion), lungs (inhalation) and dermal absorption
(insignificant except in the case of organic lead).
Children may ingest leaded paints (paint f lakes) or other
articles containing lead such as newspapers, toys, pencils and
plasters.
Inhalation of lead is hazard in battery industry, stained glass
window production, leaded gasoline motor vehicle exhaust,
miners, smelters and car finishers.
Toxicity may occur in addicts using methamphetamine by

intravenous injection since lead acetate contaminant is used
during the manufacture of phenyl-2-propane, a precursor of
methamphetamine.
Organic lead compounds (e.g., tetraethyl lead) may be

absorbed through intact skin. Once absorbed, lead is
distributed throughout soft tissues; however, bone is the
principal storage area.
Mechanism of toxicity:
 Lead reacts with sulfhydryl group of proteins, thus it
interferes with enzymes containing sulf hydryl group.
 It interferes with enzymes of heme synthesis for hemoglobin

production [delta-aminolevulinic acid (ALA) dehydratase
and coproporphyrinogen decarboxylase]. This interference
can result in anemia.
 Delta-ALA and coproporphyrin accumulate in the urine

where they serve as markers for lead intoxication.
 Lead also causes High Blood Pressure through
two mechanisms.
- First, it inhibits the Na+/K+-ATPase enzyme activity

and stimulates the Na+/Ca++ exchange pump. This will
increase the sensitivity of smooth muscle wall to
stimulate its contraction.
-Second, exposure to lead results in the release of

rennin from the kidneys, which interact with
angiotensin I leading to the formation of angiotensin
II, a powerful vasopressor.
Symptoms of acute poisoning:
 GIT: Burning sensation in mouth, esophagus and stomach
followed by severe abdominal pain. Loss of appetite,
metallic taste, colic, vomiting and constipation.
 CNS: Restlessness, irritability, convulsions, and coma.
 Blood: Anemia and hemolysis.
 Kidney and liver functions are impaired with the presence

of blood in urine.
 Diagnostically, blood lead levels > 60 mg/dl corresponds

with acute poisoning.
Symptoms of chronic toxicity (Plumbism):
 GIT:
Anorexia, loss of weight, metallic taste, abdominal pain and
constipation. Chronic toxicity of lead is characterized by
the presence of black line on the gum near the
border of the teeth.
 Red cells:
Anemia which is due to interference with the synthesis of
hemoglobin.
 Lead encephalopathy:
In adults symptoms may be limited to irritability. In children a
condition known as lead encephalitis may develop.
This condition is characterized by irritability, insomnia, headache,
restlessness, loss of memory, convulsions and coma.
 Lead palsy or myopathy:
This condition is characterized by peripheral neuritis,
paralysis, wrist and foot drop.
 Cardiovascular:
Hypertension may occur with chronic exposure.
 Reproductive:
Lead poisoning may produce decreased sperm count
or an increased number of abnormal sperm.
In women it produces sterility, miscarriages and when

birth occurs normally the infant mortality rate during the
first year is high.
 Kidney:
Fanconi-like syndrome (proteinuria, hematuria, amino-
aciduria and phosphaturia) may occur.
Ultimately leading to chronic interstitial nephritis and
renal failure.
This syndrome results from the failure of the proximal
tubules to reabsorb these substances due to the effect of
lead on mitochondria in tubule cells and its ability to
produce energy (ATP) necessary to support cellular
mechanisms associated with reabsorption.
 Diagnostically, blood lead levels in the range of

30-60
mg/dl along with these symptoms may indicate chronic
lead poisoning.
Treatment:
 GIT decontamination:
It is not recommended unless lead is visible on abdominal
radiographs.
If lead is seen on the radiograph, whole bowel irrigation should
be considered.
 Supportive measures:
a- Hemodialysis in patients with renal failure.
b- Liver and kidney function tests should be carried out.
c- Lead blood levels should be checked daily for patients taking
chelators.
Antidotes:
 - BAL chelates lead both intra- and extra-cellularly. Two
molecules of BAL combine with one atom of lead to form a
complex that is excreted in the bile and urine. In the
presence of renal impairment, BAL was once the
chelator of choice because its main route of excretion
is in the bile. BAL is administered intramuscularly once every
4 hours.
- Calcium disodium ethylenediamine tetraacetic acid
(CaNa2 EDTA) removes lead from the extracellular
compartment and increases the urinary excretion 20-50 fold.
- DMSA is an orally active water-soluble chelator. It may
remove lead from the bone and soft tissues. It
does not deplete essential metals as do BAL and
CaNa2 EDTA.
IRON
Sources of poisoning:
 The three most common preparations are ferrous
gluconate, sulfate and fumarate with 12%, 20% and 33%
elemental iron by weight, respectively. Chewable pediatric
multivitamins with iron contain up to 15 mg of elemental
iron per tablet but toxicity may occur when large quantities
are ingested.
 Ferrous sulfate is the most commonly used iron
preparations and the iron salt most frequently involved in
poisonings. Ingestions of less than 20 mg/kg of elemental
iron usually produce insignificant intoxication.
 Ingestions of 20-60 mg/kg are potentially toxic, and
ingestion of 60 mg or more are generally toxic. The
estimated lethal dose of elemental iron required for acute
iron poisoning is between 200-250 mg/kg.
 Pathophysiology:
- Generally, about 2 to 15 % is absorbed from the
gastrointestinal tract, whereas iron elimination accounts
for only 0.01 % per day.
- During periods of increased iron need (childhood,
pregnancy and blood loss) absorption of iron is
increased greatly.
- Absorbed iron is bound to the plasma protein
transferrin for transfer to storage sites in hemoglobin,
myoglobin and iron-containing enzymes and the iron
storage proteins ferritin and hemosiderin.
- Normally excess ingested iron is excreted and some is
contained within shed intestinal cells, in bile and urine,
and even smaller amounts in sweat, nails and hair.
Clinical manifestations:
The clinical effects of serious iron poisoning can be
divided into five stages.
Stage I (0.5-6 hours):
 Symptoms usually characterized by nausea, vomiting,
diarrhea and abdominal pain. CNS symptoms may
include lethargy, coma or convulsions.
Stage II (6-24 hours):
 Some patients may enter a transient phase of
improvement, which usually lasts less than 24 hours
(latent stage) and the toxicity may end with this stage for
those who have ingested small amounts of iron. During
this stage the serum iron is unloaded to intracellular
sites, where toxicity may manifest in the third stage.
Stage III (4-40 hours):
 If a large amount of iron was ingested, the latent
stage will progress to a third stage of metabolic
dysfunction, cardiovascular collapse and hepatic,
renal and neurologic failure.
Stage IV (2-4 days):

 This stage consists of hepatic failure, which may
occur 2-3 days following severe iron poisoning.
Stage V (several weeks):

 Gastric outlet obstruction
Laboratory Diagnosis:
 Deferoxamine test: It is performed by mixing 2 mL of
gastric f luid with two drops of 30% hydrogen peroxide.
Then deferoxamine is added. If iron is present, a
deferoxamine-iron complex (ferrioxamine) is formed
and turns the solution orange-red.
 Serum iron determination: Normal serum iron
concentrations range 50 to 150 mg/dl. Levels over 350
mg/dl are usually associated with signs of toxicity.
Significant toxicity frequently accompanies iron
concentration between 500 and 1000 mg/dl. Levels over
1000 mg/dl are associated with considerable morbidity.
 Other laboratory tests:
1. Serum electrolytes,
2. Complete blood count,
3. Blood sugar,
4. Blood urea nitrogen,
5. Creatinine,
6. Arterial blood gases
7. Liver and kidney function tests.
Treatment:
 Decontamination:
Undissolved tablets should be removed from the stomach
by ipecac-induced emesis.
Gastric lavage with sodium bicarbonate solution forms
insoluble ferrous carbonates and decreases additional
iron absorption.
Gastric lavage with deferoxamine is not recommended as it
has not been proven effective and may enhance iron
absorption.
Activated charcoal is of no benefit and should only be
administered if a mixed ingestion is suspected. The use
of whole bowel irrigation has been reported with
successful decontamination in a number of cases.
 Antidote: Deferoxamine (Desferal) is usually given by
intravenous and intramuscular routes. The
recommended dose is 36 mg/kg/h and daily dose should
not exceed 6 g. Rusty-red colored urine following
treatment with deferoxamine is classically referred to as
the vin rose urine change. This color change is due to the
presence of ferrioxamine, the product of iron chelation
with deferoxamine. Deferoxamine, a byproduct
produced by Streptomyces pilosus, is a highly specific
chelator of free iron in the ferric form. A dose of 100 mg
will chelate approximately 9 mg of elemental iron.
 Supportive measures: Hypotension should be treated
with norepinephrine or dopamine. Hemodialysis or
peritoneal dialysis do not effectively remove elemental
iron.

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LEAD

Toxicity may occur in addicts using methamphetamine by

Organic lead compounds (e.g., tetraethyl lead) may be

 It interferes with enzymes of heme synthesis for hemoglobin

 Delta-ALA and coproporphyrin accumulate in the urine

- First, it inhibits the Na+/K+-ATPase enzyme activity

-Second, exposure to lead results in the release of

 CNS: Restlessness, irritability, convulsions, and coma.

 Blood: Anemia and hemolysis.

 Kidney and liver functions are impaired with the presence

 Diagnostically, blood lead levels > 60 mg/dl corresponds

In women it produces sterility, miscarriages and when

 Diagnostically, blood lead levels in the range of

Stage IV (2-4 days):

Stage V (several weeks):

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