Lead toxicity

Lead (Pb)
Lead is the most commonly encountered metal in livestock poisoning.
Ø Paint – a common source of lead in poisoned animals licking of discarded storage batteries, (lead is being replaced from paints now).
Ø Industrial effluents in streams or on forage contain lead. Ex: - Musi river, Nakkavagu of Patancheru, forage (paragrass) on either side of Musi river.
Ø Grass on either side of busy highways may contain toxic amounts of lead released through automobile exhaust.
Ø Water distributed from lead pipes.
Ø Milk secreted from lead-poisoned animals can be dangerous for the young animal. Lead in milk is absorbed fast. Gastric acidity ulcerated gastric mucosa favors increased absorption. Lead crosses BBB (blood brainbarrier) and placental barriers.
Ø Calves, cattle, dog and sheep are most susceptible. Cats, goats, swine and chicken are less susceptible. Susceptibility is based on feeding habits and their probing nature.
Toxic Levels In Animals
Cattle-intakes of greater then 6-mg/kg-body weight can lead to chronic poisoning and intakes greater than 10 mg/kg BW may cause acute lead poisoning.
Sheep-generally occurs only in lambs and symptoms of poisoning appear at intakes greater than 4.5 mg/kg BW.
Pigs, Goats and Rabbits-more resistant than sheep or cows. Very minor signs of poisoning occur at intakes of 60 mg/kg BW. This is equal to blood concentrations of 130 micrograms per dl.
Horses-respiratory "roaring" occurs at intakes of 6.4 mg/kg BW. Signs of anemia occur at intakes of 7.4 mg/kg.
Birds-poultry can withstand dietary intakes of 100-mg/kg feed with no symptoms. Levels of 500 mg/kg induce serious poisoning.
Dogs and cats-nervous symptoms of poisoning appear at intakes of 5 mg/kg BW/day
Bone is the sink for lead; (hence an x-ray picture shows lead lines in bone). This is considered to be a protective mechanism of the body. Other two protective mechanisms are the sequestration of lead in liver and kidney.
Mechanism of Action
Like all other metals lead inhibits SH group of enzymes essential for cellular metabolism. The systems most affected are CNS & GI. Lead after crossing BBB, affects capillary endothelial cells with resulting cerebral oedema and hemorrhage. Capillary endothelial cell damage is said to be the primary action of lead in liver, kidney and intestine. SGOT, SGPT increase and LDH alkaline phosphatase decreases reflecting cell damage.
Lead inhibits heme synthesis leading to hemoglobin deficiency, but heme being an important component of mitochondria respiratory proteins such as cytochrome a, b, c, c1, b5 and P450 further affects cell function.
Lead causes behavioural defects in young ones. This could be due to inhibition of adenylcyclase and AchE, imbalance of neurotransmitters such as Ach and nor epinephrine or inhibition of energy metabolism or myelination of developing brain.
Muscle weakness seen in lead poisoning may be due to effect of lead on neuromuscular transmission and the peripheral nerve demyelination caused by it. Like all other heavy metals lead causes immunosuppression.

Signs: Clinical signs depend on the amount of lead ingested, species, body burden etc., and may take weeks to months. If industrial effluent is the source and the amount ingested is more, death without any signs is noticed. G I signs accompany encephalopathy. In acute toxicity, nervous signs are seen and in chronic exposure G I signs predominate.
Typical symptoms in cattle include, diarrhoea, dullness or excitement, anorexia, colic, trembling or blind or pressing the head, bawling or bellowing, and hyper motility. Normal temperature.
Other signs:
Ø Behavioral signs - anxiety, hyper excitability, bellowing, rolling eyes, pressing of head against a wall or post, attempts to climb walls, rolling of eyes, jumping into the air, frenzied or maniacal behaviour. Lead disrupts learning and memory in young ones directly or through mother’s milk.
Ø Nervous signs – depression (specially in sheep and horses), muscle spasms, paralysis of pharynx and larynx (roaring in horses) blindness, torticollis, convulsions etc.,
Ø Autonomic signs- salivation (due to inability to swallow), lacrimation, colic (tucked abdomen, tooth gnashing, groaning) constipation or diarrhoea, atony of rumen, urinary incontinence and vomiting even in cattle.
Ø Locomotor disturbances- stiff gait, ataxia, inco-ordination, muscle weakness to compulsive hyper motility (circling, pacing, running)
Ø Lesions: may not be seen in many cases. Gross lesions are – haemorrhagic gastroenteritis, congestion of vital organs and petechial or ecchymotic haemorrhages especially in coronary sulci. Anaemia, pale muscles, liver and kidney. Fluid in body cavities. Softening of kidney and cerebral cortices, inflamed abomasums/stomach and small intestine.
Microscopically-Anaemia, basophilic stippling of erythrocytes, acid-fast eosinophilic intra nuclear inclusions in renal/hepatic cells. These are not pathognomonic, but are said to be highly suggestive of Pb poisoning.
Dogs- congestion of meninges; (anaemia) very red bone marrow, radio-opacity of long bone (radius, ulna and metacarpals) metaphyses in young animals (lead – lines). Delayed closure of thoracic vertebral epiphyses, fatty and enlarged liver and spleen. Blue –line on the gums. Radiopaque material in the GI tract is helpful in diagnosis.
Differential diagnosis: OC, urea toxicity, show the same type of symptoms.
OC – body temperature is increased, marked neuromuscular signs, abnormal posturing and severe convulsive activity with postictal depression, and absence of blindness.
Urea – no blindness, diarrhoea is not prominent. Strychnine like convulsions with post ictal rigidity.
OP & carbamates have parasympathetic activity that can be treated with atropine.
Other substances that show the same signs - salt, strychnine, nicotine, fluoroacetate, arsenic, mercury and hypovitaminosis-A. In dogs the symptoms may mislead the vet. to diagnose it as either CD or Rabies.
Rx:
Cattle & Calves
1. Ca.Na 2 EDTA –
(1-2% W/V solution in 5% glucose @ 110 mg/kg b.i.d/2 days I/P or S/C.)
Skip the next 2 days, rpt. after 2 days.
(This interruption allows time for redistribution of lead from soft tissue into bone, the site where chelator acts). Ca. Na2 EDTA is not free from side effects; hence it has to be used very cautiously.
Dogs
Ca. Na2 EDTA 1% w/v solution in 5% glucose @25 mg/kg 4 times a day/5days.
D-penicillamine orally as a follow up to Ca.Na2 EDTA.
Dose- 35-110 mg/kg. Divided into 3or 4 daily doses for 1 wk. on 1wk. off.
D-penicillamine is contraindicated in animals with penicillin allergies.
DMSA(meso-2,3 dimercaptosuccinic acid)is the current drug of choice and is more specific than Ca. Na2 EDTA against lead, mercury and arsenic.
Dose-10mg/kg every 8hrs.orally for 10days.
2.Thiamine HCl. S/C or I/ M: Cattle-200 mg/kg. alternate day, Dogs 100-300 mg/kg.
3.Sedatives/tranquilizers to control nervous and behavioral signs, Gastric lavage and enema in dogs. Magnesium sulfate to precipitate Pb and act as saline purgative. I/V fluids. (contraindicated if CNS signs are seen). Antibiotics to counter infection due to immunosuppresion,
Blood lead/ ALA-D concentration is estimated to diagnose lead poisoning against the lead concentration of normal animals. Basophilic stippling of RBCs etc., confirm the existing symptomatology of lead.