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Lead - The Lethal Metal

Pathology of Lead Poisoning

Dr Sampurna Roy MD     

 

   

 

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When I wrote about Lead poisoning 6 months ago, I had no idea that a popular brand was distributing food  containing dangerous amounts of lead in my country for decades.

I'm deliberately not mentioning the name of the controversial food or brand as I'm not a politician, journalist or a sensational story writer.

As a pathologist I only write facts about pathological changes in various organs in a disease with reference to articles and text books. 

In this post I have given a brief outline of various changes in the body due to the toxic effect of lead and some interesting facts about the use of this lethal metal.

 

Pathology of Lead Intoxication:

Lead poisoning was one of the first environmental health risks in the history of the mankind.

The first clinical data is described in the Corpus Hipocraticcus.

The researchers proposed that Julius Cesar and Octavio had clinical manifestations associated with lead poisoning.

Paul of Aegina in the 7th century described the first epidemic associated with lead intoxication.

In the Middle Ages the use of lead decreased until the Renaissance period when lead poisoning mostly affected painters, metal-smithers and miners.

Lead has been recognized as a poison for millennia and has been the focus of public health regulation throughout the world.

Although the toxicity of lead was recognized centuries ago, concern was restricted to overt symptoms: colic, encephalopathy, anemia, or renal disease.

Two major reasons for lack of progress in restricting toxicity were that interest was limited to occupational exposures and there was lack of awareness of specific biochemical or metabolic effects.

Identification of subclinical effects is now possible because of the development of sensitive measures to detect cognitive and behavioral changes that are not apparent clinically and because of methods to measure the reduced activity of heme enzymes.

This progress was driven by basic and clinical research that resulted in a better understanding of cellular toxicology.

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis.

The new awareness prompted the lowering of acceptable occupational exposures, as measured by blood lead from 80 to 40 to 60 micrograms/dL range and the establishment of maximum recommended exposures in children to a blood lead level of 25 micrograms/dL.

Lead Biomarkers are generally classified into three groups: Biomarkers of i) Lead exposure, ii) Lead effect, and iii) Lead susceptibility.

Exposure occurs mainly through the respiratory and gastrointestinal systems, and the ingested and absorbed lead is stored primarily in blood, soft tissues and bone.

Lead present in bones, teeth, nails, and hair is not generally regarded as harmful.

The half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.

Amount of present in brain, kidney, bone marrow and liver can have serious effect on the patient.

Toxic effect of lead on various organs:

1) Brain:

Environmental and occupational exposure is of serious concern specially during the fetal/neonatal period.

Exposure to excessive amounts of inorganic lead during the toddler years may produce lasting adverse effects upon brain function. 

Children with blood lead levels 80 microgm Pb/ml but with concentrations lower than those in children with frank encephalopathy (120 microgm Pb/ml), exhibit mild central nervous system symptoms such as clumsiness, irritability, and hyperactivity. 

The mechanism for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission.

In lead encephalopathy, the brain is edematous and displays flattened gyri and compressed ventricles.

There may be herniation of the uncus and cerebellar tonsils.

Lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia.

Histological features include: 

(i) petechial hemorrhages

(ii) congestion, 

(iii) focal areas of necrosis of the neurons.

(iv) There may be diffuse astrocytic proliferation in both the gray and white matter

(v) Vascular lesions in the brain are particularly prominent with dilatation and proliferation of capillaries.

2) Kidney:

Epidemiological studies have demonstrated a strong association between lead exposure and the presence of renal functional abnormal. 

There may be both acute and chronic nephropathy.

Acute lead nephropathy is characterized by proximal tubular dysfunction with the development of a Fanconi-type syndrome, alterations in mitochondrial structure and the development of cytosolic and nuclear  inclusion bodies.

Intracellular lead is associated with specific high affinity proteins and can also bind to metallothionein.

Chronic lead nephropathy is irreversible and is typically accompanied by interstitial fibrosis, both  hyperplasia and atrophy of the tubules, glomerulonephritis and, ultimately, renal failure.

In addition, lead produces renal neoplasms in experimental animals.

A case of Lead nephropathy due to Sindoor been reported in India.

Lead nephropathy should be included in the differenitial diagnosis of causes of chronic kidney disease and occupational and environmental lead exposure should be investigated carefully during the medical history.

2) Liver and Gastrointestinal Tract:

 

Autopsy studies of lead-exposed patients have shown a large amount (approximately 33%) of the absorbed lead in soft tissue stored in liver.

Ingestion of lead is one of the primary causes of its hepatotoxic effects.

Lead toxicity should always be taken into account in cases of intrahepatic cholestasis with an unknown etiology.

After exposure to very high concentrations of lead, gastrointestinal colic or "Saturnine Colic"  (abdominal pain together with constipation and intestinal paralysis) is a consistent early symptom of lead poisoning in humans.

Such severe gastrointestinal effects are consistently observed in patients with a blood lead range of 30 to 80 microg/dl.

 

3) Heart:

Chronic and acute lead poisoning cause overt, clinical symptoms of cardiac and vascular damage with potentially lethal consequences.

Morphological, biochemical, and functional derangements of the heart have all been described in patients following exposure to excessive lead levels.

Disturbances in cardiac electrical and mechanical activity and postmortem evidence of morphological and biochemical derangements of the myocardium have all been reported.

There are also signs of vascular degeneration, abnormal vascular smooth muscle function, and altered blood vessel compliance  in humans chronically and acutely exposed to toxic lead levels.

Chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances.

The exact pathogenic mechanisms causing changes in the cardiovascular system is not clear.

4) Bone marrow:

 

Occupational lead exposure can cause anemia at blood lead levels >50 microg/dl.

Symptoms of hemopoietic system involvement include microcytic, hypochromic anemia with basophilic stippling of the erythrocytes.

Lead intoxication cause anemia by disrupting heme synthesis in bone marrow erythroblasts through inhibition of the enzymes delta-aminolevulinic acid dehydrogenase and ferrochelatase.

The inability to produce heme adequately is expressed as microcytic and hypochromic anemia.

Basophilic stippling of the erythrocytes is related to the clustering of ribosomes.

Iron deficiency and lead poisoning are common among infants and children in many parts of the world, and often these 2 problems are associated.

Both conditions are known to cause anemia and appear to produce a more severe form of anemia when in combination.

5) Joint :

 

Lead arthropathy is a well-known complication of gunshot injuries with retained intra-articular bullets.

Classic findings of intra-articular speckled lead deposits (occasionally with a "lead arthrogram" appearance), joint space narrowing and preserved bone density were found at radiographs in the great majority of cases.

6) Gum: There is narrow bluish discoloration of gums (Burtonís line) indicative of chronic lead poisoning (plumbism).

 

7) Nerve: The most common lead related neurologic syndrome in adults consists of a polyneuropathy involving motor fibers.

This tends to affect distal nerves and may present as wrist drop due to radial neuropathy and foot drop due to peroneal neuropathy .

 

Interesting Facts about Lead:

-  Lead is one of the earliest metals discovered and was in use by 3000 BC.

-  The ancient Romans used lead for making water pipes and lining baths, and the plumber who joins and mends pipes takes his name from the latin word "plumbum" , meaning lead.

-  Later, lead came to be used for roofing, spires, cisterns, tanks, statues and even for ornaments.

                                          

  Lead Ornament         Replica of a statue containing lead             Spires

-  The statue of King Charles II in Edinburgh is made of lead.

 

 Replica of statue of King Charles II

- The dull grey colour of lead pipes and and cables is caused by the oxygen of the air attacking the metal so as to form a very thin film or skin.

  Lead pipes

-  This film resists further attack by air or water or even by chemicals such as acids and for this reason lead is not at all easily corroded, or eaten away.

-  Unlike iron and steel, it does not need protection by painting. Underneath the film the lead is bright shiny, bluish white metal as is shown by scraping it with knife.

     

       Lead slabs

- Lead is soft which makes it easy to squeeze or roll into shape.

The ease with which lead can be shaped and its resistance to corrosion make it valuable as the outer covering for electrical cables.

It protects the insulated wires inside without making cable too stiff to bend.

- Sheet lead is used as a lining for containers or tanks holding corrosive liquids that would eat away other metals.

Thus one method of making sulphuric acid is using large lead lined boxes and is called "lead chamber" process.

- Although lead is poisonous, the water in lead pipe does not mix with the metal because it forms a thin protective coating of lead sulphate inside the pipe.

Thin sheets of tin-lead alloy (mixture) are used for for tubes holding rubber solution, liquid glue and other substances which must be kept airtight, but many tubes of this kind are made of aluminium nowadays.

-  As lead is heavier than iron or brass, it is used for making weights that must not be too bulky like boots for divers.

- Lead also melts at a lower temperature than most of the other common metals.

Soft solder, an alloy of lead and tin, has even lower melting point.

It is used for mending and joining metal articles.

- Some large buildings have water sprinklers in the ceilings for extinguishing accidental fires.

The water outlet from the sprinkler is blocked by a seal made with with an easily easily melting lead alloy.

If the room becomes too hot because of a blaze, the seal melts and the water sprays the fire.

- An alloy consisting of lead, tin, and a little antimony is called pewter and was once much used for  mugs and dishes.

 

 Antique Pewter tankard

- Lead is present in old books, toys, organ pipe and rifle bullets. As pure lead would be rather too soft, however, it is hardened by having antimony or arsenic alloyed with it.

                                         

                            Dolls containing lead                   

- When alloyed with bronze (copper and tin) lead is sometimes used for the bearings for the shafts of engines and machine.

- About one-third of the lead used is made into plates of the batteries used for storing electricity. Motor car batteries are of this kind.

- Lead is effective as a screen to block the rays from radioactive substances.

The reactors in nuclear power station are screened by lead shields.

The operators who work with X-ray machines in the radiology department of hospitals are protected the same way and the lead shields are called "lead aprons"

 

  Lead apron

- The substances obtained by combining lead with chemicals have important uses. Among these are "white lead' (lead carbonate) used for making paint and red lead (lead oxide) used as a first coat to prevent rusting when painting steelwork  and for making joints in plumbing.

- Red lead is also used for making glass and making glazing pottery.

        

 Glazing pottery from red lead

- Other lead compounds are also used for glazing and for and making paints, varnishes, glass, matches and mixtures for killing insect pests.

- Lead azide is a violent explosive used in detonators.

 

   Inside a lead factory

Lead is obtained from galena, a combination of lead and sulphur sometimes found in limestone.

The lead is obtained by crushing the galena and then roasting it to drive off the sulphur.

The roasted galena is mixed with coke and limestone and put into a furnace.

Air is blown into the lower part of the furnace to make a draught for burning the coke, and the molten lead is drawn off from the bottom.

The limestone helps to make the slag formed by the impurities run easily.

The lead thus obtained often contains small quantities of gold, silver, copper and other metals and requires further treatment to purify it.

Sometimes enough silver is recovered to pay for the purification.

The finished lead is cast into "lumps" called pigs.

Much lead is obtained from "scrap", that is from old batteries and pipes that are melted down.

 

For thousands of years lead has been extensively mined, produced, and utilized in a variety of industrial settings, such as metallurgy, construction, production of plastics, ceramics, paints and pigments.

Lead and its compounds are systemic toxic agents.

A wide range of adverse health effects (including haematological, gastrointestinal, neuropsychiatric, cardiovascular, renal, endocrine, and reproductive disorders) has been observed in exposed workers.

The general population (particularly children) may also be exposed to toxic lead levels due to air, soil, food and water contamination.

Due to improved of workplace hygienic conditions, the pathological picture of occupational lead poisoning has gradually become less serious in most industrialized countries. 

Occupational history is crucial for the diagnosis of lead poisoning to prevent unnecessary surgery and occupational-related medico-legal issues.

 

Further reading:

All diagrams and photographs from personal collection - Dr Sampurna Roy MD

Primary prevention of lead poisoning in children: a cross-sectional study to evaluate state specific lead-based paint risk reduction laws in preventing lead poisoning in children.

Lead poisoning in children from townships in the vicinity of a lead-zinc mine in Kabwe, Zambia.

Lead poisoning: towards a paleo-epidemiologic re-interpretation?.

Are children still at risk for lead poisoning?

Brief history of lead poisoning: from Egyptian civilization to the Renaissance.

Comparative observations on inorganic and organic lead neurotoxicity.

Lead poisoning and brain cell function.

Neurotoxicity and biomarkers of lead exposure: a review.

Lead nephrotoxicity and associated disorders: biochemical mechanisms.

Lead nephropathy due to Sindoor in India.

Cardiovascular actions of lead and relationship to hypertension: a review.

Anaemia and abdominal pain due to occupational lead poisoning.

 

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                "Karma is like a boomerang, whatever you give out, will come back to you"

 

 

Dr  Sampurna Roy  MD

Consultant Histopathologist (Kolkata - India)

 

 


 

 

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