The document discusses chronic lead poisoning, detailing its symptoms, sources, diagnosis, and management. Lead exposure can occur through various means, particularly in children who absorb significantly more lead than adults, leading to serious health impacts such as neurological and hematological issues. Treatment options include chelation therapy and supportive care, with emphasis on identifying and removing exposure sources.

1. CLINICAL SYMPTOMS AND MANAGEMENT OF
CHRONIC LEAD POISONING
PRESENTED BY:ASHIMA JOSEPH
IV PHARM D

2. LEAD
Lead is the commonest metal involved in chronic poisoning. It was one of the
first metals known to man and has been widely used during the last two
thousand years for domestic, industrial, and therapeutic purposes. Lead is
abundant in soil, being distributed throughout the earth’s crust.
Physical Appearances and Uses
Elemental lead exists as a highly lustrous, heavy, silvery-grey metal with a
cubic crystal structure that assumes a bluish tint as it tarnishes in air. It is
quite soft and malleable.

3. Several of its salts occur as variously coloured powders or liquids and are
used widely in industry and at home producing cumulative toxicity on chronic
exposure. Lead acetate (sugar of lead) has been used in therapeutics, lead
carbonate (white lead) is still used in paints, lead oxide (litharge) is essential
for glazing of pottery and enamel ware, and tetraethyl lead is mixed with
petrol as an antiknock to prevent detonation in internal combustion engines.
Among cosmetics, lead tetroxide is the most common compound in vermilion
(“sindoor”) applied by married Hindu women to the parting of their scalp hair,
while lead sulfide is used as a collyrium (“surma”) for the eyes by Muslims.
Summary of some of the common non-occupational sources:
■ Candle with lead-containing wicks
■ Ayurvedic medicines
■ Paint
■ Ink
■ Automobile storage battery casing; battery repair shops
■ Ceramic glazes

4. The various situations in which lead salts are used resulting in chronic
occupational, environmental, or domesic exposure are listed in the table
below

5. About 5–15% of ingested lead is absorbed by adults with less than 5%
retained. Children, however, absorb approximately 50% of ingested lead and
retain about 30%.
Usual Fatal Dose
This is not really relevant to lead since acute poisoning is very rare. The
average lethal dose is said to be 10 gm/70 kg for most lead salts, while it is
100 mg/kg for tetraethyl lead.
Toxicokinetics
■ Lead is absorbed through all portals of entry. Occupational exposure results
mainly from inhalation of contaminated air and dust of various types, while
in most other situations the mode of intake is ingestion of food and water
containing lead. Tetraethyl lead can be absorbed rapidly through intact skin.

6. ■ Following absorption, it is stored in the bones as phosphate and carbonate.
In children about 70% of total body lead is skeletal, while in adults over 95%
is in osseous tissues. Lead is drawn to those areas of the skeleton which are
growing most rapidly. These include the radius, tibia, and femur, which are
the most metabolically active. The hypermineralisation is reflected in the
form of densities which are the classic “lead lines” observed on x-ray below.
The width of the lead lines is related to the duration of exposure. Significant
amounts of skeletal lead are released from bone into the blood stream
periodically resulting in symptoms of toxicity.

7. ■ Absorbed lead which is not retained in the body is excreted primarily in the
urine (about 65%) and bile (about 35%).
Mode of Action
1. Lead combines with sulfhydryl enzymes leading to interference with their
action.
2. It decreases haeme synthesis by inactivating the enzymes involved such as
aminolaevulinic acid dehydrase, aminolaevulinic acid synthetase,
coproporphyrinogen oxidase (or decarboxylase), and ferrochelatase. This
results in anaemia.
3. Lead increases haemolysis as a result of which immature red cells are
released into circulation such as reticulocytes and basophilic stippled cells
(the result of aggregation of ribonucleic acid due to inhibition of the
enzyme pyrimidine5-nucleotidase which normally eliminates degraded
RNA).

8. 4. In the CNS, lead causes oedema and has a direct cytotoxic effect leading
to decreased nerve conduction, increased psychomotor activity, lower IQ,
and behavioural/learning disorders.
5. Lead also has deleterious effects on the CVS (hypertension and
myocarditis), kidney (nephritis),* and reproductive organs (infertility).
Lead nephropathy after chronic lead exposure has been well described.
Interstitial nephritis, reduced glomerular filtration rate, and nonspecific
proximal tubular dysfunction are typical. In addition, lead can decrease uric
acid renal excretion, thereby raising blood urate levels and predisposing to
gout (saturnine gout). Elevated urinary levels of N-acetyl-3-D
glucosaminidase and beta-2-microglobulin may serve as early markers of
renal injury
Permissible lead intake and blood levels:
a. Adults ingest 300 mcg and inhale 15 mcg of lead approximately each day,
of which only 10% is absorbed, but children may absorb upto 50%.

9. b. Minute quantities of lead are always present in the blood of even normal
individuals. Only when the concentration is high, do features of
intoxication begin to manifest. Today the accepted upper level for blood
lead (BL) is fixed as 35 mcg/100 ml. However there are reports that
adverse effects especially on the haematopoietic system can occur at
levels as low as 10 mcg/100 ml. Neurobehavioural disorders in children
can occur at BL as low as 25 mcg/100 ml. Hence, the current trend is to
consider even levels as low as 10 mcg/100 ml as unacceptable, especially
in children.
Clinical Features
1. Acute poisoning
a. This is rare. Many reported cases of acute poisoning may actually be
exacerbations of chronic lead poisoning when significant quantities of
lead are suddenly released into the bloodstream from bone.
b. Symptoms include metallic taste, abdominal pain, constipation or
diarrhoea (stools may be blackish due to lead sulfide), vomiting,
hyperactivity or lethargy, ataxia, behavioural changes, convulsions, and
coma.

10. 2. Chronic poisoning
a. Mild Toxicity (BL 40 to 60 mcg/100 ml)
– Myalgia
– Paraesthesia
– Fatigue
– Irritability
– Abdominal discomfort
b. Moderate Toxicity (BL 60 to 100 mcg/100 ml) :
– Arthralgia (especially nocturnal)
– Muscular exhaustibility
– Tremor
– Headache
– Diffuse abdominal pain
– Anorexia, metallic taste, vomiting
– Constipation
– Weight loss
– Hypertension

11. c. Severe Toxicity (BL more than 100 mcg/100 ml) :
– Lead palsy: wrist drop or foot drop
– A bluish black lead line on gums (Burton’s line)

12. – Lead colic: intermittent severe abdominal cramps. There may be tenderness
around the umbilicus.
– Lead encephalopathy: It is more common in children and is often associated
with organic lead toxicity, especially tetraethyl lead (TEL) which is lipid
soluble and is distributed widely in lipophilic tissues such as the brain. TEL
is metabolised to triethyl lead which is the major toxic compound. There is
sudden onset of vomiting, irritability, headache, ataxia, vertigo,
convulsions, psychotic manifestations, coma, and death. Mortality rate is
around 25%. Even if recovery occurs, there is often permanent brain
damage manifesting as mental retardation, cerebral palsy, optic neuropathy,
hyperkinesis, and periodic convulsions.
Diagnosis
It has been suggested that all children should be screened for lead levels (BL)
on their 1st birthday, and if possible at yearly intervals thereafter until they
are 6 years old. If at any time the BL is more than 20 mcg/100 ml, therapeutic
intervention is indicated, and if it exceeds 70 mcg/100 ml, it should be
treated as a medical emergency.

13. Laboratory tests for lead:
1. Blood
Complete blood count and peripheral smear
General and non-specific findings include low haematocrit and haemoglobin
values with normal total and differential cell counts. The peripheral smear
may either be normochromic or hypochromic, and microcytic. Basophilic
stippling is usually seen only in patients who have been significantly
poisoned for a prolonged period. Hypochromia and basophilic stippling
are strongly suggestive of lead intoxication, but their absence does not
rule out lead poisoning. It must be borne in mind that such stippled RBCs
may also be seen in arsenic and zinc poisoning.
FEP (free erythrocyte protoporphyrin) and Znp (zinc protoporphyrin levels)
(>50 mcg/100 ml)
An elevated FEP and ZnP level indicates impairment of the haeme biosynthetic
pathway and may result from lead poisoning or iron deficiency. In order to
confirm whether it is due to the former, the BL must be estimated. Today
ZnP levels are more commonly studied than FEP (vide supra). It is to be
noted that both FEP and ZnP are not significantly elevated at lower levels
of lead poisoning.

14. Blood lead level (BL)
BL can change rapidly in response to lead intake (e.g. ingestion of lead paint
chips). For short exposure periods, it usually has a linear relationship to
intake levels. Blood lead levels reflect recent exposure or exposure over a
period of up to 3 to 5 weeks. In individuals with high or chronic past
exposure, BL usually under represents the total body burden because most
lead is stored in the bone and may be found at normal levels in the blood.
However, during stressful circumstances, patients with a high body burden
may have elevated BL because of the release of lead stored in bones.
The recommended methods of estimating blood lead level (BL) include
atomic absorption spectroscopy (AAS), electro thermal atomic
absorption spectroscopy (EAAS), anodic stripping voltammetry
(ASV), inductively coupled plasma atomic emission spectroscopy
(ICPAES), and x-ray fluorescence spectroscopy. Alternative methods
include proton-induced x-ray emission (PIXE), fast neutron activation
analysis (FNAA), mass spectrometry (MS), and microwave plasma
detection.

15. 2. Urine
– The concentration of aminolaevulinic acid (ALA) in urine is widely used as
a measure of lead toxicity in workers who are exposed occupationally. For
this purpose fluorometry (after separation by HPLC) is preferred.
– Urine lead level : If this is above 150 mcg /litre it is a significant finding,
but it is unfortunately not very reliable.
– Calcium disodium EDTA mobilisation test : This test is done mainly in
children to find out whether a child whose BL is between 25 and 41
mcg/100 ml will respond to chelation therapy with a brisk lead diuresis.
Children whose BL is more than 45 mcg/100 ml should not receive this
provocative test; they should be referred for chelation therapy immediately.
An 8 hour calcium disodium EDTA chelation provocative test is considered
positive if the lead excretion ratio is more than 0.6 (though some clinicians
use a cut-off of 0.5). Children with positive chelation test results should
undergo a 5-day course of chelation.
– Urine porphyrin level:
Patients with lead poisoning usually excrete elevated levels of porphyrins in
the urine

16. 3. Bone
– The x-ray fluorescence technique is brief and non-invasive and carries low-
risk. It is based on the specific atomic property of lead to emit characteristic
x-rays upon stimulation induced by external irradiation. The stimulated
radiation is monitored externally by a solid state detector and can be
expressed in terms of lead concentration in the bone. Because emitted
radiation is considerably attenuated by the overlying tissue, the tibial shaft
is chosen as the measurement site because of its thin overlying skin.
– Radiology:
This involves evaluation of the ends of long bones for arrest of growth line,
and of the abdomen for radiopaque densities. Radiological examination of
the abdomen may show radiopaque foreign material, if the material has
been ingested during the preceding 24 to 36 hours. The significant finding
in bone is the appearance of dense transverse bands or lead lines extending
across the metaphyses of the long bones, and along margins of flat bones
such as the iliac crest. The width of the lead line varies depending upon the
amount of lead ingested and the length of time it has taken. It usually takes
4 to 8 weeks of heavy exposure for dense bands to develop.

17. Treatment
1. Severe acute poisoning with encephalopathy: This is a medical
emergency and the following measures must be undertaken immediately
a. BAL 4 mg/kg immediately (in children).
b. Cranial CT scan: to rule out cerebral oedema.
If there is cerebral oedema, it can be managed by the following measures:
• Controlled hyperventilation, maintaining an arterial CO2 tension of 25 to
30 mmHg, can reduce intracranial pressure in patients with rapidly
worsening mental status, lateralising neurologic findings or evidence of
impending herniation. Monitor intracranial pressure continuously.
Monitor cardiovascular function, renal function, and serum electrolytes
carefully.
• Diuretics
» Mannitol 20%: Adult: 1 to 1.5 gm/kg by infusion over 10 to 20 minutes.
Child: 0.5 to 1 gm/kg by IV infusion over 10 to 20 minutes.
» Glycerol: 0.3 to 1 gm/kg orally.
» Loop Diuretics: Furosemide and/or ethacrynic acid may be useful as an
adjunct in the treatment of cerebral oedema.

18. • Corticosteroids:
 Dexamethasone—low dose - 16 mg/day in divided doses.
 Dexamethasone—high dose— 1 to 2 mg/kg/day in divided doses.
c. KUB: to rule out lead chips in GI tract.
d. For seizures: Treat seizures with intravenous diazepam (Adult: up to 10 mg
slowly, repeat if necessary; Children: 0.1 to 0.3 mg/kg slowly). Seizures
from lead encephalopathy may be resistant to anticonvulsant therapy;
barbiturate coma and aggressive control of ICP may be needed.
e. Foley catheterisation: to monitor urinary specific gravity, sediment, lead
level.
f. CaNa2 EDTA 75 mg/kg/day IV infusion.
g. After the initial dose of BAL, repeat the same dose at 4 hourly intervals until
blood lead level falls below 40 mcg/100 ml. Then reduce BAL to 12
mg/kg/day in 3 divided doses.
h. Reduce CaNa2 EDTA to 50 mg/kg/day as condition improves.
– Continue the above regimen until patient is asymptomatic and can tolerate
oral chelation with D-penicillamine or DMSA.

19. 2. Severe acute poisoning without encephalopathy: (BL more than 70
mcg/100 ml) –
a. BAL 12 mg/kg/day.
b. EDTA 50 mg/kg/day.
c. Discontinue BAL when the BL falls below 40 mcg/100 ml, but continue
EDTA for 5 more days.
d. Change to oral chelation subsequently which may have to be continued
until the BL falls below 15 mcg/100 ml, or 3 months have been
completed.
3. Moderate poisoning: (BL between 45 and 70 mcg/100 ml) –
a. EDTA 50 mg/kg/day.
b. When blood lead falls below 40 mcg/100 ml, begin oral chelation.
4. Mild poisoning: (BL between 20 and 35 mcg/100 ml) –
D-Penicillamine 30 mg/kg/day in 3 divided doses. Start with ¼th of the
calculated dose. Double this after 1 week. Double again (to full dose)
after 1 week. Continue this until the BL falls to less than 15 mcg/100 ml,
or 3 months have been completed.

20. In addition to the above protocol, the following supportive measures must be
instituted as applicable –
■ Thiamine 10 to 50 mg/kg is said to improve neurological manifestations of lead
poisoning.
■ In acute poisoning, or in the event of radiopacities in the GI tract on x-ray,
stomach wash can be done.
■ Lead colic usually responds to IV calcium gluconate.
■ Correct iron deficiency if present.
■ IV fluids, (maintain specific gravity of urine under 1.020).
■ If intracranial pressure is high due to cerebral oedema, administer mannitol or
steroids as required (vide supra).
■ Organic lead poisoning is mainly managed symptomatically. Chelation is done
only if there is production of inorganic lead in the body from organic lead.
■ After one round of chelation therapy, allow an interval of 2 weeks and then
esimate the BL. Repeat chelation if necessary. Rebounds are common.
■ And finally the sine qua non of treament of heavy metal poisoning: remove the
patient from the source of exposure.
In recent times, a new chelating agent called Succimer has been introduced in the
management of lead poisoning. It is said to be more efficacious and less toxic.

21. REFERENCES
• Textbook of Modern Clinical Toxicology by V.V. Pillai,
Edition:4,
Page No.:83 -90
• https://pharmadost.info/lead-poisoning/