Download Lecture No. 9

Metal poisoning – mercury,
lead, cadmium
Lecture No. 9
Copyright © Mgr. Zuzana Široká, PhD.
Mercury - Hg
• Only metal which is liquid at room temperature
• Both organic and inorganic compounds, all toxic
• Sources: earth’s crust and industry, burning of fosil fuels,
waste
• Cummulation in water environment
• Water microorganisms transform pure or inorganic mercury
into methylmercury – most common source of poisonings –
incorporation into food chain (fish)
• Other cases of intoxication usually occupational, mistakes –
Iraq (wheat seed with antifungal phenylmercury compound
– exchanged for food), Minamata disease (fishermen)
Elemental mercury
• Liquid
• Almost no absorption in GIT
• Vapours are more dangerous, perfect absorption via
lungs
• Once in the blood circulation, the target organ are
kidneys, where it can cummulate and be deposited
for several months
• Also crosses blood-brain barrier (change to
inorganic mercury with longer deposition times) and
placental barrier
• Excreted via urine, faeces and milk
Inorganic mercury compounds:
• HgCl2, Hg(CN)2, Hg(NO3)2
• Transported bound to blood peptides, they do not
cross barriers much
• Mercury binds with covalent bond to -SH,
-COOH and – His
• This influences function of many enzymes and cell
processes
• Water soluble salts moreover coagulate peptides and
are corrosive
• They damage kidney tubules and GIT mucosa
• Only traces excreted to milk
Organic mercury compounds:
• Methoxyethylmercury and arylmercury compounds
(e.g. phenylmercury) – release mercuric ions – act like
inorganic compounds
• Methyl- and ethylmercury – firm bond, whole
compound toxic
• Bind with –Cys and –SH, block enzymes, destroy
haematoencephalic (blood-brain) barrier, increase
permeability
• Don't have corrosive effect on mucosas
• In blood transported bound to erythrocytes
• They have high affinity to neural tissue (change to
inorganic mercury with longer deposition times) ,
cummulate also in kidneys
• Cross the placenta and have fetotoxic effect
• Excretion to faeces, urine, milk, sweat, saliva
• Deposition in hair and skin, excretion very slow
• Clinical signs:
- in dogs, cats and young cattle – more stimulation of CNS
- in cattle, pigs and poultry – more depression of CNS
in dogs: blindness, involuntary chewing
in cats: weakness, ataxia, rigidity of hind limbs, convulsions,
glass-like gaze, miaowing, hypersalivation
in calves: ataxia, limping, stumbling, clonuses of eyelids and ears,
hypersensitivity, malfunction of swallowing, disturbance of
vision, convulsions, opistotonus, coma, death
in cattle: anorexia, loss of weight, weakness, loss of coordination,
salivation, lacrimation, diarrhoea and colic, loss of teeth, swollen
lymphatic nodes, disturbances in EKG, cough, dyspnoe, eczema,
hyperkeratosis. Convulsions very rare
in pigs: inappetence, colic, diarrhoea, hypermotility, tremors, loss
of coordination, they are hunched, paralysis of hind limbs
in poultry: ataxia, loss of coordination, pale cere and lobes
 Acute intoxication: more often in inorganic poisoning,
mainly GIT signs, oliguria, uraemia, typical mercury bluish
gum line, decrease of blood pressure, sometimes CNS
disturbances
 Chronic intoxication: typical for methylmercury, not GIT
signs, damage of CNS, kidneys, again bluish margin on
gingiva, loss of teeth, tremor
• Pathoanatomical examination:
- reduction of cerebellum, leptomeningitis in cats, congestion
and haemorhagia in brain, stomatitis, enteritis, petechias
- histology – swollen axons, demyelinisation, vacuolisation
on neurons, hyperplasia of epithelium
• Treatment: chelate agents – DMSA, penicilamin (only in
inorganic forms!), vitamin E and Se – antioxidants,
spironolacton – blocks binding of organic mercury
compounds to erythrocytes in acute poisoning, thiosulfate –
increases elimination of mercury by kidneys
Lead - Pb
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Soft, grey metal
Known since ancient times
Absolutely abiogenic to organisms
Used in pipes, tetraethyl-lead as a petrol
additive, red-lead (minium) primer paintings
• Most poisonings in cattle (lead paintings,
batteries in silage), but also dogs, wild animals
• Both inorganic and organic compounds – like in
mercury, different characteristics
• Absorption and elimination:
- Inorganic lead: toxic after ingestion
- Organic lead: toxic after skin contact, ingestion,
inhalation
- Absorption is promoted by calcium, zinc and iron deficit
and by fats in food, higher in young animals
- Transported bound to erythrocytes (90 %)
- High deposition in tissues – first in liver, then
redistributed to bones (inorg.), kidneys, muscles and hair
- Bone-lead becomes mobilized through pregnancy or
fracture healing
- Excretion via bile to faeces, also to urine and milk
- Inorganic compounds acummulate more and elimination
is very slow, organic compounds excreted much quicker
- Normal blood level of lead cca 0,1 mg/kg, above 0,4 it is
considered as toxic
• Mechanism of action:
- Inorganic lead (mainly):
- Disturbs saccharide metabolism, metabolism of haem inhibits Ala-D (Delta-aminolevulinic acid dehydratase)
– increased concentration of aminolevulinic acid in
urine, and other enzymes involved in haem formation
- The toxicity comes from its ability to mimic other
biologically important metals - calcium, iron and zinc
and to interact with proteins
- Organic lead (mainly):
- interferes with excitatory neurotransmission by
glutamate
- it is a potent inhibitor of the NMDA receptor, a
protein playing an important role in brain development
and cognition (also in development of schizophrenia)
- doesn't influence synthesis of haem much
• Clinical signs of intoxication:
- Acute intoxication:
- from 12 – 92 hours after absorption
- apathy, atonia of rumen, anorexia, CNS disturbances
and brain oedema – tremor of head, neck, loss of
coordination, salivation, gnashing of teeth,
aggressiveness, convulsions, blindness, death due to
respiration collapse
- Subacute intoxication:
- similar symptoms, but more severe GIT damage,
changing of constipation and severe diarrhoea, strong
colic pains (Saturnine or Poitou colic), mydriasis,
opistotonus
- Chronic intoxication:
- inappetence, anorexia, paresis, paralysis of n. recurens
in horse – whistling, typical greyish gum line (Burton
line), CNS disturbances
•
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Pathological examination:
Typical smell from cadaver, petechias
Green-grey colour of muscles
Corrosive changes on GIT mucosa
Dystrophic kidneys
• Diagnostics:
- Samples of blood, urine, muscle, liver etc.
- Assessment of lead in these samples + assessment of
aminolevulinic acid in blood and urine
•
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Treatment:
Usually only in pets
Gastrolavage, administration of activated charcoal, laxatives
Chelating agents – EDTA, penicilamin, dimercaprol
Cadmium - Cd
• No constructive purpose in the body
• Extremely toxic even in low concentrations,
accumulates in organisms and ecosystems
• Chemical properties similar to zinc – exchange in an
organism (also can replace Cu, Fe, Ca)
• Sources: earth crust, fossil fuels, plastic materials
industry, electronic industry, tobacco fume
• Absorption after ingestion (1-5%) or by inhalation
(better bioavailability)
• The first documented case of mass cadmium poisoning
in the world - in Toyama Prefecture, Japan in 1950 –
Itai-Itai disease (river polluted with waste from
factory, water used on rice fields – poisoning from rice)
- In blood transported bound to proteins (formation of
complexes), in higher concentrations bound to
erythrocytes
- Deposition in liver, kidneys and gonads. Slow excretion
(up to 10 years). Does not go to milk and to foetus.
• Mechanism of action:
- Inhibition of many enzymes, antagonist to many metals –
Zn, Cu, Ca, Fe
- Disturbance of cholecalciferol (vit. D) production, thus
influences Ca metabolism
- Inhibition of a specific testis hydrolase – affects activity
of gonads
- Xenoestrogennic element
- Formation of complexes, which are digested in kidney –
release of Cd - damage
• Clinical signs:
- Acute exposure:
- Cadmium fumes may cause flu like symptoms
including chills, fever, and muscle ache
- More severe exposures can cause tracheo-bronchitis,
pneumonitis, and pulmonary oedema. Symptoms of
inflammation may start hours after the exposure and
include cough, dryness and irritation of the nose and
throat, headache, dizziness, weakness, fever, chills, and
chest pain.
- Ingestion of any significant amount of cadmium
causes immediate poisoning and damage to the liver and
the kidneys. Also CNS disturbances occur and changes
in blood count
- Chronic exposure:
- Osteomalacia, osteoporosis – disturbance of vitamin
D and calcium metabolism
- Pain in the joints and the back, and also increased
risk of fractures. In extreme cases of cadmium
poisoning, the mere body weight causes a fracture
- The kidneys lose their function to remove acids
from the blood. The kidney damage is irreversible.
- Gout, a form of arthritis due to the accumulation of
uric acid crystals in the joints (hyperuricemia).
- Some patients may lose their sense of smell
(anosmia)
- Damage of gonads, suspected carcinogen – tumours
of testes
• Pathological examination:
- gastritis, enteritis, nephritis, stomatitis,
degeneration of liver, necrosis on testes
• Treatment :
- Chelating agents – EDTA,
DMSA
- Administration of calcium
More info:
http://www.ilo.org/encyclopedia/?doc&nd=857200247&n
h=0
http://enhs.umn.edu/hazards/hazardssite/mercury/merchea
ltheffects.html
http://www.niehs.nih.gov/
http://www.ra.mahidol.ac.th/journal/index.php?command
=preview&selvol=27&selno=1&selids=156
http://www.nsc.org/library/facts/lead.htm
http://www.calpoison.org/public/lead.html
http://www.lead.org.au/au.html
http://www.atsdr.cdc.gov/toxprofiles/tp5.pdf
http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/
group29/introtox.htm