2. Introduction
⢠Physical properties: Metallic arsenic (black in color) is not poisonous, as it is
not absorbed from the GIT. It is a normal constituent of all animal tissues, in
minute amounts.
⢠Toxic Compounds and its Uses
i. Arsenious oxide or arsenic trioxide
ii. Copper arsenite (Scheeleâs green) and copper acetoarsenite (Paris green or
emerald green)
iii. Sodium and potassium arsenate
iv. Arsenic sulfide
v. Arseniuretted hydrogen or arsine
vi. Natural sources of arsenic are soil, water and some sea fish (mussels, prawns).
Cause of endemic toxicity (from shallow tube-wells inserted for drinking water).
vii. Tobacco smoke, particularly cigars also contain arsenic, and in some beers as
impurities.
4. Mechanism of action
⢠Arsenic interferes with cellular respiration by uncoupling mitochondrial oxidative
phosphorylation
by combining with the sulfhydryl groups of mitochondrial enzymes, especially pyruvate
dehydrogenase
and certain phosphatases. Consequently, conversion of pyruvate to acetyl CoA is decreased,
citric acid cycle activity is decreased and production of cellular ATP is decreased.
⢠It inhibits cellular glucose uptake, gluconeogenesis, fatty acid oxidation and further production
of acetyl
CoA.
⢠Locally, it causes irritation of the mucous membranes, and remotely, depression of the
nervous system.
⢠Arsenic is a carcinogenic substance since lung, skin and bladder (transitional cell) carcinoma
has been observed in populations with multiple exposures
5.
6. Absorption
⢠It is absorbed orally through the GIT, skin
and lungs (arsine) or parenter
⢠It is present in almost all tissues, and
found in the greatest quantity in the liver,
followed by kidneys and spleen. In cases,
where the patient survives, it is found in
the muscles (for months), bones, hair,
nails and skin for years.
⢠It is excreted mainly by the kidneys
(urine), but some part through feces, bile,
sweat, milk, nails and hair.
⢠Arsenic is secreted into the stomach and
intestines after absorption, even when
given by routes other than oral.
⢠In cases of intermittent chronic poisoning
there will be successive deposits of
arsenic in the hair and nails.er than
mouth.
Excretion
7. Types
SIGNS & SYMPTOMS
Arsenic poisoning clinically manifests in two forms -
1. ACUTE POISONING:
2. CHRONIC ARSENIC POISONING / ARSENICOSIS / ARSENICISM
8. 1. ACUTE POISONING:
⢠Symptoms occur within 10 min to 1 hour of ingestion but may be delayed if taken with
food
⢠Fatal dose: 120â200 mg of arsenic trioxide (adults), 2 mg/kg (children).4
⢠Fatal period: 1â2 days.
⢠In acute exposures cholera like gastrointestinal symptoms. Respiratory failure and
pulmonary edema are common features associated with poisoning.
⢠In fulminant type, when large dose (> 3 g) is taken, the GIT symptoms are absent and
death occurs in 1â3 hours from shock and peripheral vascular failure.
⢠In narcotic type, the GIT symptoms are less. There is giddiness, formication,
tenderness of the muscles, delirium, coma and death. Rarely, there is complete
paralysis of the extremities.
⢠Arsine gas exposure causes hemolysis, damages the liver and kidneys
(hemoglobinuria and renal failure) and depresses the CNS. There is nausea,
vomiting, shaking chills, backache and anemia. The urine appears black due to
hemoglobinuria. Death may be preceded by anuria and convulsions.
9. SIGNS AND SYMPTOMS
1. GIT : Sweetish metallic taste, nausea, persistent vomiting, burning in mouth and throat,
and difficulty in swallowing, garlic odor in breath, intense thirst, pain in esophagus and
abdomen, purging accompanied by tenesmus, pain and irritation about the anus.
Initially, defecation is frequent and involuntary, dark-colored, but later it become
colorless, odorless and watery resembling rice-water.
2. RENAL: Oliguria, uremia, albuminuria, red cells and casts, pain during pulmonary
edema, ARDS, micturition.
3. CVS : Hypotension, pulmonary edema, ARDS, circulatory collapse, ventricular
tachycardia and fibrillation.
4. Hepatic :Fatty infiltration.
5. MUSCLE : Pain in limbs, weakness.
6. CNS : Headache, vertigo, hyperthermia, tremors, convulsions, coma, general paralysis.
7. Skin : Delayed loss of hair, skin eruptions, hyperkeratoses
10.
11.
12. Laboratory Investigations
⢠Urine: Excretion of > 50 Οg/l in 24 h urine is indicative of poisoning. Metabolites of arsenic
may be recovered in a urine specimen.
⢠Blood (serum arsenic > 0.9 Οg/dl), stool, liver, kidney and bones show presence of
arsenic. As with all heavy metals, microcytic hypochromic anemia is common.
⢠Hair: Arsenic > 75 Οg% is suggestive of poisoning.
⢠Nails: Presence of > 100 Οg% of arsenic is suggestive of poisoning.
⢠Radiopaque sign on abdominal X-ray.
⢠ECG: QRS broadening, QT prolongation, ST depression and T-wave flattening.
13.
14. Treatment
Hemodynamic stabilization and large amounts of solutions because of significant GI loss
i. Gastric lavage is done repeatedly with large amount of warm water and milk; activated charcoal
does not adsorb arsenic appreciably and is not recommended in patients whom co-ingestants are
not suspected.
ii. Demulcents (butter or greasy substances) prevent absorption.
iii. Whole bowel irrigation with polyethylene glycolmay be effective to prevent GIT absorption of
arsenic.
iv. Antidote is BAL or dimercaprol, given in a dose of3â5 mg/kg IM 4 hourly for 2 days, 6 hourly for
1 day and then 12 hourly for 10 days. Oral succimer(DMSA), 10 mg/kg every 8 hourly for 10 days
or dimerval (DMPS, drug of choice for treating most heavy metal poisonings), 200 mg IV 4 hourly
until oral product can be given in a dose of 100 mg TDS or QID may be used instead of BAL.
v. Alkalis should not be given by mouth as they increase the solubility of arsenic.
vi. Purgatives (castor oil/magnesium sulfate) are given to remove unabsorbed poison from
intestine.
vii. Glucose-saline with sodium bicarbonate is helpful to combat shock and improve alkali reserve.
viii. Hemodialysis or exchange transfusion may be done
15. Post-Mortem Findings
External
i. The body looks emaciated due to dehydration.
ii. Rigor mortis appears early.
iii. Putrefaction is delayed due to anti-bacterial action of arsenic and partly due to dehydration.
iv. The eyeballs are sunken and the skin is cyanosed.
v. Blood tinged vomitus may be found on body and clothes
Internal
i. The mucous membrane of the mouth, pharynx and esophagus may show inflammation or ulceration.
ii. Hemorrhages may be found in the abdominal organs and mesentery, and occasionally in the larynx,
trachea and lungs.
iii. Lungs: Congested, pulmonary edema with subpleural ecchymoses.
iv. Heart: Subendocardial petechial hemorrhages of the ventricle may be found, even when the
stomach shows little signs of irritation
16. v. Stomach: Mucosa is swollen, edematous, desquamated and red, either generally or in
patches, especially in the pyloric region. Usually, groups of petechiae are seen scattered
over the mucosa, but sometimes large submucosal and subperitoneal hemorrhages may be
seenâred velvety appearance. A mass of sticky mucus covers the mucosa in which
particles of arsenic may be seen. Congestion is most marked along the crest of the rugae.
Inflammation is more marked at the greater curvature, posterior part and the cardiac end of
the stomach.
vi. Small intestine: It contains large flakes of mucus with very little fecal matter. The
mucosa is pale violet and shows signs of inflammation with submucous hemorrhages along
its whole length.
vii. Cecum and rectum show slight inflammation.
viii. Liver, spleen and kidneys: Congested, enlarged and show cloudy swelling, and
occasionally fatty degeneration. Nephritis, and scarring of renal cortices are seen.
ix. Brain: Edema with patchy necrosis or hemorrhagic encephalitis. The meninges are
congested.
17.
18. 2. CHRONIC POISONING:
Chronic arsenic poisoning may occur due to:
1) Recovery from an acute poisoning.
2) Accidental ingestion of small doses repeatedly by those working with the metal.
3) Intake of food/drink in which there are traces of arsenic (may be homicidal in nature).
⢠It is divided into four stages
i. GIT disturbances
ii. Catarrhal changes
iii. Skin rashes
iv. Nervous disturbances.
⢠A metallic taste, excessive salivation, and garlic odor of breath and sweat may indicate chronic arsenic
poisoning. Melanosis and leucomelanosis with or without keratosis are the earliest symptoms of
arsenicosis.
19. Signs and symptons
⢠GIT : Nausea, vomiting, abdominal cramps, loss of appetite, constipation or diarrhea,
salivation.
⢠Ocular : Congestion, watering of the eyes, photophobia.
⢠RS : Cough, hoarseness of voice, bronchial catarrh, hemoptysis, dyspnea.
⢠SKIN
ďRash resembling fading measles rash
ďRaindrop pigmentation : Speckled brown pigmentation, mostly on the skin flexures,
temples, shoulders, eyelids and neck
ďLeucomelanosis : Macular areas of depigmentation on normal/hyperpigmented skin
ďAldrich-Mees lines : development of white bands of opacity in the nails of fingers and
toes
ďHyperkeratosis of the palms and soles with irregular thickening of the nails
⢠CNS : Peripheral neuropathy with tingling, numbness of hands and feet, polyneuritis,
anesthesia, paraesthesia with painful swelling (erythromelalgia), encephalopathy.
⢠CVS : Hypertension, ischemic heart disease, cardiac failure, dependent edema.
⢠Renal: Chronic nephritis, urine may be red or green in color, dysuria and anuria may develop
21. Treatment
i. Remove the patient from the source of exposure and administer BAL in usual doses.
ii. Vitamin B complex and IV sodium thiosulfate are useful.
iii. Symptomatic treatment.
22. Postmortem findings
External: Emaciation, pigmentation, keratosis, alopecia, white streaks on nails, jaundice,
wasting of muscles, and ulceration of nasal septum.
Internal
i. Stomach: It may be normal or may show a chronic gastritis. Some rugae may show
patchy inflammatory redness or focal ulceration.
ii. Small intestine: Reddish with thickened mucosa.
iii. Liver: Hepatomegaly, fatty degeneration or even necrosis with non-cirrhotic portal
fibrosis.
iv. Kidneys: Tubular necrosis.
v. Heart: Myocardial necrosis may be seen.
⢠Bone marrow histopathology will show hypoplasia.
⢠If arsenic poisoning is suspected, hair or tissue samples should be obtained for
confirmation.
23. Medicolegal Importance
⢠It was considered as an ideal homicidal poison as it was-
1. Cheap, colourless, tasteless, odourless
2. Easy to obtain
3. Easily administered with food and onset is gradual
4. Symptoms were similar to cholera
⢠Accidental poisoning in case of admixture with food or improper medical use
⢠Accidental chronic poisoning with contaminated tube well water is common in Asia
⢠Sometimes ingested or applied locally on abortion sticks to procure abortion.
⢠Arsenic exposure can be occupational in those working in metal foundry, mining, glass
production or in the semiconductor industry.
⢠It can be detected in decomposed/buried bodies in hair , nails etc. as it retards putrefaction.