Accepted Manuscript

Title: Lead poisoning

Authors: Vaibhav Shukla, Priyanka Shukla, Avanish Tiwari

PII: S0976-2884(18)30063-8
DOI: https://doi.org/10.1016/j.injms.2018.04.003
Reference: INJMS 175

To appear in:

Received date: 31-3-2018

Revised date: 5-4-2018
Accepted date: 6-4-2018

Please cite this article as: Shukla V, Shukla P, Tiwari A, Lead poisoning, Indian Journal
of Medical Specialities (2010), https://doi.org/10.1016/j.injms.2018.04.003

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TITLE PAGE

Title

Lead poisoning

Authors
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Dr Vaibhav Shukla*, Professor, Dept of Medicine, Era’s Lucknow Medical College
Lucknow

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Dr Priyanka Shukla, Associate Professor, Dept of Microbiology, Era’s Lucknow Medical

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2

College Lucknow

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3
Dr Avanish Tiwari, Junior Resident, Dept of Medicine, Era’s Lucknow Medical College

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Lucknow

Medical College Lucknow U

Corresponding author: Dr Vaibhav Shukla, Professor, Dept of Medicine, Era’s Lucknow
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E mail: v_shukla2005@rediffmail.com
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Address: 44 D Vinay Nagar Krishna Nagar Lucknow
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Abstract
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Lead is not known to have any physiological role in the body but is ubiquitous in nature. In
our country there are many sources of lead exposure, in particular paints and recycling of
batteries . Lead is a persistent metal and is present in water, soil and dust. After being
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absorbed through GIT or respiratory system, it is stored in soft tissues as well as bones. Lead
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tends to affect many organ systems in the body particularly the nervous system and kidneys.
There are no safe levels and data suggests that low level exposure to lead may also affect
health of individuals. The diagnosis of lead toxicity can be done by measuring blood lead
levels and K x ray fluorescence (KXRF) instruments which measure lead levels in bone. The
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treatment consists of chelating agents like BAL , EDTA & DMSA. Eliminating lead from
potential sources of exposure would go a long way in preventing effects of lead toxicity.
1 Introduction

Lead is ubiquitous in nature. It can occur in elemental form like bullets , inorganic
compounds such as lead oxide, lead chromate, lead sulphide or as an organic form like
tetraethyl lead. The most common sources of inorganic lead exposure include paints and lead
contaminated soil. Lead based paints are widely used in India. Lead based paints are also
used in toys. Enamel paints may have as high as 1,40,000 ppm of lead in them. The highest
concentration of lead is found in yellow and orange coloured paints. The other sources of

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lead exposure include drinking water as lead is used in water pipes, battery making ,
soldering, glass manufacturing industries and other industrial emissions . Automobile

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emissions were an important source of lead exposure in the past but with use of lead free
petrol, this is now less common. Recycling of batteries is also an important source of lead

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exposure. Vermillion (sindoor) , kajal and lipstick are also sources of lead . In our country

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another source of lead exposure is herbal and traditional medicines which are in rampant use.
Certain herbal products were found to be having as much as 5,37,000 µgm/ gm of lead 1 In a
very recent study on ayurvedic medicines , 65% of them were found to be having lead and

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some of them in very high concentrations .2 Lead is also found in food which is stored in
containers which are painted with lead based paints. Table 1 shows the common sources of
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lead exposure.
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Lead exposure mainly occurs through respiratory and gastrointestinal systems.
The amount of lead absorbed through intestine is 10-15%. The amount of lead absorbed is
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increased if there is deficiency of iron , calcium or zinc. Of the lead which is inhaled, 30-
40% is absorbed in the blood. Once absorbed into the circulation , lead is bound to
erythrocytes with average clearance half time of 35 days3 and is distributed to soft tissues.
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Lead is also stored in bones and these stores can persist for several years. When bone
metabolism increases like pregnancy or post menopausal osteoporosis , then this stored lead
is released in the circulation and causes lead toxicity. Liver is the largest repository of lead
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among soft tissues4.

2 Mechanism of toxicity
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The toxic effects of lead are due to its combination with sulphydryl group in proteins thus
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inhibiting sulphydryl dependent enzymes. Lead causes a disruption in haemoglobin synthesis

by inhibiting sulphydryl dependent enzymes such as ferrochelatase & aminolevulinic acid
dehydratase which are critical for heme synthesis. This also causes a rise in free erythrocyte
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protoporphyrin. The other sulphydryl enzymes inhibited by lead include superoxide

dismutase, G6PD & catalase, among others. Inhibition of these enzymes leads to production
of reactive oxygen species with resultant oxidative stress, Oxidative stress has an important
role to play in lead toxicity .5 In the nervous system lead also interferes with excitatory
neurotransmission by glutamate. Lead also competes with calcium in various biologic
systems including nervous system. It may thus effect neurotransmitor release that is calcium
dependent .6
3 Clinical features

3.1 Acute lead poisoning

The symptoms of lead toxicity can be non specific . Acute lead poisoning is uncommon.
Abdominal colic, constipation, fatigue can occur. At lead levels between 60-80 µgm/dl there
may be impaired neurotransmission and neuronal cell death with peripheral neuropathy,
impaired hematopoiesis resulting in anemia and renal tubular dysfunction. At levels 80-120
µgm/dl there may be acute encephalopathy with convulsions , coma and death .

3.2 Chronic lead poisoning

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Patients with chronic lead toxicity present with abdominal pain of colicky nature, anemia,

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hypertension, hearing impairment, accelerated decline in cognition and peripheral
neuropathy. Renal insufficiency is also a common feature in occupationally exposed

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individuals . Lead can cause proximal tubular damage, glomerular sclerosis and interstitial

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fibrosis. There may be proteinuria ,tubulointerstitial fibrosis with or without renal failure.

3.3 Lead and nervous system

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Early symptoms are irritability, headache, reduced attention span and memory loss. The most
common presentation of chronic lead exposure is peripheral neuropathy .This is usually a
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motor neuropathy and there is commonly weakness of extensors of wrist and fingers
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Autonomic neuropathy may also occur. Sensory neuropathy although rare , has been
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reported. 8 The action of lead on nervous system is to effect calcium based reactions and
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neuronal signalling. Lead exposure affects all neurotransmitters in the brain. Features of lead
encephalopathy include drowsiness , irritability, seizures, gait disturbance and coma. The
chances of developing encephalopathy increase as blood lead levels increase and are more
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probable when blood levels exceed 70 µgm/dl.

3.4 Lead and renal system

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Lead nephropathy is a well documented entity in occupational exposure. Early signs of

chronic lead intoxication are due to proximal tubule dysfunction resulting in hyperuricemia
due to diminished urate excretion. The triad of gout, hypertension and renal insufficiency
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should raise suspicion about lead exposure. Chronic interstitial nephritis may also be
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presenting feature of chronic lead exposure . Kidney biopsy shows interstitial fibrosis and
tubule atrophy although this is non specific 9

3.5 Lead and cardiovascular system

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Elevated lead levels are associated increased cardiovascular mortality. There is strong
evidence that raised lead levels are associated with risk of developing hypertension .10 The
exact mechanism of lead induced hypertension is not known. However studies indicate that
lead induced renal dysfunction may have a role to play in the pathogenesis of hypertension.
Oxidative stress may also play a major role in hypertension. Although hypertension and
deranged renal function are the mechanisms proposed for effect of lead on cardiovascular
disease, other mechanisms are likely to be involved.11

The increased cardiovascular mortality seen in individuals with lead toxicity has been linked
to increased lead levels both in the blood as well as bone, with a greater association for bone
levels of lead .12 Weisskopf et al13 analyzed cardiovascular mortality & bone lead levels in
around 850 male participants . After multivariable analysis, it was shown that individuals
with higher bone lead levels were more likely to die of all causes as well as cardiovascular
causes.

Menke et al14 studied nearly 14,000 participants with blood lead levels <10 μg/dL . The

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follow up period was twelve years. After multivariate adjustment, the risk of cardiovascular

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events was significantly greater in individuals who had higher blood lead levels (≥ 3.62
μg/dL), as compared with those who had lower blood lead levels (< 1.94 μg/dL). All-cause

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mortality was higher by 25% in the individuals who had higher blood lead levels, whereas
cardiovascular mortality , mortality from myocardial infarction and mortality from stroke

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was higher by more than 2-fold . There was an increased prevalence of peripheral arterial
disease in individuals with higher blood lead levels. ECG conduction delays have also been
reported with lead levels > 40µgm/dl.

3.6 Lead and hematopoetic system U

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Lead affects the hematopoietic system by inhibiting the synthesis of hemoglobin . The life
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span of circulating erythrocytes is also reduced due to increased fragility of cell membranes .
Both these processes lead to anemia. In a study on swans and geese ,it was found that
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haemoglobin, PCV and MCHC were reduced significantly in these avian species as blood
lead levels increased.15 In a recent study done in China on children, logistic regression
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analysis revealed that higher blood lead levels were associated with reduced platelet count in
addition to reduced haemoglobin and RBC counts 16
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3.7 Lead and reproductive system

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Excessive lead exposure can affect the reproductive system , both in men and women. The
effects of lead in men include reduced motility as well as number of sperms with retarted
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sperm activity 17 Reduced libido has also been reported with high lead levels. Male infertility
and changes in levels of serum testosterone are also reported. Lead is also known to affect
the functions of the prostate gland. Most of these effects have been seen in lead exposed
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workers, and some are at levels presently considered 'acceptable'. The effects of lead in
women include infertility, spontaneous abortions, , pre-eclampsia, pregnancy induced
hypertension, premature membrane rupture and premature delivery. Low birth weight
,reduced head circumference and birth length have also been reported. The evidence
implicating a possible teratogenic effect of lead is much less clear18

3.8 Lead and hepatotoxicity

 Studies have shown that lead toxicity leads to inhibition of CYP450. But it tends to induce
CYP51 , an important enzyme in synthesis of cholesterol thereby increasing cholesterol
levels19. Lead nitrate also causes proliferation of liver cells in rats without concomittent liver
cell necrosis.

3.9 Lead and skin

In a recent study in Iran , skin hyperpigmentation was reported in patients of lead

poisoning.20

4 Diagnosis

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Measurement of blood lead levels is the standard screening test for lead toxicity. There is no

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blood lead level below which no harm occurs. But for diagnostic purpose blood levels more
than 10 µgm/dl are considered abnormal. The blood levels only represent the acute or recent

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exposure to lead and don’t take into account the accumulated bone lead levels.

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Basophilic stippling of RBCs with a normocytic normochromic anemia are found in patients
of lead toxicity.

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Cortical bone lead measured by radiographic fluoroscopy is a sensitive marker for cumulative
lead exposure. Development of K xray fluorescence (KXRF) instruments has made
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estimation of bone lead levels easier, giving better understanding of cumulative exposure of
lead over years.
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5 Treatment
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Treatment of lead toxicity involves prevention of further exposure, decontamination,

supportive care and chelation. Adequate intake of iron and calcium should be encouraged.
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This will retard absorption of lead. Vitamin C may play a role in excretion of lead from
kidneys
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Chelation therapy with BAL and EDTA is recommended for lead levels above 70 µgm/dl in
children and above 80 µ/dl in adults. BAL( 300-450 mg/m2/day in divided doses for 3-5
days) is given intramuscular while CaNaEDTA ( 1000-1500 mg/ m2/day for 5 days ) is given
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as continuous intravenous infusion. Dimercaptosuccinic acid (DMSA) and D penicillamine

may also be used as chelating agent. Table 2 shows treatment of lead toxicity based on levels
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of lead in blood.
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6 Conclusion

Lead is present throughout the environment and is not known to have any physiological role
in the body. In our country its harmful effects are more likely to be seen due its use in paints
and recycling of batteries. One needs to be aware of the toxic effects of lead so that
appropriate and timely theapy can be instituted in affected individuals.
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TABLE 1

COMMON SOURCES OF LEAD EXPOSURE

LEAD BASED PAINTS

HOUSEHOLD DUST
LEAD WATER PIPES
SOIL AROUND HOMES
HERBAL AND TRADITIONAL MEDICINES
TOYS WHICH ARE PAINTED
INDUSTRIAL- battery making ,soldering, glass making

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LEAD GLAZED CERAMIC WARE, FOOD IN CANS WHICH ARE PAINTED

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Table 2

Blood level Treatment

<5µgm/dl
5-29µgm/dl U
No treatment, monitoring of levels
Discuss health risks, minimise exposure,
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monitor
30-40µgm/dl Medical evaluation, remove source of
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exposure, monitor every 6 months
41-60µgm/dl Same as above, monitor 2 monthly
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> 60µgm/dl If symptomatic administer EDTA or DMSA

If asymptomatic remove source of exposure,
monitoring monthly
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>80µgm/dl Treat with EDTA or DMSA if

encephalopathy treat with BAL.
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